Dentomaxillofacial characteristics of ectodermal dysplasia.

PubMed

Nakayama, Yumiko; Baba, Yoshiyuki; Tsuji, Michiko; Fukuoka, Hiroki; Ogawa, Takuya; Ohkuma, Mizue; Moriyama, Keiji

2015-02-01

The aim of this retrospective hospital-based study was to elucidate the dentomaxillofacial characteristics of ectodermal dysplasia. Six Japanese individuals (one male and five female; age range, 12.7-27.2 years) underwent comprehensive examinations, including history recording, cephalometric analysis, panoramic radiography, and analysis of dental models. All the subjects had two or more major manifestations for clinical diagnosis of ectodermal dysplasia (e.g., defects of hair, teeth, nails, and sweat glands). They presented hypodontia (mean number of missing teeth, 9.5; range, 5-14), especially in the premolar region, and enamel dysplasia. Five subjects had bilateral molar occlusion, whereas one subject had unilateral molar occlusion. The common skeletal features were small facial height, maxillary hypoplasia, counterclockwise rotation of the mandible, and mandibular protrusion. Interestingly, the maxillary first molars were located in higher positions and the upper anterior facial height was smaller than the Japanese norm. The results suggest that vertical and anteroposterior maxillary growth retardation, rather than lack of occlusal support due to hypodontia, leads to reduced anterior facial height in individuals with ectodermal dysplasia. © 2014 Japanese Teratology Society.

An evaluation of clinical, radiological and three-dimensional dental tomography findings in ectodermal dysplasia cases

PubMed Central

Doğan, Mehmet-Sinan; Callea, Michele; Aksoy, Orhan; Clarich, Gabriella; Günay, Ayşe; Günay, Ahmet; Güven, Sedat; Maglione, Michele; Akkuş, Zeki

2015-01-01

Background This study aimed to review the results related to head and jaw disorders in cases of ectodermal dysplasia. The evaluation of ectodermal dysplasia cases was made by clincal examination and examination of the jaw and facial areas radiologically and on cone-beam 3-dimensional dental tomography (CBCT) images. Material and Methods In the 36 cases evaluated in the study, typical clinical findings of pure hypohidrotic ectodermal displasia (HED) were seen, such as missing teeth, dry skin, hair and nail disorders. CBCT images were obtained from 12 of the 36 cases, aged 1.5- 45 years, and orthodontic analyses were made on these images. Results The clinical and radiological evaluations determined, hypodontia or oligodontia, breathing problems, sweating problems, a history of fever, sparse hair, saddle nose, skin peeling, hypopigmentation, hyperpigmentation, finger and nail deformities, conical teeth anomalies, abnormal tooth root formation, tooth resorption in the root, gingivitis, history of epilepsy, absent lachrymal canals and vision problems in the cases which included to the study. Conclusions Ectodermal dysplasia cases have a particular place in dentistry and require a professional, multi-disciplinary approach in respect of the chewing function, orthognathic problems, growth, oral and dental health. It has been understood that with data obtained from modern technologies such as three-dimensional dental tomography and the treatments applied, the quality of life of these cases can be improved. Key words: Ectodermal dysplasia, three-dimensional dental tomography. PMID:25662550

KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia.

PubMed

Shamseldin, Hanan E; Khalifa, Ola; Binamer, Yousef M; Almutawa, Abdulmonem; Arold, Stefan T; Zaidan, Hamad; Alkuraya, Fowzan S

2017-01-01

Ectodermal dysplasia is a highly heterogeneous group of disorders that variably affect the derivatives of the ectoderm, primarily skin, hair, nails and teeth. TP63, itself mutated in ectodermal dysplasia, links many other ectodermal dysplasia disease genes through a regulatory network that maintains the balance between proliferation and differentiation of the epidermis and other ectodermal derivatives. The ectodermal knockout phenotype of five mouse genes that regulate and/or are regulated by TP63 (Irf6, Ikkα, Ripk4, Stratifin, and Kdf1) is strikingly similar and involves abnormal balance towards proliferation at the expense of differentiation, but only the first three have corresponding ectodermal phenotypes in humans. We describe a multigenerational Saudi family with an autosomal dominant form of hypohidrotic ectodermal dysplasia in which positional mapping and exome sequencing identified a novel variant in KDF1 that fully segregates with the phenotype. The recapitulation of the phenotype we observe in this family by the Kdf1-/- mouse suggests a causal role played by the KDF1 variant.

Prosthodontic management of a patient with ectodermal dysplasia.

PubMed

Nandini, Yamini

2013-12-01

Ectodermal dysplasia is a rare congenital disease that affects the ectodermal structures. It is characterized by hypotrichosis, hypohidrosis and hypodontia. A 14-year-old boy with ectodermal dysplasia presenting with oligodontia and marked resorption of the maxillary and mandibular alveolar ridges is reported. Prosthetic rehabilitation in the form of a maxillary and mandibular partial denture was made with metal crowns on existing lower teeth to achieve appropriate vertical dimension. Significant improvement in speech, masticatory function and facial esthetics was achieved. Removable prosthodontics can provide an acceptable solution to esthetic, functional and psychological rehabilitation in patients with ectodermal dysplasia.

[Clinical and molecular study in a child with X-linked hypohidrotic ectodermal dysplasia].

PubMed

Callea, Michele; Yavuz, Izzet; Clarich, Gabriella; Cammarata-Scalisi, Francisco

2015-12-01

Ectodermal dysplasia encompasses more than 200 clinically distinct entities, which affect at least two structures derived from the ectoderm, including the skin, hair, nails, teeth, sweat glands, and sebaceous glands. X-linked hypohidrotic ectodermal dysplasia is the most common type and is caused by mutation of the EDA gene that encodes Ectodysplasin-A. It occurs in less than 1 in 100 000 individuals and is clinically characterized by hypodontia, hypohidrosis, hypotrichosis, and eye dis orders. We present a child evaluated in a multidisciplinary manner with clinical and molecular diagnosis of X-linked hypohidrotic ectodermal dysplasia with type missense mutation c.1133C> T; p.T378M in EDA gene.

Hypohidrotic ectodermal dysplasia: a clinical case with a longitudinal approach.

PubMed

Fraiz, Fabian Calixto; Gugisch, Renato Cordeiro; Cavalcante-Leão, Bianca Lopes; Macedo, Liliane Moreira

2014-11-01

This paper describes a clinical case of a male with hypohidrotic ectodermal dysplasia submitted to rehabilitation and occlusal dental interventions with follow-up from 3 to 14 years of age. Due to the severe effects on function and esthetics, the clinical manifestations of ectodermal dysplasia exert a negative impact on quality of life. However, oral rehabilitation in childhood poses a challenge due to growth and development. A male with hypohidrotic ectodermal dysplasia began dental intervention at the age of 3 years. The clinical and radiographic exams revealed the absence of several primary and permanent teeth and abnormal shape of the primary maxillary incisors. The facial characteristics were compatible with hypohidrotic ectodermal dysplasia, such as a prominent brow, everted lips, fattened bridge of the nose and small vertical facial height. The treatment proposed involved rehabilitation through successive temporary partial dentures, functional orthopedics of the jaws, esthetic reconstruction of the anterior teeth, timely occlusal intervention and preventive actions for the control of dental caries and plaque. The present case demonstrates that early care plays a fundamental role in minimizing the biopsychosocial consequences of hypohidrotic ectodermal dysplasia and preparing the patient for future oral rehabilitation. Although, the literature offers a number of papers describing dental treatment for ectodermal dysplasia, few cases include long-term follow-up and the use of a functional orthopedic appliance in combination with removable dentures in such patients.

Hereditary hypohidrotic ectodermal dysplasia: report of a rare case.

PubMed

Paramkusam, Geetha; Meduri, Venkateswarlu; Nadendla, Lakshmi Kavitha; Shetty, Namratha

2013-09-01

Hereditary Hypohidrotic Ectodermal Dysplasia (HHED), an X-linked, recessive, Mendelian character, is seen usually in males and it is inherited through female carriers. It is characterised by congenital dysplasia of one or more ectodermal structures and it is manifested by hypohidrosis, hypotrichosis and hypodontia. It results from abnormal morphogenesis of cutaneous and oral embryonic ectoderm. Here, we are presenting a rare case of HHED in a 19 year female with classic features of this condition.

Hereditary Hypohidrotic Ectodermal Dysplasia: Report of a Rare Case

PubMed Central

Paramkusam, Geetha; Meduri, Venkateswarlu; Nadendla, Lakshmi Kavitha; Shetty, Namratha

2013-01-01

Hereditary Hypohidrotic Ectodermal Dysplasia (HHED), an X-linked, recessive, Mendelian character, is seen usually in males and it is inherited through female carriers. It is characterised by congenital dysplasia of one or more ectodermal structures and it is manifested by hypohidrosis, hypotrichosis and hypodontia. It results from abnormal morphogenesis of cutaneous and oral embryonic ectoderm. Here, we are presenting a rare case of HHED in a 19 year female with classic features of this condition. PMID:24179947

Infantile bilateral glaucoma in a child with ectodermal dysplasia.

PubMed

Callea, Michele; Vinciguerra, Agatino; Willoughby, Colin E; Deroma, Laura; Clarich, Gabriella

2013-01-01

Ectodermal dysplasia is a rare disease which affects at least two ectodermal-derived structures such as hair, nails, skin, sweat glands and teeth. Approximately 200 different conditions have been classified as an ectodermal dysplasia and X-linked hypohidrotic ectodermal dysplasia (XHED) represents the commonest form. Clinically, XHED is characterized by hypotrichosis, hypohidrosis and hypodontia. A variety of ocular manifestations have been reported in XHED, the most common being dryness of eyes due to tear deficiency and instability of the film secondary to the absence of meibomian gland function. Here we report a child with the distinctive clinical features of XHED confirmed with molecular diagnosis who presented with infantile bilateral glaucoma, in addition to the classical ocular involvement in XHED.

An evaluation of clinical, radiological and three-dimensional dental tomography findings in ectodermal dysplasia cases.

PubMed

Doğan, Mehmet-Sinan; Callea, Michele; Yavuz, Ìzzet; Aksoy, Orhan; Clarich, Gabriella; Günay, Ayse; Günay, Ahmet; Güven, Sedat; Maglione, Michele; Akkuş, Zeki

2015-05-01

This study aimed to review the results related to head and jaw disorders in cases of ectodermal dysplasia. The evaluation of ectodermal dysplasia cases was made by clinical examination and examination of the jaw and facial areas radiologically and on cone-beam 3-dimensional dental tomography (CBCT) images. In the 36 cases evaluated in the study, typical clinical findings of pure hypohidrotic ectodermal displasia (HED) were seen, such as missing teeth, dry skin, hair and nail disorders. CBCT images were obtained from 12 of the 36 cases, aged 1.5- 45 years, and orthodontic analyses were made on these images. The clinical and radiological evaluations determined, hypodontia or oligodontia, breathing problems, sweating problems, a history of fever, sparse hair, saddle nose, skin peeling, hypopigmentation, hyperpigmentation, finger and nail deformities, conical teeth anomalies, abnormal tooth root formation, tooth resorption in the root, gingivitis, history of epilepsy, absent lachrymal canals and vision problems in the cases which included to the study. Ectodermal dysplasia cases have a particular place in dentistry and require a professional, multi-disciplinary approach in respect of the chewing function, orthognathic problems, growth, oral and dental health. It has been understood that with data obtained from modern technologies such as three-dimensional dental tomography and the treatments applied, the quality of life of these cases can be improved.

Odonto-onycho-dermal dysplasia in a patient homozygous for a WNT10A nonsense mutation and mild manifestations of ectodermal dysplasia in carriers of the mutation.

PubMed

Krøigård, Anne Bruun; Clemmensen, Ole; Gjørup, Hans; Hertz, Jens Michael; Bygum, Anette

2016-03-10

Odonto-onycho-dermal dysplasia (OODD) is a rare form of ectodermal dysplasia characterized by severe oligodontia, onychodysplasia, palmoplantar hyperkeratosis, dry skin, hypotrichosis, and hyperhidrosis of the palms and soles. The ectodermal dysplasias resulting from biallelic mutations in the WNT10A gene result in highly variable phenotypes, ranging from isolated tooth agenesis to OODD and Schöpf-Schulz-Passarge syndrome (SSPS). We identified a female patient, with consanguineous parents, who was clinically diagnosed with OODD. Genetic testing showed that she was homozygous for a previously reported pathogenic mutation in the WNT10A gene, c.321C > A, p.Cys107*. The skin and nail abnormalities were for many years interpreted as psoriasis and treated accordingly. A thorough clinical examination revealed hypotrichosis and hyperhidrosis of the soles and dental examination revealed agenesis of permanent teeth except the two maxillary central incisors. Skin biopsies from the hyperkeratotic palms and soles showed the characteristic changes of eccrine syringofibroadenomatosis, which has been described in patients with ectodermal dysplasias. Together with a family history of tooth anomalies, this lead to the clinical suspicion of a hereditary ectodermal dysplasia. This case illustrates the challenges of diagnosing ectodermal dysplasia like OODD and highlights the relevance of interdisciplinary cooperation in the diagnosis of rare conditions.

Ectodermal dysplasia (ED) syndrome.

PubMed

Chee, Siew-Yin; Wanga, Chung-Hsing; Lina, Wei-De; Tsaia, Fuu-Jen

2014-01-01

Ectodermal dysplasia (ED) syndrome comprises a large, heterogeneous group of inherited disorders that are defined by primary defects in the development of 2 or more tissues derived from the embryonic ectoderm. The tissues primarily involved are the skin and its appendages (including hair follicles, eccrine glands, sebaceous glands, nails) and teeth. The clinical features include sparse hair, abnormal or missing teeth, and an inability to sweat due to lack of sweat glands. One such case report of ectodermal dysplasia is presented here.

Characterization of X-linked Hypohidrotic Ectodermal Dysplasia (XL-HED) Hair and Sweat Gland Phenotypes Using Phototrichogram Analysis and Live Confocal Imaging

PubMed Central

Jones, Kyle B.; Goodwin, Alice F.; Landan, Maya; Seidel, Kerstin; Tran, Dong-Kha; Hogue, Jacob; Chavez, Miquella; Fete, Mary; Yu, Wenli; Hussein, Tarek; Johnson, Ramsey; Huttner, Kenneth; Jheon, Andrew H.; Klein, Ophir D.

2015-01-01

Hypohidrotic ectodermal dysplasia (HED) is the most common type of ectodermal dysplasia (ED), which encompasses a large group of syndromes that share several phenotypic features such as missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. X-linked hypohidrotic ectodermal dysplasia (XL-HED) is associated with mutations in ectodysplasin (EDA1). Hypohidrosis due to hypoplastic sweat glands and thin, sparse hair are phenotypic features that significantly affect the daily lives of XL-HED individuals and therefore require systematic analysis. We sought to determine the quality of life of individuals with XL-HED and to quantify sweat duct and hair phenotypes using confocal imaging, pilocarpine iontophoresis, and phototrichogram analysis. Using these highly sensitive and non-invasive techniques, we demonstrated that 11/12 XL-HED individuals presented with a complete absence of sweat ducts and that none produced sweat. We determined that the thin hair phenotype observed in XL-HED was due to multiple factors, such as fewer terminal hairs with decreased thickness and slower growth rate, as well as fewer follicular units and fewer hairs per unit. The precise characterization of XL-HED phenotypes using sensitive and non-invasive techniques presented in our study will improve upon larger genotype-phenotype studies and in the assessment of future therapies in XL-HED. PMID:23687000

Using implants for prosthodontic rehabilitation of a 4-year-old with ectodermal dysplasia.

PubMed

Toomarian, Lida; Ardakani, Mohammad Reza Talebi; Ramezani, Jamileh; Adli, Amin Rezaei; Tabari, Zahra Alizadeh

2014-01-01

Ectodermal dysplasia (ED) is an inherited disorder that affects ectodermally derived organs, such as teeth. Pathogenesis is thought to involve an altered epithelium-mesenchymal interaction. ED patients have oligodontia (or sometimes anodontia) in addition to other abnormalities involving the skin, sweat glands, or hair. Many different subtypes have been introduced in the literature. This article describes the case of a 4-year-old patient who, after being diagnosed with ED, was put on a treatment plan that involved mandibular implants, reshaping of the maxillary primary central incisors, and prosthetic dental rehabilitation. Due to the child's rapid growth, both dentures were changed 9 months post-treatment. Two years post-treatment, the maxillary denture was changed again and the child was placed under close supervision.

Acro-Dermato-Ungual-Lacrimal-Tooth Syndrome: An Uncommon Member of the Ectodermal Dysplasias.

PubMed

Whittington, Adam; Stein, Sarah; Kenner-Bell, Brandi

2016-09-01

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare form of autosomal dominant ectodermal dysplasia due to mutations in the TP63 gene, a locus that has also been implicated in other syndromic forms of ectodermal dysplasia. It shares many phenotypic characteristics with other TP63 gene mutation syndromes, often making an accurate diagnosis difficult. Long-term management and follow-up of the various sequelae of ectodermal dysplasia require an accurate diagnosis. We report a familial case of ADULT syndrome in a daughter, mother, and son and provide a brief review of the clinical characteristics of this syndrome. © 2016 Wiley Periodicals, Inc.

Ectodermal Dysplasia: A Genetic Review

PubMed Central

Prashanth, S

2012-01-01

Abstract Ectodermal dysplasia is a rare hereditary disorder with a characteristic physiognomy. It is a genetic disorder affecting the development or function of the teeth, hair, nails and sweat glands. Depending on the particular syndrome ectodermal dysplasia can also affect the skin, the lens or retina of the eye, parts of the inner ear, the development of fingers and toes, the nerves and other parts of the body. Each syndrome usually involves a different combination of symptoms, which can range from mild to severe. The history and lessons learned from hypohidrotic ectodermal dysplasia (HED) may serve as an example for unraveling of the cause and pathogenesis of other ectodermal dysplasia syndromes by demonstrating that phenotypically identical syndromes can be caused by mutations in different genes (EDA, EDAR, EDARADD), that mutations in the same gene can lead to different phenotypes and that mutations in the genes further downstream in the same signaling pathway (NEMO) may modify the phenotype quite profoundly. The aim of this paper is to describe and discuss the etiology, genetic review, clinical manifestations and treatment options of this hereditary disorder. How to cite this article: Deshmukh S, Prashanth S. Ectodermal Dysplasia: A Genetic Review. Int J Clin Pediatr Dent 2012; 5(3):197-202. PMID:25206167

Ectodermal dysplasia: a genetic review.

PubMed

Deshmukh, Seema; Prashanth, S

2012-09-01

Ectodermal dysplasia is a rare hereditary disorder with a characteristic physiognomy. It is a genetic disorder affecting the development or function of the teeth, hair, nails and sweat glands. Depending on the particular syndrome ectodermal dysplasia can also affect the skin, the lens or retina of the eye, parts of the inner ear, the development of fingers and toes, the nerves and other parts of the body. Each syndrome usually involves a different combination of symptoms, which can range from mild to severe. The history and lessons learned from hypohidrotic ectodermal dysplasia (HED) may serve as an example for unraveling of the cause and pathogenesis of other ectodermal dysplasia syndromes by demonstrating that phenotypically identical syndromes can be caused by mutations in different genes (EDA, EDAR, EDARADD), that mutations in the same gene can lead to different phenotypes and that mutations in the genes further downstream in the same signaling pathway (NEMO) may modify the phenotype quite profoundly. The aim of this paper is to describe and discuss the etiology, genetic review, clinical manifestations and treatment options of this hereditary disorder. How to cite this article: Deshmukh S, Prashanth S. Ectodermal Dysplasia: A Genetic Review. Int J Clin Pediatr Dent 2012; 5(3):197-202.

Diagnosis of X-Linked Hypohidrotic Ectodermal Dysplasia by Meibography and Infrared Thermography of the Eye.

PubMed

Kaercher, Thomas; Dietz, Jasna; Jacobi, Christina; Berz, Reinhold; Schneider, Holm

2015-09-01

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of ectodermal dysplasia. Clinical characteristics include meibomian gland disorder and the resulting hyperevaporative dry eye. In this study, we evaluated meibography and ocular infrared thermography as novel methods to diagnose XLHED. Eight infants, 12 boys and 14 male adults with XLHED and 12 healthy control subjects were subjected to a panel of tests including the ocular surface disease index (OSDI), meibography and infrared thermography, non-invasive measurement of tear film break-up time (NIBUT) and osmolarity, Schirmer's test, lissamine green staining and fluorescein staining. Sensitivity and specificity were determined for single tests and selected test combinations. Meibography had 100% sensitivity and specificity for identifying XLHED. Infrared thermography, a completely non-invasive procedure, revealed a typical pattern for male subjects with XLHED. It was, however, less sensitive (86% for adults and 67% for children) than meibography or a combination of established routine tests. In adults, OSDI and NIBUT were the best single routine tests (sensitivity of 86% and 71%, respectively), whereas increased tear osmolarity appeared as a rather unspecific ophthalmic symptom. In children, NIBUT was the most convincing routine test (sensitivity of 91%). Meibography is the most reliable ophthalmic examination to establish a clinical diagnosis in individuals with suspected hypohidrotic ectodermal dysplasia, even before genetic test results are available. Tear film tests and ocular surface staining are less sensitive in children, but very helpful for estimating the severity of ocular surface disease in individuals with known XLHED.

Individualized Plastic Reconstruction Strategy for Patients With Ectodermal Dysplasia Syndrome.

PubMed

Hou, Yikang; Jin, Yunbo; Lin, Xiaoxi; Chai, Gang; Zhang, Yan; Qi, Zuoliang

2017-06-01

Ectodermal dysplasia syndrome is a hereditary disease of ectodermal origin. Appearances of nail dystrophy, alopecia or hypotrichosis, saddle nose deformity, and palmoplantar hyperkeratosis are usually associated with a lack of sweat glands as well as partial or complete absence of teeth. These manifestations are usually corrected only with oral rehabilitation by mounting dentures. In this study, plastic rehabilitation was developed to correct the special features of patients with ectodermal dysplasia. Four men and 1 woman with ectodermal dysplasia syndrome were treated. Four patients showed dysostosis of the midface, and rhinoplasty with costal bone was performed, whereas cosmetic operation aiming to repair soft tissue defects was adopted for the last patient. After plastic corrections, all 5 patients were satisfied with the results and had no social embarrassment.

Phenotypic heterogeneity and mutational spectrum in a cohort of 45 Italian males subjects with X-linked ectodermal dysplasia.

PubMed

Guazzarotti, L; Tadini, G; Mancini, G E; Giglio, S; Willoughby, C E; Callea, M; Sani, I; Nannini, P; Mameli, C; Tenconi, A A; Mauri, S; Bottero, A; Caimi, A; Morelli, M; Zuccotti, G V

2015-04-01

Ectodermal dysplasias (EDs) are a group of genetic disorders characterized by the abnormal development of the ectodermal-derived structures. X-linked hypohidrotic ectodermal dysplasia, resulting from mutations in ED1 gene, is the most common form. The main purpose of this study was to characterize the phenotype spectrum in 45 males harboring ED1 mutations. The study showed that in addition to the involvement of the major ectodermal tissues, the majority of patients also have alterations of several minor ectodermal-derived structures. Characterizing the clinical spectrum resulting from ED1 gene mutations improves diagnosis and can direct clinical care. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anhidrotic ectodermal dysplasia gene region cloned in yeast artificial chromosomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kere, J.; Grzeschik, K.H.; Limon, J.

1993-05-01

Anhidrotic ectodermal dysplasia (EDA), an X-chromosomal recessive disorder, is expressed in a few females with chromosomal translocations involving bands Xq12-q13. Using available DNA markers from the region and somatic cell hybrids the authors mapped the X-chromosomal breakpoints in two such translocations. The breakpoints were further mapped within a yeast artificial chromosome contig constructed by chromosome walking techniques. Genomic DNA markers that map between the two translocation breakpoints were recovered representing putative portions of the EDA gene. 32 refs., 3 figs., 1 tab.

Molecular genetic analysis of consanguineous Pakistani families with autosomal recessive hypohidrotic ectodermal dysplasia.

PubMed

Bibi, Nosheen; Ahmad, Saeed; Ahmad, Wasim; Naeem, Muhammad

2011-02-01

Hypohidrotic ectodermal dysplasia is an inherited disorder characterized by defective development of teeth, hairs and sweat glands. X-linked hypohidrotic ectodermal dysplasia is caused by mutations in the EDA gene, and autosomal forms of hypohidrotic ectodermal dysplasia are caused by mutations in either the EDAR or the EDARADD genes. To study the molecular genetic cause of autosomal recessive hypohidrotic ectodermal dysplasia in three consanguineous Pakistani families (A, B and C), genotyping of 13 individuals was carried out by using polymorphic microsatellite markers that are closely linked to the EDAR gene on chromosome 2q11-q13 and the EDARADD gene on chromosome 1q42.2-q43. The results revealed linkage in the three families to the EDAR locus. Sequence analysis of the coding exons and splice junctions of the EDAR gene revealed two mutations: a novel non-sense mutation (p.E124X) in the probands of families A and B and a missense mutation (p.G382S) in the proband of family C. In addition, two synonymous single-nucleotide polymorphisms were also identified. The finding of mutations in Pakistani families extends the body of evidence that supports the importance of EDAR for the development of hypohidrotic ectodermal dysplasia. © 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.

Dental and maxillofacial characteristics of six Japanese individuals with ectrodactyly-ectodermal dysplasia-clefting syndrome.

PubMed

Okamura, Erika; Suda, Naoto; Baba, Yoshiyuki; Fukuoka, Hiroki; Ogawa, Takuya; Ohkuma, Mizue; Ahiko, Nozomi; Yasue, Akihiro; Tengan, Toshimoto; Shiga, Momotoshi; Tsuji, Michiko; Moriyama, Keiji

2013-03-01

Objective : Ectrodactyly-ectodermal dysplasia-clefting syndrome is a congenital anomaly characterized by ectodermal dysplasia, ectrodactyly, cleft lip and palate, and lacrimal duct anomalies. Because this syndrome is frequently accompanied by a congenital lack of teeth, narrow palate, and malocclusion, comprehensive orthodontic intervention is required. Design : To highlight the specific dental and maxillofacial characteristics of ectrodactyly-ectodermal dysplasia-clefting syndrome, six Japanese individuals diagnosed with the syndrome are described here. Patients : The subjects consisted of two boys and four girls (age range, 6.0 to 13.9 years) diagnosed with ectrodactyly-ectodermal dysplasia-clefting syndrome by medical and dental specialists. Their conditions included ectodermal dysplasia (hypodontia, microdontia, enamel hypoplasia, and abnormalities in hair and nails), cleft lip and/or palate, and ectrodactyly. Cephalograms, panoramic x-rays, and dental casts were taken; systemic complications were recorded at the first visit to our dental hospital. Results : All individuals had severe oligodontia with 9 to 18 missing teeth. The missing teeth were mainly maxillary and mandibular incisors and second bicuspids, arranged in a symmetrical manner. Cephalometric analysis showed retruded and short maxilla due to cleft lip and/or palate. It is interesting that all individuals showed a characteristically shaped mandibular symphysis with a retruded point B. It is likely that this unusual symphyseal morphology is due to the lack of mandibular incisors. Conclusions : This study demonstrates the presence of severe oligodontia in the incisal and premolar regions and describes a characteristic maxillary and mandibular structure in Japanese individuals with ectrodactyly-ectodermal dysplasia-clefting syndrome.

Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET.

PubMed

Shalom-Feuerstein, Ruby; Serror, Laura; Aberdam, Edith; Müller, Franz-Josef; van Bokhoven, Hans; Wiman, Klas G; Zhou, Huiqing; Aberdam, Daniel; Petit, Isabelle

2013-02-05

Ectodermal dysplasia is a group of congenital syndromes affecting a variety of ectodermal derivatives. Among them, ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome is caused by single point mutations in the p63 gene, which controls epidermal development and homeostasis. Phenotypic defects of the EEC syndrome include skin defects and limbal stem-cell deficiency. In this study, we designed a unique cellular model that recapitulated major embryonic defects related to EEC. Fibroblasts from healthy donors and EEC patients carrying two different point mutations in the DNA binding domain of p63 were reprogrammed into induced pluripotent stem cell (iPSC) lines. EEC-iPSC from both patients showed early ectodermal commitment into K18(+) cells but failed to further differentiate into K14(+) cells (epidermis/limbus) or K3/K12(+) cells (corneal epithelium). APR-246 (PRIMA-1(MET)), a small compound that restores functionality of mutant p53 in human tumor cells, could revert corneal epithelial lineage commitment and reinstate a normal p63-related signaling pathway. This study illustrates the relevance of iPSC for p63 related disorders and paves the way for future therapy of EEC.

Mini-implants: alternative for oral rehabilitation of a child with ectodermal dysplasia.

PubMed

Mello, Bianca Zeponi Fernandes; Silva, Thiago Cruvinel; Rios, Daniela; Machado, Maria Aparecida Andrade Moreira; Valarelli, Fabrício Pinelli; Oliveira, Thais Marchini

2015-01-01

Ectodermal dysplasia is a rare congenital disease that affects several structures of ectodermal origin. The most commonly related oral characteristics are hypodontia, malformed teeth and underdeveloped alveolar ridges. New alternative treatments are needed due to the failure of the conventional prosthesis retention. This case report outlines the oral rehabilitation treatment of a 9-year-old girl with ectodermal dysplasia. The treatment was performed with conventional prosthesis upon mini-implants. The mini-implants provided prosthetic retention. The patient reported a good adaptation of the dental prosthesis and satisfaction with the treatment. The increased self-esteem improved the socialization skills of the girl. In this case report, use of prosthesis with mini-implants was satisfactory for prosthetic retention. However, clinical studies with long-term follow-up are needed to test the mini-implants as an alternative for oral rehabilitation of children with ectodermal dysplasia.

Mutation of KREMEN1, a modulator of Wnt signaling, is responsible for ectodermal dysplasia including oligodontia in Palestinian families.

PubMed

Issa, Yasmin A; Kamal, Lara; Rayyan, Amal Abu; Dweik, Dima; Pierce, Sarah; Lee, Ming K; King, Mary-Claire; Walsh, Tom; Kanaan, Moien

2016-10-01

Tooth development is controlled by the same processes that regulate formation of other ectodermal structures. Mutations in the genes underlying these processes may cause ectodermal dysplasia, including severe absence of primary or permanent teeth. Four consanguineous Palestinian families presented with oligodontia and hair and skin features of ectodermal dysplasia. Appearance of ectodermal dysplasia was consistent with autosomal recessive inheritance. Exome sequencing followed by genotyping of 56 informative relatives in the 4 families suggests that the phenotype is due to homozygosity for KREMEN1 p.F209S (c.626 T>C) on chromosome 22 at g.29,521,399 (hg19). The variant occurs in the highly conserved extracellular WSC domain of KREMEN1, which is known to be a high affinity receptor of Dickkopf-1, a component of the Dickkopf-Kremen-LRP6 complex, and a potent regulator of Wnt signaling. The Wnt signaling pathway is critical to development of ectodermal structures. Mutations in WNT10A, LRP6, EDA, and other genes in this pathway lead to tooth agenesis with or without other ectodermal anomalies. Our results implicate KREMEN1 for the first time in a human disorder and provide additional details on the role of the Wnt signaling in ectodermal and dental development.

Ectodermal Dysplasia with Anodontia: A Report of Two Cases

PubMed Central

Bani, Mehmet; Tezkirecioglu, Ali Melih; Akal, Nese; Tuzuner, Tamer

2010-01-01

Ectodermal dysplasia is a hereditary disorder that occurs as a consequence of disturbances in the ectoderm of the developing embryo. The triad of nail dystrophy, alopecia or hypotrichosis and palmoplantar hyperkeratosis is usually accompanied by a lack of sweat glands and a partial or complete absence of primary and/or permanent dentition. Two case reports illustrating the prosthetic rehabilitation of 2 young boys with anhidrotic ectodermal dysplasia associated with severe anodontia are presented. Since the oral rehabilitation of these cases is often difficult; particularly in pediatric patients, treatment should be administered by a multidisciplinary team involving pediatric dentistry, orthodontics, prosthodontics and oral-maxillofacial surgery. PMID:20396456

p63 in skin development and ectodermal dysplasias

PubMed Central

Koster, Maranke I.

2010-01-01

The transcription factor p63 is critically important for skin development and maintenance. Processes that require p63 include epidermal lineage commitment, epidermal differentiation, cell adhesion, and basement membrane formation. Not surprisingly, alterations in the p63 pathway underlie a subset of ectodermal dysplasias, developmental syndromes in which the skin and skin appendages do not develop normally. This review summarizes the current understanding of the role of p63 in normal development and ectodermal dysplasias. PMID:20445549

Ectodermal Dysplasia: A Clinical Overview for the Dental Practitioner.

PubMed

Halai, Tina; Stevens, Claire

2015-10-01

The term ectodermal dysplasia (ED) is used to describe a group of rare congenital disorders characterized by abnormalities of two or more ectodermal structures such as the skin, hair, nails, teeth and sweat glands. This paper will give an overview of the aetiology of ED and describe the manifestations and dental management of this condition. In particular, the important role of the dental practitioner in the identification and management of patients with ED will be highlighted. CPD/Clinical Relevance: Dental practitioners should be aware of the oral features of ectodermal dysplasia and be able to make timely referrals and provide appropriate continuing care for these patients.

Hypohidrotic ectodermal dysplasia with ankylosis of temporomandibular joint and cleft palate: A rare presentation

PubMed Central

Goyal, Manisha; Pradhan, Gaurav; Gupta, Sunita; Kapoor, Seema

2015-01-01

The ectodermal dysplasias are a heterogenous group of diseases, which have one or more anomalies of the hair, teeth, nails, and sweat glands. Hypohidrotic ectodermal dysplasia (HED) is the most common type and is usually transmitted as an X-linked recessive trait. It is characterized by classical triad of hypotrichosis, anhidrosis/hypohidrosis, and hypodontia/anodontia. Here, we describe an Indian boy affected with HED and rare features including ankylosis of temporomandibular joint and cleft palate. PMID:25684924

FOXI2: a possible gene contributing to ectodermal dysplasia.

PubMed

Kurban, Mazen; Zeineddine, Savo Bou; Hamie, Lamiaa; Safi, Remi; Abbas, Ossama; Kibbi, Abdul Ghani; Bitar, Fadi; Nemer, Georges

2017-12-01

Cardio-facio-cutaneous syndrome (CFC), Noonan syndrome (NS), and Costello syndrome are a group of diseases that belong to the RASopathies. The syndromes share clinical features making diagnosis a challenge. To investigate the phenotype and genotype of a 10-year-old Iraqi girl with overlapping features of CFC, NS, and Costello syndromes, with additional features of ectodermal dysplasia. DNA was examined by exome sequencing and protein expression by immunohistochemistry. Exome sequencing identified a mutation in the SOS1 gene and a de novo deletion in the FOXI2 gene which was neither present in the international databases, nor in 400 chromosomes from the same population. Based on immunohistochemical staining, FOXI2 was identified in the basal cell layer of the skin and overlapped with the expression of P63, a major player in ectodermal dysplasia. We therefore suggest screening for FOXI2 mutation in the setting of ectodermal features that are not associated with genes known to contribute to ectodermal dysplasia.

Multidisciplinary management of hypohydrotic ectodermal dysplasia – a case report

PubMed Central

Joseph, Suja; Cherackal, George J; Jacob, Jose; Varghese, Alex K

2015-01-01

Key Clinical Message Hypohydrotic ectodermal dysplasia is a hereditary disorder, which affects ectodermal derivatives. It manifests several abnormalities of the teeth, and is commonly inherited through female carriers. This case report presents a patient with compromised esthetics and function. A multidisciplinary approach was planned involving an oral pathologist, endodontist, orthodontist and a prosthodontist. PMID:25984305

Anesthetic management of a pediatric patient with hypohidrotic ectodermal dysplasia undergoing emergency surgery.

PubMed

Ahiskalioglu, Elif Oral; Ahiskalioglu, Ali; Firinci, Binali; Dostbil, Aysenur; Aksoy, Mehmet

2015-01-01

Ectodermal dysplasias are rare conditions with a triad of hypotrichosis, anodontia and anhidrosis. In literature review there have been only a few reports of anesthetic management of patients with ectodermal dysplasias. Hyperthermia is a very serious risk which may occur due to the defect of sweat glands. The present case involves a 10-year-old child with ectodermal dysplasia who presented with an acute abdomen and was considered for an emergency surgery. Our aim was to demonstrate the successful management of this case using a combination of general and epidural anesthesia. It is important for anesthesiologist to have information about this syndrome in case of emergency operations, since it can prevent serious complications and even save lives. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Clinical outcomes of implant therapy in ectodermal dysplasia patients: a systematic review.

PubMed

Wang, Y; He, J; Decker, A M; Hu, J C; Zou, D

2016-08-01

The purpose of this review was to determine the outcome of oral function reconstruction in ectodermal dysplasia (ED) patients who have received dental implant therapy. A search was made of the PubMed and Web of Science databases; key words used were "(ectodermal dysplasia) AND (implant OR implants)", with supplementary retrieval key words "dental implant", "zygomatic implant", "anodontia", and "edentulous". Patient age, use of bone graft, implant site, type of implant, and survival rate of the implants were included in the subsequent data analysis. Forty-five articles published between 1988 and October 2015 were included in this analysis. The cases of a total of 96 patients were retrieved (22 children and 74 adults); these patients received a total of 701 implants. Fourteen implants were removed during a median follow-up time of 24 months. The 24-month implant survival rate was 97.9% in adult subjects and 98.6% in children. Sixty-eight percent of adult patients underwent bone augmentation prior to implant placement. Based on this review, dental implants are commonly used in the oral reconstruction of ED patients. However, long-term data on bone augmentation and implant success are needed, as well as additional clinical evidence on bone resorption, the esthetic outcomes of implant therapy, and physiological considerations in ED patients. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

The management of ectodermal dysplasia and severe hypodontia. International conference statements.

PubMed

Hobkirk, J A; Nohl, F; Bergendal, B; Storhaug, K; Richter, M K

2006-09-01

An international conference on ectodermal dysplasias and hypodontia, held in London in 2004, featured a session devoted to the management of the ectodermal dysplasias and severe hypodontia. This paper presents a set of statements prepared by an international specialist panel, including representatives of patient support groups, who presented and subsequently debated a series of papers on this subject. The following topics were explored: potential roles of patient support groups; core care standards, including the roles and composition of medical and dental multidisciplinary teams for treating these conditions; the format of a baseline data set for patients with an ED; and priorities for research in ectodermal dysplasias, with particular regard to laboratory and clinical studies, and research methodology. The statements are intended to form an international framework for developing patient care pathways, and collaborative research in this field.

Unusual manifestations of ectodermal dysplasia-syndactyly syndrome type I in two Yemeni siblings.

PubMed

Mohammad, Alshami

2015-01-15

Ectodermal dysplasias (EDs) are a group of genodermatoses characterized by malformations of tissues derived from the ectoderm, including the skin, its appendages (hair, nails, sweat glands), teeth, and the breasts. Ectodermal dysplasia syndactyly syndrome (EDSS) is a rare, newly described type of ED involving syndactyly. We report 2 Yemeni siblings with typical EDSS manifestations, including bilateral, partial cutaneous syndactyly of the fingers and toes; sparse, coarse, brittle scalp hair, eyebrows, and eyelashes; and conical, widely spaced teeth with enamel notches. In addition, the siblings presented with other features hitherto not described for this syndrome, such as adermatoglyphia, onychogryphosis, hypoplastic widely spaced nipples, hypoplastic thumbs, and red scalp hair.

Requirement of Smad4 from Ocular Surface Ectoderm for Retinal Development.

PubMed

Li, Jing; Wang, Shusheng; Anderson, Chastain; Zhao, Fangkun; Qin, Yu; Wu, Di; Wu, Xinwei; Liu, Jia; He, Xuefei; Zhao, Jiangyue; Zhang, Jinsong

2016-01-01

Microphthalmia is characterized by abnormally small eyes and usually retinal dysplasia, accounting for up to 11% of the blindness in children. Right now there is no effective treatment for the disease, and the underlying mechanisms, especially how retinal dysplasia develops from microphthalmia and whether it depends on the signals from lens ectoderm are still unclear. Mutations in genes of the TGF-β superfamily have been noted in patients with microphthalmia. Using conditional knockout mice, here we address the question that whether ocular surface ectoderm-derived Smad4 modulates retinal development. We found that loss of Smad4 specifically on surface lens ectoderm leads to microphthalmia and dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the delayed or failed differentiation and apoptosis of retinal cells. Microarray analyses revealed that members of Hedgehog and Wnt signaling pathways are affected in the knockout retinas, suggesting that ocular surface ectoderm-derived Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest that defective of ocular surface ectoderm may affect retinal development.

Requirement of Smad4 from Ocular Surface Ectoderm for Retinal Development

PubMed Central

Li, Jing; Wang, Shusheng; Anderson, Chastain; Zhao, Fangkun; Qin, Yu; Wu, Di; Wu, Xinwei; Liu, Jia; He, Xuefei; Zhao, Jiangyue; Zhang, Jinsong

2016-01-01

Microphthalmia is characterized by abnormally small eyes and usually retinal dysplasia, accounting for up to 11% of the blindness in children. Right now there is no effective treatment for the disease, and the underlying mechanisms, especially how retinal dysplasia develops from microphthalmia and whether it depends on the signals from lens ectoderm are still unclear. Mutations in genes of the TGF-β superfamily have been noted in patients with microphthalmia. Using conditional knockout mice, here we address the question that whether ocular surface ectoderm-derived Smad4 modulates retinal development. We found that loss of Smad4 specifically on surface lens ectoderm leads to microphthalmia and dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the delayed or failed differentiation and apoptosis of retinal cells. Microarray analyses revealed that members of Hedgehog and Wnt signaling pathways are affected in the knockout retinas, suggesting that ocular surface ectoderm-derived Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest that defective of ocular surface ectoderm may affect retinal development. PMID:27494603

A case of probable autosomal recessive ectodermal dysplasia with corkscrew hairs and mental retardation in a family with tuberous sclerosis.

PubMed

Argenziano, G; Monsurrò, M R; Pazienza, R; Delfino, M

1998-02-01

We describe a woman with a probable autosomal recessive ectodermal dysplasia with corkscrew hairs and mental retardation in a family with tuberous sclerosis. Other findings included syndactyly, typical facies, dental abnormalities, dermatoglyphic hypoplasia, epidermal ridge sweat pore count slightly below normal, and keratosis pilaris. Clinical studies and genetic analysis excluded the diagnosis of tuberous sclerosis in our patient. We conclude that she has ectodermal dysplasia associated with mental retardation. This association has been described previously; it suggests the possible interrelationship of a community of ectodermal dysplasia syndromes with a distinctive structural hair abnormality (pili torti et canaliculi), variable midfacial malformations, limb defects, and other features such as mental retardation. The similarity of our patient to that described by Whiting et al. and Abramovits-Ackerman et al. suggests the autonomy of this syndrome.

A novel mutation in homeobox DNA binding domain of HOXC13 gene underlies pure hair and nail ectodermal dysplasia (ECTD9) in a Pakistani family.

PubMed

Khan, Anwar Kamal; Muhammad, Noor; Aziz, Abdul; Khan, Sher Alam; Shah, Khadim; Nasir, Abdul; Khan, Muzammil Ahmad; Khan, Saadullah

2017-04-12

Pure hair and nail ectodermal dysplasia (PHNED) is a congenital disorder of hair abnormalities and nail dysplasia. Both autosomal recessive and dominant inheritance fashion of PHNED occurs. In literature, to date, five different forms of PHNED have been reported at molecular level, having three genes known and two loci with no gene yet. In this study, a four generations consanguineous family of Pakistani origin with autosomal recessive PHNED was investigated. Affected members exhibited PHNED phenotypes with involvement of complete hair loss and nail dysplasia. To screen for mutation in the genes (HOXC13, KRT74, KRT85), its coding exons and exons-intron boundaries were sequenced. The 3D models of normal and mutated HOXC13 were predicted by using homology modeling. Through investigating the family to known loci, the family was mapped to ectodermal dysplasia 9 (ECTD9) loci with genetic address of 12q13.13. Mutation screening revealed a novel missense mutation (c.929A > C; p.Asn310Thr) in homeobox DNA binding domain of HOXC13 gene in affected members of the family. Due to mutation, loss of hydrogen bonding and difference in potential energy occurs, which may resulting in alteration of protein function. This is the first mutation reported in homeodomain, while 5 th mutation reported in HOXC13 gene causing PHNED.

Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia.

PubMed

Schneider, Holm; Faschingbauer, Florian; Schuepbach-Mallepell, Sonia; Körber, Iris; Wohlfart, Sigrun; Dick, Angela; Wahlbuhl, Mandy; Kowalczyk-Quintas, Christine; Vigolo, Michele; Kirby, Neil; Tannert, Corinna; Rompel, Oliver; Rascher, Wolfgang; Beckmann, Matthias W; Schneider, Pascal

2018-04-26

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia (XLHED), in which the development of sweat glands is irreversibly impaired, an condition that can lead to life-threatening hyperthermia. We observed normal development of mouse fetuses with Eda mutations after they had been exposed in utero to a recombinant protein that includes the receptor-binding domain of EDA. We administered this protein intraamniotically to two affected human twins at gestational weeks 26 and 31 and to a single affected human fetus at gestational week 26; the infants, born in week 33 (twins) and week 39 (singleton), were able to sweat normally, and XLHED-related illness had not developed by 14 to 22 months of age. (Funded by Edimer Pharmaceuticals and others.).

Ectrodactyly, Ectodermal dysplasia, and Cleft Lip-Palate Syndrome; Its Association with Conductive Hearing Loss

ERIC Educational Resources Information Center

Robinson, Geoffrey C.; And Others

1973-01-01

Conductive hearing loss associated with the ectrodactyly, ectodermal dysplasia, and cleft lip palate syndrome was reported in one sporadic case and in a pedigree with four cases in three generations. (GW)

Novel homozygous mutation, c.400C>T (p.Arg134*), in the PVRL1 gene underlies cleft lip/palate-ectodermal dysplasia syndrome in an Asian patient.

PubMed

Yoshida, Kazue; Hayashi, Ryota; Fujita, Hideki; Kubota, Masaya; Kondo, Mai; Shimomura, Yutaka; Niizeki, Hironori

2015-07-01

Cleft lip/palate-ectodermal dysplasia syndrome is a rare, autosomal recessive disorder caused by homozygous loss-of-function mutations of the poliovirus receptor-like 1 (PVRL1) gene encoding nectin-1. Nectin-1 is a cell-cell adhesion molecule that is important for the initial step in the formation of adherens junctions and tight junctions; it is expressed in keratinocytes, neurons, and the developing face and palate. Clinical manifestations comprise a unique facial appearance with cleft lip/palate, ectodermal dysplasia, cutaneous syndactyly of the fingers and/or toes, and in some cases, mental retardation. We present the first report, to our knowledge, of an Asian individual with cleft lip/palate-ectodermal dysplasia syndrome with a novel PVRL1 mutation. A 7-year-old Japanese boy, the first child of a consanguineous marriage, showed hypohidrotic ectodermal dysplasia with sparse, brittle, fine, dry hair and hypodontia, the unique facial appearance with cleft lip/palate, cutaneous syndactyly of the fingers and mild mental retardation. Scanning electron microscopic examination of the hair demonstrated pili torti and pili trianguli et canaliculi. Mutation analysis of exon 2 of PVRL1 revealed a novel homozygous nonsense mutation, c.400C>T (p.Arg134*). His parents were heterozygous for the mutant alleles. All four PVRL1 mutations identified in cleft lip/palate-ectodermal dysplasia syndrome to date, including this study, resulted in truncated proteins that lack the transmembrane domain and intracellular domain of nectin-1, which is necessary to initiate the cell-cell adhesion process. © 2015 Japanese Dermatological Association.

Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.

PubMed

Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J; Schneider, Pascal

2014-02-14

Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated.

Generation and Characterization of Function-blocking Anti-ectodysplasin A (EDA) Monoclonal Antibodies That Induce Ectodermal Dysplasia*

PubMed Central

Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J.; Schneider, Pascal

2014-01-01

Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated. PMID:24391090

Prosthetic Rehabilitation of a Child Suffering from Hypohidrotic Ectodermal Dysplasia with Complete Anodontia

PubMed Central

Nikhil, M; Chugh, Anshul; Narwal, Anjali

2012-01-01

ABSTRACT A 7-year-old male, described in the case report, exhibited many of the manifestations of ectodermal dysplasia as well as behavioral problems. The treatment to improve his appearance and oral function included a removable prosthesis. The results were significant improvements in speech, masticatory function, and facial esthetics, contributing to the development of normal dietary habits, and the improved and more rapid social integration of the child. How to cite this article: Bala S, Nikhil M, Chugh A, Narwal A. Prosthetic Rehabilitation of a Child Suffering from Hypohidrotic Ectodermal Dysplasia with Complete Anodontia. Int J Clin Pediatr Dent 2012;5(2):148-150. PMID:25206157

Hypohidrotic Ectodermal Dysplasia: Breastfeeding Complications Due to Impaired Breast Development.

PubMed

Wahlbuhl-Becker, Mandy; Faschingbauer, Florian; Beckmann, Matthias W; Schneider, Holm

2017-04-01

Background X-linked hypohidrotic ectodermal dysplasia (XLHED), the most common form of ectodermal dysplasia, is caused by mutations in the gene EDA. While only affected men develop the full-blown clinical picture, females who are heterozygous for an EDA mutation often also show symptoms such as hypodontia, hypotrichosis and hypohidrosis. These women may also suffer from malformations of the mammary gland which represent not just a cosmetic problem but can limit their breastfeeding capability. This paper summarizes the findings of the first systematic study on the impact of hypohidrotic ectodermal dysplasia on breastfeeding. Patients Thirty-eight adult female members of the German-Swiss-Austrian ectodermal dysplasia patient support group participated in a structured interview; most of them also agreed to a photodocumentation of their mammary region. Thirty-one women carried mutations in EDA (Group A) and seven were affected by other forms of hypohidrotic ectodermal dysplasia (Group B). Results 39 % of the women of Group A reported that their breasts were of different size or entirely absent on one side. In Group B, 86 % of the women reported differently sized or even absent breasts; two of these women lacked both breasts entirely. Most women described their nipples as exceptionally flat. 10 % of the women of Group A had more than two nipples. The high percentage of deviations from the norm was confirmed in the photodocumentation. Both groups had few or no sebaceous glands of Montgomery in the areolar region. Around 80 % of interviewed women had children and had attempted to breastfeed their first child. 67 % of the mothers in Group A had had difficulty in breastfeeding their infants and generally attributed this difficulty to their flat nipples. All of the mothers in Group B reported difficulties in breastfeeding; 60 % had not been able to breastfeed their first child. Conclusion Mothers with hypohidrotic ectodermal dysplasia very often have difficulty in breastfeeding because of their impaired breast development. This causal relationship needs to be taken into account in lactation counseling.

Ectodermal dysplasia with blindness in sibs on the island of Rodrigues.

PubMed Central

Wallis, C E; Beighton, P

1992-01-01

A brother and sister from the island of Rodrigues had mental retardation, blindness owing to severe ocular malformations, short stature, dysmorphic facial features, hypotrichosis, and dental abnormalities. It is likely that they have a hitherto unrecognised autosomal recessive ectodermal dysplasia syndrome. Images PMID:1583659

[Pigmentosum retinis and tubulo-interstitial nephronophtisis in Sensenbrenner syndrome: a case report].

PubMed

Costet, C; Betis, F; Bérard, E; Tsimaratos, M; Sigaudy, S; Antignac, C; Gastaud, P

2000-02-01

Sensenbrenner syndrome or cranio-ectodermal dysplasia is an extremely rare autosomal recessive condition (12 cases reported in literature). Our observation shows the possibility of both ocular and renal involvement associated with cranio-ectodermal abnormalities. and method:We report the case of a girl who presented a typical cranio-ectodermal syndrome with dolicocephaly, short thorax, short limbs, short fingers and teeth abnormalities. At five years, she was found to have pigmentosum retinitis with amblyopy and moderate hyperopia. A chronic renal failure with uncontrollable hypertension underwent a cadaveric-donor transplantation at the age of six years. Two years later, the pigmentosum retinitis was stable. The kidney histology revealed a tubulo-interstitial nephronophtisis. The molecular analysis of the NPH 1 locus, which was associated with nephronophtisis, was negative. Our observation and two recent publications have in common ocular and renal abnormalities associated with cranio-ectodermal dysplasia. The underlying genetic defect would involve not only morphogenesis but also development and maturation of organs as eye and kidney. Sensenbrenner syndrome would thus be similar to certain disorders affecting the eye, kidney, skeleton and ectodermal structures such as the EEM, Senior-Loken, Mainzer-Saldino, and Jeune syndromes. The retinal dystrophy falls within the spectrum of clinical and genetic forms of pigmentosum retinitis. Our observation would confirm possible links between Sensenbrenner syndrome and oculorenal syndromes.

Prosthodontic Management of Hypohidrotic Ectodermal Dysplasia with Anodontia: A Case Report in Pediatric Patient and Review of Literature

PubMed Central

Ladda, R; Gangadhar, SA; Kasat, VO; Bhandari, AJ

2013-01-01

Ectodermal dysplasias are rare hereditary disorders characterized by abnormal development of certain tissues and structures of ectodermal origin. The condition is important for dentists as it affects teeth resulting in hypodontia or anodontia and dentist plays an important role in rehabilitation of the patient. Affected young children with anodontia not only have difficulties in eating and speaking but can also feel that they look different from their contemporaries. Well-fitting and functioning prosthesis could be a great help during their schooling years as it will improve appearance and thus boost their self confidence. We report a case of hypohidrotic ectodermal dysplasia in an 8-year-old boy who exhibited anodontia and was successfully rehabilitated with conventional complete dentures in both maxillary and mandibular arches. The aim of the treatment was to improve psychological development apart from promoting better functioning of the stomatognathic system. PMID:23919206

PubMed Central

Wahlbuhl-Becker, Mandy; Faschingbauer, Florian; Beckmann, Matthias W.; Schneider, Holm

2017-01-01

Background X-linked hypohidrotic ectodermal dysplasia (XLHED), the most common form of ectodermal dysplasia, is caused by mutations in the gene EDA. While only affected men develop the full-blown clinical picture, females who are heterozygous for an EDA mutation often also show symptoms such as hypodontia, hypotrichosis and hypohidrosis. These women may also suffer from malformations of the mammary gland which represent not just a cosmetic problem but can limit their breastfeeding capability. This paper summarizes the findings of the first systematic study on the impact of hypohidrotic ectodermal dysplasia on breastfeeding. Patients Thirty-eight adult female members of the German-Swiss-Austrian ectodermal dysplasia patient support group participated in a structured interview; most of them also agreed to a photodocumentation of their mammary region. Thirty-one women carried mutations in EDA (Group A) and seven were affected by other forms of hypohidrotic ectodermal dysplasia (Group B). Results 39 % of the women of Group A reported that their breasts were of different size or entirely absent on one side. In Group B, 86 % of the women reported differently sized or even absent breasts; two of these women lacked both breasts entirely. Most women described their nipples as exceptionally flat. 10 % of the women of Group A had more than two nipples. The high percentage of deviations from the norm was confirmed in the photodocumentation. Both groups had few or no sebaceous glands of Montgomery in the areolar region. Around 80 % of interviewed women had children and had attempted to breastfeed their first child. 67 % of the mothers in Group A had had difficulty in breastfeeding their infants and generally attributed this difficulty to their flat nipples. All of the mothers in Group B reported difficulties in breastfeeding; 60 % had not been able to breastfeed their first child. Conclusion Mothers with hypohidrotic ectodermal dysplasia very often have difficulty in breastfeeding because of their impaired breast development. This causal relationship needs to be taken into account in lactation counseling. PMID:28553001

A survey of children affected by ectomermal dysplasia syndromes shows an increased prevalence of atopic disorders and immune deficiency

USDA-ARS?s Scientific Manuscript database

Ectodermal dysplasia (ED) syndromes are rare genetic disorders that affect the development of tissues derived from the embryonic ectoderm. Studies and anecdotal experience have indicated that atopic disorders (AD) and immune deficiencies (ID) may be associated with ED in children. Some ED genotypes ...

A Splice Defect in the EDA Gene in Dogs with an X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) Phenotype.

PubMed

Waluk, Dominik P; Zur, Gila; Kaufmann, Ronnie; Welle, Monika M; Jagannathan, Vidhya; Drögemüller, Cord; Müller, Eliane J; Leeb, Tosso; Galichet, Arnaud

2016-09-08

X-linked hypohidrotic ectodermal dysplasia (XLHED) caused by variants in the EDA gene represents the most common ectodermal dysplasia in humans. We investigated three male mixed-breed dogs with an ectodermal dysplasia phenotype characterized by marked hypotrichosis and multifocal complete alopecia, almost complete absence of sweat and sebaceous glands, and altered dentition with missing and abnormally shaped teeth. Analysis of SNP chip genotypes and whole genome sequence data from the three affected dogs revealed that the affected dogs shared the same haplotype on a large segment of the X-chromosome, including the EDA gene. Unexpectedly, the whole genome sequence data did not reveal any nonsynonymous EDA variant in the affected dogs. We therefore performed an RNA-seq experiment on skin biopsies to search for changes in the transcriptome. This analysis revealed that the EDA transcript in the affected dogs lacked 103 nucleotides encoded by exon 2. We speculate that this exon skipping is caused by a genetic variant located in one of the large introns flanking this exon, which was missed by whole genome sequencing with the illumina short read technology. The altered EDA transcript splicing most likely causes the observed ectodermal dysplasia in the affected dogs. These dogs thus offer an excellent opportunity to gain insights into the complex splicing processes required for expression of the EDA gene, and other genes with large introns. Copyright © 2016 Waluk et al.

Craniofacial morphometric analysis of individuals with X-linked hypohidrotic ectodermal dysplasia.

PubMed

Goodwin, Alice F; Larson, Jacinda R; Jones, Kyle B; Liberton, Denise K; Landan, Maya; Wang, Zhifeng; Boekelheide, Anne; Langham, Margaret; Mushegyan, Vagan; Oberoi, Snehlata; Brao, Rosalie; Wen, Timothy; Johnson, Ramsey; Huttner, Kenneth; Grange, Dorothy K; Spritz, Richard A; Hallgrímsson, Benedikt; Jheon, Andrew H; Klein, Ophir D

2014-09-01

Hypohidrotic ectodermal dysplasia (HED) is the most prevalent type of ectodermal dysplasia (ED). ED is an umbrella term for a group of syndromes characterized by missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. The X-linked recessive (XL), autosomal recessive (AR), and autosomal dominant (AD) types of HED are caused by mutations in the genes encoding ectodysplasin (EDA1), EDA receptor (EDAR), or EDAR-associated death domain (EDARADD). Patients with HED have a distinctive facial appearance, yet a quantitative analysis of the HED craniofacial phenotype using advanced three-dimensional (3D) technologies has not been reported. In this study, we characterized craniofacial morphology in subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED) by use of 3D imaging and geometric morphometrics (GM), a technique that uses defined landmarks to quantify size and shape in complex craniofacial morphologies. We found that the XLHED craniofacial phenotype differed significantly from controls. Patients had a smaller and shorter face with a proportionally longer chin and midface, prominent midfacial hypoplasia, a more protrusive chin and mandible, a narrower and more pointed nose, shorter philtrum, a narrower mouth, and a fuller and more rounded lower lip. Our findings refine the phenotype of XLHED and may be useful both for clinical diagnosis of XLHED and to extend understanding of the role of EDA in craniofacial development.

Management of Severely Atrophic Maxilla in Ectrodactyly Ectodermal Dysplasia-cleft Syndrome.

PubMed

Rachmiel, Adi; Turgeman, Shahar; Emodi, Omri; Aizenbud, Dror; Shilo, Dekel

2018-02-01

Ectrodactyly ectodermal dysplasia-cleft syndrome is a rare genetic syndrome with an incidence of 1/90,000 live births, characterized by cleft lip and palate, severely hypoplastic maxilla, and hypodontia. Patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome suffer from a severely hypoplastic maxilla that is highly difficult to treat using traditional orthognathic methods. In this study, we propose using distraction osteogenesis to achieve a major advancement while maintaining good stability and minimal relapse. To our knowledge, this is the first description of patients with this syndrome treated using distraction osteogenesis. Five patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome were included in the study. All patients had been operated on according to the well-established protocol of cleft lip and palate reconstruction before maxillary distraction osteogenesis. Hard and soft-tissue changes were evaluated by cone beam computed tomography and lateral cephalograms before distraction osteogenesis (T1), at the postdistraction point (T2) and after 1 year of follow-up (T3). Examination revealed marked maxillary advancement in all our patients with a significant mean difference in hard tissue parameters (condylion to A point = 18 mm; nasion-sella line to A point = 15.2 degrees) and a notable improvement in facial convexity (20.9 degrees). One year follow-up measurements demonstrated mild relapse rates of 6% in the horizontal plane. We conclude that despite the challenging anatomic and physiological features of ectrodactyly ectodermal dysplasia-cleft patients, by enhancing current surgical techniques, there is promising potential for improved patient outcomes, achieving normognathic facial appearance with implant supported rehabilitation.

Management of Severely Atrophic Maxilla in Ectrodactyly Ectodermal Dysplasia-cleft Syndrome

PubMed Central

Rachmiel, Adi; Emodi, Omri; Aizenbud, Dror; Shilo, Dekel

2018-01-01

Background: Ectrodactyly ectodermal dysplasia-cleft syndrome is a rare genetic syndrome with an incidence of 1/90,000 live births, characterized by cleft lip and palate, severely hypoplastic maxilla, and hypodontia. Patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome suffer from a severely hypoplastic maxilla that is highly difficult to treat using traditional orthognathic methods. In this study, we propose using distraction osteogenesis to achieve a major advancement while maintaining good stability and minimal relapse. To our knowledge, this is the first description of patients with this syndrome treated using distraction osteogenesis. Methods: Five patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome were included in the study. All patients had been operated on according to the well-established protocol of cleft lip and palate reconstruction before maxillary distraction osteogenesis. Hard and soft-tissue changes were evaluated by cone beam computed tomography and lateral cephalograms before distraction osteogenesis (T1), at the postdistraction point (T2) and after 1 year of follow-up (T3). Results: Examination revealed marked maxillary advancement in all our patients with a significant mean difference in hard tissue parameters (condylion to A point = 18 mm; nasion-sella line to A point = 15.2 degrees) and a notable improvement in facial convexity (20.9 degrees). One year follow-up measurements demonstrated mild relapse rates of 6% in the horizontal plane. Conclusions: We conclude that despite the challenging anatomic and physiological features of ectrodactyly ectodermal dysplasia-cleft patients, by enhancing current surgical techniques, there is promising potential for improved patient outcomes, achieving normognathic facial appearance with implant supported rehabilitation. PMID:29616174

Conventional Complete Denture in Patients with Ectodermal Dysplasia

PubMed Central

Vilanova, Larissa Soares Reis; Sánchez-Ayala, Alfonso; Ribeiro, Giselle Rodrigues; Campos, Camila Heitor; Farias-Neto, Arcelino

2015-01-01

Ectodermal dysplasia is described as heritable conditions that involve anomalies of structures derived from the ectoderm, including hypodontia. In the cases of edentulous young patients, who did not finish their craniofacial growth, treatment with conventional complete denture is a suitable alternative. The aim of this study was to report a case of mandibular edentulism treated with conventional complete denture in a thirteen-year-old patient diagnosed with hidrotic ectodermal dysplasia. Typical features, such as frontal bossing, depressed nasal bridge, protuberant lips, scarce hair, and brittle nails, were visualized during the extraoral examination. The intraoral inspection and radiographic analysis revealed oligodontia, dental malformation, and prolonged retention of deciduous teeth at maxilla and total edentulism at mandible. A conventional complete denture was planned and constructed following the same steps of technique as recommended in adults. Although this option is not a definitive treatment, the patient and his parents were satisfied with his improvement in chewing and speech, as well as with the aesthetic benefits. PMID:26425372

Early implant placement for a patient with ectodermal dysplasia: Thirteen years of clinical care.

PubMed

Knobloch, Lisa A; Larsen, Peter E; Saponaro, Paola C; L'Homme-Langlois, Emilie

2017-11-29

Patients with ectodermal dysplasia have abnormalities of 2 or more structures that originate from the ectoderm. The oral manifestations often include the congenital absence of teeth and malformed teeth. This clinical report describes the interdisciplinary care from childhood through the definitive dental rehabilitation completed at skeletal maturation to replace the missing teeth in a patient with ectodermal dysplasia. Treatment began at 9 years of age with an implant-assisted mandibular overdenture to improve function and replace the missing mandibular teeth. Orthodontic treatment for the consolidation of space, composite resin restorations, and interim removable dental prostheses were provided to improve esthetics and replace the missing maxillary teeth. Skeletal growth was monitored, and orthognathic surgery was performed at the cessation of growth. The definitive rehabilitation consisted of a mandibular fixed dental prosthesis supported by dental implants and a maxillary removable dental prosthesis to restore the patient to esthetics and function. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Ectoderm-targeted overexpression of the glucocorticoid receptor induces hypohidrotic ectodermal dysplasia.

PubMed

Cascallana, Jose Luis; Bravo, Ana; Donet, Eva; Leis, Hugo; Lara, Maria Fernanda; Paramio, Jesús M; Jorcano, José L; Pérez, Paloma

2005-06-01

Hypohidrotic ectodermal dysplasia is a human syndrome defined by maldevelopment of one or more ectodermal-derived tissues, including the epidermis and cutaneous appendices, teeth, and exocrine glands. The molecular bases of this pathology converge in a dysfunction of the transcription factor nuclear factor of the kappa-enhancer in B cells (NF-kappaB), which is essential to epithelial homeostasis and development. A number of mouse models bearing disruptions in NF-kappaB signaling have been reported to manifest defects in ectodermal derivatives. In ectoderm-targeted transgenic mice overexpressing the glucocorticoid receptor (GR) [keratin 5 (K5)-GR mice], the NF-kappaB activity is greatly decreased due to functional antagonism between GR and NF-kappaB. Here, we report that K5-GR mice exhibit multiple epithelial defects in hair follicle, tooth, and palate development. Additionally, these mice lack Meibomian glands and display underdeveloped sweat and preputial glands. These phenotypic features appear to be mediated specifically by ligand-activated GR because the synthetic analog dexamethasone induced similar defects in epithelial morphogenesis, including odontogenesis, in wild-type mice. We have focused on tooth development in K5-GR mice and found that an inhibitor of steroid synthesis partially reversed the abnormal phenotype. Immunostaining revealed reduced expression of the inhibitor of kappaB kinase subunits, IKKalpha and IKKgamma, and diminished p65 protein levels in K5-GR embryonic tooth, resulting in a significantly reduced kappaB-binding activity. Remarkably, altered NF-kappaB activity elicited by GR overexpression correlated with a dramatic decrease in the protein levels of DeltaNp63 in tooth epithelia without affecting Akt, BMP4, or Foxo3a. Given that many of the 170 clinically distinct ectodermal dysplasia syndromes still remain without cognate genes, deciphering the molecular mechanisms of this mouse model with epithelial NF-kappaB and p63 dysfunction may provide important clues to understanding the basis of other ectodermal dysplasia syndromes.

Noninvasive Prenatal Diagnosis of Hypohidrotic Ectodermal Dysplasia by Tooth Germ Sonography.

PubMed

Wünsche, S; Jüngert, J; Faschingbauer, F; Mommsen, H; Goecke, T; Schwanitz, K; Stepan, H; Schneider, H

2015-08-01

Hypohidrotic ectodermal dysplasia, a potentially life-threatening heritable disorder, may be recognized already in utero by characteristic features such as oligodontia and mandibular hypoplasia. As therapeutic options and prognosis depend on the time point of diagnosis, early recognition was attempted during routine prenatal ultrasound examinations. Fetuses of nine pregnant women (one triplet and eight singleton pregnancies) with family histories of hypohidrotic ectodermal dysplasia were investigated by sonography between the 20th and 24th week of gestation. In 4 male and 2 female fetuses reduced amounts of tooth germs were detected, whereas 5 fetal subjects showed the normal amount. Three-dimensional ultrasound evaluation revealed mandibular hypoplasia in 5 of the 6 fetuses with oligodontia. Molecular genetic analysis and/or clinical findings after birth confirmed the prenatal sonographic diagnosis in each subject. In subjects with a family history of hypohidrotic ectodermal dysplasia, the diagnosis of this rare condition can be established noninvasively by sonography in the second trimester of pregnancy. Early recognition of the disorder may help to prevent dangerous hyperthermic episodes in infancy and may allow timely therapeutic interventions. © Georg Thieme Verlag KG Stuttgart · New York.

Ectodermal dysplasias: A clinical classification and a causal review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinheiro, M.; Freire-Maia, N.

1994-11-01

The authors present a causal review of 154 ectodermal dysplasias (EDs) as classified into 11 clinical subgroups. The number of EDs in each subgroup varies from one to 43. The numbers of conditions due to autosomal dominant, autosomal recessive, and X-linked genes are, respectively, 41, 52, and 8. In 53 conditions cause is unknown; 35 of them present some causal (genetic) suggestion.

Genitourinary malformations: an under-recognized feature of ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome.

PubMed

Hyder, Zerin; Beale, Victoria; O'Connor, Ruth; Clayton-Smith, Jill

2017-04-01

The ectodermal dysplasia and cleft lip/palate (EEC) syndrome describes the association of ectrodactyly, ectodermal dysplasia and orofacial clefting. As with many autosomal dominant disorders, there is variability in expression and not all of these three core features are present in every individual with the condition. Moreover, there may be additional associated features, which are under-recognized. One of these is the presence of genitourinary anomalies, some of which cause significant morbidity. This report details a further two patients with EEC syndrome and genitourinary involvement, including flaccid megacystis with detrusor muscle failure, bilateral hydronephrosis and megaureter, requiring significant renal and urological involvement during their childhood. We go on to review the literature on the diagnosis and management of genitourinary malformations in EEC syndrome.

Molecular basis of hypohidrotic ectodermal dysplasia: an update.

PubMed

Trzeciak, Wieslaw H; Koczorowski, Ryszard

2016-02-01

Recent advances in understanding the molecular events underlying hypohidrotic ectodermal dysplasia (HED) caused by mutations of the genes encoding proteins of the tumor necrosis factor α (TNFα)-related signaling pathway have been presented. These proteins are involved in signal transduction from ectoderm to mesenchyme during development of the fetus and are indispensable for the differentiation of ectoderm-derived structures such as eccrine sweat glands, teeth, hair, skin, and/or nails. Novel data were reviewed and discussed on the structure and functions of the components of TNFα-related signaling pathway, the consequences of mutations of the genes encoding these proteins, and the prospect for further investigations, which might elucidate the origin of HED.

A novel homozygous missense variant in NECTIN4 (PVRL4) causing ectodermal dysplasia cutaneous syndactyly syndrome.

PubMed

Ahmad, Farooq; Nasir, Abdul; Thiele, Holger; Umair, Muhammad; Borck, Guntram; Ahmad, Wasim

2018-02-12

Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare form of ectodermal dysplasia including anomalies of hair, nails, and teeth along with bilateral cutaneous syndactyly of hands and feet. In the present report, we performed a clinical and genetic characterization of a consanguineous Pakistani family with four individuals affected by EDSS1. We performed exome sequencing using DNA of one affected individual. Exome data analysis identified a novel homozygous missense variant (c.242T>C; p.(Leu81Pro)) in NECTIN4 (PVRL4). Sanger sequencing validated this variant and confirmed its cosegregation with the disease phenotype in the family members. Thus, our report adds a novel variant to the NECTIN4 mutation spectrum and contributes to the NECTIN4-related clinical characterization. © 2018 John Wiley & Sons Ltd/University College London.

Hypohidrotic ectodermal dysplasia, osteopetrosis, lymphedema, and immunodeficiency in an infant with multiple opportunistic infections.

PubMed

Carlberg, Valerie M; Lofgren, Sabra M; Mann, Julianne A; Austin, Jared P; Nolt, Dawn; Shereck, Evan B; Davila-Saldana, Blachy; Zonana, Jonathan; Krol, Alfons L

2014-01-01

Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and immunodeficiency (OL-HED-ID) is a rare X-linked disorder with only three reported prior cases in the English-language literature. We describe a case of OL-HED-ID in a male infant who initially presented with congenital lymphedema, leukocytosis, and thrombocytopenia of unknown etiology at 7 days of age. He subsequently developed gram-negative sepsis and multiple opportunistic infections including high-level cytomegalovirus viremia and Pneumocystis jiroveci pneumonia. The infant was noted to have mildly xerotic skin, fine sparse hair, and periorbital wrinkling, all features suggestive of ectodermal dysplasia. Skeletal imaging showed findings consistent with osteopetrosis, and immunologic investigation revealed hypogammaglobulinemia and mixed T- and B-cell dysfunction. Genetic testing revealed a novel mutation in the nuclear factor kappa beta (NF-KB) essential modulator (NEMO) gene, confirming the diagnosis of OL-HED-ID. Mutations in the NEMO gene have been reported in association with hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and incontinentia pigmenti. In this case, we report a novel mutation in the NEMO gene associated with OL-HED-ID. This article highlights the dermatologic manifestations of a rare disorder, OL-HED-ID, and underscores the importance of early recognition and prompt intervention to prevent life-threatening infections. © 2013 Wiley Periodicals, Inc.

Prosthetic rehabilitation in a pediatric patient with hypohidrotic ectodermal dysplasia: a case report.

PubMed

Quintanilha, Luís Eduardo Lavigne Paranhos; Carneiro-Campos, Luís Eduardo; Antunes, Lívia Azeredo Alves; Antunes, Leonardo Santos; Fernandes, Claudio Pinheiro; Abreu, Fernanda Volpe

2017-01-01

Hypohidrotic ectodermal dysplasia (HED) is a rare ectodermal disease with a systemic expression. Oral abnormalities are common and may include hypodontia and shape irregularities in the primary and permanent dentitions. Rehabilitation of the dental arches in pediatric patients with HED is a challenge because HED is a multifactorial disease that demands a complicated treatment approach and most dentists have limited experience or training in the necessary treatment. In addition, pediatric patients often lack the patience or ability to cooperate with complex prosthetic treatment. This case report describes a simplified technique used to fabricate complete dentures for a 4-year-old HED patient in 4 sessions.

Influence of oral rehabilitation on the oral health-related quality of life of a child with ectodermal dysplasia.

PubMed

de Alencar, Nashalie Andrade; Reis, Kátia Rodrigues; Antonio, Andréa Gonçalves; Maia, Lucianne Cople

2015-01-01

Ectodermal dysplasia (ED) is a rare congenital hereditary disorder among a group of syndromes characterized by abnormalities of ectodermic structures. The purpose of this report is to compare the oral health-related quality of life (OHRQoL) before and after complete oral rehabilitation of a five-year-old boy with ED. Delivery of upper and lower dentures resulted in immediate improvement of the child's OHRQoL. Although ED affects patients physically and emotionally, the early oral rehabilitation of young patients is crucial to improve their social interaction and restore their speech and masticatory function.

Herediatary anhidrotic ectodermal dysplasia. Studies in a Nigerian famil.

PubMed

Familusi, J B; Jaiyesimi, F; Ojo, C O; Attah, E B

1975-08-01

Studies in a Nigerian family with hereditary anhidrous ectodermal dysplasia are reported. Microscopical examinations of finger tips for sweat pores were diagnostic in phenotypes, and it is suggested that this simple nonsurgical procedure is a preferred alternative to skin biopsies in the diagnosis of the syndrome. The clinical implications of a tropical environment for the syndrome, as well as the factors that may favour maintenance of the gene in such an environment are discussed.

Ectodermal dysplasias: a new clinical-genetic classification

PubMed Central

Priolo, M.; Lagana, C.

2001-01-01

The ectodermal dysplasias (EDs) are a large and complex nosological group of diseases, first described by Thurnam in 1848. In the last 10 years more than 170 different pathological clinical conditions have been recognised and defined as EDs, all sharing in common anomalies of the hair, teeth, nails, and sweat glands. Many are associated with anomalies in other organs and systems and, in some conditions, with mental retardation.
The anomalies affecting the epidermis and epidermal appendages are extremely variable and clinical overlap is present among the majority of EDs. Most EDs are defined by particular clinical signs (for example, eyelid adhesion in AEC syndrome, ectrodactyly in EEC). To date, few causative genes have been identified for these diseases.
We recently reviewed genes known to be responsible for EDs in light of their molecular and biological function and proposed a new approach to EDs, integrating both molecular-genetic data and corresponding clinical findings. Based on our previous report, we now propose a clinical-genetic classification of EDs, expand it to other entities in which no causative genes have been identified based on the phenotype, and speculate on possible candidate genes suggested by associated "non-ectodermal" features.


Keywords: ectodermal dysplasia; clinical-functional correlation; epithelial-mesenchymal interaction; ectodermal structural proteins PMID:11546825

Ophthalmic manifestations in patients with ectodermal dysplasia syndromes.

PubMed

Keklikci, Ugur; Yavuz, Izzet; Tunik, Selcuk; Ulku, Zelal Baskan; Akdeniz, Sedat

2014-01-01

Ectodermal dysplasia (ED) is a disorder that results from abnormal formation of at least two of the four major ectodermal derivatives in the developing embryo. The ectoderm of the embryo forms the skin, teeth, hair and nails, sweat glands and part of the eyes. The aim of this article is to reveal ophthalmologic symptoms and signs as multidisciplinary, reliable criteria for ectodermal dysplasia. In this retrospective study, 24 patients with ED were analyzed from the recorded data. Ophthalmological examination of the patients, who had previously received the diagnosis of ED in the dental department, was done. During the examination, ocular symptoms related to tear film, corneal changes, lacrimal duct, periorbital hyperpigmentation, alteration lashes and eyebrows were evaluated. The age ranged between 3-45, and the mean and standard deviation (Mean ± SD) was 15.8 ± 7.4 years. The number of males was 13 (54.2%) and females, 11 (45.8%). Eighteen patients (75.0%) suffered from ocular complaints related to the ocular surface. In 11 of the patients with ED, there were dry eye symptoms. While the mean age of cases with eye involvement was 17.5, it was 23.1 in cases with dry eye symptoms. In the study, it was observed that, in patients with ED, ocular complaints, particularly dry eye symptoms, may increase as age advances.

Bilateral congenital lacrimal fistulas in an adult as part of ectrodactyly-ectodermal dysplasia-clefting syndrome: A rare anomaly.

PubMed

Ghosh, Debangshu; Saha, Somnath; Basu, Sumit Kumar

2015-10-01

Ectrodactyly-ectodermal dysplasia and clefting syndrome or "Lobster claw" deformity is a rare congenital anomaly that affects tissues of ectodermal and mesodermal origin. Nasolacrimal duct (NLD) obstruction with or without atresia of lacrimal passage is a common finding of such a syndrome. The authors report here even a rarer presentation of the syndrome which manifested as bilateral NLD obstruction and lacrimal fistula along with cleft lip and palate, syndactyly affecting all four limbs, mild mental retardation, otitis media, and sinusitis. Lacrimal duct obstruction and fistula were managed successfully with endoscopic dacryocystorhinostomy (DCR) which is a good alternative to lacrimal probing or open DCR in such a case.

ORAI1 mutations abolishing store-operated Ca2+ entry cause anhidrotic ectodermal dysplasia with immunodeficiency.

PubMed

Lian, Jayson; Cuk, Mario; Kahlfuss, Sascha; Kozhaya, Lina; Vaeth, Martin; Rieux-Laucat, Frédéric; Picard, Capucine; Benson, Melina J; Jakovcevic, Antonia; Bilic, Karmen; Martinac, Iva; Stathopulos, Peter; Kacskovics, Imre; Vraetz, Thomas; Speckmann, Carsten; Ehl, Stephan; Issekutz, Thomas; Unutmaz, Derya; Feske, Stefan

2017-11-16

Store-operated Ca 2+ entry (SOCE) through Ca 2+ release-activated Ca 2+ channels is an essential signaling pathway in many cell types. Ca 2+ release-activated Ca 2+ channels are formed by ORAI1, ORAI2, and ORAI3 proteins and activated by stromal interaction molecule (STIM) 1 and STIM2. Mutations in the ORAI1 and STIM1 genes that abolish SOCE cause a combined immunodeficiency (CID) syndrome that is accompanied by autoimmunity and nonimmunologic symptoms. We performed molecular and immunologic analysis of patients with CID, anhidrosis, and ectodermal dysplasia of unknown etiology. We performed DNA sequencing of the ORAI1 gene, modeling of mutations on ORAI1 crystal structure, analysis of ORAI1 mRNA and protein expression, SOCE measurements, immunologic analysis of peripheral blood lymphocyte populations by using flow cytometry, and histologic and ultrastructural analysis of patient tissues. We identified 3 novel autosomal recessive mutations in ORAI1 in unrelated kindreds with CID, autoimmunity, ectodermal dysplasia with anhidrosis, and muscular dysplasia. The patients were homozygous for p.V181SfsX8, p.L194P, and p.G98R mutations in the ORAI1 gene that suppressed ORAI1 protein expression and SOCE in the patients' lymphocytes and fibroblasts. In addition to impaired T-cell cytokine production, ORAI1 mutations were associated with strongly reduced numbers of invariant natural killer T and regulatory T (Treg) cells and altered composition of γδ T-cell and natural killer cell subsets. ORAI1 null mutations are associated with reduced numbers of invariant natural killer T and Treg cells that likely contribute to the patients' immunodeficiency and autoimmunity. ORAI1-deficient patients have dental enamel defects and anhidrosis, representing a new form of anhidrotic ectodermal dysplasia with immunodeficiency that is distinct from previously reported patients with anhidrotic ectodermal dysplasia with immunodeficiency caused by mutations in the nuclear factor κB signaling pathway (IKBKG and NFKBIA). Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Keratoprosthesis in Ectodermal Dysplasia.

PubMed

Wozniak, Rachel A F; Gonzalez, Mithra; Aquavella, James V

2016-07-01

To describe the complex surgical management and novel medical approach for a keratoprosthesis (KPro Boston type I) in a monocular, 73-year-old patient with ectodermal dysplasia and chronic, noninfectious corneal necrosis. Best-corrected visual acuity (BCVA) was measured with Snellen letters. Surgical intervention included an amniotic membrane graft, complete replacement of the KPro, conjunctival flap graft, corneal donor tissue grafts combined with inferior rectus muscle advancement, periosteal tissue graft, tarso-conjunctival flap construction, and symblepharolysis. Infliximab was used as a medical adjunctive therapy. Initial KPro placement provided a BCVA of 20/25 and long-term stability. Subsequent chronic melting at the optic border necessitated numerous surgeries to prevent extrusion and failure. Ultimate fistulization was addressed with the formation of a surgical pocket. The addition of infliximab promoted ocular surface stability, and the patient has maintained a BCVA of 20/80. Ectodermal dysplasia can result in eyelid and corneal abnormalities, requiring a KPro for visual restoration. In the setting of chronic, sterile corneal melt, novel surgical approaches and the off-label use of infliximab allowed for visual rehabilitation.

A Novel Splicesite Mutation in the EDAR Gene Causes Severe Autosomal Recessive Hypohydrotic (Anhidrotic) Ectodermal Dysplasia in an Iranian Family.

PubMed

Torkamandi, Shahram; Gholami, Milad; Mohammadi-Asl, Javad; Rezaie, Somaye; Zaimy, Mohammad Ali; Omrani, Mir Davood

2016-01-01

Hypohidrotic ectodermal dysplasia (HED) is a rare congenital disorder arising from deficient development of ectoderm-derived structures including skin, nails, glands and teeth. The phenotype of HED is associated with mutation in EDA, EDAR, EDARADD and NEMO genes, all of them disruptingNF-κB signaling cascade necessary for initiation, formation and differentiation in the embryo and adult. Here we describe a novel acceptor splice site mutation c.730-2 A>G(IVS 8-2 A>G) in EDAR gene in homozygous form in all affected members of a family,and in heterozygous form in carriers. Bioinformatics analysis showed that this mutation can create a new broken splicing site and lead to aberrant splicing.

Review of ectodermal dysplasia: case report on treatment planning and surgical management of oligodontia with implant restorations.

PubMed

Li, Dehua; Liu, Yanpu; Ma, Wei; Song, Yingliang

2011-10-01

Dental implants have proven to be a reliable modality for the rehabilitation of missing teeth. However, there are limited reports on managing anodontia related to ectodermal dysplasia in the scientific literature. The severely reduced bone quantity due to the congenital absence of multiple natural teeth is the biggest challenge for the surgeon. There are a variety of bone augmentation procedures to establish adequate bone quantity, and the surgical planning should be used on an individual case basis. This is a report of a 19-year-old male patient affected by hypohidrotic ectodermal dysplasia. Oligodontia associated with severe atrophy of jaws was the chief complaint for seeking treatment. Based on clinical and radiographic examinations, 2 bone augmentation procedures were used to obtain sufficient width of alveolus for implant placement by performing an onlay bone graft in the maxilla and vertical distraction osteogenesis in the mandible. The treatment planning was discussed and informed consent was obtained.

Ocular and non-ocular manifestations of hypohidrotic ectodermal dysplasia

PubMed Central

Tyagi, Pallavi; Tyagi, Vipin; Hashim, Adnan A

2011-01-01

Hypohidrotic ectodermal dysplasia (HED) is a group of rare multisystemic genetic syndromes that affects ectodermal structures such as skin, hair, nails, teeth and sweat glands. The authors present a case of a child with ocular and dermatological signs of HED along with severe involvement of other multiple organ systems. The family history could be traced to four generations and there was an observed trend of increase in severity of signs and symptoms occurring at younger age. The purpose of this case report is to create awareness in ophthalmic community of its diagnosis and clinical manifestations. This case highlights the role of multidisciplinary approach for management of systemic disease, genetic evaluation of affected individuals and carriers and genetic counselling. PMID:22700604

An unusual case of ectodermal dysplasia: combating senile features at an early age

PubMed Central

Gupta, Mudit; Sundaresh, Kumbar Jayadevappa; Batra, Manu; Rathva, Vandana J

2014-01-01

Ectodermal dysplasia (ED) refers to a group of inherited diseases that have developmental defects in at least two major structures derived from the ectoderm, that is, hair, teeth, nails and sweat glands. Although more than 192 distinct disorders have been described, the most common is X-linked recessive hypohidrotic ED (Christ-Siemens-Touraine syndrome). Since such patients usually presents with missing teeth, dentists are usually the first person to diagnose such cases. Diagnosis of such cases is important because absence of sweat glands can lead to hyperthermia which can be life-threatening if proper care is not taken. Through this manuscript, we report a case of anhidrotic ED affecting deciduous and permanent dentition, which is rare. PMID:24493109

Ocular surface involvements in ectrodactyly-ectodermal dysplasia-cleft syndrome.

PubMed

Kennedy, David P; Chandler, John W; McCulley, James P

2015-06-01

To present the ocular manifestation of 2 cases of ectrodactyly-ectodermal dysplasia-cleft syndrome, a multiple congenital anomaly syndrome caused by a single point mutation of the p63 gene that controls epidermal development and homeostasis and to present treatment options. Patient 1 presented with mild signs and symptoms of dry eye and limbal stem cell deficiency with retention of 20/30 vision. Patient 2 presented with severe signs and symptoms of limbal stem cell deficiency with diffuse corneal scarring and counting fingers vision. This second patient's course was complicated by allergic conjunctivitis and advanced steroid-induced glaucoma. The cause of visual loss in ectrodactyly-ectodermal dysplasia-cleft syndrome appears to be multifactorial and likely includes inflammation of the ocular surface, tear film abnormalities, eyelid abnormalities, and limbal stem cell deficiency. Treatment modalities including lubrication, contact lenses, and limbal stem cell transplantation are reviewed. The ophthalmic conditions seen in ectrodactyly-ectodermal dysplasia-cleft syndrome frequently lead to vision loss. Early correct diagnosis and appropriate therapy are paramount because p63 gene mutations have a critical role in maintaining the integrity of the ocular surface in the setting of limbal stem cell deficiency, especially if there are other ocular surface insults such as lid disease, meibomian gland dysfunction and toxicity from topical medications. Patients should be monitored at regular, frequent intervals; and particular attention should be taken to avoid adverse secondary effects of these conditions and medications. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Ear nose throat manifestations in hypoidrotic ectodermal dysplasia.

PubMed

Callea, Michele; Teggi, Roberto; Yavuz, Izzet; Tadini, Gianluca; Priolo, Manuela; Crovella, Sergio; Clarich, Gabriella; Grasso, Domenico Leonardo

2013-11-01

The ectodermal dysplasias (EDs) are a large and complex group of inherited disorders. In various combinations, they all share anomalies in ectodermal derived structures: hair, teeth, nails and sweat gland function. Clinical overlap is present among EDs. Few causative genes have been identified, to date. Altered gene expression is not limited to the ectoderm but a concomitant effect on developing mesenchymal structures, with modification of ectodermal-mesenchymal signaling, takes place. The two major categories of ED include the hidrotic and hypohidrotic form, the latter more frequent; they differentiate each other for the presence or absence of sweat glands. We report Ear Nose Throat manifestations of ED, linked to the reduction of mucous glands in the nasal fossae with reduced ciliar function, and decrease salivary glands function. Often patients report an increased rate of infections of the upper respiratory tract and of the ear. Nasal obstruction due to the presence of nasal crusting, hearing loss and throat hoarseness are the most represented symptoms. Environmental measures, including a correct air temperature and humidification, is mandatory above all in subjects affected by hypohidrotic form. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Herediatary anhidrotic ectodermal dysplasia. Studies in a Nigerian famil.

PubMed Central

Familusi, J B; Jaiyesimi, F; Ojo, C O; Attah, E B

1975-01-01

Studies in a Nigerian family with hereditary anhidrous ectodermal dysplasia are reported. Microscopical examinations of finger tips for sweat pores were diagnostic in phenotypes, and it is suggested that this simple nonsurgical procedure is a preferred alternative to skin biopsies in the diagnosis of the syndrome. The clinical implications of a tropical environment for the syndrome, as well as the factors that may favour maintenance of the gene in such an environment are discussed. Images FIG. 1 FIG. 2 FIG. 4 FIG. 5 FIG. 6 PMID:1200681

Oral health considerations in a patient with oligosymptomatic ectrodactyly-ectodermal dysplasia-cleft syndrome.

PubMed

Sharma, Gaurav; Nagpal, Archna

2017-01-01

Ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome-a complex, pleiotropic disorder resulting in multiple congenital anomalies-has an unpredictable clinical expression and is typically manifested as an autosomal-dominant trait. This article presents a rare case of oligosymptomatic EEC syndrome in a 19-year-old man who exhibited atypical dental findings but no cleft lip or palate. This article is intended to create awareness about this rare syndrome and highlight the role of oral healthcare specialists in improving the quality of life for patients with EEC.

X-Linked Hypohidrotic Ectodermal Dysplasia: New Features and a Novel EDA Gene Mutation.

PubMed

Savasta, Salvatore; Carlone, Giorgia; Castagnoli, Riccardo; Chiappe, Francesca; Bassanese, Francesco; Piras, Roberta; Salpietro, Vincenzo; Brazzelli, Valeria; Verrotti, Alberto; Marseglia, Gian L

2017-01-01

We described a 5-year-old male with hypodontia, hypohidrosis, and facial dysmorphisms characterized by a depressed nasal bridge, maxillary hypoplasia, and protuberant lips. Chromosomal analysis revealed a normal 46,XY male karyotype. Due to the presence of clinical features of hypohidrotic ectodermal dysplasia (HED), the EDA gene, located at Xq12q13.1, of the patient and his family was sequenced. Analysis of the proband's sequence revealed a missense mutation (T to A transversion) in hemizygosity state at nucleotide position 158 in exon 1 of the EDA gene, which changes codon 53 from leucine to histidine, while heterozygosity at this position was detected in the slightly affected mother; moreover, this mutation was not found in the publically available Human Gene Mutation Database. To date, our findings indicate that a novel mutation in EDA is associated with X-linked HED, adding it to the repertoire of EDA mutations. © 2017 S. Karger AG, Basel.

A Novel Splicesite Mutation in the EDAR Gene Causes Severe Autosomal Recessive Hypohydrotic (Anhidrotic) Ectodermal Dysplasia in an Iranian Family

PubMed Central

Torkamandi, Shahram; Gholami, Milad; Mohammadi-asl, Javad; Rezaie, Somaye; Zaimy, Mohammad Ali; Omrani, Mir Davood

2016-01-01

Hypohidrotic ectodermal dysplasia (HED) is a rare congenital disorder arising from deficient development of ectoderm-derived structures including skin, nails, glands and teeth. The phenotype of HED is associated with mutation in EDA, EDAR, EDARADD and NEMO genes, all of them disruptingNF-κB signaling cascade necessary for initiation, formation and differentiation in the embryo and adult. Here we describe a novel acceptor splice site mutation c.730-2 A>G(IVS 8-2 A>G) in EDAR gene in homozygous form in all affected members of a family,and in heterozygous form in carriers. Bioinformatics analysis showed that this mutation can create a new broken splicing site and lead to aberrant splicing. PMID:28357203

Genotype-phenotype correlation in boys with X-linked hypohidrotic ectodermal dysplasia.

PubMed

Burger, Kristin; Schneider, Anne-Theres; Wohlfart, Sigrun; Kiesewetter, Franklin; Huttner, Kenneth; Johnson, Ramsey; Schneider, Holm

2014-10-01

X-linked hypohidrotic ectodermal dysplasia (XLHED), the most frequent form of ectodermal dysplasia, is a genetic disorder of ectoderm development characterized by malformation of multiple ectodermal structures such as skin, hair, sweat and sebaceous glands, and teeth. The disease is caused by a broad spectrum of mutations in the gene EDA. Although XLHED symptoms show inter-familial and intra-familial variability, genotype-phenotype correlation has been demonstrated with respect to sweat gland function. In this study, we investigated to which extent the EDA genotype correlates with the severity of XLHED-related skin and hair signs. Nineteen male children with XLHED (age range 3-14 years) and seven controls (aged 6-14 years) were examined by confocal microscopy of the skin, quantification of pilocarpine-induced sweating, semi-quantitative evaluation of full facial photographs with respect to XLHED-related skin issues, and phototrichogram analysis. All eight boys with known hypomorphic EDA mutations were able to produce at least some sweat and showed less severe cutaneous signs of XLHED than the anhidrotic XLHED patients (e.g., perioral and periorbital eczema or hyperpigmentation, regional hyperkeratosis, characteristic wrinkles under the eyes). As expected, individuals with XLHED had significantly less and thinner hair than healthy controls. However, there were also significant differences in hair number, diameter, and other hair characteristics between the group with hypomorphic EDA mutations and the anhidrotic patients. In summary, this study indicated a remarkable genotype-phenotype correlation of skin and hair findings in prepubescent males with XLHED. © 2014 Wiley Periodicals, Inc.

A novel mutation in the EDAR gene causes severe autosomal recessive hypohidrotic ectodermal dysplasia.

PubMed

Henningsen, Emil; Svendsen, Mathias Tiedemann; Lildballe, Dorte Launholt; Jensen, Peter Kjestrup Axel

2014-08-01

We report on a 2-year-old girl presenting with a severe form of hypohidrotic ectodermal dysplasia (HED). The patient presented with hypotrichosis, anodontia, hypohidrosis, frontal bossing, prominent lips and ears, dry, pale skin, and dermatitis. The patient had chronic rhinitis with malodorous nasal discharge. The girl was the second born child of first-cousin immigrants from Northern Iraq. A novel homozygous mutation (c.84delC) in the EDAR gene was identified. This mutation most likely causes a frameshift in the protein product (p.S29fs*74). This results in abolition of all ectodysplasin-mediated NF-kB signalling. This complete loss-of-function mutation likely accounts for the severe clinical abnormalities in ectodermal structures in the described patient. © 2014 Wiley Periodicals, Inc.

Clinical Variability in a Family with an Ectodermal Dysplasia Syndrome and a Nonsense Mutation in the TP63 Gene.

PubMed

Eisenkraft, Arik; Pode-Shakked, Ben; Goldstein, Nurit; Shpirer, Zvi; van Bokhoven, Hans; Anikster, Yair

2015-01-01

Mutations in the TP63 gene have been associated with a variety of ectodermal dysplasia syndromes, among which the clinically overlapping Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) and the Rapp-Hodgkin syndromes. We report a multiplex nonconsanguineous family of Ashkenazi-Jewish descent, in which the index patient presented with a persistent scalp skin lesion, dystrophic nails and light thin hair. Further evaluation revealed over 10 affected individuals in the kindred, over four generations, exhibiting varying degrees of ectodermal involvement. Analysis of the TP63 gene from four of the patients and from two healthy individuals of the same family was performed. Gene sequencing of the patients revealed a nonsense mutation leading to a premature termination codon (PTC) (p.Gln16X). The same mutation was found in all tested affected individuals in the family, but gave rise to marked phenotypic variability with minor clinical manifestations in some individuals, underscoring the clinical heterogeneity associated with the recently described PTC-causing mutations.

Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura.

PubMed

Ramírez-Alejo, Noé; Alcántara-Montiel, Julio C; Yamazaki-Nakashimada, Marco; Duran-McKinster, Carola; Valenzuela-León, Paola; Rivas-Larrauri, Francisco; Cedillo-Barrón, Leticia; Hernández-Rivas, Rosaura; Santos-Argumedo, Leopoldo

2015-10-01

NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females. Copyright © 2015 Elsevier Inc. All rights reserved.

Karyotyping, dermatoglyphic, and sweat pore analysis of five families affected with ectodermal dysplasia

PubMed Central

Sidhu, Manpreet; Kale, Alka D; Kotrashetti, Vijayalakshmi S

2012-01-01

Background: Hereditary ectodermal dysplasia is a genetic recessive trait characterized by hypohydrosis, hypotrichosis, and hypodontia. The affected individual show characteristic physiognomy like protruded forehead, depressed nasal bridge, periorbital wrinkling, protruded lips, etc. There is marked decrease in sweat and salivary secretion. Due to skin involvement palm and sole ridge patterns are disrupted. Aim: In this study an attempt has been made to classify the affected members according to the degree of penetrance by pedigree analysis and also study karyotyping for cytogenetics, dermatoglyphic analysis for the various ridge patterns and variations in the number of sweat glands by sweat pore analysis in affected individuals. Materials and Methods: A total of five families who were affected with ectodermal dysplasia were considered. Pedigree analysis was drawn up to three generation by obtaining history. Dermatoglyphics and sweat pore analysis was done by obtaining palm and finger print impression using stamp pad ink. Karyotyping was done by collecting 3–5 ml peripheral blood. Karyotyping was prepared using lymphocyte culture. Chromosomes were examined at 20 spreads selected randomly under ×100 magnification. Results were analyzed by calculating mean values and percentage was obtained. Results: Karyotyping did not show any abnormalities, dermatoglyphic analysis and sweat pore counts showed marked variations when compared with normal. Moreover, pedigree analysis confirmed the status of the disease as that of the recessive trait. Conclusion: Large number of affected patients needs to be evaluated for dermatoglypic analysis. Genetic aspect of the disease needs to be looked into the molecular level in an attempt to locate the gene locus responsible for ectodermal dysplasia and its manifestation. PMID:23248471

A Novel Homozygous Missense Mutation in HOXC13 Leads to Autosomal Recessive Pure Hair and Nail Ectodermal Dysplasia.

PubMed

Li, Xiaoxiao; Orseth, Meredith Lee; Smith, J Michael; Brehm, Mary Abigail; Agim, Nnenna Gebechi; Glass, Donald Alexander

2017-03-01

Pure hair and nail ectodermal dysplasia (PHNED) is a rare disorder that presents with hypotrichosis and nail dystrophy while sparing other ectodermal structures such as teeth and sweat glands. We describe a homozygous novel missense mutation in the HOXC13 gene that resulted in autosomal recessive PHNED in a Hispanic child. The mutation c.812A>G (p.Gln271Arg) is located within the DNA-binding domain of the HOXC13 gene, cosegregates within the family, and is predicted to be maximally damaging. This is the first reported case of a missense HOXC13 mutation resulting in PHNED and the first reported case of PHNED identified in a North American family. Our findings illustrate the critical role of HOXC13 in human hair and nail development. © 2017 Wiley Periodicals, Inc.

A distinct type of hidrotic ectodermal dysplasia.

PubMed

Halal, F; Setton, N; Wang, N S

1991-03-15

Four individuals from 2 generations of a family had a hidrotic type of ectodermal dysplasia (ED). Males and females were similarly affected. They had trichodysplasia, with absent eyebrows and eyelashes; normal teeth, onychodysplasia; normal sweating; mild retrognathia; abnormal dermatoglyphics; and mental retardation. Additional variable manifestations included irregular menses, high implanted or prominent ears, café-au-lait spot, keratosis pilaris, supernumerary nipple, and mild hearing loss. Their previously undescribed condition could be classified as an ED of 1-3 (trichoonychial) subgroup of group A according to Freire-Maia's classification and is inherited as an autosomal recessive trait.

Autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency caused by a novel NFKBIA mutation, p.Ser36Tyr, presents with mild ectodermal dysplasia and non-infectious systemic inflammation.

PubMed

Yoshioka, Takakazu; Nishikomori, Ryuta; Hara, Junichi; Okada, Keiko; Hashii, Yoshiko; Okafuji, Ikuo; Nodomi, Seishiro; Kawai, Tomoki; Izawa, Kazushi; Ohnishi, Hidenori; Yasumi, Takahiro; Nakahata, Tatsutoshi; Heike, Toshio

2013-10-01

Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is characterized by hypohidrosis, dental abnormalities, sparse hair, and immunodeficiency. Autosomal dominant (AD)-EDA-ID, caused by a heterozygous mutation within NFKBIA, is very rare and its clinical features remain largely unknown. This study describes a patient with AD-EDA-ID harboring a novel NFKBIA mutation who presented with mild EDA and non-infectious systemic inflammation. The clinical presentation of an AD-EDA-ID patient was described and immunological, genetic, and biochemical analyses were performed, with a focus on nuclear factor kappa B (NF-κB) activation. The patient presented with symptoms of mild EDA-ID, namely sparse hair and hypohidrosis, although a skin biopsy confirmed the presence of sweat glands. There were no dental abnormalities. The patient also suffered from non-infectious inflammation, which responded to systemic corticosteroid therapy; however, the patient remained ill. Immunological analyses revealed reduced Toll-like receptor/IL-1 (TLR/IL-1) and tumor necrosis factor (TNF) receptor family responses to various stimuli. Genetic analysis identified a de novo heterozygous missense mutation, p.Ser36Tyr, in NFKBIA, resulting in defective NFKBIA degradation and impaired NF-κB activation. The patient was diagnosed with AD-EDA-ID and underwent hematopoietic stem cell transplantation. Engraftment was successful, with few signs of acute graft versus host disease. However, the patient suffered hemolytic anemia and thrombocytopenia, and died from a brain hemorrhage due to intractable thrombocytopenia. AD-EDA-ID patients can present with mild ectodermal dysplasia and non-infectious inflammation, rather than with recurrent infections. Also, hematopoietic stem cell transplantation for AD-EDA-ID is still a clinical challenge.

[Clinical and molecular study in a family with autosomal dominant hypohidrotic ectodermal dysplasia].

PubMed

Callea, Michele; Cammarata-Scalisi, Francisco; Willoughby, Colin E; Giglio, Sabrina R; Sani, Ilaria; Bargiacchi, Sara; Traficante, Giovanna; Bellacchio, Emanuele; Tadini, Gianluca; Yavuz, Izzet; Galeotti, Angela; Clarich, Gabriella

2017-02-01

Hypohidrotic ectodermal dysplasia (HED) is a rare disease characterized by deficiency in development of structure derived from the ectoderm and is caused by mutations in the genes EDA, EDAR, or EDARADD. Phenotypes caused by mutations in these three may exhibit similar clinical features, explained by a common signaling pathway. Mutations in EDA gene cause X linked HED, which is the most common form. Mutations in EDAR and EDARADD genes cause autosomal dominant and recessive form of HED. The most striking clinical findings in HED are hypodontia, hypotrichosis and hypohidrosis that can lead to episodes of hyperthermia. We report on clinical findings in a child with HED with autosomal dominant inheritance pattern with a heterozygous mutation c.1072C>T (p.Arg358X) in the EDAR gene. A review of the literature with regard to other cases presenting the same mutation has been carried out and discussed. Sociedad Argentina de Pediatría.

Respiratory problems in patients with ectodermal dysplasia syndromes.

PubMed

Fete, Timothy

2014-10-01

The ectodermal dysplasias (EDs) are a heterogeneous group of disorders characterized by a deficiency of ectoderm- and mesoderm-derived tissues and appendages, particularly hair, skin, teeth, and nails. Many of these disorders are associated with a greater risk of respiratory disease than found in the general population. There are no published papers that comprehensively describe these findings and the possible etiologies. Patients have been reported with dramatic decrease in mucous glands in the respiratory tract. Anatomic defects, including cleft palate, that predispose to respiratory infection, are associated with several of the ED syndromes. Atopy and immune deficiencies have been shown to have a higher prevalence in ED syndromes. Clinicians who care for patients affected by ED syndromes should be aware of the potential respiratory complications, and consider evaluation for structural anomalies, atopy and immunodeficiency in individuals with recurrent or chronic respiratory symptoms. © 2014 Wiley Periodicals, Inc.

Cleft palate and ADULT phenotype in a patient with a novel TP63 mutation suggests lumping of EEC/LM/ADULT syndromes into a unique entity: ELA syndrome.

PubMed

Prontera, Paolo; Garelli, Emanuela; Isidori, Ilenia; Mencarelli, Amedea; Carando, Adriana; Silengo, Margherita Cirillo; Donti, Emilio

2011-11-01

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare condition belonging to the group of ectodermal dysplasias caused by TP63 mutations. Its clinical phenotype is similar to ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) and limb-mammary syndrome (LMS), and differs from these disorders mainly by the absence of cleft lip and/or palate. We report on a 39-year-old patient who was found to be heterozygous for a c.401G > T (p.Gly134Val) de novo mutation of TP63. This patient had the ADULT phenotype associated with cleft palate. Our findings, rather than extend the clinical spectrum of ADULT syndrome, suggest that cleft palate can no longer be considered an element for differential diagnosis for ADULT, EEC, and LMS. Our data, added to other reports on overlapping phenotypes, support the combining of these three phenotypes into a unique entity that we propose to call "ELA syndrome," which is an acronym of ectrodactyly-ectodermal dysplasia-cleft lip and palate, limb-mammary, and ADULT syndromes. Copyright © 2011 Wiley Periodicals, Inc.

[Prenatal diagnosis of X-linked anhidrotic ectodermal dysplasia with X-chromosome inversion].

PubMed

Shi, Hui-juan; Fang, Qun; Wang, Lian-tang

2005-07-13

To investigate the possibility of prenatal diagnosis of the fetal suspected to be affected by anhidrotic ectodermal dysplasia (EDA) in a family with X-linked EDA so as to provide a basis for prenatal diagnosis and genetic counseling of this disorder. Pedigree analysis and genetic counseling were performed in a family after a proband was diagnosed with EDA. The peripheral blood samples were collected from the proband, a 12-year-old boy, his mother, and his 2 aunts, one being pregnant, to undergo chromosome karyotype analysis. The fetus Puncture of umbilical vein was performed to collect the blood of fetus for chromosome examination. Induced abortion was conducted due to the diagnosis of the fetus with EDA. Autopsy, immunohistochemistry of the skin tissues of face, breast, epigastrium, and thigh, and X-ray photography of the lower jawbone were made. Pericentric inversion occurring at one of the X-chromosome [inv (x) (p22q13)] was found in the proband and his nephew (the fetus), both patients, and his mother and his second aunt (the pregnant woman), both carriers. Autopsy of the fetus showed epidermis dysplasia and deficiency of hair follicle and sebaceous gland. Immunohistochemistry showed that epithelial membrane antigen and cytokeratin were negatively expressed in the fetal skin tissues. Pedigree analysis and genetic counseling for the family members of EDA patients and prenatal and postpartum examination for the fetus help diagnose EDA.

Gene p63: In ectrodactyly-ectodermal dysplasia clefting, ankyloblepharon-ectodermal dysplasia, Rapp-Hodgkin syndrome.

PubMed

van Straten, Cornelia; Butow, Kurt-W

2013-01-01

An analysis was made of three different syndromes associated with p63 gene mutations, known as ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC), ankyloblepharon-ectodermal dysplasia clefting syndrome (AEC or Hay-Wells) and Rapp-Hodgkin syndrome (RHS). The postoperative complications associated with their cleft reconstructions were also evaluated. Extensive demographic information, in particular of the clinical appearances, associated malformations, and the types and complications of the reconstructive surgical procedures, were recorded of these syndromic cases occurring in a database of 3621 facial cleft deformity patients. The data was analyzed using the Microsoft Excel program. A total of 10 (0.28%) cases of p63 associated syndromes were recorded: EEC (6), RHS (3), and AEC (1). The following clinical cleft appearances were noted - EEC = 6: CLA 1 -right side unilateral (female); CLAP 4 - right side (1) + left side (1) unilateral (male + female); bilateral (2) (males); hPsP 1 (female) (divided in 3 Black, 2 White, 1 Indian); RHS = 3: CLAP 2 (White males); hPsP 1 (White female); AEC = 1: CLAP bilateral (White male). Other features of the syndromes were: skin, hand, foot, tooth, hair and nail involvement, and light sensitivity. Postoperative complications included: (i) stenosis of nasal opening, especially after reconstruction of the bilateral cleft lip and the columella lengthening (2 cases), (ii) premaxilla-prolabium fusion (2 cases), (iii) repeated occurrence of oro-nasal fistula in the hard palate (4 cases), and (iv) dysgnathial development of midfacial structures (3 cases). Three different p63 associated syndromes (EEC, AEC, and RHS) were diagnosed (0.27% of the total facial cleft deformities database). The majority of the cases presented with a bilateral CLAP in males only. A number of females and males had unilateral CLA. The hPsP-cleft was recorded in females only. The associated ectodermal component most probably had a profoundly negative influence on postoperatively wound healing, which was observed in particular at the nasal openings, the premaxilla sulcus and in the hard palate mucosa. The reconstruction of p63 associated syndromes is a greater challenge than the usual cleft reconstruction to the surgeon.

Correlating interleukin-12 stimulated interferon-γ production and the absence of ectodermal dysplasia and anhidrosis (EDA) in patients with mutations in NF-κB essential modulator (NEMO).

PubMed

Haverkamp, Margje H; Marciano, Beatriz E; Frucht, David M; Jain, Ashish; van de Vosse, Esther; Holland, Steven M

2014-05-01

Patients with hypomorphic mutations in Nuclear Factor-κB Essential Modulator (NEMO) are immunodeficient (ID) and most display ectodermal dysplasia and anhidrosis (EDA). We compared cytokine production by NEMO-ID patients with and without EDA. PBMCs of NEMO-ID patients, four with EDA carrying E315A, C417R, D311N and Q403X, and three without EDA carrying E315A, E311_L333del and R254G, were cultured with PHA, PHA plus IL-12p70, LPS, LPS plus IFN-γ, TNF and IL-1β. The production of various cytokines was measured in the supernatants. Fifty-nine healthy individuals served as controls. PBMCs of NEMO-ID patients without EDA produce subnormal amounts of IFN-γ after stimulation with PHA, but normal amounts of IFN-γ after PHA plus IL-12p70. In contrast, IFN-γ production by patients with EDA was low in both cases. Patients with EDA also generate lower PHA-stimulated IL-10 and IL-1β than controls, whereas the production of these cytokines by patients without EDA was normal. Responses of PBMCs in NEMO-ID patients with EDA to PHA with and without IL-12p70 appear less robust than in NEMO-ID patients without EDA. This possibly indicates a better preserved NEMO function in our patients without EDA.

EDA mutation as a cause of hypohidrotic ectodermal dysplasia: a case report and review of the literature.

PubMed

Huang, S X; Liang, J L; Sui, W G; Lin, H; Xue, W; Chen, J J; Zhang, Y; Gong, W W; Dai, Y; Ou, M L

2015-08-28

Ectodermal dysplasia (ED) represents a collection of rare disorders that result from a failure of development of the tissues derived from the embryonic ectoderm. ED is often associated with hair, teeth, and skin abnormalities, which are serious conditions affecting the quality of life of the patient. To date, a large number of genes have been found to be associated with this syndrome. Here, we report a patient with hypohidrotic ED (HED) without family history. We identified that this patient's disorder arises from an X-linked HED with a mutation in the EDA gene (G299D) found by whole-exome sequencing. In addition, in this paper we summarize the disease-causing mutations based on current literature. Overall, recent clinical and genetic research involving patients with HED have uncovered a large number of pathogenic mutations in EDA, which might contribute to a full understanding of the function of EDA and the underlying mechanisms of HED caused by EDA mutations.

A novel missense mutation in the gene EDARADD associated with an unusual phenotype of hypohidrotic ectodermal dysplasia.

PubMed

Wohlfart, Sigrun; Söder, Stephan; Smahi, Asma; Schneider, Holm

2016-01-01

Hypohidrotic ectodermal dysplasia (HED) is a rare disorder characterized by deficient development of structures derived from the ectoderm including hair, nails, eccrine glands, and teeth. HED forms that are caused by mutations in the genes EDA, EDAR, or EDARADD may show almost identical phenotypes, explained by a common signaling pathway. Proper interaction of the proteins encoded by these three genes is important for the activation of the NF-κB signaling pathway and subsequent transcription of the target genes. Mutations in the gene EDARADD are most rarely implicated in HED. Here we describe a novel missense mutation, c.367G>A (p.Asp123Asn), in this gene which did not appear to influence the interaction between EDAR and EDARADD proteins, but led to an impaired ability to activate NF-κB signaling. Female members of the affected family showed either unilateral or bilateral amazia. In addition, an affected girl developed bilateral ovarian teratomas, possibly associated with her genetic condition. © 2015 Wiley Periodicals, Inc.

Novel variant in the TP63 gene associated to ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome.

PubMed

Gonzalez, Francisco; Loidi, Lourdes; Abalo-Lojo, Jose M

2017-01-01

Ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome is a disorder resulting from anomalous embryonic development of ectodermal tissues. There is evidence that AEC syndrome is caused by mutations in the TP63 gene, which encodes the p63 protein. This is an important regulatory protein involved in epidermal proliferation and differentiation. Genome sequencing was performed in DNA from peripheral blood leukocytes of a newborn with AEC syndrome and her parents. Variants were searched in all coding exons and intron-exon boundaries of the TP63 gene. A heterozygous missense variant (NM_003722.4:c.1063G>C (p.Asp355His) was found in the newborn patient. No variants were found in either of the parents. We identified a previously unreported variant in TP63 gene which seems to be involved in the somatic malformations found in the AEC syndrome. The absence of this variant in both parents suggests that the variant appeared de novo.

Implant-supported Oral Rehabilitation in Child with Ectodermal Dysplasia - 4-year Follow-up.

PubMed

Cezária Triches, Thaisa; Ximenes, Marcos; Oliveira de Souza, João Gustavo; Rodrigues Lopes Pereira Neto, Armando; Cardoso, Antônio Carlos; Bolan, Michele

2017-01-01

Ectodermal dysplasia (ED) is an anomaly determined by genetic factors that alter ectodermal structures such as skin, hair, nails, glands, and teeth. Children affected by this condition require extensive, comprehensive, and multidisciplinary treatment. An 8-year-old female patient visited the Dentistry Clinic of the Federal University of Santa Catarina with the chief complaint of multiple missing teeth. The mother reported that the patient had ED. Clinical and radiographic examination revealed the congenital absence of several primary and permanent teeth and tooth germs. Subsequent oral rehabilitation comprised the application of a maxillary denture and mandibular implant-supported fixed prosthesis. The child was also supplied with a wig for further enhancement of esthetics aimed at improving her emotional wellbeing. Psychological follow-up and speech therapy were also provided. After 4 years of follow-up, implant-supported oral rehabilitation has proved to be a satisfactory treatment option, allowing restoration of masticatory, phonetic, and esthetic function, as well as an improvement in the patient's self-esteem and social wellbeing.

Mutation in WNT10A Is Associated with an Autosomal Recessive Ectodermal Dysplasia: The Odonto-onycho-dermal Dysplasia

PubMed Central

Adaimy, Lynn ; Chouery, Eliane ; Mégarbané, Hala ; Mroueh, Salman ; Delague, Valérie ; Nicolas, Elsa ; Belguith, Hanen ; de Mazancourt, Philippe ; Mégarbané, André 

2007-01-01

Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity-mapping strategy, we assigned the disease locus to an ∼9-cM region at chromosome 2q35-q36.2, located between markers rs16853834 and D2S353, with a maximum multipoint LOD score of 5.7. Screening of candidate genes in this region led us to identify the same c.697G→T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in all patients. At the protein level, the mutation is predicted to result in a premature truncated protein of 232 aa instead of 417 aa. This is the first report to our knowledge of a human phenotype resulting from a mutation in WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases. PMID:17847007

Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia.

PubMed

Adaimy, Lynn; Chouery, Eliane; Megarbane, Hala; Mroueh, Salman; Delague, Valerie; Nicolas, Elsa; Belguith, Hanen; de Mazancourt, Philippe; Megarbane, Andre

2007-10-01

Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity-mapping strategy, we assigned the disease locus to an ~9-cM region at chromosome 2q35-q36.2, located between markers rs16853834 and D2S353, with a maximum multipoint LOD score of 5.7. Screening of candidate genes in this region led us to identify the same c.697G-->T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in all patients. At the protein level, the mutation is predicted to result in a premature truncated protein of 232 aa instead of 417 aa. This is the first report to our knowledge of a human phenotype resulting from a mutation in WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases.

Dermatopathia pigmentosa reticularis: A rare reticulate pigmentary disorder

PubMed Central

Shanker, Vinay; Gupta, Mudita

2013-01-01

Dermatopathia pigmentosa reticularis is a rare ectodermal dysplasia with a triad of generalized reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy. We report a case of a 21 year old woman who had generalized reticulate pigmentation, diffuse noncicatricial alopecia and onychodystrophy of finger and toe nails. Along with this triad she had palmoplantar keratoderma and poorly developed dermatoglyphics. There was no evidence of involvement of other ectodermally derived organ. PMID:23440032

Prevalence of atopic disorders and immunodeficiency in patients with ectodermal dysplasia syndromes

PubMed Central

Mark, Barry J.; Becker, Bradley A.; Halloran, Donna R.; Bree, Alanna F.; Sindwani, Raj; Fete, Mary D.; Motil, Kathleen J.; Srun, Sopheak W.; Fete, Timothy J.

2013-01-01

Background Ectodermal dysplasia (ED) syndromes are a diverse group of disorders that affect multiple ectodermally derived tissues. Small studies and case reports suggest an increase in atopy and primary immunodeficiencies (PIDs) among patients with ED syndromes. Objective To determine the prevalence of clinical symptoms suggestive of atopy or immunodeficiency among a large cohort of children with ED syndromes. Methods A 9-page questionnaire was mailed to families who were members of the National Foundation for Ectodermal Dysplasias. The surveys were completed by parents of children younger than 18 years with a diagnosis of an ED syndrome or carrier state. Portions of the questionnaire were adapted from previously validated questionnaires developed by the International Study of Asthma and Allergies in Childhood (ISAAC). Results We received 347 completed questionnaires (41%). When compared with the 13- to 14-year-old children surveyed by ISAAC, we found both all-aged and age-matched children with ED syndromes, respectively, had significantly higher rates of asthma (32.2% and 37.2% vs 16.4%), rhinitis symptoms (76.1% and 78.3% vs 38.9%), and eczema (58.9% and 48.9% vs 8.2%). The prevalence of physician-diagnosed food allergies (20.7%) and PIDs (6.1%) in these ED patients also exceeded known rates in the general pediatric population. Conclusion This large-scale, retrospective study demonstrates a greater reported prevalence of symptoms suggestive of atopic disorders and PIDs among children with ED syndromes than the general pediatric population. A combination of genetic and environmental factors in ED syndromes may contribute to breaches of skin and mucosal barriers, permitting enhanced transmission and sensitization to irritants, allergens, and pathogens. PMID:22626597

Novel EDA mutation in X-linked hypohidrotic ectodermal dysplasia and genotype-phenotype correlation.

PubMed

Zeng, B; Lu, H; Xiao, X; Zhou, L; Lu, J; Zhu, L; Yu, D; Zhao, W

2015-11-01

X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by abnormalities of hair, teeth, and sweat glands, while non-syndromic hypodontia (NSH) affects only teeth. Mutations in Ectodysplasin A (EDA) underlie both XLHED and NSH. This study investigated the genetic causes of six hypohidrotic ectodermal dysplasia (HED) patients and genotype-phenotype correlation. The EDA gene of six patients with HED was sequenced. Bioinformatics analysis and structural modeling for the mutations were performed. The records of 134 patients with XLHED and EDA-related NSH regarding numbers of missing permanent teeth from this study and 20 articles were reviewed. Nonparametric tests were used to analyze genotype-phenotype correlations. In four of the six patients, we identified a novel mutation c.852T>G (p.Phe284Leu) and three reported mutations: c.467G>A (p.Arg156His), c.776C>A (p.Ala259Glu), and c.871G>A (p.Gly291Arg). They were predicted to be pathogenic by bioinformatics analysis and structural modeling. Genotype-phenotype correlation analysis revealed that truncating mutations were associated with more missing teeth. Missense mutations and the mutations affecting the TNF homology domain were correlated with fewer missing teeth. This study extended the mutation spectrum of XLHED and revealed the relationship between genotype and the number of missing permanent teeth. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

BK virus encephalopathy and sclerosing vasculopathy in a patient with hypohidrotic ectodermal dysplasia and immunodeficiency.

PubMed

Darbinyan, Armine; Major, Eugene O; Morgello, Susan; Holland, Steven; Ryschkewitsch, Caroline; Monaco, Maria Chiara; Naidich, Thomas P; Bederson, Joshua; Malaczynska, Joanna; Ye, Fei; Gordon, Ronald; Cunningham-Rundles, Charlotte; Fowkes, Mary; Tsankova, Nadejda M

2016-07-13

Human BK polyomavirus (BKV) is reactivated under conditions of immunosuppression leading most commonly to nephropathy or cystitis; its tropism for the brain is rare and poorly understood. We present a unique case of BKV-associated encephalopathy in a man with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) due to IKK-gamma (NEMO) mutation, who developed progressive neurological symptoms. Brain biopsy demonstrated polyomavirus infection of gray and white matter, with predominant involvement of cortex and distinct neuronal tropism, in addition to limited demyelination and oligodendroglial inclusions. Immunohistochemistry demonstrated polyoma T-antigen in neurons and glia, but expression of VP1 capsid protein only in glia. PCR analysis on both brain biopsy tissue and cerebrospinal fluid detected high levels of BKV DNA. Sequencing studies further identified novel BKV variant and disclosed unique rearrangements in the noncoding control region of the viral DNA (BKVN NCCR). Neuropathological analysis also demonstrated an unusual form of obliterative fibrosing vasculopathy in the subcortical white matter with abnormal lysosomal accumulations, possibly related to the patient's underlying ectodermal dysplasia. Our report provides the first neuropathological description of HED-ID due to NEMO mutation, and expands the diversity of neurological presentations of BKV infection in brain, underscoring the importance of its consideration in immunodeficient patients with unexplained encephalopathy. We also document novel BKVN NCCR rearrangements that may be associated with the unique neuronal tropism in this patient.

Ectodermal dysplasia

MedlinePlus

... fever, because the skin cannot sweat and control temperature properly. Affected adults are unable to tolerate a ... need special measures to keep a normal body temperature. Depending on which genes are affected, other symptoms ...

Evaluation of Masticatory Stimulation Effect on the Maxillary Transversal Growth in Ectodermal Dysplasia Children.

PubMed

Sfeir, Elia; Nahass, Mona G; Mourad, Ayman

2017-01-01

Severe oligodontia is one of the most important symptoms in children with hypohidrotic ectodermal dysplasia (HED). The growth of the maxilla is a key consideration in restoring their mouth. The aim of this study was to evaluate the transversal maxillary sutural growth, after passive masticatory stimulation, in HED children. We also thought to assess the efficiency and functional outcome of the proposed propriocep-tive passive expansion (PPE) prosthetic device. We studied 13 children (age 6-11 years) suffering from HED with severe oligodontia. Their maxilla was restored by a PPE device formed from two parts and joined by a passive slide system. Distance between the two parts was noted at the anterior and posterior regions at each control visit over an average of 23 months. We also conducted and filled a satisfaction questionnaire over the same period. We tested the hypothesis that the posterior expansion is greater than the anterior expansion (one-tailed Student's t-test with p-value <0.05). Best-fit linear and quadratic models were used to explore the relationship between age, duration of observation, and the rate of growth. The average opening of the device was 2.27 mm in the anterior region and 2.96 mm in the posterior region. The questionnaire response was positive for all children. There are no significant linear or quadratic relationships between the data at the 5% significance level. The posterior expansion is greater than the anterior expansion at the 5% significance level (p-value 0.000394). Further studies are mandatory to assess the reliability of our particular intervention and treatment modalities for these cases. The PPE device, we propose, assures function and esthetics in the long- term. It enhances stimulation by a passive way that leads to physiological growth of the palatal suture. Using this PPE device to restore the maxilla in children with HED promotes physiological growth. The passive nature of this prosthesis helps by eliminating the need for any changes or replacement over time. Sfeir E, Nahass MG, Mourad A. Evaluation of Masticatory Stimulation Effect on the Maxillary Transversal Growth in Ectodermal Dysplasia Children. Int J Clin Pediatr Dent 2017;10(1):55-61.

Inducible Transgenic Models of BRCA1 Function

DTIC Science & Technology

1998-10-01

development, and for signs of hyperplasia, dysplasia and neoplasia. Specific Aim 3. Inducibly abolish Brcal expression in the mammary epithelium of...abnormalities in mammary epithelial proliferation, differentiation and development, and for signs of hyperplasia, dysplasia and neoplasia. 6...Lyu MS, Kozak CA and Leder P. Expression of Brcal is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice

Eight Mutations of Three Genes (EDA, EDAR, and WNT10A) Identified in Seven Hypohidrotic Ectodermal Dysplasia Patients.

PubMed

Zeng, Binghui; Xiao, Xue; Li, Sijie; Lu, Hui; Lu, Jiaxuan; Zhu, Ling; Yu, Dongsheng; Zhao, Wei

2016-09-19

Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the teeth, hair, and sweat glands. Ectodysplasin A (EDA), Ectodysplasin A receptor (EDAR), and EDAR-associated death domain (EDARADD) are candidate genes for HED, but the relationship between WNT10A and HED has not yet been validated. In this study, we included patients who presented at least two of the three ectodermal dysplasia features. The four genes were analyzed in seven HED patients by PCR and Sanger sequencing. Five EDA and one EDAR heterozygous mutations were identified in families 1-6. Two WNT10A heterozygous mutations were identified in family 7 as a compound heterozygote. c.662G>A (p.Gly221Asp) in EDA and c.354T>G (p.Tyr118*) in WNT10A are novel mutations. Bioinformatics analyses results confirmed the pathogenicity of the two novel mutations. In family 7, we also identified two single-nucleotide polymorphisms (SNPs) that were predicted to affect the splicing of EDAR. Analysis of the patient's total RNA revealed normal splicing of EDAR. This ascertained that the compound heterozygous WNT10A mutations are the genetic defects that led to the onset of HED. Our data revealed the genetic basis of seven HED patients and expended the mutational spectrum. Interestingly, we confirmed WNT10A as a candidate gene of HED and we propose WNT10A to be tested in EDA-negative HED patients.

Cloning of the anhidrotic ectodermal dysplasia gene: Identification of cDNAs associated with CpG islands mapped near translocation breakpoint in two female patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, A.K.; Schlessinger, D.; Kere, J.

1994-09-01

The gene for the X chromosomal developmental disorder anhidrotic ectodermal dysplasia (EDA) has been mapped to Xq12-q13 by linkage analysis and is expressed in a few females with chromosomal translocations involving band Xq12-q13. A yeast artificial chromosome (YAC) contig (2.0 Mb) spanning two translocation breakpoints has been assembled by sequence-tagged site (STS)-based chromosomal walking. The two translocation breakpoints (X:autosome translocations from the affected female patients) have been mapped less than 60 kb apart within a YAC contig. Unique probes and intragenic STSs (mapped between the two translocations) have been developed and a somatic cell hybrid carrying the translocated X chromosomemore » from the AK patient has been analyzed by isolating unique probes that span the breakpoint. Several STSs made from intragenic sequences have been found to be conserved in mouse, hamster and monkey, but we have detected no mRNAs in a number of tissues tested. However, a probe and STS developed from the DNA spanning the AK breakpoint is conserved in mouse, hamster and monkey, and we have detected expressed sequences in skin cells and cDNA libraries. In addition, unique sequences have been obtained from two CpG islands in the region that maps proximal to the breakpoints. cDNAs containing these sequences are being studied as candidates for the gene affected in the etiology of EDA.« less

2008 International Conference on Ectodermal Dysplasias Classification Conference Report

PubMed Central

Salinas, Carlos F.; Jorgenson, Ronald J.; Wright, J. Timothy; DiGiovanna, John J.; Fete, Mary D.

2009-01-01

There are many ways to classify ectodermal dysplasia syndromes. Clinicians in practice use a list of syndromes from which to choose a potential diagnosis, paging through a volume, such as Freire-Maia and Pinheiro's corpus, matching their patient's findings to listed syndromes. Medical researchers may want a list of syndromes that share one (monothetic system) or several (polythetic system) traits in order to focus research on a narrowly defined group. Special interest groups may want a list from which they can choose constituencies, and insurance companies and government agencies may want a list to determine for whom to provide (or deny) health care coverage. Furthermore, various molecular biologists are now promoting classification systems based on gene mutation (e.g. TP63 associated syndromes) or common molecular pathways. The challenge will be to balance comprehensiveness within the classification with usability and accessibility so that the benefits truly serve the needs of researchers, health care providers and ultimately the individuals and families directly affected by ectodermal dysplasias. It is also recognized that a new classification approach is an ongoing process and will require periodical reviews or updates. Whatever scheme is developed, however, will have far-reaching application for other groups of disorders for which classification is complicated by the number of interested parties and advances in diagnostic acumen. Consensus among interested parties is necessary for optimizing communication among the diverse groups whether it be for equitable distribution of funds, correctness of diagnosis and treatment, or focusing research efforts. PMID:19681152

Scanning Electron Microscopic Hair Shaft Analysis in Ectodermal Dysplasia Syndromes.

PubMed

Hirano-Ali, Stefanie A; Reed, Ashley M; Rowan, Brandon J; Sorrells, Timothy; Williams, Judith V; Pariser, David M; Hood, Antoinette F; Salkey, Kimberly

2015-01-01

The objective of the current study was to catalog hair shaft abnormalities in individuals with ectodermal dysplasia (ED) syndromes using scanning electron microscopy (SEM) and to compare the findings with those in unaffected controls. This is the second of a two-part study, the first of which used light microscopy as the modality and was previously published. Scanning electron microscopy was performed in a blinded manner on hair shafts from 65 subjects with seven types of ED syndromes and 41 unaffected control subjects. Assessment was performed along the length of the shaft and in cross section. Hair donations were collected at the 28th Annual National Family Conference held by the National Foundation for Ectodermal Dysplasia. Control subjects were recruited from a private dermatology practice and an academic children's hospital outpatient dermatology clinic. SEM identified various pathologic hair shaft abnormalities in each type of ED and in control patients. When hairs with all types of ED were grouped together and compared with those of control patients, the difference in the presence of small diameter and shallow and deep grooves was statistically significant (p < 0.05). When the EDs were separated according to subtype, statistically significant findings were also seen. SEM is a possible adjuvant tool in the diagnosis of ED syndromes. There are significant differences, with high specificity, between the hairs of individuals with ED and those of control subjects and between subtypes. © 2015 Wiley Periodicals, Inc.

Telescopic overdenture for oral rehabilitation of ectodermal dysplasia patient.

PubMed

Gupta, Charu; Verma, Mahesh; Gupta, Rekha; Gill, Shubhra

2015-09-01

Reduced number of teeth with underdeveloped alveolar ridges poses a greatest prosthetic challenge in rehabilitation of ectodermal dysplasia patients (ED). Furthermore, surgical risks and financial constraints may preclude the implant supported prosthesis, the most desirable treatment option in an adult ED patient. Long edentulous span does not permit fixed dental prosthesis (FDP) as well. Telescopic denture by incorporating the best of both fixed and removable prosthesis can be a viable treatment alternative for ED patients with compromised dentition and limited finances. A 21-year-old young girl presented with chief complaint of esthetics and mastication due to missing upper and lower teeth. A provisional diagnosis of ED was made based on familial history, physical, and oral examination. This clinical report describes management of an adult ED patient by means of telescopic overdenture prosthesis in mandibular arch and FDP in maxillary arch which restored esthetics, function, and social confidence of the patient in a cost effective manner.

Telescopic overdenture for oral rehabilitation of ectodermal dysplasia patient

PubMed Central

Gupta, Charu; Verma, Mahesh; Gupta, Rekha; Gill, Shubhra

2015-01-01

Reduced number of teeth with underdeveloped alveolar ridges poses a greatest prosthetic challenge in rehabilitation of ectodermal dysplasia patients (ED). Furthermore, surgical risks and financial constraints may preclude the implant supported prosthesis, the most desirable treatment option in an adult ED patient. Long edentulous span does not permit fixed dental prosthesis (FDP) as well. Telescopic denture by incorporating the best of both fixed and removable prosthesis can be a viable treatment alternative for ED patients with compromised dentition and limited finances. A 21-year-old young girl presented with chief complaint of esthetics and mastication due to missing upper and lower teeth. A provisional diagnosis of ED was made based on familial history, physical, and oral examination. This clinical report describes management of an adult ED patient by means of telescopic overdenture prosthesis in mandibular arch and FDP in maxillary arch which restored esthetics, function, and social confidence of the patient in a cost effective manner. PMID:26604583

Amino-terminal residues of ΔNp63, mutated in ectodermal dysplasia, are required for its transcriptional activity.

PubMed

Lena, Anna Maria; Duca, Sara; Novelli, Flavia; Melino, Sonia; Annicchiarico-Petruzzelli, Margherita; Melino, Gerry; Candi, Eleonora

2015-11-13

p63, a member of the p53 family, is a crucial transcription factor for epithelial development and skin homeostasis. Heterozygous mutations in TP63 gene have been associated with human ectodermal dysplasia disorders. Most of these TP63 mutations are missense mutations causing amino acidic substitutions at p63 DNA binding or SAM domains that reduce or abolish the transcriptional activity of mutants p63. A significant number of mutants, however, resides in part of the p63 protein that apparently do not affect DNA binding and/or transcriptional activity, such as the N-terminal domain. Here, we characterize five p63 mutations at the 5' end of TP63 gene aiming to understand the pathogenesis of the diseases and to uncover the role of ΔNp63α N-terminus residues in determining its transactivation potential. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetics Home Reference: hypohidrotic ectodermal dysplasia

MedlinePlus

... chromosome , one of the two sex chromosomes . In males (who have only one X chromosome ), one altered ... copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much ...

X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry.

PubMed

Fete, Mary; Hermann, Julie; Behrens, Jeffrey; Huttner, Kenneth M

2014-10-01

The web-based Ectodermal Dysplasia International Registry (EDIR) is a comprehensive patient-reported survey contributing to an understanding of ectodermal dysplasia (ED). XLHED is the most common of the genetic ED syndromes and was the primary diagnosis reported by 223/835 respondents (141 males and 82 females). Overall, 96% of XLHED registrants reported as least one other affected family member and 21% reported a family history of infant or childhood deaths, consistent with the published mortality data in this disorder. In general, XLHED is diagnosed by the triad of decreased sweating, reduced hair, and hypodontia (present in 89%, 74%, and 74% of XLHED respondents). Additionally, the registry dataset confirmed a spectrum of life-long XLHED clinical complications including recurrent sinus infections (49% males, 52% females), nasal congestion often foul smelling and interfering with feeding (73% males, 27% females), eczema (66% males, 40% females), wheezing (66% males, 45% females), and a hoarse, raspy voice (67% males, 23% females). The Registry results also highlighted features consistently differentiating XLHED from the non-hypohidrotic ED syndromes including the frequency of infant/childhood deaths, the presence of limb/digit abnormalities, feeding issues related to nasal discharge, dentures, and a diagnosis of asthma. These results represent the largest collection of data on a broad-spectrum of health-related issues affecting ED patients. This project provides information for expanding knowledge of the natural history of XLHED, and as such may facilitate the diagnosis and treatment of its varied and lifelong medical challenges. © 2014 Wiley Periodicals, Inc.

Detection of a molecular deletion at the DXS732 locus in a patient with X-linked hypohidrotic ectodermal dysplasia (EDA), with the identification of a unique junctional fragment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zonana, J.; Gault, J.; Jones, M.

1993-01-01

X-linked hypohidrotic ectodermal dysplasia (EDA) has been localized to the Xq12-q13.1. A panel of genomic DNA samples from 80 unrelated males with EDA has been screened for deletions at seven genetic loci within the Xq12-13 region. A single individual was identified with a deletion at the DXS732 locus by hybridization with the mouse genomic probe pcos169E/4. This highly conserved DNA probe is from locus DXCrc169, which is tightly linked to the Ta locus, the putative mouse homologue of EDA. The proband had the classical phenotype of EDA, with no other phenotypic abnormalities, and a normal cytogenetic analysis. A human genomicmore » DNA clone, homologous to pcos169E/4, was isolated from a human X-chromosome cosmid library. On hybridization with the cosmid, the proband was found to be only partially deleted at the DXS732 locus, with a unique junctional fragment identified in the proband and in three of his maternal relatives. This is the first determination of carrier status for EDA in females, by direct mutation analysis. Failure to detect deletion of the other loci tested in the proband suggests that the DXS732 locus is the closest known locus to the EDA gene. Since the DXS732 locus contains a highly conserved sequence, it must be considered to be a candidate locus for the EDA gene itself. 18 refs., 3 figs., 1 tab.« less

The same IkappaBalpha mutation in two related individuals leads to completely different clinical syndromes.

PubMed

Janssen, Riny; van Wengen, Annelies; Hoeve, Marieke A; ten Dam, Monique; van der Burg, Miriam; van Dongen, Jacques; van de Vosse, Esther; van Tol, Maarten; Bredius, Robbert; Ottenhoff, Tom H; Weemaes, Corry; van Dissel, Jaap T; Lankester, Arjan

2004-09-06

Both innate and adaptive immune responses are dependent on activation of nuclear factor kappaB (NF-kappaB), induced upon binding of pathogen-associated molecular patterns to Toll-like receptors (TLRs). In murine models, defects in NF-kappaB pathway are often lethal and viable knockout mice have severe immune defects. Similarly, defects in the human NF-kappaB pathway described to date lead to severe clinical disease. Here, we describe a patient with a hyper immunoglobulin M-like immunodeficiency syndrome and ectodermal dysplasia. Monocytes did not produce interleukin 12p40 upon stimulation with various TLR stimuli and nuclear translocation of NF-kappaB was impaired. T cell receptor-mediated proliferation was also impaired. A heterozygous mutation was found at serine 32 in IkappaBalpha. Interestingly, his father has the same mutation but displays complex mosaicism. He does not display features of ectodermal dysplasia and did not suffer from serious infections with the exception of a relapsing Salmonella typhimurium infection. His monocyte function was impaired, whereas T cell function was relatively normal. Consistent with this, his T cells almost exclusively displayed the wild-type allele, whereas both alleles were present in his monocytes. We propose that the T and B cell compartment of the mosaic father arose as a result of selection of wild-type cells and that this underlies the widely different clinical phenotype.

Evaluation of Masticatory Stimulation Effect on the Maxillary Transversal Growth in Ectodermal Dysplasia Children

PubMed Central

Nahass, Mona G; Mourad, Ayman

2017-01-01

Aims Severe oligodontia is one of the most important symptoms in children with hypohidrotic ectodermal dysplasia (HED). The growth of the maxilla is a key consideration in restoring their mouth. The aim of this study was to evaluate the transversal maxillary sutural growth, after passive masticatory stimulation, in HED children. We also thought to assess the efficiency and functional outcome of the proposed propriocep-tive passive expansion (PPE) prosthetic device. Materials and methods We studied 13 children (age 6-11 years) suffering from HED with severe oligodontia. Their maxilla was restored by a PPE device formed from two parts and joined by a passive slide system. Distance between the two parts was noted at the anterior and posterior regions at each control visit over an average of 23 months. We also conducted and filled a satisfaction questionnaire over the same period. We tested the hypothesis that the posterior expansion is greater than the anterior expansion (one-tailed Student’s t-test with p-value <0.05). Best-fit linear and quadratic models were used to explore the relationship between age, duration of observation, and the rate of growth. Results The average opening of the device was 2.27 mm in the anterior region and 2.96 mm in the posterior region. The questionnaire response was positive for all children. There are no significant linear or quadratic relationships between the data at the 5% significance level. The posterior expansion is greater than the anterior expansion at the 5% significance level (p-value 0.000394). Limitations Further studies are mandatory to assess the reliability of our particular intervention and treatment modalities for these cases. Conclusion The PPE device, we propose, assures function and esthetics in the long- term. It enhances stimulation by a passive way that leads to physiological growth of the palatal suture. Clinical significance Using this PPE device to restore the maxilla in children with HED promotes physiological growth. The passive nature of this prosthesis helps by eliminating the need for any changes or replacement over time. How to cite this article Sfeir E, Nahass MG, Mourad A. Evaluation of Masticatory Stimulation Effect on the Maxillary Transversal Growth in Ectodermal Dysplasia Children. Int J Clin Pediatr Dent 2017;10(1):55-61. PMID:28377657

Genetics Home Reference: anhidrotic ectodermal dysplasia with immune deficiency

MedlinePlus

... The proteins produced from these two genes regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related ... proteins with impaired function, which reduces activation of nuclear factor-kappa-B. These changes disrupt certain signaling ...

Genetics Home Reference: focal dermal hypoplasia

MedlinePlus

... in people with focal dermal hypoplasia is an omphalocele , which is an opening in the wall of ... Dermal Hypoplasia MedlinePlus Encyclopedia: Ectodermal dysplasia MedlinePlus Encyclopedia: Omphalocele General Information from MedlinePlus (5 links) Diagnostic Tests ...

Quantitative proteomics of the human skin secretome reveal a reduction in immune defense mediators in ectodermal dysplasia patients.

PubMed

Burian, Marc; Velic, Ana; Matic, Katarina; Günther, Stephanie; Kraft, Beatrice; Gonser, Lena; Forchhammer, Stephan; Tiffert, Yvonne; Naumer, Christian; Krohn, Michael; Berneburg, Mark; Yazdi, Amir S; Maček, Boris; Schittek, Birgit

2015-03-01

In healthy human skin host defense molecules such as antimicrobial peptides (AMPs) contribute to skin immune homeostasis. In patients with the congenital disease ectodermal dysplasia (ED) skin integrity is disturbed and as a result patients have recurrent skin infections. The disease is characterized by developmental abnormalities of ectodermal derivatives and absent or reduced sweating. We hypothesized that ED patients have a reduced skin immune defense because of the reduced ability to sweat. Therefore, we performed a label-free quantitative proteome analysis of wash solution of human skin from ED patients or healthy individuals. A clear-cut difference between both cohorts could be observed in cellular processes related to immunity and host defense. In line with the extensive underrepresentation of proteins of the immune system, dermcidin, a sweat-derived AMP, was reduced in its abundance in the skin secretome of ED patients. In contrast, proteins involved in metabolic/catabolic and biosynthetic processes were enriched in the skin secretome of ED patients. In summary, our proteome profiling provides insights into the actual situation of healthy versus diseased skin. The systematic reduction in immune system and defense-related proteins may contribute to the high susceptibility of ED patients to skin infections and altered skin colonization.

Stem Cell Fate Determination during Development and Regeneration of Ectodermal Organs

PubMed Central

Jiménez-Rojo, Lucía; Granchi, Zoraide; Graf, Daniel; Mitsiadis, Thimios A.

2012-01-01

The development of ectoderm-derived appendages results in a large variety of highly specialized organs such as hair follicles, mammary glands, salivary glands, and teeth. Despite varying in number, shape, and function, all these ectodermal organs develop through continuous and reciprocal epithelial–mesenchymal interactions, sharing common morphological and molecular features especially during their embryonic development. Diseases such as ectodermal dysplasias can affect simultaneously these organs, suggesting that they may arise from common multipotent precursors residing in the embryonic ectoderm. During embryogenesis, these putative ectodermal stem cells may adopt different fates and consequently be able to generate a variety of tissue-specific stem cells, which are the sources for the various cell lineages that form the diverse organs. The specification of those common epithelial precursors, as well as their further lineage commitment to tissue-specific stem cells, might be controlled by specific signals. It has been well documented that Notch, Wnt, bone morphogenetic protein, and fibroblast growth factor signaling pathways regulate cell fate decisions during the various stages of ectodermal organ development. However, the in vivo spatial and temporal dynamics of these signaling pathways are not yet well understood. Improving the current knowledge on the mechanisms involved in stem cell fate determination during organogenesis and homeostasis of ectodermal organs is crucial to develop effective stem cell-based therapies in order to regenerate or replace pathological and damaged tissues. PMID:22539926

Stem Cell Fate Determination during Development and Regeneration of Ectodermal Organs.

PubMed

Jiménez-Rojo, Lucía; Granchi, Zoraide; Graf, Daniel; Mitsiadis, Thimios A

2012-01-01

The development of ectoderm-derived appendages results in a large variety of highly specialized organs such as hair follicles, mammary glands, salivary glands, and teeth. Despite varying in number, shape, and function, all these ectodermal organs develop through continuous and reciprocal epithelial-mesenchymal interactions, sharing common morphological and molecular features especially during their embryonic development. Diseases such as ectodermal dysplasias can affect simultaneously these organs, suggesting that they may arise from common multipotent precursors residing in the embryonic ectoderm. During embryogenesis, these putative ectodermal stem cells may adopt different fates and consequently be able to generate a variety of tissue-specific stem cells, which are the sources for the various cell lineages that form the diverse organs. The specification of those common epithelial precursors, as well as their further lineage commitment to tissue-specific stem cells, might be controlled by specific signals. It has been well documented that Notch, Wnt, bone morphogenetic protein, and fibroblast growth factor signaling pathways regulate cell fate decisions during the various stages of ectodermal organ development. However, the in vivo spatial and temporal dynamics of these signaling pathways are not yet well understood. Improving the current knowledge on the mechanisms involved in stem cell fate determination during organogenesis and homeostasis of ectodermal organs is crucial to develop effective stem cell-based therapies in order to regenerate or replace pathological and damaged tissues.

A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene

PubMed Central

2011-01-01

Background Hypohidrotic ectodermal dysplasia (HED) is a congenital disorder characterized by sparse hair, oligodontia, and inability to sweat. It is caused by mutations in any of three Eda pathway genes: ectodysplasin (Eda), Eda receptor (Edar), and Edar-associated death domain (Edaradd), which encode ligand, receptor, and intracellular adaptor molecule, respectively. The Eda signaling pathway activates NF-κB, which is central to ectodermal differentiation. Although the causative genes and the molecular pathway affecting HED have been identified, no curative treatment for HED has been established. Previously, we found a rat spontaneous mutation that caused defects in hair follicles and named it sparse-and-wavy (swh). Here, we have established the swh rat as the first rat model of HED and successfully identified the swh mutation. Results The swh/swh rat showed sparse hair, abnormal morphology of teeth, and absence of sweat glands. The ectoderm-derived glands, meibomian, preputial, and tongue glands, were absent. We mapped the swh mutation to the most telomeric part of rat Chr 7 and found a Pro153Ser missense mutation in the Edaradd gene. This mutation was located in the death domain of EDARADD, which is crucial for signal transduction and resulted in failure to activate NF-κB. Conclusions These findings suggest that swh is a loss-of-function mutation in the rat Edaradd and indicate that the swh/swh rat would be an excellent animal model of HED that could be used to investigate the pathological basis of the disease and the development of new therapies. PMID:22013926

Two-sided Ubiquitin Binding of NF-κB Essential Modulator (NEMO) Zinc Finger Unveiled by a Mutation Associated with Anhidrotic Ectodermal Dysplasia with Immunodeficiency Syndrome*

PubMed Central

Ngadjeua, Flora; Chiaravalli, Jeanne; Traincard, François; Raynal, Bertrand; Fontan, Elisabeth; Agou, Fabrice

2013-01-01

Hypomorphic mutations in the X-linked human NEMO gene result in various forms of anhidrotic ectodermal dysplasia with immunodeficiency. NEMO function is mediated by two distal ubiquitin binding domains located in the regulatory C-terminal domain of the protein: the coiled-coil 2-leucine zipper (CC2-LZ) domain and the zinc finger (ZF) domain. Here, we investigated the effect of the D406V mutation found in the NEMO ZF of an ectodermal dysplasia with immunodeficiency patients. This point mutation does not impair the folding of NEMO ZF or mono-ubiquitin binding but is sufficient to alter NEMO function, as NEMO-deficient fibroblasts and Jurkat T lymphocytes reconstituted with full-length D406V NEMO lead to partial and strong defects in NF-κB activation, respectively. To further characterize the ubiquitin binding properties of NEMO ZF, we employed di-ubiquitin (di-Ub) chains composed of several different linkages (Lys-48, Lys-63, and linear (Met-1-linked)). We showed that the pathogenic mutation preferentially impairs the interaction with Lys-63 and Met-1-linked di-Ub, which correlates with its ubiquitin binding defect in vivo. Furthermore, sedimentation velocity and gel filtration showed that NEMO ZF, like other NEMO related-ZFs, binds mono-Ub and di-Ub with distinct stoichiometries, indicating the presence of a new Ub site within the NEMO ZF. Extensive mutagenesis was then performed on NEMO ZF and characterization of mutants allowed the proposal of a structural model of NEMO ZF in interaction with a Lys-63 di-Ub chain. PMID:24100029

The prevalence of X-linked hypohidrotic ectodermal dysplasia (XLHED) in Denmark, 1995-2010.

PubMed

Nguyen-Nielsen, Mary; Skovbo, Stine; Svaneby, Dea; Pedersen, Lars; Fryzek, Jon

2013-05-01

X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterised by hypohidrosis, sparse hair, and teeth abnormalities. Infants with XLHED have an increased risk of death by hyperpyrexia. XLHED is the most common form of hypohidrotic ectodermal dysplasia (HED); however, no population-based prevalence estimates are available. We aimed to: 1) estimate the prevalence of XLHED in the Danish population per January 1, 2011; 2) identify the most frequent age at time of diagnosis; and 3) quantify the most frequent clinical feature associated with XLHED. We conducted a nationwide cross-sectional study (1995-2010). We leveraged national medical registries and data from clinical departments to categorise XLHED cases into three groups: 1) Molecularly-confirmed XLHED; 2) Clinically-diagnosed HED (registered with ICD-10 Q 82.4); and 3) Possible HED (registered with sufficient clinical features based on a clinical algorithm that we designed). We identified 90 molecularly-confirmed XLHED, 146 clinically-diagnosed HED, and 988 possible HED cases between 1995 and 2010 (total n = 1224). The prevalence was 21.9 per 100,000 overall and 1.6 per 100,000 when restricting to molecularly-confirmed XLHED cases. The most frequent age at time of XLHED diagnosis occurred between the ages of 11 and 18 years. Teeth abnormalities occurred in 79% of all cases and 52% of molecularly-confirmed cases as a primary clinical marker. We present the first ever population-based prevalence estimates of XLHED and suggest that the prevalence of XLHED may be higher than previously estimated. Diagnosis occurs most frequently during adolescence and teeth abnormalities were the most frequent clinical marker of XLHED. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Successful treatment with infliximab for inflammatory colitis in a patient with X-linked anhidrotic ectodermal dysplasia with immunodeficiency.

PubMed

Mizukami, Tomoyuki; Obara, Megumi; Nishikomori, Ryuta; Kawai, Tomoki; Tahara, Yoshihiro; Sameshima, Naoki; Marutsuka, Kousuke; Nakase, Hiroshi; Kimura, Nobuhiro; Heike, Toshio; Nunoi, Hiroyuki

2012-02-01

X-linked anhidrotic ectodermal dysplasia with immunodeficiency (X-EDA-ID) is caused by hypomorphic mutations in the gene encoding nuclear factor-κB essential modulator protein (NEMO). Patients are susceptibile to diverse pathogens due to insufficient cytokine and frequently show severe chronic colitis. An 11-year-old boy with X-EDA-ID was hospitalized with autoimmune symptoms and severe chronic colitis which had been refractory to immunosuppressive drugs. Since tumor necrosis factor (TNF) α is responsible for the pathogenesis of NEMO colitis according to intestinal NEMO and additional TNFR1 knockout mice studies, and high levels of TNFα-producing mononuclear cells were detected in the patient due to the unexpected gene reversion mosaicism of NEMO, an anti-TNFα monoclonal antibody was administered to ameliorate his abdominal symptoms. Repeated administrations improved his colonoscopic findings as well as his dry skin along with a reduction of TNFα-expressing T cells. These findings suggest TNF blockade therapy is of value for refractory NEMO colitis with gene reversion.

Joint kinematics and kinetics during walking and running in 32 patients with hip dysplasia 1 year after periacetabular osteotomy

PubMed Central

Jacobsen, Julie S; Nielsen, Dennis B; Sørensen, Henrik; Søballe, Kjeld; Mechlenburg, Inger

2014-01-01

Background and purpose — Hip dysplasia can be treated with periacetabular osteotomy (PAO). We compared joint angles and joint moments during walking and running in young adults with hip dysplasia prior to and 6 and 12 months after PAO with those in healthy controls. Patients and methods — Joint kinematics and kinetics were recorded using a 3-D motion capture system. The pre- and postoperative gait characteristics quantified as the peak hip extension angle and the peak joint moment of hip flexion were compared in 23 patients with hip dysplasia (18–53 years old). Similarly, the gait patterns of the patients were compared with those of 32 controls (18–54 years old). Results — During walking, the peak hip extension angle and the peak hip flexion moment were significantly smaller at baseline in the patients than in the healthy controls. The peak hip flexion moment increased 6 and 12 months after PAO relative to baseline during walking, and 6 months after PAO relative to baseline during running. For running, the improvement did not reach statistical significance at 12 months. In addition, the peak hip extension angle during walking increased 12 months after PAO, though not statistically significantly. There were no statistically significant differences in peak hip extension angle and peak hip flexion moment between the patients and the healthy controls after 12 months. Interpretation — Walking and running characteristics improved after PAO in patients with symptomatic hip dysplasia, although gait modifications were still present 12 months postoperatively. PMID:25191933

Naegeli-Franceschetti-Jadassohn syndrome: A rare case.

PubMed

Shah, Bela J; Jagati, Ashish K; Gupta, Neha P; Dhamale, Suyog S

2015-01-01

Naegeli-Franceschetti-Jadassohn Syndrome (NFJS) is a rare, autosomal dominant inherited form of ectodermal dysplasia, caused by mutation in the KRT14 gene. We report here a case of NFJS in a 27-year-old male who presented with reticulate hyperpigmentation over skin, dental changes, absence of dermatoglyphics, hypohidrosis, and hair changes.

Removable partial dentures vs overdentures in children with ectodermal dysplasia: two case reports.

PubMed

Maroulakos, G; Artopoulou, I I; Angelopoulou, M V; Emmanouil, D

2016-06-01

Ectodermal dysplasia (ED) represents a disorder group characterised by abnormal development of the ectodermal derivatives. Removable partial dentures (RPD), complete dentures (CD) or overdentures (OD) are most often the treatment of choice for young affected patients. Prosthetic intervention is of utmost importance in the management of ED patients, as it resolves problems associated with functional, aesthetic, and psychological issues, and improves a patient's quality of life. However, few studies present the principles and guidelines that can assist in the decision-making process of the most appropriate removable prosthesis. The purpose of this study was to suggest a simple treatment decision-making algorithm for selecting an effective and individualised rehabilitative treatment plan, considering different parameters. The cases and treatment of two young ED patients are described and each one was treated with either RPDs or ODs. Periodic recalls were employed to manage problems, and monitor the changes associated with occlusion and fit of the prostheses in relation to each patient's growth. Both patients were followed up for more than 2 years and reported significant improvement in their appearance, masticatory function, and social behaviour as a result of the prosthetic rehabilitation. The main factors guiding the decision process towards the choice of an RPD or an OD are the presence of posterior natural teeth, facial aesthetics, lip support, number and size of existing natural teeth, and the occlusal vertical dimension.

Neuromotor outcomes in infants with bronchopulmonary dysplasia.

PubMed

Karagianni, Paraskevi; Tsakalidis, Christos; Kyriakidou, Maria; Mitsiakos, Georgios; Chatziioanidis, Helias; Porpodi, Maria; Evangeliou, Athanasios; Nikolaides, Nikolaos

2011-01-01

We examine the neuromotor outcomes of preterm infants with bronchopulmonary dysplasia. Two hundred and nineteen infants (gestational age, ≤ 32 weeks; birth weight, ≤ 1500 g) were studied. Neuromotor development was assessed using the Hammersmith Infant Neurological Examination. All potential risk factors associated with neuromotor scores (P < 0.015) were included in the generalized linear model (multiple linear regression) to determine if bronchopulmonary dysplasia had an independent relationship with neuromotor scores. Infants with severe bronchopulmonary dysplasia had lower global scores at ages 6 and 12 months. After adjustment for confounding factors, scores of infants with severe bronchopulmonary dysplasia were reduced by 13.2 units, whereas scores for those with periventricular leukomalacia were reduced by 11.1 units, at age 6 months. At age 12 months, scores for those with periventricular leukomalacia were reduced by 11.9 units. Duration of hospital stay reduced scores by 0.1 for each additional day increase in hospital. Bronchopulmonary dysplasia constitutes a major cause of poor neuromotor outcomes at age 6 months, but improvements in motor outcomes occur over time. Copyright © 2011 Elsevier Inc. All rights reserved.

WNT10A missense mutation associated with a complete Odonto-Onycho-Dermal Dysplasia syndrome

PubMed Central

Nawaz, Sadia; Klar, Joakim; Wajid, Muhammad; Aslam, Muhammad; Tariq, Muhammad; Schuster, Jens; Baig, Shahid Mahmood; Dahl, Niklas

2009-01-01

Wnt signalling is one of a few pathways that are crucial for controlling genetic programs during embryonic development as well as in adult tissues. WNT10A is expressed in the skin and epidermis and it has shown to be critical for the development of ectodermal appendages. A nonsense mutation in WNT10A was recently identified in odonto-onycho-dermal dysplasia (OODD; MIM 257980), a rare syndrome characterised by severe hypodontia, nail dystrophy, smooth tongue, dry skin, keratoderma and hyperhydrosis of palms and soles. We identified a large consanguineous Pakistani pedigree comprising six individuals affected by a complete OODD syndrome. Autozygosity mapping using SNP array analysis showed that the affected individuals are homozygous for the WNT10A gene region. Subsequent mutation screening showed a homozygous c.392C>T transition in exon 3 of WNT10A, which predicts a p.A131V substitution in a conserved α-helix domain. We report here on the first inherited missense mutation in WNT10A with associated ectodermal features. PMID:19471313

WNT10A missense mutation associated with a complete odonto-onycho-dermal dysplasia syndrome.

PubMed

Nawaz, Sadia; Klar, Joakim; Wajid, Muhammad; Aslam, Muhammad; Tariq, Muhammad; Schuster, Jens; Baig, Shahid Mahmood; Dahl, Niklas

2009-12-01

Wnt signalling is one of a few pathways that are crucial for controlling genetic programs during embryonic development as well as in adult tissues. WNT10A is expressed in the skin and epidermis and it has shown to be critical for the development of ectodermal appendages. A nonsense mutation in WNT10A was recently identified in odonto-onycho-dermal dysplasia (OODD; MIM 257980), a rare syndrome characterised by severe hypodontia, nail dystrophy, smooth tongue, dry skin, keratoderma and hyperhydrosis of palms and soles. We identified a large consanguineous Pakistani pedigree comprising six individuals affected by a complete OODD syndrome. Autozygosity mapping using SNP array analysis showed that the affected individuals are homozygous for the WNT10A gene region. Subsequent mutation screening showed a homozygous c.392C>T transition in exon 3 of WNT10A, which predicts a p.A131V substitution in a conserved alpha-helix domain. We report here on the first inherited missense mutation in WNT10A with associated ectodermal features.

Naegeli–Franceschetti–Jadassohn syndrome: A rare case

PubMed Central

Shah, Bela J.; Jagati, Ashish K.; Gupta, Neha P.; Dhamale, Suyog S.

2015-01-01

Naegeli–Franceschetti–Jadassohn Syndrome (NFJS) is a rare, autosomal dominant inherited form of ectodermal dysplasia, caused by mutation in the KRT14 gene. We report here a case of NFJS in a 27-year-old male who presented with reticulate hyperpigmentation over skin, dental changes, absence of dermatoglyphics, hypohidrosis, and hair changes. PMID:26753140

Hypohidrotic ectodermal dysplasia: dental, clinical, genetic and dermatoglyphic findings of three cases.

PubMed

Kargül, B; Alcan, T; Kabalay, U; Atasu, M

2001-01-01

Patients with hypohidrotic ectodermal dysplasia (HED) are characterized by the clinical manifestations of hypodontia, hypohidrosis, hypotrichosis and a highly characteristic facial physiognomy. This disorder is inherited as an X-linked trait. This report presents three cases with HED in which the clinical evaluation (intraoral and radiological), genetic findings and SEM examination of hair. Boys 6 to 14 year old and a 11 year old girl were referred to the Marmara University, Faculty of Dentistry, complaining of oligodontia in the maxillary and mandibular arches and delay in eruption of other teeth. Peg-shaped teeth have been observed. The dermatoglyphs of the patients were striking. SEM examination of hair demonstrated a distinctly abnormal longitudinal grooving along the entire length of each hair and a desquamation of the surface cuticles. The treatment was planned in a multidisciplinary odontological group involving pediatric dentistry, orthodontics, prosthodontics and oral surgery and maxillofacial radiology of future dental habilitation. A specially designed overdenture, a removable prosthesis and osseointegrated implants were constructed. Periodic recall visits were advised, to monitor the dentures and implants during periods of growth and development, and eruption of the permanent teeth.

Dental implants in patients with ectodermal dysplasia: A systematic review.

PubMed

Chrcanovic, Bruno Ramos

2018-05-21

This study sought to assess the clinical outcome and survival rate of oral implants placed in individuals with ectodermal dysplasia (ED), based on previously published studies. An electronic search without time restrictions was undertaken in 5 databases (PubMed/Medline, Web of Science, ScienceDirect, J-Stage, Lilacs). Descriptive statistics, Kaplan Meier estimator and implant failure probability were calculated. 90 publications were included, reporting 228 ED patients that received 1472 implants (1392 conventional, 47 zygomatic, 33 mini-implants). Mean age of the patients was 20.2 ± 6.8 years (2-56). Patients had a mean of 3.2 ± 2.5 maxillary and 2.1 ± 2.6 mandibular permanent teeth (min-max, 0-14). Patients received a mean of 8.2 ± 3.8 implants (1-20). Most implants were placed in the third decade of life, 24.6% of the implants were placed in children (0-17 years of age). 1391 implants had information on follow-up (72 failures, 5.2%). The 20-year CSR was 84.6%. The probability of failure was 4.5% (95%CI 3.5%-5.6%, p < 0.001). Additional treatments performed were Le Fort I (99 implants, 20 patients, 3.5% failed), grafting (497 implants, 77 patients, 5.2% failed), distraction osteogenesis (79 implants, 16 patients, 10.1% failed). Mean follow-up was 42.9 ± 41.9 months (min-max, 2-240). Dental implants placed in ED patients, either infants or adults, present a high survival rate (20-year CSR 84.6%). Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Prosthetic rehabilitation of patients with hypohidrotic ectodermal dysplasia: A systematic review.

PubMed

Schnabl, D; Grunert, I; Schmuth, M; Kapferer-Seebacher, I

2018-04-21

Hypohidrotic ectodermal dysplasia (HED) comprises a large group of inherited disorders of ectodermal structures, characterised by hypo- or anhidrosis, hypotrichosis and hypo- or oligo- or anodontia. We aimed to systematically assess the spectrum of prosthodontic approaches with regard to the patients' age and to provide clinical implications for practicing dentists. An electronic and manual search was conducted in four databases (Medline, LIVIVO, Cochrane Library, Web of Science Core Collection). Publications of multiple study designs written in English or German without data restrictions, reporting on prosthodontic treatment of patients diagnosed with HED and afflicted with oligo- or anodontia, were included. In total, 75 articles on 146 patients were analysed according to the patients' age. In children aged 2-17 years, removable full or partial (over)dentures represented standard treatment. In the mandible, implant-supported removable dentures on two interforaminal implants presented an alternative, already in young childhood. In cases with more than six teeth per jaw, also fixed (resin) bridges were used, frequently after orthodontic treatment. In adults, fixed or removable reconstructions with the help of up to eight implants per jaw, usually placed after bone augmentation procedures, were standard. Ten case reports/series with long-term follow-up illustrated the need for consistent maintenance including denture renewals. Prosthodontic rehabilitation should start in early childhood and needs to be revised in accordance with the patients' growth. Treatment should be carried out by a multidisciplinary team addressing variable demands in different age groups. © 2018 John Wiley & Sons Ltd.

Non-invasive diagnosis of sweat gland dysplasia using optical coherence tomography and reflectance confocal microscopy in a family with anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome).

PubMed

Reinholz, M; Gauglitz, G G; Giehl, K; Braun-Falco, M; Schwaiger, H; Schauber, J; Ruzicka, T; Berneburg, M; von Braunmühl, T

2016-04-01

Anhidrotic ectodermal dysplasia (AED) is an inherited syndrome, which originates mainly from genetic alteration of the ectodysplasin A (EDA) gene. It regularly affects the adnexa of the skin which results in a characteristic phenotype of the patients including hypo- or anhidrosis leading to severe disturbances in the regulation of body temperature. To prevent the development of the symptoms in early childhood promising therapeutic approaches are currently under clinical investigation. In this context, timely diagnosis of this genetic syndrome is crucial. The purpose of our study was the investigation of modern non-invasive imaging methods such as optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) in the immediate diagnosis of AED. We examined a 3-year-old boy with the suspicion for an AED syndrome and his family members with RCM and OCT to document presence and characteristic features of sweat glands in comparison to non-affected individuals. The patient and the affected brother showed significantly reduced sweat glands in the imaging compared to the controls. The genetic analysis revealed a mutation of the EDA gene for hemizygosity previously associated with AED and the mother was revealed as the conductor of the genetic alteration. With the help of non-invasive imaging, we were able to detect sweat gland dysplasia in the affected family members without performing a biopsy which led us to the diagnosis of an AED. The application of modern dermatological imaging techniques might serve as valuable supplementary tools in the immediate, non-invasive diagnosis of genetic syndromes especially in newborns when early therapeutic approaches are planned. © 2015 European Academy of Dermatology and Venereology.

High Resolution Thermography In Medicine

NASA Astrophysics Data System (ADS)

Clark, R. P.; Goff, M. R.; Culley, J. E.

1988-10-01

A high resolution medical thermal imaging system using an 8 element SPRI1E detector is described. Image processing is by an Intellect 100 processor and is controlled by a DEC LSI 11/23 minicomputer. Image storage is with a 170 Mbyte winchester disc together with archival storage on 12 inch diameter optical discs having a capacity of 1 Gbyte per side. The system is currently being evaluated for use in physiology and medicine. Applications outlined include the potential of thermographic screening to identify genetic carriers in X-linked hypohidrotic ectodermal dysplasia (XED), detailed vas-cular perfusion studies in health and disease and the relation-ship between cutaneous blood flow, neurological peripheral function and skin surface temperature.

Tricho-odonto-onycho-dermal dysplasia and WNT10A mutations.

PubMed

Kantaputra, P; Kaewgahya, M; Jotikasthira, D; Kantaputra, W

2014-04-01

We report on three novel (IVS2+1G>A splice site, c.1066G>T, and c.1039G>T, and one previously reported (c.637G>A) WNT10A mutations in three patients affected with odonto-onycho-dermal dysplasia (OODD; OMIM 275980). OODD is a rare form of autosomal recessive ectodermal dysplasia involving hair, teeth, nails, and skin, characterized by hypodontia (tooth agenesis), smooth tongue with marked reduction of filiform and fungiform papillae, nail dysplasia, dry skin, palmoplantar keratoderma, and hyperhidrosis of palms and soles. The novel IVS+1G>A splice site mutation is predicted to cause significant protein alteration. The other novel mutations we found including c.1066G>T and c.1039G>T are predicted to cause p.Gly356Cys and p.Glu347X, respectively. Barrel-shaped mandibular incisors and severe hypodontia appear to be associated with homozygous or compound heterozygous mutations of WNT10A. The name "tricho-odonto-onycho-dermal dysplasia" is suggested to replace "odonto-onycho-dermal dysplasia" because hair anomalies including hypotrichosis and slow-growing hair have been reported in numerous reported patients with this syndrome. © 2014 Wiley Periodicals, Inc.

Microcephaly, ectodermal dysplasia, multiple skeletal anomalies and distinctive facial appearance: delineation of cerebro-dermato-osseous-dysplasia.

PubMed

Castori, Marco; Pascolini, Giulia; Parisi, Valentina; Sana, Maria Elena; Novelli, Antonio; Nürnberg, Peter; Iascone, Maria; Grammatico, Paola

2015-04-01

In 1980, a novel multiple malformation syndrome has been described in a 17-year-old woman with micro- and turricephaly, intellectual disability, distinctive facial appearance, congenital atrichia, and multiple skeletal anomalies mainly affecting the limbs. Four further sporadic patients and a couple of affected sibs are also reported with a broad clinical variability. Here, we describe a 4-year-old girl strikingly resembling the original report. Phenotype comparison identified a recurrent pattern of multisystem features involving the central nervous system, and skin and bones in five sporadic patients (including ours), while the two sibs and a further sporadic case show significant phenotypic divergence. Marked clinical variability within the same entity versus syndrome splitting is discussed and the term "cerebro-dermato-osseous dysplasia" is introduced to define this condition. © 2015 Wiley Periodicals, Inc.

A novel c.1037C > G (p.Ala346Gly) mutation in TP63 as cause of the ectrodactyly-ectodermal dysplasia and cleft lip/palate (EEC) syndrome

PubMed Central

Alves, Leandro Ucela; Pardono, Eliete; Otto, Paulo A.; Mingroni Netto, Regina Célia

2015-01-01

Ectrodactyly – ectodermal dysplasia and cleft lip/palate (EEC) syndrome (OMIM 604292) is a rare disorder determined by mutations in the TP63 gene. Most cases of EEC syndrome are associated to mutations in the DNA binding domain (DBD) region of the p63 protein. Here we report on a three-generation Brazilian family with three individuals (mother, son and grandfather) affected by EEC syndrome, determined by a novel mutation c.1037C > G (p.Ala346Gly). The disorder in this family exhibits a broad spectrum of phenotypes: two individuals were personally examined, one presenting the complete constellation of EEC syndrome manifestations and the other presenting an intermediate phenotype; the third affected, a deceased individual not examined personally and referred to by his daughter, exhibited only the split-hand/foot malformation (SHFM). Our findings contribute to elucidate the complex phenotype-genotype correlations in EEC syndrome and other related TP63-mutation syndromes. The possibility of the mutation c.1037C > G being related both to acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome and SHFM is also raised by the findings here reported. PMID:25983622

Ectodysplasin A Pathway Contributes to Human and Murine Skin Repair.

PubMed

Garcin, Clare L; Huttner, Kenneth M; Kirby, Neil; Schneider, Pascal; Hardman, Matthew J

2016-05-01

The highly conserved ectodysplasin A (EDA)/EDA receptor signaling pathway is critical during development for the formation of skin appendages. Mutations in genes encoding components of the EDA pathway disrupt normal appendage development, leading to the human disorder hypohidrotic ectodermal dysplasia. Spontaneous mutations in the murine Eda (Tabby) phenocopy human X-linked hypohidrotic ectodermal dysplasia. Little is known about the role of EDA signaling in adult skin homeostasis or repair. Because wound healing largely mimics the morphogenic events that occur during development, we propose a role for EDA signaling in adult wound repair. Here we report a pronounced delay in healing in Tabby mice, demonstrating a functional role for EDA signaling in adult skin. Moreover, pharmacological activation of the EDA pathway in both Tabby and wild-type mice significantly accelerates healing, influencing multiple processes including re-epithelialization and granulation tissue matrix deposition. Finally, we show that the healing promoting effects of EDA receptor activation are conserved in human skin repair. Thus, targeted manipulation of the EDA/EDA receptor pathway has clear therapeutic potential for the future treatment of human pathological wound healing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Quantification of taurodontism: interests in the early diagnosis of hypohidrotic ectodermal dysplasia.

PubMed

Gros, C-I; Clauss, F; Obry, F; Manière, M C; Schmittbuhl, M

2010-04-01

The aim of this study was to provide a quantification of taurodontism in Hypohidrotic Ectodermal Dysplasia (HED) and to report its occurrence in a cohort of HED patients to assess phenotypic-genotypic correlations. Of 68 HED patients retrospectively reviewed, 16 patients aged 7-51 years were selected and compared with a control sample (n = 351). The pulp surface index of the first lower permanent molar was calculated from the panoramic radiograph of each individual, and statistical comparisons between the HED patients and the control sample were performed. Whatever the genetic disorder, 81.25% of the HED patients exhibited a relative enlargement (>or=1 s.d.) of the pulp. Major deviations (>5 s.d.) were respectively related to men affected by large deletion of the EDA gene or missense mutation. The autosomal recessive form was linked to a relative moderate pulp enlargement (3.44 s.d.). In NEMO forms, the increase of pulp size in men appeared to be less marked than in EDA mutations. This study provides for the first time an objective assessment of pulp enlargement in HED patients, and the various degrees of taurodontism depicted could be interesting dental phenotypic markers of HED forms.

Disturbances of dental development distinguish patients with oligodontia-ectodermal dysplasia from isolated oligodontia.

PubMed

Dhamo, B; Kuijpers, M A R; Balk-Leurs, I; Boxum, C; Wolvius, E B; Ongkosuwito, E M

2018-02-01

To investigate phenotypic differences in dental development between isolated oligodontia and oligodontia-ectodermal dysplasia (ED). A total of 129 patients diagnosed with isolated oligodontia and 22 patients with oligodontia as part of ED were eligible. The phenotype of dental development was assessed for the frequency of missing a certain tooth, dental age, development of each tooth present, abnormal size and abnormal shape of teeth. The data were analysed building linear, ordinal and logistic regression models. Compared to patients with isolated oligodontia, patients with oligodontia-ED missed more frequently central incisors and second molars in both jaws, and lateral incisors in the mandible (P < .05). Oligodontia-ED was associated with delayed development of the permanent dentition (β = -0.10; 95% CI: -0.17, -0.03). Specifically, the maxillary teeth: right central incisor, right lateral incisor, right second premolar and left second premolar were delayed approximately from 2 to 4 developmental stages. In addition, the left mandibular second premolar was 3 developmental stages delayed. Abnormal shape of teeth was 7 times more evident in patients with oligodontia-ED compared to patients with isolated oligodontia (OR = 6.54; 95% CI: 2.34, 18.28). The abnormal size of teeth was not a distinctive characteristic for oligodontia-ED. Oligodontia-ED distinguishes from isolated oligodontia by more disturbances in dental development. The abnormal shape of incisors and canines in a patient with oligodontia can raise suspicions for accompanying ectodermal abnormalities. © 2017 The Authors. Orthodontics & Craniofacial Research Published by John Wiley & Sons Ltd.

Psychoeducational Characteristics of Children with Hypohidrotic Ectodermal Dysplasia

PubMed Central

Maxim, Rolanda A.; Zinner, Samuel H.; Matsuo, Hisako; Prosser, Theresa M.; Fete, Mary; Leet, Terry L.; Fete, Timothy J.

2012-01-01

Objective. Hypohidrotic ectodermal dysplasia (HED) is an X-linked hereditary disorder characterized by hypohidrosis, hypotrichosis, and anomalous dentition. Estimates of up to 50% of affected children having intellectual disability are controversial. Method. In a cross-sectional study, 45 youth with HED (77% males, mean age 9.75 years) and 59 matched unaffected controls (70% males, mean age 9.79 years) were administered the Kaufman Brief Intelligence Test and the Kaufman Test of Educational Achievement, and their parents completed standardized neurodevelopmental and behavioral measures, educational, and health-related information regarding their child, as well as standardized and nonstandardized data regarding socioeconomic information for their family. Results. There were no statistically significant differences between the two groups in intelligence quotient composite and educational achievement scores, suggesting absence of learning disability in either group. No gender differences within or between groups were found on any performance measures. Among affected youth, parental education level correlated positively with (1) cognitive vocabulary scores and cognitive composite scores; (2) educational achievement for mathematics, reading, and composite scores. Conclusion. Youth affected with HED and unaffected matched peers have similar profiles on standardized measures of cognition, educational achievement, and adaptive functioning although children with HED may be at increased risk for ADHD. PMID:22536143

Personalized Stem Cell Therapy to Correct Corneal Defects Due to a Unique Homozygous-Heterozygous Mosaicism of Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome.

PubMed

Barbaro, Vanessa; Nasti, Annamaria Assunta; Raffa, Paolo; Migliorati, Angelo; Nespeca, Patrizia; Ferrari, Stefano; Palumbo, Elisa; Bertolin, Marina; Breda, Claudia; Miceli, Francesco; Russo, Antonella; Caenazzo, Luciana; Ponzin, Diego; Palù, Giorgio; Parolin, Cristina; Di Iorio, Enzo

2016-08-01

: Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome is a rare autosomal dominant disease caused by mutations in the p63 gene. To date, approximately 40 different p63 mutations have been identified, all heterozygous. No definitive treatments are available to counteract and resolve the progressive corneal degeneration due to a premature aging of limbal epithelial stem cells. Here, we describe a unique case of a young female patient, aged 18 years, with EEC and corneal dysfunction, who was, surprisingly, homozygous for a novel and de novo R311K missense mutation in the p63 gene. A detailed analysis of the degree of somatic mosaicism in leukocytes from peripheral blood and oral mucosal epithelial stem cells (OMESCs) from biopsies of buccal mucosa showed that approximately 80% were homozygous mutant cells and 20% were heterozygous. Cytogenetic and molecular analyses excluded genomic alterations, thus suggesting a de novo mutation followed by an allelic gene conversion of the wild-type allele by de novo mutant allele as a possible mechanism to explain the homozygous condition. R311K-p63 OMESCs were expanded in vitro and heterozygous holoclones selected following clonal analysis. These R311K-p63 OMESCs were able to generate well-organized and stratified epithelia in vitro, resembling the features of healthy tissues. This study supports the rationale for the development of cultured autologous oral mucosal epithelial stem cell sheets obtained by selected heterozygous R311K-p63 stem cells, as an effective and personalized therapy for reconstructing the ocular surface of this unique case of EEC syndrome, thus bypassing gene therapy approaches. This case demonstrates that in a somatic mosaicism context, a novel homozygous mutation in the p63 gene can arise as a consequence of an allelic gene conversion event, subsequent to a de novo mutation. The heterozygous mutant R311K-p63 stem cells can be isolated by means of clonal analysis and given their good regenerative capacity, they may be used to successfully correct the corneal defects present in this unique case of ectrodactyly-ectodermal dysplasia-clefting syndrome. ©AlphaMed Press.

Impacted Lower Second Permanent Molars at the Ramus and Coronoid Process: A New Clinical Symptom of the WNT10A Mutation in Ectodermal Dysplasia.

PubMed

Sfeir, Elia; Aboujaoude, Samia

2017-01-01

Hidrotic ectodermal dysplasia (ED) with the WNT10A mutation produces variable dentofacial symptoms. The aim of this study was to describe a new clinical symptom, i.e., specific to the WNT10A mutation in hidrotic ED. The study investigated the migratory trend of the lower second permanent molars to the ramus or coronoid process. To the best of authors' knowledge, no data in the literature describe this trend in cases of hidrotic ED. A three-generation family pedigree was established for seven families after the diagnosis of hidrotic ED in a 10-year-old boy. Thereafter, a genetic and clinical study was conducted on three families with at least one individual affected by hidrotic ED (20 individuals). We selected the children with molar germs 37 and 47. The eruption axes of these germs were then traced on the panoramic images at the initial time (T 0 ) and 1 year later (T 0 + 1 year), and the deviations between these axes were measured. A significant familial consanguinity was shown. Eight subjects presented with the hidrotic ED phenotype. Among them, three individuals carried germs 37 and 47. Over time, the measured deviations between the eruption axes of the latter displayed, in the majority of the cases, a distal inclination toward the ramus. A larger sample size is mandatory to assess the frequencies and treatment modalities. The presence of germs in the lower second permanent molars in patients with hidrotic ED is an important clinical symptom that should be monitored to detect and prevent ectopic migration of these teeth. In hidrotic ED cases, the study of the presence of the second lower permanent germs must include clinical and radiological examinations. Establishing an inter-ceptive treatment is necessary to prevent the migration of the molars in question. How to cite this article: Sfeir E, Aboujaoude S. Impacted Lower Second Permanent Molars at the Ramus and Coronoid Process: A New Clinical Symptom of the WNT10A Mutation in Ectodermal Dysplasia. Int J Clin Pediatr Dent 2017;10(4):363-368.

Ectodysplasin A in Biological Fluids and Diagnosis of Ectodermal Dysplasia.

PubMed

Podzus, J; Kowalczyk-Quintas, C; Schuepbach-Mallepell, S; Willen, L; Staehlin, G; Vigolo, M; Tardivel, A; Headon, D; Kirby, N; Mikkola, M L; Schneider, H; Schneider, P

2017-02-01

The tumor necrosis factor (TNF) family ligand ectodysplasin A (EDA) is produced as 2 full-length splice variants, EDA1 and EDA2, that bind to EDA receptor (EDAR) and X-linked EDA receptor (XEDAR/EDA2R), respectively. Inactivating mutations in Eda or Edar cause hypohidrotic ectodermal dysplasia (HED), a condition characterized by malformations of the teeth, hair and glands, with milder deficiencies affecting only the teeth. EDA acts early during the development of ectodermal appendages-as early as the embryonic placode stage-and plays a role in adult appendage function. In this study, the authors measured EDA in serum, saliva and dried blood spots. The authors detected 3- to 4-fold higher levels of circulating EDA in cord blood than in adult sera. A receptor binding-competent form of EDA1 was the main form of EDA but a minor fraction of EDA2 was also found in fetal bovine serum. Sera of EDA-deficient patients contained either background EDA levels or low levels of EDA that could not bind to recombinant EDAR. The serum of a patient with a V262F missense mutation in Eda, which caused a milder form of X-linked HED (XLHED), contained low levels of EDA capable of binding to EDAR. In 2 mildly affected carriers, intermediate levels of EDA were detected, whereas a severely affected carrier had no active EDA in the serum. Small amounts of EDA were also detectable in normal adult saliva. Finally, EDA could be measured in spots of wild-type adult or cord blood dried onto filter paper at levels significantly higher than that measured in EDA-deficient blood. Measurement of EDA levels combined with receptor-binding assays might be of relevance to aid in the diagnosis of total or partial EDA deficiencies.

XEDAR activates the non-canonical NF-κB pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verhelst, Kelly, E-mail: Kelly.Verhelst@irc.VIB-UGent.be; Department of Biomedical Molecular Biology, Ghent University, Ghent; Gardam, Sandra, E-mail: s.gardam@garvan.org.au

2015-09-18

Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR hasmore » been reported to activate canonical nuclear factor κB (NF-κB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-κB pathway, characterized by the processing of p100 (NF-κB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKα. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. - Highlights: • XEDAR activates the non-canonical NF-κB pathway. • XEDAR-induced processing of p100 depends on XEDAR interaction with TRAF3 and TRAF6. • XEDAR-induced processing of p100 depends on NIK and IKKα activity. • Overexpression of XEDAR leads to NIK accumulation. • XEDAR-induced processing of p100 is negatively regulated by TRAF3 cIAP1 and A20.« less

Oral Rehabilitation of a Patient With Ectodermal Dysplasia Treated With Fresh-Frozen Bone Allografts and Computer-Guided Implant Placement: A Clinical Case Report.

PubMed

Maiorana, Carlo; Poli, Pier Paolo; Poggio, Carlo; Barbieri, Paola; Beretta, Mario

2017-05-01

Ectodermal dysplasia (ED) is an inherited disorder characterized by abnormality of ectodermally derived structures. A recurrent oral finding is oligodontia, which in turn leads to a severely hypotrophic alveolar process with typical knife-edge morphology and adverse ridge contours. This unfavorable anatomy can seriously hamper proper implant placement. Fresh-frozen bone (FFB) allografts recently have been proposed to augment the residual bone volume for implant placement purposes; however, scientific evidence concerning the use of FFB to treat ED patients is absent. Similarly, data reporting computer-aided template-guided implant placement in medically compromised patients are limited. Thus the purpose of this report is to illustrate the oral rehabilitation of a female patient affected by ED and treated with appositional FFB block grafts and consecutive computer-guided flapless implant placement in a 2-stage procedure. Fixed implant-supported dental prostheses were finally delivered to the patient, which improved her self-esteem and quality of life. During the follow-up recall 1 year after the prosthetic loading, the clinical examination showed healthy peri-implant soft tissues with no signs of bleeding on probing or pathologic probing depths. The panoramic radiograph confirmed the clinical stability of the result. Peri-implant marginal bone levels were radiographically stable with neither pathologic bone loss at the mesial and distal aspects of each implant nor peri-implant radiolucency. Within the limitations of this report, the use of FFB allografts in association with computer-aided flapless implant surgery might be considered a useful technique in patients affected by ED. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Molecular and Therapeutic Characterization of Anti-ectodysplasin A Receptor (EDAR) Agonist Monoclonal Antibodies*

PubMed Central

Kowalczyk, Christine; Dunkel, Nathalie; Willen, Laure; Casal, Margret L.; Mauldin, Elizabeth A.; Gaide, Olivier; Tardivel, Aubry; Badic, Giovanna; Etter, Anne-Lise; Favre, Manuel; Jefferson, Douglas M.; Headon, Denis J.; Demotz, Stéphane; Schneider, Pascal

2011-01-01

The TNF family ligand ectodysplasin A (EDA) and its receptor EDAR are required for proper development of skin appendages such as hair, teeth, and eccrine sweat glands. Loss of function mutations in the Eda gene cause X-linked hypohidrotic ectodermal dysplasia (XLHED), a condition that can be ameliorated in mice and dogs by timely administration of recombinant EDA. In this study, several agonist anti-EDAR monoclonal antibodies were generated that cross-react with the extracellular domains of human, dog, rat, mouse, and chicken EDAR. Their half-life in adult mice was about 11 days. They induced tail hair and sweat gland formation when administered to newborn EDA-deficient Tabby mice, with an EC50 of 0.1 to 0.7 mg/kg. Divalency was necessary and sufficient for this therapeutic activity. Only some antibodies were also agonists in an in vitro surrogate activity assay based on the activation of the apoptotic Fas pathway. Activity in this assay correlated with small dissociation constants. When administered in utero in mice or at birth in dogs, agonist antibodies reverted several ectodermal dysplasia features, including tooth morphology. These antibodies are therefore predicted to efficiently trigger EDAR signaling in many vertebrate species and will be particularly suited for long term treatments. PMID:21730053

Anticipated stigma and blameless guilt: Mothers' evaluation of life with the sex-linked disorder, hypohidrotic ectodermal dysplasia (XHED).

PubMed

Clarke, Angus

2016-06-01

Practical experience of a genetic disorder may influence how parents approach reproduction, if they know their child may be affected by an inherited condition. One important aspect of this practical experience is the stigmatisation which family members may experience or witness. We outline the concept of stigma and how it affects those in families with a condition that impacts upon physical appearance. We then consider the accounts given by females in families affected by the rare sex-linked disorder, X-linked hypohidrotic ectodermal dysplasia (XHED), which principally affects males but can be passed through female carriers to affect their sons. The stigmatisation of affected males is as important in the accounts given by their womenfolk as the physical effects of the condition; this impacts on their talk about transmission of the disorder to the next generation. Perspectives may also change over time. The mothers of affected sons differ from their daughters, who do not yet have children, and from their mothers, who may express more strongly their sense of guilt at having transmitted the condition, despite there being no question of moral culpability. We conclude with suggestions about other contexts where the possibility of stigma may influence reproductive decisions. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

Comparison of perceptions of oral health-related quality of life in adolescents affected with ectodermal dysplasias relative to caregivers.

PubMed

Kohli, Richie; Levy, Steven; Kummet, Colleen M; Dawson, Deborah V; Stanford, Clark M

2011-01-01

The objective of this study was to assess the perceived oral health-related quality of life (OHQoL) of adolescents affected with one of the ectodermal dysplasias (EDs). Data were collected from 2003 to 2007 in a cross-sectional study of a convenience sample of individuals affected by ED (n = 35) using the Child Perceptions Questionnaire (CPQ11-14) for children and the Parent-Caregiver Perceptions Questionnaire for their caregivers. The main findings of this study were that individuals who were affected with ED in the older age group (15- to 19-year-olds) perceived more functional problems than younger individuals (11- to 14-year-olds) (p= .04). Females with ED (n = 13) perceived more emotional problems than males (n = 22; p= .01). Although caregivers tended to report slightly higher OHQoL scores (indicating worse OHQoL), no significant differences were observed between children's and parents' total OHQoL and individual domains' median scores (p > .05). Thus, the perceptions of oral health and well-being may vary by age and gender for children who have ED. Caution is warranted concerning using parents as proxies for their children when assessing the child's OHQoL. ©2011 Special Care Dentistry Association and Wiley Periodicals, Inc.

Oral Rehabilitation of Adult Edentulous Siblings Severely Lacking Alveolar Bone Due to Ectodermal Dysplasia: A Report of 2 Clinical Cases and a Literature Review.

PubMed

Wu, Yiqun; Zhang, Chenping; Squarize, Cristiane H; Zou, Duohong

2015-09-01

The oral conditions of adult edentulous patients with ectodermal dysplasia (ED) often lead to decreased physical and psychological health, and the negative effects can become as extreme as social and psychological isolation. However, restoring oral function of adult edentulous patients with ED using zygomatic implants (ZIs) or conventional implants (CIs) remains challenging for dentists because of the severe atrophy of these patients' alveolar ridges. This report describes 2 cases of adult edentulous siblings with ED; they exhibited severe alveolar bone atrophy and were treated with ZIs and CIs as bases to augment the bone in their anterior jaws. For these patients, bone augmentation was completed with an autogenous fibular graft. Although there was mild evidence of bone graft resorption in the maxilla, the bone augmentation procedures were successful in the 2 patients. Effective osseointegration of the implants was obtained. After placement, the functional and esthetic results of the oral rehabilitation were acceptable. More importantly, restoration of the patients' oral function enhanced their self-confidence and self-esteem. Therefore, restoring oral function in adult patients with ED and edentulous jaws using ZIs and CIs as the bases for bone augmentation is an effective approach. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

EDAR-induced hypohidrotic ectodermal dysplasia: a clinical study on signs and symptoms in individuals with a heterozygous c.1072C > T mutation

PubMed Central

2014-01-01

Background Mutations in the EDAR-gene cause hypohidrotic ectodermal dysplasia, however, the oral phenotype has been described in a limited number of cases. The aim of the present study was to clinically describe individuals with the c.1072C > T mutation (p. Arg358X) in the EDAR gene with respect to dental signs and saliva secretion, symptoms from other ectodermal structures and to assess orofacial function. Methods Individuals in three families living in Sweden, where some members had a known c.1072C > T mutation in the EDAR gene with an autosomal dominant inheritance (AD), were included in a clinical investigation on oral signs and symptoms and self-reported symptoms from other ectodermal structures (n = 37). Confirmation of the c.1072C > T mutation in the EDAR gene were performed by genomic sequencing. Orofacial function was evaluated with NOT-S. Results The mutation was identified in 17 of 37 family members. The mean number of missing teeth due to agenesis was 10.3 ± 4.1, (range 4–17) in the mutation group and 0.1 ± 0.3, (range 0–1) in the non-mutation group (p < 0.01). All individuals with the mutation were missing the maxillary lateral incisors and one or more of the mandibular incisors; and 81.3% were missing all four. Stimulated saliva secretion was 0.9 ± 0.5 ml/min in the mutation group vs 1.7 ± 0.6 ml/min in the non-mutation group (p < 0.01). Reduced ability to sweat was reported by 82% in the mutation group and by 20% in the non-mutation group (p < 0.01). The mean NOT-S score was 3.0 ± 1.9 (range 0–6) in the mutation group and 1.5 ± 1.1 (range 0–5) in the non-mutation group (p < 0.01). Lisping was present in 56% of individuals in the mutation group. Conclusions Individuals with a c.1072C > T mutation in the EDAR-gene displayed a typical pattern of congenitally missing teeth in the frontal area with functional consequences. They therefore have a need for special attention in dental care, both with reference to tooth agenesis and low salivary secretion with an increased risk for caries. Sweating problems were the most frequently reported symptom from other ectodermal structures. PMID:24884697

Risk factors for early cytologic abnormalities after loop electrosurgical excision procedure.

PubMed

Dietrich, Charles S; Yancey, Michael K; Miyazawa, Kunio; Williams, David L; Farley, John

2002-02-01

To evaluate risk factors for early cytologic abnormalities and recurrent cervical dysplasia after loop electrosurgical excision procedure (LEEP). A retrospective analysis was performed of all pathology records for LEEPs performed at our institution from January 1996 through July 1998. Follow-up cytology from 2 through 12 months after LEEP was reviewed. Patients with abnormal cytology were referred for further colposcopic evaluation. Statistical analysis using chi2 test for trend, proportional hazards model test, Fisher exact tests, and life table analysis were performed to identify risk factors for early cytologic abnormalities after LEEP and to determine relative risk of recurrent dysplasia. A total of 298 women underwent LEEP during the study period, and 29% of these had cytologic abnormalities after LEEP. Grade of dysplasia, ectocervical marginal status, endocervical marginal status, and glandular involvement with dysplasia were not found to be independent risk factors for early cytologic abnormalities. However, when risk factors were analyzed cumulatively, the abnormal cytology rate increased from 24% with no risk factors to 67% with three risk factors present (P =.037). Of patients with abnormal cytology after LEEP, 40% developed subsequent dysplasia, and the mean time to diagnosis was approximately 6 months. The relative risk of subsequent dysplasia ranged from a 20% increase to twice the risk if post-LEEP cytology was low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion, respectively. Based on these results, consideration should be given for early colposcopic examination of patients who have evidence of marginal involvement or endocervical glandular involvement with dysplasia. These patients are at increased risk for abnormal cytology and recurrent dysplasia. This initial visit should occur at 6 months, as the mean time to recurrence of dysplasia was 6.5 months.

First report on an X-linked hypohidrotic ectodermal dysplasia family with X chromosome inversion: Breakpoint mapping reveals the pathogenic mechanism and preimplantation genetics diagnosis achieves an unaffected birth.

PubMed

Wu, Tonghua; Yin, Biao; Zhu, Yuanchang; Li, Guangui; Ye, Lijun; Liang, Desheng; Zeng, Yong

2017-12-01

To investigate the etiology of X-linked hypohidrotic ectodermal dysplasia (XLHED) in a family with an inversion of the X chromosome [inv(X)(p21q13)] and to achieve a healthy birth following preimplantation genetic diagnosis (PGD). Next generation sequencing (NGS) and Sanger sequencing analysis were carried out to define the inversion breakpoint. Multiple displacement amplification, amplification of breakpoint junction fragments, Sanger sequencing of exon 1 of ED1, haplotyping of informative short tandem repeat markers and gender determination were performed for PGD. NGS data of the proband sample revealed that the size of the possible inverted fragment was over 42Mb, spanning from position 26, 814, 206 to position 69, 231, 915 on the X chromosome. The breakpoints were confirmed by Sanger sequencing. A total of 5 blastocyst embryos underwent trophectoderm biopsy. Two embryos were diagnosed as carriers and three were unaffected. Two unaffected blastocysts were transferred and a singleton pregnancy was achieved. Following confirmation by prenatal diagnosis, a healthy baby was delivered. This is the first report of an XLHED family with inv(X). ED1 is disrupted by the X chromosome inversion in this XLHED family and embryos with the X chromosomal abnormality can be accurately identified by means of PGD. Copyright © 2017. Published by Elsevier B.V.

Developmental disorders of the dentition: an update

PubMed Central

Klein, Ophir D.; Oberoi, Snehlata; Huysseune, Ann; Hovorakova, Maria; Peterka, Miroslav; Peterkova, Renata

2013-01-01

Dental anomalies are common congenital malformations that can occur either as isolated findings or as part of a syndrome. This review focuses on genetic causes of abnormal tooth development and the implications of these abnormalities for clinical care. As an introduction, we describe general insights into the genetics of tooth development obtained from mouse and zebrafish models. This is followed by a discussion of isolated as well as syndromic tooth agenesis, including Van der Woude syndrome, ectodermal dysplasias, oral-facial-digital syndrome type I, Rieger syndrome, holoprosencephaly, and tooth anomalies associated with cleft lip and palate. Next, we review delayed formation and eruption of teeth, as well as abnormalities in tooth size, shape and form. Finally, isolated and syndromic causes of supernumerary teeth are considered, including cleidocranial dysplasia and Gardner syndrome. PMID:24124058

Identification of a de novo variant in CHUK in a patient with an EEC/AEC syndrome-like phenotype and hypogammaglobulinemia.

PubMed

Khandelwal, Kriti D; Ockeloen, Charlotte W; Venselaar, Hanka; Boulanger, Cécile; Brichard, Bénédicte; Sokal, Etienne; Pfundt, Rolph; Rinne, Tuula; van Beusekom, Ellen; Bloemen, Marjon; Vriend, Gerrit; Revencu, Nicole; Carels, Carine E L; van Bokhoven, Hans; Zhou, Huiqing

2017-05-17

The cardinal features of Ectrodactyly, Ectodermal dysplasia, Cleft lip/palate (EEC), and Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndromes are ectodermal dysplasia (ED), orofacial clefting, and limb anomalies. EEC and AEC are caused by heterozygous mutations in the transcription factor p63 encoded by TP63. Here, we report a patient with an EEC/AEC syndrome-like phenotype, including ankyloblepharon, ED, cleft palate, ectrodactyly, syndactyly, additional hypogammaglobulinemia, and growth delay. Neither pathogenic mutations in TP63 nor CNVs at the TP63 locus were identified. Exome sequencing revealed de novo heterozygous variants in CHUK (conserved helix-loop-helix ubiquitous kinase), PTGER4, and IFIT2. While the variant in PTGER4 might contribute to the immunodeficiency and growth delay, the variant in CHUK appeared to be most relevant for the EEC/AEC-like phenotype. CHUK is a direct target gene of p63 and encodes a component of the IKK complex that plays a key role in NF-κB pathway activation. The identified CHUK variant (g.101980394T>C; c.425A>G; p.His142Arg) is located in the kinase domain which is responsible for the phosphorylation activity of the protein. The variant may affect CHUK function and thus contribute to the disease phenotype in three ways: (1) the variant exhibits a dominant negative effect and results in an inactive IKK complex that affects the canonical NF-κB pathway; (2) it affects the feedback loop of the canonical and non-canonical NF-κB pathways that are CHUK kinase activity-dependent; and (3) it disrupts NF-κB independent epidermal development that is often p63-dependent. Therefore, we propose that the heterozygous CHUK variant is highly likely to be causative to the EEC/AEC-like and additional hypogammaglobulinemia phenotypes in the patient presented here. © 2017 Wiley Periodicals, Inc.

[Pili trianguli et canaliculi. A case report of uncombable hair in relation to atopic eczema and tooth anomalies].

PubMed

Beringer, K; Botzi, C; Hemmer, W; Focke, M; Götz, M; Jarisch, R

2000-04-01

We report on a child with pili trianguli et canaliculi. This hair shaft abnormality belongs to a heterogeneous group of diseases which are included under the synonym uncombable hair. The diagnosis was confirmed by scanning electron microscopy, revealing hair shafts with a characteristic longitudinal groove. In addition the girl suffered from atopic eczema and tooth anomalies. Our findings suggest that this disorder could represent a tricho-odontal subtype of ectodermal dysplasia.

Use of somatostatin analogues to treat chylothorax in a child with Generalised Lymphatic Dysplasia

PubMed Central

Brodlie, Malcolm; Abdelgalil, Sara; Mansour, Sahar; Spencer, David A.

2011-01-01

Generalised Lymphatic Dysplasia is a rare condition that may be associated with significant chylothoraces. The management of such effusions is often challenging. We present the case of a 15-year-old girl with bilateral chylothoraces and lymphoedema of her limbs. A clinical diagnosis of Generalised Lymphatic Dysplasia was made and long-term treatment with somatostatin analogues (somatostatin initially followed by monthly octreotide) was initiated. Over 12 months there was symptomatic benefit with some objective improvement in lung function and no adverse effects. After a year of treatment there was some reaccumulation of fluid, however this did not require any intervention. This is the first paediatric report of the use of somatostatin analogues to manage chylothorax in Generalised Lymphatic Dysplasia and we conclude that they represent a potentially useful treatment modality. Experience is only anecdotal however and further studies are required to establish an evidence base with regard to efficacy and safety. PMID:26056769

Surgical management of subvalvular aortic stenosis and mitral dysplasia in a golden retriever.

PubMed

White, R N; Boswood, A; Garden, O A; Hammond, R A

1997-06-01

A 12-month-old neutered male golden retriever was presented with a history of lethargy and exercise intolerance. Clinical examination, electrocardiography, radiography and echocardiography supported a diagnosis of fixed subvalvular aortic stenosis with a Doppler pressure gradient of 77.5 mmHg. Surgical inspection also revealed gross structural abnormalities of the mitral valve consistent with mitral dysplasia. Intervention consisted of resection of the dysplastic mitral valve and the subvalvular aortic stenosis. The mitral valve was replaced with a bioprosthetic valve. Total cardiopulmonary bypass time was 65 minutes and aortic cross-clamp time was 55 minutes. A full recovery was made and 11 months postoperatively the aortic transvalvular gradient was 30 mmHg. At the time of writing, 12 months after surgery, the dog was clinically normal and requires no medication.

Variability in dentofacial phenotypes in four families with WNT10A mutations

PubMed Central

Vink, Christian P; Ockeloen, Charlotte W; ten Kate, Sietske; Koolen, David A; Ploos van Amstel, Johannes Kristian; Kuijpers-Jagtman, Anne-Marie; van Heumen, Celeste C; Kleefstra, Tjitske; Carels, Carine E L

2014-01-01

This article describes the inter- and intra-familial phenotypic variability in four families with WNT10A mutations. Clinical characteristics of the patients range from mild to severe isolated tooth agenesis, over mild symptoms of ectodermal dysplasia, to more severe syndromic forms like odonto-onycho-dermal dysplasia (OODD) and Schöpf–Schulz–Passarge syndrome (SSPS). Recurrent WNT10A mutations were identified in all affected family members and the associated symptoms are presented with emphasis on the dentofacial phenotypes obtained with inter alia three-dimensional facial stereophotogrammetry. A comprehensive overview of the literature regarding WNT10A mutations, associated conditions and developmental defects is presented. We conclude that OODD and SSPS should be considered as variable expressions of the same WNT10A genotype. In all affected individuals, a dished-in facial appearance was observed which might be helpful in the clinical setting as a clue to the underlying genetic etiology. PMID:24398796

A rare connexin 26 mutation in a patient with a forme fruste of keratitis-ichthyosis-deafness (KID) syndrome.

PubMed

Neoh, Ching Yin; Chen, Huijia; Ng, See Ket; Lane, Ellen Birgitte; Common, John Edmund Armourer

2009-10-01

Keratitis-ichthyosis-deafness (KID) syndrome is a rare ectodermal dysplasia characterized by generalized erythrokeratotic plaques, sensorineural hearing loss, and vascularizing keratitis. Cutaneous changes and hearing loss typically present in early childhood, whereas ocular symptoms present later. Mutations in the connexin (Cx) 26 gene, GJB2, are now established to underlie many of the affected cases, with the majority of patients harboring the p.D50N mutation. A rare patient demonstrating features of incomplete KID syndrome associated with an uncommon Cx26 gene mutation is described. The patient presented late in adolescence with partial features of KID syndrome. There was limited cutaneous involvement and the rare association of cystic acne. Both hearing impairment and ophthalmic involvement were mild in severity. Genetic mutation analysis revealed a previously described, rare mutation in GJB2, resulting in a glycine to arginine change at codon 12 (p.G12R). This report describes a patient exhibiting characteristics suggestive of a late-onset, incomplete form of KID syndrome with the GJB2 mutation (p.G12R). The p.G12R mutation has only been described in one other patient with KID syndrome, whose clinical presentation was not characterized.

Hip Dysplasia: Clinical Signs and Physical Examination Findings.

PubMed

Syrcle, Jason

2017-07-01

Hip dysplasia is a common developmental disorder of the dog, consisting of varying degrees of hip laxity, progressive remodeling of the structures of the hip, and subsequent development of osteoarthritis. It is a juvenile-onset condition, with clinical signs often first evident at 4 to 12 months of age. A tentative diagnosis of hip dysplasia can be made based on signalment, history, and physical examination findings. The Ortolani test is a valuable tool for identifying juvenile dogs affected with this condition. Further diagnostics can then be prioritized, contributing to prompt diagnosis and appropriate treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular markers in dysplasia of the larynx: expression of cyclin-dependent kinase inhibitors p21, p27 and p53 tumour suppressor gene in predicting cancer risk.

PubMed

Jeannon, J-P; Soames, J V; Aston, V; Stafford, F W; Wilson, J A

2004-12-01

Premalignant conditions affect the larynx. Dysplasia can progress in severity resulting in cancer depending on many clinical, pathological and molecular factors. The purpose of this study was to examine the expression of the p21 and p27 cyclin-dependent kinase inhibitors and p53 tumour suppressor gene in dysplasia of the larynx. A total of 114 cases of untreated dysplasia were selected from the archives of the University of Newcastle. p21, p27 and p53 immunohistochemistry was performed and the cases followed up. Twenty-eight dysplasias (24%) subsequently developed into cancers. Expression of the molecular factors studied was not associated with cancer progression. p53 expression was associated with smoking (P = 0.005). In contrast, grade of dysplasia was significantly associated with cancer risk (odds ratio 6.7; P = 0.0001). The majority (75%) of cancers were detected within 12 months of dysplasia being diagnosed.

Characterization of a human X-linked gene from the DXS732E locus in the candidate region for the anhidrotic ectodermal dysplasia (EDA) gene (Xq13.1)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gault, J.; Zonana, J.; Zeltinger, J.

A conserved mouse genomic clone was used to identify a homologous human genomic clone (the DXS732E locus), which was subsequently employed to isolate cDNAs from a human fetal brain library. Nine unique overlapping cDNAs were isolated, and sequences analysis of 3.9 kb identified a putative 1 kb ORF. GRAIL analysis of the sequence supported the hypothesis that the putative ORF was coding sequence, and Prosite analysis of the putative ORF identified potential glycosylation and phosphorylation sites. The 5{prime} end of the gene maps within a CpG island, and comparison of cDNA sequences indicate the gene is alternatively spliced at itsmore » 3{prime} end. Northern analysis and RT-PCR indicate that two different sized messages appear to be expressed with the gene expressed in human fetal kidney, intestine, brain, and muscle. The gene is expressed in 77 day human skin, a time when hair follicle formation occurs. Anhidrotic ectodermal dysplasia (EDA) results in the abnormal morphogenesis of hair, teeth and eccrine sweat glands. A positional cloning strategy towards cloning the EDA gene had been used, and deletion and X-autosome translocation patients have been useful in further delimiting the EDA region. The present gene at the DXS732E locus is partially deleted in one EDA patient who does not have other apparent abnormalities. No rearrangements of the gene have been detected in two female X-autosome translocation EDA patients, nor in four additional male patients with submicroscopic molecular deletions.« less

Ectodysplasin signalling deficiency in mouse models of hypohidrotic ectodermal dysplasia leads to middle ear and nasal pathology

PubMed Central

Azar, Ali; Piccinelli, Chiara; Brown, Helen; Headon, Denis; Cheeseman, Michael

2016-01-01

Hypohidrotic ectodermal dysplasia (HED) results from mutation of the EDA, EDAR or EDARADD genes and is characterized by reduced or absent eccrine sweat glands, hair follicles and teeth, and defective formation of salivary, mammary and craniofacial glands. Mouse models with HED also carry Eda, Edar or Edaradd mutations and have defects that map to the same structures. Patients with HED have ear, nose and throat disease, but this has not been investigated in mice bearing comparable genetic mutations. We report that otitis media, rhinitis and nasopharyngitis occur at high frequency in Eda and Edar mutant mice and explore the pathogenic mechanisms related to glandular function, microbial and immune parameters in these lines. Nasopharynx auditory tube glands fail to develop in HED mutant mice and the functional implications include loss of lysozyme secretion, reduced mucociliary clearance and overgrowth of nasal commensal bacteria accompanied by neutrophil exudation. Heavy nasopharynx foreign body load and loss of gland protection alters the auditory tube gating function and the auditory tubes can become pathologically dilated. Accumulation of large foreign body particles in the bulla stimulates granuloma formation. Analysis of immune cell populations and myeloid cell function shows no evidence of overt immune deficiency in HED mutant mice. Our findings using HED mutant mice as a model for the human condition support the idea that ear and nose pathology in HED patients arises as a result of nasal and nasopharyngeal gland deficits, reduced mucociliary clearance and impaired auditory tube gating function underlies the pathological sequelae in the bulla. PMID:27378689

Cutting Balloon Angioplasty (CBA) for the Treatment of Renal Artery Fibromuscular Dysplasia (FMD) in Six Patients: 5-Year Long-Term Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cotroneo, Antonio Raffaele; Amoroso, Luigi; Giammarino, Alberto

PurposeTo evaluate long-term outcomes in terms of hypertension control, recurrent stenosis, and reinterventions from patients who underwent cutting balloon angioplasty (CBA) for symptomatic renal artery fibromuscular dysplasia (FMD).Materials and MethodsFrom 2011, six consecutive renal artery FMD women underwent CBA for poorly controlled hypertension, despite antihypertensive therapy. Follow-up consisted of blood pressure monitoring and duplex ultrasonography at 1, 6, and 12 months and thereafter annually for 5 years.ResultsAll treatments were technically successful. Recurrence of hypertension was found in two patients within 12 months, and reinterventions were performed using CBA.ConclusionResults show the efficacy of CBA for renal artery FMD.

Naegeli-Franceschetti-Jadassohn Syndrome and Dermatopathia Pigmentosa Reticularis: Two Allelic Ectodermal Dysplasias Caused by Dominant Mutations in KRT14

PubMed Central

Lugassy, Jennie; Itin, Peter; Ishida-Yamamoto, Akemi; Holland, Kristen; Huson, Susan; Geiger, Dan; Hennies, Hans Christian; Indelman, Margarita; Bercovich, Dani; Uitto, Jouni; Bergman, Reuven; McGrath, John A.; Richard, Gabriele; Sprecher, Eli

2006-01-01

Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa reticularis (DPR) are two closely related autosomal dominant ectodermal dysplasia syndromes that clinically share complete absence of dermatoglyphics (fingerprint lines), a reticulate pattern of skin hyperpigmentation, thickening of the palms and soles (palmoplantar keratoderma), abnormal sweating, and other subtle developmental anomalies of the teeth, hair, and skin. To decipher the molecular basis of these disorders, we studied one family with DPR and four families with NFJS. We initially reassessed linkage of NFJS/DPR to a previously established locus on 17q11.2-q21. Combined multipoint analysis generated a maximal LOD score of 8.3 at marker D17S800 at a recombination fraction of 0. The disease interval was found to harbor 230 genes, including a large cluster of keratin genes. Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate with the disease trait in all five families. In contrast with KRT14 mutations affecting the central α-helical rod domain of keratin 14, which are known to cause epidermolysis bullosa simplex, NFJS/DPR-associated mutations were found in a region of the gene encoding the nonhelical head (E1/V1) domain and are predicted to result in very early termination of translation. These data suggest that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands. Among other functions, the N-terminal part of keratin molecules has been shown to confer protection against proapoptotic signals. Ultrastructural examination of patient skin biopsy specimens provided evidence for increased apoptotic activity in the basal cell layer where KRT14 is expressed, suggesting that apoptosis is an important mechanism in the pathogenesis of NFJS/DPR. PMID:16960809

Hereditary ectodermal dysplasia: A retrospective study

PubMed Central

More, Chandramani B.; Bhavsar, Khusbhu; Joshi, Jigar; Varma, Saurabh N.; Tailor, Mansi

2013-01-01

Background: Ectodermal dysplasia (ED) is a group of rare, inherited disorders characterized by sparse hair, missing teeth and inability to sweat. Objective: To review and analyze cases of ED with an emphasis on clinical manifestations and parent's marriage history. Methodology: The present retrospective study was conducted by assessing the clinical records of nineteen cases of ED, available in the archives of the department; for age, gender, family history of consanguineous marriage and clinical manifestations. Results: It was observed that ED was more prevalent in males, with a ratio of 1.7:1. The hypohydrotic type was more common (78.95%) than hydrotic type (21.05%). The marriage history of parents revealed that 66.67% had consanguineous marriage and had 68.42% offspring's affected with ED; whereas 33.33% had history of non-consanguineous marriage and had 31.58% offspring's affected with ED. The clinical manifestations observed were- dry skin(94.74%); scaly skin(42.11%); sparse hair on scalp, eyebrows and eyelashes(100%); frontal bossing(63.18%); saddle nose (57.89%); hypertelorism (47.37%); nail abnormality(52.63%); normal sweat glands(21.05%); abnormal sweat glands(78.95%); hypoplastic maxilla(52.63%); protuberant lips (57.89%); palmo-plantar keratosis(21.05%); wrinkled & hyper pigmented facial skin(84.21%); partial anodontia(94.74%); conical shaped teeth(84.21%); high arched palate(68.42%); thin alveolar bone(100.00%); taurodontism(21.05%) and cleft lip & cleft palate(05.26%). The number of teeth present in all the cases ranged from 0 to 19. Conclusion: ED patients suffer from social problems and poor psychological and physiological development as a result of unacceptable esthetics and abnormal function of orofacial structures. Oral rehabilitation thus becomes mandatory, although it is often difficult; particularly in pediatric patients. PMID:24082749

Associations between ectodermal dysplasia, psychological distress and quality of life in a group of adults with oligodontia.

PubMed

Saltnes, Solfrid Sørgjerd; Jensen, Janicke Liaaen; Sæves, Rønnaug; Nordgarden, Hilde; Geirdal, Amy Østertun

2017-11-01

The aim of this study was to assess demographics, self-reported signs of ectodermal dysplasia (problems with hair, nails, skin and sweat glands), present teeth, previous dental treatment, psychological distress and QoL in individuals with oligodontia, and to explore the associations between these factors. We also aimed to compare the level of psychological distress and QoL between the study group and normative samples. Forty-seven individuals with oligodontia registered at a resource centre in Norway were included in the study. The participants completed self-administered questionnaires on demographics, ED signs, dental treatments, psychological distress and QoL (overall, health-related- and oral health-related QoL). Relevant statistics (independent t-test, correlation analysis and hierarchical multiple regressions) were used. Thirty-five participants reported ED signs. Forty-one participants had tooth replacements (nine had removable dentures). Sixteen had ≤10 present teeth, 13 perceived dry mouth and seven were unemployed. Persons with ≤10 present teeth had higher anxiety- and depression-scores than those having >10 present teeth. Unemployment, dry mouth and removable dentures indicated poor health-related- and oral health related QoL. Compared to a normative sample; the study group had significantly poorer mental health (MH)-related QoL, mean (SD); (51.1(8.2) versus 46.8(9.3), p < .001) and more anxiety, mean (SD); (4.5(3.1) versus 6.7(3.6), p < .001). ED signs and treatments were most important for psychological distress and MH related QoL (MCS), whereas demographic parameters were most important for the other QoL measures. The psychological burden of oligodontia is significant, emphasizing the importance of a holistic approach by caregivers.

High-resolution mapping of the x-linked hypohidrotic ectodermal dysplasia (EDA) locus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zonana, J.; Jones, M.; Litt, M.

1992-11-01

The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously localized to the subchromosomal region Xq11-q21.1. The authors have extended previous linkage studies and analyzed linkage between the EDA locus and 10 marker loci, including five new loci, in 41 families. Four of the marker loci showed no recombination with the EDA locus, and six other loci were also linked to the EDA locus with recombination fractions of .009-.075. Multipoint analysis gave support to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and PGK1 loci distal to EDA. Further ordering of the loci couldmore » be inferred from a human-rodent somatic cell hybrid derived from an affected female with EDA and an X;9 translocation and from studies of an affected male with EDA and a submicroscopic deletion. Three of the proximal marker loci, which showed no recombination with the EDA locus, when used in combination, were informative in 92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453 had heterozygosites of 72% and 76%, respectively, and when used jointly, they were doubly informative in 52% of females. The human DXS732 locus was defined by a conserved mouse probe pcos169E/4 (DXCrc169 locus) that consegregates with the mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of recombination between EDA and the DXSA732 locus lends support to the hypothesis that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain candidate sequences for the Ta and EDA genes, respectively. 36 refs., 1 fig., 5 tabs.« less

Dermatologic findings of focal dermal hypoplasia (Goltz syndrome).

PubMed

Bree, Alanna F; Grange, Dorothy K; Hicks, M John; Goltz, Robert W

2016-03-01

Goltz syndrome, caused by mutations in PORCN, is an X-linked dominant ectodermal dysplasia which is also known as focal dermal hypoplasia. This name is derived from the predominant pathologic skin findings of the syndrome. Nineteen Goltz-affected participants attended a multidisciplinary scientific and clinical conference convened by the National Foundation for Ectodermal Dysplasia which allowed further characterization of the features of this very rare condition. At birth, the affected areas of skin are typically erythematous and fragile. The hallmark cutaneous features, which vary widely due to mosacism and X-inactivation, include the previously described skin changes of asymmetric Blaschko-linear and reticulated atrophy, pigmentary changes, and telangectasias. Lipomatous changes and papillomas as characteristically defined were reported in the majority of patients. A newly recognized skin finding was progressive hyperpigmented freckling that occurred within the hypopigmented areas which were noted to be photosensitive. Many patients also had a pebbly texture to the central face, dorsal hands and feet. Punctate erosions within the atrophic areas and hypohidrosis were also common. Most had patchy alopecia and many had diffusely thin hair. Scanning electron microscopy of the hair shafts revealed abnormalities in the majority of participants with several different features identified, including atrophic hairs with reduced diameters, markedly flattened hairs as noted in cross-sectional views, trichorrhexis nodosa, pili torti, and pili trianguli et canaliculi. Nail changes included V-nicking and longitudinal ridging of the nail plate, in addition to micronychia. Early recognition of the dermatologic features, in addition to the variable but universal limb anomalies, of Goltz syndrome will allow early and accurate diagnosis without the need for extensive diagnostic studies, while also allowing for accurate prognosis and appropriate genetic counseling. © 2016 Wiley Periodicals, Inc.

[Locomotor development in infants with developmental dysplasia of the hip or idiopathic clubfoot undergoing orthopedic treatment. Prospective comparative study].

PubMed

Masquijo, J J; Campos, L; Torres-Gómez, A; Allende, V

2013-10-01

Several disorders of early childhood, such as developmental dysplasia of the hip (DDH) and clubfoot, requires orthopedic treatment that limits active mobility of the lower extremities for a period of time. The aim of our study was to evaluate the impact on locomotor development of the orthopedic treatment in infants less than one year-old. The study included a prospective cohort of consecutive patients diagnosed with developmental dysplasia of the hip (Group A, 24 patients), and clubfoot (Group B, 32 patients) treated from January 2007 to June 2009. A third group (Group C) of 50 healthy children was used as control. The variables evaluated were: months with a brace, age to sit without support, age at the start of crawling, and age at the beginning of walking. The results obtained were analyzed. Comparisons between the three groups were performed using the Kruskal-Wallis test and Mann-Whitney test. We chose a value of P<.05 as level of statistical significance. The analysis of independent samples showed that the mean age at which the patients began to sit were similar: 6.12, 6.42 and 6.19 months, respectively (P=.249). The mean age for crawling was similar, although with a slight trend toward statistical significance: 8.84, 9.38 and 9.17 months, respectively (P=.08). The age at which they started walking was different between the three groups: 12.14, 13.21 and 12.41 months, respectively (P<.001). Orthopedic treatment of DDH and clubfoot in children less than one year-old slightly slows down the course of normal locomotor development. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

p38α MAPK Is Required for Tooth Morphogenesis and Enamel Secretion*

PubMed Central

Greenblatt, Matthew B.; Kim, Jung-Min; Oh, Hwanhee; Park, Kwang Hwan; Choo, Min-Kyung; Sano, Yasuyo; Tye, Coralee E.; Skobe, Ziedonis; Davis, Roger J.; Park, Jin Mo; Bei, Marianna; Glimcher, Laurie H.; Shim, Jae-Hyuck

2015-01-01

An improved understanding of the molecular pathways that drive tooth morphogenesis and enamel secretion is needed to generate teeth from organ cultures for therapeutic implantation or to determine the pathogenesis of primary disorders of dentition (Abdollah, S., Macias-Silva, M., Tsukazaki, T., Hayashi, H., Attisano, L., and Wrana, J. L. (1997) J. Biol. Chem. 272, 27678–27685). Here we present a novel ectodermal dysplasia phenotype associated with conditional deletion of p38α MAPK in ectodermal appendages using K14-cre mice (p38αK14 mice). These mice display impaired patterning of dental cusps and a profound defect in the production and biomechanical strength of dental enamel because of defects in ameloblast differentiation and activity. In the absence of p38α, expression of amelogenin and β4-integrin in ameloblasts and p21 in the enamel knot was significantly reduced. Mice lacking the MAP2K MKK6, but not mice lacking MAP2K MKK3, also show the enamel defects, implying that MKK6 functions as an upstream kinase of p38α in ectodermal appendages. Lastly, stimulation with BMP2/7 in both explant culture and an ameloblast cell line confirm that p38α functions downstream of BMPs in this context. Thus, BMP-induced activation of the p38α MAPK pathway is critical for the morphogenesis of tooth cusps and the secretion of dental enamel. PMID:25406311

A retrospective 3- to 5-year study of the reconstruction of oral function using implant-supported prostheses in patients with hypohidrotic ectodermal dysplasia.

PubMed

Zou, Duohong; Wu, Yiqun; Wang, Xu Dong; Huang, Wei; Zhang, Zhiyong; Zhang, Zhiyuan

2014-10-01

The aim of this study was to evaluate oral function rehabilitation in patients with hypohidrotic ectodermal dysplasia (HED) using implant-supported prostheses based on bone augmentation. From September 2005 and March 2009, 25 HED patients were chosen for clinical data analysis in this study. The criteria for patient selection included the following: the display of clinical features of HED, the number of congenitally missing teeth (>5), the patient age (>16 years), the patient's willingness, and the patient's tolerance for bone graft surgery and implant placement. Follow-up evaluations were initiated from the time of implant prosthetic placement and scheduled annually for 3-5 years. The effects of oral function reconstruction were assessed based on the cumulative survival and success rates of implants, the health of the peri-implant area, and the degree of patient satisfaction. Twenty-five HED patients received 169 conventional implants and 10 zygomatic implants (179 total implants). During 3-5 years of post-loading evaluations, 5 of the 179 implants failed and 3 implants were removed. The 3-year success and cumulative survival rates were 97.2% and 98.3%, respectively. Furthermore, periodontal probing and radiographic assessments showed that the 3-year incidence of peri-implantitis was 4.5%. Finally, HED patients expressed high degrees of satisfaction with their facial contours, masticatory function, pronunciation ability, and comfort with the implant-supported prostheses. The results of this 3- to 5-year retrospective study indicate that the oral function of HED patients can be effectively reconstructed using bone augmentation and implant-supported prostheses; however, longer term results are warranted in the future.

The Prevalence and Treatment of Hip Dysplasia in Prader-Willi Syndrome (PWS).

PubMed

Trizno, Anastasiya A; Jones, Alexander S; Carry, Patrick M; Georgopoulos, Gaia

2018-03-01

Prader-Willi syndrome (PWS) is a genetic disorder with multisystem involvement. There are a number of associated orthopaedic manifestations, the most recognized of which is scoliosis. The aim of this study was to assess the prevalence of hip dysplasia and to investigate its treatment in patients with PWS. Following IRB approval, all patients seen at our institution's Prader-Willi multidisciplinary clinic were retrospectively reviewed. Only patients with an ultrasound, anteroposterior (AP) spine, AP abdomen, AP hip radiograph, and/or skeletal survey were included in the study. The presence of hip dysplasia was determined based on ultrasonographic and/or radiographic measurements performed by a single fellowship trained pediatric orthopaedic surgeon. A multivariable logistic regression analysis was used to test the association between patient demographics and the prevalence of hip dysplasia. Age at diagnosis, treatment type, and outcomes were recorded for patients that underwent treatment for hip dysplasia. Hip dysplasia was identified in 30% (27/90) of the patient population. Two of the 27 patients (7.4%) had normal films but had a history of resolved hip dysplasia. Prevalence was not associated with sex (P=0.7072), genetic subtype (P=0.5504), race (P=0.8537), ethnicity (P=0.2191), or duration of follow-up (P=0.4421). Eight of the 27 patients (30%) underwent hip treatment by Pavlik harness (2/8), Pavlik harness and closed reduction (1/8), closed reduction (3/8), open reduction (1/8), and unspecified hip surgery (1/8). The mean age at diagnosis was 2 months for the patients that were successfully treated for hip dysplasia (3/8) and 12 months for those who had residual dysplasia following the treatment (5/8). Our study demonstrates a higher prevalence of hip dysplasia in patients with PWS than previously documented. The age at which hip dysplasia develops remains unknown; therefore, we recommend an ultrasound screening for all infants with PWS at 6 weeks of age and subsequent radiographic studies at 1, 2, 5, 10, and 15 years of age to allow for early diagnosis and intervention. Level III-retrospective comparative study.

The Oak Ridge Polycystic Kidney mouse: modeling ciliopathies of mice and men.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lehman, J M; Michaud III, Edward J; Schoeb, T

2008-08-01

The Oak Ridge Polycystic Kidney (ORPK) mouse was described nearly 14 years ago as a model for human recessive polycystic kidney disease. The ORPK mouse arose through integration of a transgene into an intron of the Ift88 gene resulting in a hypomorphic allele (Ift88Tg737Rpw). The Ift88Tg737Rpw mutation impairs intraflagellar transport (IFT), a process required for assembly of motile and immotile cilia. Historically, the primary immotile cilium was thought to have minimal importance for human health; however, a rapidly expanding number of human disorders have now been attributed to ciliary defects. Importantly, many of these phenotypes are present and can bemore » analyzed using the ORPK mouse. In this review, we highlight the research conducted using the OPRK mouse and the phenotypes shared with human cilia disorders. Furthermore, we describe an additional follicular dysplasia phenotype in the ORPK mouse, which alongside the ectodermal dysplasias seen in human Ellis-van Creveld and Sensenbrenner's syndromes, suggests an unappreciated role for primary cilia in the skin and hair follicle.« less

Johnson-McMillin syndrome, a neuroectodermal syndrome with conductive hearing loss and microtia: report of a new case.

PubMed

Schweitzer, Daniela N; Yano, Shoji; Earl, Dawn L; Graham, John M

2003-07-30

In 1983, Johnson et al. described 16 related individuals with alopecia, anosmia or hyposmia, conductive hearing loss, microtia and/or atresia of the external auditory canal, and hypogonadotrophic hypogonadism inherited in an autosomal dominant pattern. Other less constant manifestations included facial asymmetry, mental retardation, congenital heart defect, cleft palate, and choanal stenosis. An isolated case was reported later (Johnston et al. [1987: Am J Med Genet 26: 925-927]) and thereafter an affected mother and son (Hennekam and Holtus [1993: Am J Med Genet 47: 714-716]). We describe an additional unrelated female patient with features resembling those of the previously reported cases. She presented with intrauterine growth deficiency, microcephaly, alopecia, bilateral microtia with canal atresia, conductive hearing loss, partial left facial palsy, posterior cleft palate, left choanal stenosis, tetralogy of Fallot, developmental delay, and right thumb polydactyly. Because the phenotypic abnormalities in this syndrome affect the brain, facial structures, ectoderm and its derivatives, outflow tract of the heart, and Rathke's pouch derivatives, this has suggested to previous authors etiologic involvement of the ectoderm and neuroectoderm of the first and second branchial arches, Rathke's pouch, and the diencephalon. Microtia with conductive hearing loss differentiates the condition from other ectodermal dysplasias. In the initial report, females appeared somewhat less affected than males, and there was male-to-male transmission. The mother of our patient manifests subtle features, which suggest she may be a mildly affected female. Additionally, there is a family history of early-onset alopecia in the maternal grandfather's relatives. Copyright 2003 Wiley-Liss, Inc.

Conference Report: International Research Symposium on Ankyloblepharon-Ectodermal Defects-Cleft Lip and/or Palate (AEC) Syndrome

PubMed Central

Fete, Mary; vanBokhoven, Hans; Clements, Suzanne; McKeon, Frank; Roop, Dennis R.; Koster, Maranke I.; Missero, Caterina; Attardi, Laura D.; Lombillo, Vivian A.; Ratovitski, Edward; Julapalli, Meena; Ruths, Derek; Sybert, Virginia P.; Siegfried, Elaine C.; Bree, Alanna F.

2009-01-01

Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) Syndrome (Hay-Wells syndrome, MIM #106220) is a rare autosomal dominant ectodermal dysplasia syndrome. It is due to mutations in the p63 gene, known to be a regulatory gene with many downstream gene targets. TP63 is important in the differentiation and proliferation of the epidermis, as well as many other processes including limb and facial development. It is also known that mutations in p63 lead to skin erosions. These erosions, especially on the scalp, are defining features of AEC syndrome and cause significant morbidity and mortality in these patients. It was this fact that led to the 2003 AEC Skin Erosion Workshop. That conference laid the groundwork for the International Research Symposium for AEC Syndrome held at Texas Children's Hospital in 2006. The conference brought together the largest cohort of individuals with AEC syndrome, along with a multitude of physicians and scientists. The overarching goals were to define the clinical and pathologic findings for improved diagnostic criteria, to obtain tissue samples for further study and to define future research directions. The symposium was successful in accomplishing these aims as detailed in this conference report. Following our report, we also present eleven manuscripts within this special section that outline the collective clinical, pathologic and mutational data from eighteen individuals enrolled in the concurrent Baylor College of Medicine IRB-approved protocol: Characterization of AEC syndrome. These collaborative findings will hopefully provide a stepping stone to future translational projects of p63 and p63-related syndromes. PMID:19353643

Florid cemento-osseous dysplasia mimicking apical periodontitis: A case report.

PubMed

Rekabi, Ali Reza; Ashouri, Rezvan; Torabi, Molok; Parirokh, Masoud; Abbott, Paul V

2013-12-01

Cemento-osseous dysplasia may present as a focal, periapical or florid lesion in the mandible or maxilla. The lesion may sometimes appear similar to peri-radicular lesions on a periapical radiograph. This report presents a case with irreversible pulpitis and root resorption as well as a mixed radiolucent/radiopaque lesion around a mandibular molar tooth root. Root canal treatment was performed and because of the radiographic signs of root resorption and the patient's fear of having a malignant disease, periapical surgery was also performed. The histopathology report confirmed the presence of florid cement-osseous dysplasia which was mimicking apical periodontitis. Follow-up radiography 12 months after the surgery illustrated complete healing of the radiolucent area. © 2011 The Authors. Australian Endodontic Journal © 2011 Australian Society of Endodontology.

Restoration of Oral Function for Adult Edentulous Patients with Ectodermal Dysplasia: A Prospective Preliminary Clinical Study.

PubMed

Wu, Yiqun; Wang, Xu Dong; Wang, Feng; Huang, Wei; Zhang, Zhiyong; Zhang, Zhiyuan; Kaigler, Darnell; Zou, Duohong

2015-10-01

Therapy with zygomatic implants (ZIs) or conventional implants (CIs) has proven to be an effective method to restore oral function for systemically healthy patients. However, it is still a major challenge to fully restore oral function to edentulous adult patients with ectodermal dysplasia (ED). The aim of this study was to determine an effective treatment protocol for restoring oral function using ZIs and CIs to edentulous adult ED patients. Ten edentulous adult ED patients were treated in this study. The treatment protocol involved the following: (1) bone augmentation in the region of the anterior teeth; (2) placement of two ZIs and four CIs in the maxilla, and four CIs in the mandible; (3) fabrication of dental prosthesis; and (4) psychological and oral education. Following treatment of these patients, implant success rates, biological complications, patient satisfaction, and psychological changes were recorded. Although there was evidence of bone graft resorption in the maxilla, bone augmentation of the mandible was successful in all patients. Nine CIs in the maxilla failed and were removed. All ZIs were successful, and the CIs success rates were 77.50% in the maxilla and 100% in the mandible, with a mean of 88.75%. The mean peri-implant bone resorption for the CIs ranged from 1.3 ± 0.4 mm to 1.8 ± 0.6 mm, and four cases exhibited gingival hyperplasia in the maxilla and mandible. One hundred percent of the patients were satisfied with the restoration of their oral function, and >50% of the patients exhibited enhanced self-confidence and self-esteem. This study demonstrates that oral function can be restored in edentulous adult ED patients using a comprehensive and systematic treatment protocol involving psychological and oral education, bone augmentation, implant placement, and denture fabrication. Despite these positive outcomes, bone augmentation remains challenging in the anterior region of the maxilla for edentulous adult ED patients. © 2015 Wiley Periodicals, Inc.

Incidence of Biliary Reflux Esophagitis After Laparoscopic Omega Loop Gastric Bypass in Morbidly Obese Patients.

PubMed

Salama, Tamer M Said; Hassan, Mohamed Ibrahim

2017-06-01

Omega loop gastric bypass is a successful bariatric surgery with numerous favorable circumstances as being basic, effective on weight reduction and treatment of obesity associated metabolic disorder, the short expectation to learn and adapt, and the simplicity of correction and inversion. However, there are arguments about the possibility of biliary reflux and/or the potential danger of gastroesophageal malignancy after the procedure. Fifty patients experiencing morbid obesity with body mass index >40 or >35 kg/m 2 with two related comorbidities, for example, diabetes type II, hypertension, or dyslipidemia, underwent omega loop gastric bypass with a follow-up period up to 18 months, investigating for any symptom of reflux infection by upper gastrointestinal tract endoscopy and pH metry. Reflux esophagitis (a gastroesophageal reflux disease) was detected in 3 patients (6%); 2 cases (4%) showed (Grade A) acidic reflux esophagitis at 6 and 12 months postoperatively. Just 1 case (2%) had experienced gastroesophageal biliary reflux esophagitis (Grade A) at 12 months. No metaplasia or dysplasia was detected in the endoscopic biopsies. Omega loop gastric bypass is a safe and effective bariatric procedure with low incidence of postoperative biliary reflux, metaplasia, or dysplasia at the esophagogastric junction, confirmed 18 months after the operation.

Dynamic long leg casting fixation for treating 12- to 18-month-old infants with developmental dysplasia of the hip.

PubMed

Cai, Zhencun; Li, Lianyong; Zhang, Lijun; Ji, Shijun; Zhao, Qun

2017-02-01

Objective To evaluate the effect of dynamic long leg casting in paediatric patients with developmental dysplasia of hip (DDH) diagnosed at 12-18 months. Methods The adductor tenotomy, closed reduction, and dynamic long leg casting method was adopted to treat paediatric patients with DDH. The hips were divided into four groups according to the Tonnis radiographic dislocation classification. Groups were also classified according to the baseline acetabular index (AI): 30°-35°, 36°-40°, and > 40°. The outcomes of the reductions were evaluated according to McKay's hip function criteria and Severin's radiological criteria. Results A total of 246 patients (339 hips) had complete follow-up data. After 3 months of orthosis fixation, the results were satisfactory in 264 hips (77.88%). Hip function was rated as 'excellent' or 'good' in 43 of 51 (84.31%) Tonnis type 1 hips, 125 of 155 (80.65%) type 2 hips, 70 of 90 (77.78%) type 3 hips, and 34 of 43 (79.07%) type 4 hips. The higher the baseline AI, the lower the rates of 'excellent' and 'good' hip function. Favourable radiological results (Severin types I and II) were found in 266 of 339 (78.47) hips. Conclusions Dynamic long leg casting is an effective method for treating patients with DDH aged 12-18 months at diagnosis.

Seizure Freedom in Children With Pathology-Confirmed Focal Cortical Dysplasia.

PubMed

Mrelashvili, Anna; Witte, Robert J; Wirrell, Elaine C; Nickels, Katherine C; Wong-Kisiel, Lily C

2015-12-01

We evaluated the temporal course of seizure outcome in children with pathology-confirmed focal cortical dysplasia and explored predictors of sustained seizure freedom. We performed a single-center retrospective study of children ≤ 18 years who underwent resective surgery from January 1, 2000 through December 31, 2012 and had pathology-proven focal cortical dysplasia. Surgical outcome was classified as seizure freedom (Engel class I) or seizure recurrence (Engel classes II-IV). Fisher exact and nonparametric Wilcoxon ranksum tests were used, as appropriate. Survival analysis was based on seizure-free outcome. Patients were censored at the time of seizure recurrence or seizure freedom at last follow-up. Thirty-eight patients were identified (median age at surgery, 6.5 years; median duration of epilepsy, 3.3 years). Median time to last follow-up was 13.5 months (interquartile range, 7-41 months). Twenty patients (53%) were seizure free and 26 patients (68%) attained seizure freedom for a minimum of 3 months. Median time to seizure recurrence was 38 months (95% confidence interval, 6-109 months), and the cumulative seizure-free rate was 60% at 12 months (95% confidence interval, 43%-77%). Clinical features associated with seizure freedom at last follow-up included older age at seizure onset (P = .02), older age at surgery (P = .04), absent to mild intellectual disability before surgery (P = .05), and seizure freedom for a minimum of 3 months (P < .001). Favorable clinical features associated with sustained seizure freedom included older age at seizure onset, older age at surgery, absent or mild intellectual disability at baseline, and seizure freedom for a minimum of 3 months. Copyright © 2015 Elsevier Inc. All rights reserved.

Outcome of epilepsy surgery in focal cortical dysplasia

PubMed Central

Kral, T; Clusmann, H; Blumcke, I; Fimmers, R; Ostertun, B; Kurthen, M; Schramm, J

2003-01-01

Objective: To describe the outcome of surgery in patients with drug resistant epilepsy and a histopathological diagnosis of focal cortical dysplasia. Methods and subjects: Analysis of histories and presurgical and follow up data was carried out in 53 patients with a histological diagnosis of focal cortical dysplasia. Their mean age was 24.0 years (range 5 to 46), and they included 14 children and adolescents. Mean age at seizure onset was 12.4 years (0.4 to 36) and mean seizure duration was 11.6 years (1 to 45). Results: The presurgical detection rate of focal cortical dysplasia with magnetic resonance imaging (MRI) was 96%. There were 24 temporal and 29 extratemporal resections; additional multiple subpial transections were done in 12 cases to prevent spread of seizure discharges. There was a 6% rate of complications with permanent neurological deficit, but no deaths. All resected specimens were classified by neuropathological criteria as focal cortical dysplasia. Balloon cells were seen in most cases of extratemporal focal cortical dysplasia. After a mean follow up of 50 months, 38 patients (72%) were seizure-free, two (4%) had less than two seizures a year, nine (17%) had a reduction of seizure frequency of more than 75%, and four (8%) had no improvement. Seizure outcome was similar after temporal and extratemporal surgery. The patients in need of multilobar surgery had the poorest outcome. Conclusions: Circumscribed lesionectomy of focal dysplastic lesions provides seizure relief in patients with chronic drug resistant temporal and extratemporal epilepsy. There was a trend for the best seizure outcome to be in patients with early presurgical evaluation and early surgery, and in whom lesions were identified on the preoperative MRI studies. PMID:12531945

Surveillance and management of dysplasia in ulcerative colitis.

PubMed

Rodriguez, Sarah A; Collins, Judith M; Knigge, Kandice L; Eisen, Glenn M

2007-03-01

Recently updated practice guidelines give specific recommendations on surveillance and management of dysplasia in patients with ulcerative colitis. Previous studies of gastroenterologists in the United States and the United Kingdom demonstrated inconsistent surveillance techniques and limited understanding of the implications of dysplasia. To demonstrate current surveillance practices and management of dysplasia among U.S. gastroenterologists. An 18-item questionnaire was mailed to 1000 gastroenterologists in the United States who were randomly selected from an American Gastroenterological Association mailing list. United States. A total of 334 questionnaires were returned, and 312 were analyzed: 25% of respondents were in academic practice and 75% were in private practice. The majority were in practice more than 10 years. Nearly 80% begin surveillance colonoscopy at 8 to 10 years of disease duration for patients with pancolitis, and 54% report sending at least 31 biopsy specimens. Sixty percent of respondents did not recommend immediate colectomy for a confirmed finding of low-grade dysplasia, instead opting for repeat colonoscopy in 3 to 12 months. Physicians who took fewer biopsy specimens were more likely to recommend continued surveillance for low-grade dysplasia compared with those who took a greater number of biopsy specimens. Limitations included the response rate of 33% and the potential for recall bias. Most U.S. gastroenterologists are practicing surveillance in patients with ulcerative colitis in accordance with published guidelines. There is widespread variation in the management of dysplasia and raised lesions, and the majority of U.S. gastroenterologists do not recommend immediate colectomy for a finding of low-grade dysplasia.

Is topical delta-aminolevulinic acid adequate for photodynamic therapy in Barrett's esophagus? A pilot study.

PubMed

Ortner, M -A; Zumbusch, K; Liebetruth, J; Ebert, B; Fleige, B; Dietel, M; Lochs, H

2002-08-01

The methods of endoscopic ablation of metaplastic and dysplastic areas in Barrett's esophagus so far described, are not satisfactory with respect to efficacy and safety. Therefore we investigated whether photodynamic therapy (PDT) with topical delta-aminolevulinic acid (delta-ALA) leads to ablation of specialized columnar epithelium and eradication of low-grade dysplasia while not producing phototoxicity and systemic side effects. 14 patients with histologically proven Barrett's esophagus, seven of whom had evidence of low-grade dysplasia, underwent endoscopic treatment with topical delta-ALA. Photoactivation (wavelength, 632 nm) was performed at 1.5 - 2 hours after drug administration using an argon dye laser. Patients received omeprazole 80 mg daily for 2 months; thereafter; maintenance therapy depended on reflux symptoms. Patients were endoscopically re-evaluated after 7 days, and subsequently at 3, 6, 12 and up to 48 months (mean follow up 33 months). Re-treatment with high-dose topical delta-ALA was offered to the 11 patients with remaining metaplasia and was carried out in five of them. Low-grade dysplasia was eradicated in all patients. One patient with no dysplasia before PDT developed a high-grade dysplasia after PDT. Complete ablation of Barrett's metaplasia was observed in 21 % of the patients after the first treatment session and in 20 % after the second treatment session. The mean reduction in the length of Barrett's metaplasia was 1.54 +/- 1.29 cm after the first PDT session and 1.02 +/- 0.80 cm after the second PDT session. Post-endoscopic pain and photosensitivity reactions were less frequent with low-dose delta-ALA PDT than with high-dose PDT (pain 15 %, 100 %, respectively; P = 0.001 by Fisher's exact test; phototoxicity, 0 %, 50 %, respectively; P = 0.021 by Fisher's exact test). Low-dose topical administration of delta-ALA provides ablation of low-grade dysplasia in the range obtained with oral delta-ALA. In addition, it is safe and well tolerated. Since, however, topical administration of delta-ALA is not able to consistently eradicate Barrett's esophagus, alternative methods will have to be developed.

Subglottic stenosis in short-statured children: a case for further investigation of airway symptoms in patients with skeletal dysplasias.

PubMed

Lee, Jonathan H; Ellison, Jay W; Schears, Gregory J; Thompson, Dana M

2006-01-01

Clinical evaluation of children with skeletal dysplasias is often concentrated on morphologic and radiographic assessments, but many of these patients also have disease processes of the ear, nose, and throat. We report a case of an 11-month-old girl with an unknown short-limbed dwarfism, similar to acromicric dysplasia, with grade II subglottic stenosis. Laryngotracheoplasty with anterior autologous costal cartilage graft and posterior cricoid split was performed at age 13 months, with subsequent improvement of her airway status. In cases of children with skeletal dysplasias and obstructive airway symptoms, formal otolaryngologic evaluation is warranted for definitive diagnosis and treatment.

[Bilateral anophthalmia and left-sided orbital tumor : case of an eight-month-old infant].

PubMed

Hundertmark, P; Dierks, P; Gottschalk, J; Kreusch, T; Wiegand, W

2011-08-01

An 8-month-old infant from Russia with bilateral anophthalmia presented with an expanding orbital tumor. The tumor was extirpated and the histological examination revealed a non-malignant pseudocystic process with residual neuro-ectodermal structures.

Does severity of femoral trochlear dysplasia affect outcome in patellofemoral instability treated by medial patellofemoral ligament reconstruction and anterior tibial tuberosity transfer?

PubMed

Moitrel, G; Roumazeille, T; Arnould, A; Migaud, H; Putman, S; Ramdane, N; Pasquier, G

2015-10-01

Medial patellofemoral ligament (MPFL) reconstruction associated to anterior tibial tuberosity transfer (ATTT) is recommended in objective patellofemoral instability (PFI). Efficacy, however, has not been precisely determined in trochlear dysplasia with spur. A case-control study was performed in a PFI population, comparing groups with trochlear dysplasia with and without spur (S+ vs. S-) to assess the impact of trochlear dysplasia on (1) patellofemoral stability, (2) functional results and complications, and (3) patellofemoral cartilage status on MRI. Trochlear spur does not affect outcome in PFI managed by MPFL reconstruction and ATTT. Twenty-eight knees (26 patients) with PFI were analyzed retrospectively and divided into 2 groups of 14 knees each according to presence of trochlear spur (S+ vs. S-). All 28 knees had undergone ATTT and MPFL reconstruction by semitendinosus autograft. Results were assessed on Lille and IKDC functional scores, and cartilage status was determined on MRI at last follow-up. At a mean 24 months' follow-up (range, 12-52 months), there was no recurrence of dislocation. IKDC and Lille scores tended to improve in both groups, although the only significant improvement was in IKDC score (S- gain, 21.3±16; S+ gain, 18.1±14) (P=0.01). IKDC scores at last follow-up were better in the S+ than S- group (79±19 [range, 21-92] vs. 68±13 [range, 35-84], respectively; P=0.012). Lille scores showed no significant inter-group differences in mean gain (P=0.492) or mean value (P=0.381). The S+ group showed more cartilage lesions (n=14/14 knees, including 12/14 with grade≥2 lesions) than the S- group (n=9/14 knees, all grade≤2). MPFL reconstruction with ATTT provided good short-term patellofemoral stability independently of the severity of trochlear dysplasia. Functional results and gain on IKDC, however, were poorer in case of dysplasia with trochlear spur. This is probably due to cartilage lesions, observed more frequently pre- and post-operatively in the spur group, especially as there was no significant difference in Lille Score, which highlights stability. III, retrospective case-control study. Copyright © 2015. Published by Elsevier Masson SAS.

Familial Uncombable Hair Syndrome: Ultrastructural Hair Study and Response to Biotin.

PubMed

Boccaletti, V; Zendri, E; Giordano, G; Gnetti, L; De Panfilis, G

2007-01-01

We report a family affected to the fourth generation by uncombable hair syndrome. This syndrome is characterized by unruly, dry, blond hair with a tangled appearance. The family pedigree strongly supports the hypothesis of autosomal dominant inheritance; some members of the family had, apart from uncombable hair, minor signs of atopy and ectodermal dysplasia, such as abnormalities of the nails. The diagnosis was confirmed by means of extensive scanning electron microscopy. A trial with oral biotin 5 mg/day was started on two young patients with excellent results as regards the hair appearance, although scanning electron microscopy did not show structural changes in the hair. After a 2-year-period of follow-up, hair normality was maintained without biotin, while nail fragility still required biotin supplementation for control.

[Use of bevacizumab (Avastin) in KID syndrome: case report].

PubMed

Caye, Luiza; Scheid, Karin; Pizzol, Melissa Manfroi Dal; Freda, Roberto

2010-01-01

KID syndrome is a congenital ectodermal dysplasia characterized by the association of keratitis, hyperkeratotic skin lesions and neurosensorial hearing loss. Ocular involvement occurs in 95% of patients. Although KID syndrome cutaneous manifestations have been studied in-depth, the treatment and prognosis of ophthalmic impairment have not been described in detail. At present, the treatment of the ocular damage caused by the syndrome is symptomatic and there are no studies defining a treatment that could change the disease course. In this case, ophthalmologic findings of a patient with KID syndrome and the use of subconjunctival bevacizumab to treat corneal neovascularization are described. In spite of the absence of improvement in this patient and the few reports of this disease, additional studies with bevacizumab to treat corneal deep neovascularization are suggested.

Analysis of Altered Micro RNA Expression Profiles in Focal Cortical Dysplasia IIB.

PubMed

Li, Lin; Liu, Chang-Qing; Li, Tian-Fu; Guan, Yu-Guang; Zhou, Jian; Qi, Xue-Ling; Yang, Yu-Tao; Deng, Jia-Hui; Xu, Zhi-Qing David; Luan, Guo-Ming

2016-04-01

Focal cortical dysplasia type IIB is a commonly encountered subtype of developmental malformation of the cerebral cortex and is often associated with pharmacoresistant epilepsy. In this study, to investigate the molecular etiology of focal cortical dysplasia type IIB, the authors performed micro ribonucleic acid (RNA) microarray on surgical specimens from 5 children (2 female and 3 male, mean age was 73.4 months, range 50-112 months) diagnosed of focal cortical dysplasia type IIB and matched normal tissue adjacent to the lesion. In all, 24 micro RNAs were differentially expressed in focal cortical dysplasia type IIB, and the microarray results were validated using quantitative real-time polymerase chain reaction (PCR). Then the putative target genes of the differentially expressed micro RNAs were identified by bioinformatics analysis. Moreover, biological significance of the target genes was evaluated by investigating the pathways in which the genes were enriched, and the Hippo signaling pathway was proposed to be highly related with the pathogenesis of focal cortical dysplasia type IIB. © The Author(s) 2015.

Isolation and characterization of the human CDX1 gene: A candidate gene for diastrophic dysplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonner, C.; Loftus, S.; Wasmuth, J.J.

1994-09-01

Diastrophic dysplasia is an autosomal recessive disorder characterized by short stature, dislocation of the joints, spinal deformities and malformation of the hands and feet. Multipoint linkage analysis places the diastrophic dysplasia (DTD) locus in 5q31-5q34. Linkage disequilibrium mapping places the DTD locus near CSFIR in the direction of PDGFRB (which is tandem to CSFIR). This same study tentatively placed PDGFRB and DTD proximal to CSFIR. Our results, as well as recently reported work from other laboratories, suggest that PDGFRB (and possibly DTD) is distal rather than proximal to CSFIR. We have constructed a cosmid contig covering approximately 200 kb ofmore » the region containing CSFIR. Several exons have been {open_quotes}trapped{close_quotes} from these cosmids using exon amplification. One of these exons was trapped from a cosmid isolated from a walk from PDGFRB, approximately 80 kb from CSFIR. This exon was sequenced and was determined to be 89% identical to the nucleotide sequence of exon two of the murine CDX1 gene (100% amino acid identity). The exon was used to isolate the human CDX gene. Sequence analysis of the human CDX1 gene indicates a very high degree of homology to the murine gene. CDX1 is a caudal type homeobox gene expressed during gastrulation. In the mouse, expression during gastrulation begins in the primitive streak and subsequently localizes to the ectodermal and mesodermal cells of the primitive streak, neural tube, somites, and limb buds. Later in gastrulation, CDX1 expression becomes most prominent in the mesoderm of the forelimbs, and, to a lesser extent, the hindlimbs. CDX1 is an intriguing candidate gene for diastrophic dysplasia. We are currently screening DNA from affected individuals and hope to shortly determine whether CDX1 is involved in this disorder.« less

[Usefulness of systematic chromoendoscopy with a double dye staining technique for the detection of dysplasia in patients with premalignant gastric lesions].

PubMed

Yep-Gamarra, Víctor; Díaz-Vélez, Cristian; Araujo, Isis; Ginès, Àngels; Fernández-Esparrach, Gloria

2016-02-01

Premalignant gastric lesions have an increased risk to develop gastric cancer. To evaluate the usefulness of systematic endoscopy that includes chromoendoscopy with a double dye staining technique for the detection of dysplasia in patients with premalignant gastric lesions. This longitudinal, prospective study was performed in patients with gastric atrophy, intestinal metaplasia or dysplasia who were referred for endoscopy less than 6 months after the initial diagnosis. The second endoscopy was performed in three phases: phase 1, exhaustive and systematic review of the mucosa with photographic documentation and biopsies of suspicious areas; phase 2, chromoendoscopy with a double dye staining technique using acetic acid 1.2% and indigo carmine 0.5%; phase 3, topographic mapping and random biopsies. A total of 50 patients were included. Nine (18%) had atrophic gastritis, 38 (76%) had intestinal metaplasia, and 3 (6%) had low-grade dysplasia. Systematic endoscopy with chromoendoscopy using a double dye staining technique detected more patients with dysplasia (9 versus 3, p<.05), and a larger number of biopsies with the diagnosis of dysplasia were obtained. This occurred for visible (6 vs. 0, p<.05) and non-visible lesions (6 vs. 3, p=NS). In one patient, initial low-grade dysplasia was not detected again in the systematic endoscopy, giving a global endoscopic performance for the detection of lesions of 92%. Patients with premalignant gastric lesions have synchronous lesions with greater histological severity, which are detected when systematic endoscopy is conducted with indigo carmine dye added to acetic acid. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Radiofrequency ablation for early oesophageal squamous neoplasia: Outcomes form United Kingdom registry

PubMed Central

Haidry, Rehan J; Butt, Mohammed A; Dunn, Jason; Banks, Matthew; Gupta, Abhinav; Smart, Howard; Bhandari, Pradeep; Smith, Lesley Ann; Willert, Robert; Fullarton, Grant; John, Morris; Di Pietro, Massimo; Penman, Ian; Novelli, Marco; Lovat, Laurence B

2013-01-01

AIM: To report outcomes on patients undergoing radiofrequency ablation (RFA) for early oesophageal squamous neoplasia from a National Registry. METHODS: A Prospective cohort study from 8 tertiary referral centres in the United Kingdom. Patients with squamous high grade dysplasia (HGD) and early squamous cell carcinoma (ESCC) confined to the mucosa were treated. Visible lesions were removed by endoscopic mucosal resection (EMR) before RFA. Following initial RFA treatment, patients were followed up 3 monthly. Residual flat dysplasia was treated with RFA until complete reversal dysplasia (CR-D) was achieved or progression to invasive Squamous cell cancer defined as infiltration into the submucosa layer or beyond. The main outcome measures were CR-D at 12 mo from start of treatment, long term durability, progression to cancer and adverse events. RESULTS: Twenty patients with squamous HGD/ESCC completed treatment protocol. Five patients (25%) had EMR before starting RFA treatment. CR-D was 50% at 12 mo with a median of 1 RFA treatment, mean 1.5 (range 1-3). Two further patients achieved CR-D with repeat RFA after this time. Eighty per cent with CR-D remain dysplasia free at latest biopsy, with median follow up 24 mo (IQR 17-54). Six of 20 patients (30%) progressed to invasive cancer at 1 year. Four patients (20%) required endoscopic dilatations for symptomatic structuring after treatment. Two of these patients have required serial dilatations thereafter for symptomatic dysphagia with a median of 4 dilatations per patient. The other 2 patients required only a single dilatation to achieve an adequate symptomatic response. One patient developed cancer during follow up after end of treatment protocol. CONCLUSION: The role of RFA in these patients remains unclear. In our series 50% patients responded at 12 mo. These figures are lower than limited published data. PMID:24106401

Photodynamic therapy (PDT) in Barrett's esophagus with dysplasia or early cancer.

PubMed

Foroulis, Christophoros N; Thorpe, James A C

2006-01-01

Esophagectomy is the standard treatment for high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC) arising within Barrett's esophagus. Results of photodynamic therapy (PDT) were retrospectively studied to evaluate the effectiveness of PDT in ablating HGD and/or IMC complicating Barrett's esophagus. Thirty-one patients unfit for or refusing esophagectomy (male: 20, mean age: 73.4+/-9.3 years) underwent Porfimer sodium PDT ablation of their HGD (15 patients), HGD plus IMC (10 patients) or submucosal/limited T2 adenocarcinoma (6 patients). The mean Barrett's length was 5.8+/-2.2 cm. Pre-PDT endoscopic mucosal resection or Nd:YAG laser ablation of mucosal nodularity within Barrett's segment was offered in six patients. The main PDT complications were esophagitis (16.1%), photoreactions (12.9%) and stricture requiring dilatation (6.25%). The median post-PDT follow-up was 14 months. The long-term results were (a) for HGD/IMC: initial complete response (endoscopic and histologic absence of HGD-IMC) to PDT was observed in 80.95% of patients, partial response (no endoscopic abnormality, residual IMC-HGD on biopsy) in 9.52%, no response in 9.52% (the recurrence rate after an initial complete response was 17.64%) and (b) for T1b/limited T2 tumors: two patients died from cancer after 24 and 46 months, no evidence of tumor was found in two patients after 12 and 19 months and tumor recurrence was seen in two after 15 and 17 months. The mean survival was 22.1+/-12.3 months. PDT is effective in ablating HGD/IMC complicating Barrett's esophagus in the majority of cases, while it also seems to be quite effective in treating T1b/limited T2 carcinomas.

Development of gastric dysplasia in pernicious anaemia: a clinical and endoscopic follow up study of 80 patients.

PubMed Central

Armbrecht, U; Stockbrügger, R W; Rode, J; Menon, G G; Cotton, P B

1990-01-01

The development of gastric dysplasia and neoplasia in patients with pernicious anaemia has been evaluated in a prospective clinical and endoscopic follow up study. After initial screening of 80 patients between 1978 and 1980, one patient underwent total gastrectomy for a gastric malignancy and 12 were kept under surveillance and underwent endoscopy at a mean interval of 14 months. In the remaining 67 patients further investigation was attempted six to seven years after the initial investigation. The continuous follow up study identified carcinoids in one patient and an adenoma with severe dysplasia in a further patient. The grade and site of mucosal dysplasia differed from one investigation to the next, but no overall progression was observed. Of the 79 patients, eight had died by the time of the reinvestigation, two of unknown cause and six of causes unrelated to pernicious anaemia. In 38 of the remaining 71 patients, clinical data only were available, with no evidence of new gastric malignancy. In 27 patients it was possible to perform an upper gastrointestinal endoscopy, when no change in the degree of dysplasia was detected. In six patients no follow up information was obtainable. In conclusion, patients with pernicious anaemia should be investigated by upper gastrointestinal endoscopy soon after diagnosis. Polyps should be removed wherever possible. In the presence of severe mucosal dysplasia or polyps that are not removed, frequent reinvestigation should be performed, provided the patient is eligible for gastric surgery. In the remaining patients, follow up endoscopies at about five year intervals would seem sufficient. PMID:2083855

Outcomes of Hip Arthroscopy for Patients with Symptomatic Borderline Dysplasia

PubMed Central

Nawabi, Danyal H.; Bedi, Asheesh; Ranawat, Anil S.; Kelly, Bryan T.

2015-01-01

Objectives: The outcomes of hip arthroscopy in the treatment of dysplasia are variable. Arthroscopy in severe dysplasia (LCEA<18°) results in poor outcomes and iatrogenic instability. However, in milder forms of dysplasia, favorable outcomes have been demonstrated at short-term follow-up. The purpose of this study was to compare outcomes of hip arthroscopy in borderline dysplastic patients to a control group of non-dysplastic patients undergoing hip arthroscopy for femorocetabular impingement (FAI). Methods: Between March 2009 and May 2012, 1381 patients (1593 hips) undergoing hip arthroscopy for intra-articular hip disorders were prospectively enrolled into a registry. From this cohort, a borderline dysplasia (BD) group comprising 44 patients (46 hips) with a LCEA ≥ 18° and ≤ 25° and a minimum of 2 years follow-up, was identified. A control group of 100 patients (123 hips) was also identified that had a LCEA ≥ 26° and ≤ 40°, and a minimum of 2 years follow-up. Patient-reported outcome scores, including the Modified Harris Hip Score (mHHS), the Hip Outcome Score-Activity of Daily Living (HOS-ADL), the Sport-specific Subscale (HOS-SSS), and the International Hip Outcome Tool (iHOT-33), were obtained preoperatively and at 6 months, 1, 2, and 3 years postoperatively. Continuous and categorical variables were compared with independent-samples t-tests and chi-square or Fisher's exact tests (as appropriate) respectively. Changes in outcomes scores within groups were assessed via paired t-tests. Results: The mean age (±SD) of the BD and control groups was 29.3 ± 9.2 years and 29.1 ± 10.1 years respectively. There were 24 females (55%) in the BD group and 53 females (53%) in the control group (p=0.86). The mean LCEA was 21.8° (range, 18°-25°) in the BD group and 31.7° (range, 26°-40°) in the control group (p<0.001). The mean Tönnis angle was 6.2° (range, 1°-12°) in the BD group and 2.6° (range, -10°-12°) in the control group (p<0.001). The mean preoperative alpha angle was 63.7 ± 10.3° in the BD group and 58.6 ± 13.9° in the control group (p=0.02). A subgroup analysis of alpha angle by sex showed that females had significantly lower alpha angles than males (59.2° vs 69.1°; p=0.001). Labral re-fixation and a complete capsular closure was performed in over 70% and 90% of patients in both groups respectively. At a mean follow-up of 33.2 months (range, 24-58), there was significant improvement (p<0.001) in all patient reported outcome scores in both groups. However, BD patients had smaller mean improvements in all outcomes scores, and for HOS-SSS this difference was large (difference:-6.8; p=0.112). After adjustment for age, sex, alpha angle, and pre-operative score via multiple regression there was no significant difference between the BD and control groups. Importantly, female sex did not appear to be a predictor for inferior outcomes. One patient in the BD group was revised at 13 months and is awaiting a PAO. One patient in the control group required a revision arthroscopy at 30 months. Conclusion: While we recommend caution in treating symptomatic dysplasia with hip arthroscopy, our results indicate that in borderline dysplasia, favorable outcomes can be expected when a careful approach of labral re-fixation and capsular closure is employed. These outcomes are similar to non-dysplastic patients undergoing hip arthroscopy at a mean of 33 months follow-up. Further follow-up in larger cohorts is necessary to prove the durability and safety of hip arthroscopy in this challenging group.

Chemopreventive Activity of MGN-3/Biobran Against Chemical Induction of Glandular Stomach Carcinogenesis in Rats and Its Apoptotic Effect in Gastric Cancer Cells.

PubMed

Badr El-Din, Nariman K; Abdel Fattah, Salma M; Pan, Deyu; Tolentino, Lucilene; Ghoneum, Mamdooh

2016-12-01

In the current study, we investigated the chemopreventive activity of arabinoxylan rice bran, MGN-3/Biobran, against chemical induction of glandular stomach carcinogenesis in rats. Gastric cancer was induced by carcinogen methylnitronitrosoguanidine (MNNG), and rats received MNNG alone or MNNG plus Biobran (40 mg/kg body weight) for a total of 8 months. Averaged results from 2 separate readings showed that exposure to MNNG plus Biobran caused gastric dysplasia and cancer (adenocarcinoma) in 4.5/12 rats (9/24 readings, 37.5%), with 3.5/12 rats (7/24 readings, 29.2%) showing dysplasia and 1/12 rats (8.3%) developing adenocarcinoma. In contrast, in rats treated with MNNG alone, 8/10 (80%) developed dysplasia and adenocarcinoma, with 6/10 rats (60%) showing dysplasia and 2/10 rats (20%) developing adenocarcinoma. The effect of combining both agents was also associated with significant suppression of the expression of the tumor marker Ki-67 and remarkable induction in the apoptotic gastric cancer cells via mitochondrial-dependent pathway as indicated by the upregulation in p53 expression, Bax expression, downregulation in Bcl-2 expression, an increase in Bax/Bcl-2 ratio, and an activation of caspase-3. In addition, Biobran treatment induced cell-cycle arrest in the subG1 phase, where the hypodiploid cell population was markedly increased. Moreover, Biobran treatment protected rats against MNNG-induced significant decrease in lymphocyte levels. We conclude that Biobran provides protection against chemical induction of glandular stomach carcinogenesis in rats and may be useful for the treatment of human patients with gastric cancer. © The Author(s) 2016.

Del(12)(p11.21p12.2) associated with an asphyxiating thoracic dystrophy or chondroectodermal dysplasia-like syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagai, T.; Kato, R.; Hasegawa, T.

1995-01-02

We describe a 5-year-old Japanese boy who has some radiographic findings characteristic of asphyxiating thoracic dystrophy (ATD)-chondroectodermal dysplasia with a de novo chromosome abnormality. He also has mild mental retardation, short stature, hypoplastic hair and skin, oligodontia, small thoracic cage, hypoplastic pelvis and cone-shaped epiphyses of hands. On cytogenetic studies he was found to have a de novo del(12)(p11.21p12.2). These results suggest that the locus of the gene associated with ATD-chondroectodermal dysplasia may be situated at 12p11.21p12.2. 11 refs., 2 figs.

Endoscopic Ultrasound in Barrett's Oesophagitis with Dysplasia

PubMed Central

Wray, Andrew; Rice, Paul; Love, Mark

2012-01-01

Purpose With the advent of conservative therapies including photodynamic therapy and endoscopic mucosal resection for Barrett's and high grade dysplasia, accurate staging has become increasingly important. We report our experience with endoscopic ultrasound (EUS) in these patients. Materials and Methods Retrospective review of 25 consecutive patients referred for EUS for assessment of Barrett's with high grade dysplasia and /or stricture or polyp. The findings were compared with subsequent surgical pathology, or endoscopy and biopsy follow up. Results Nine patients were found to have invasive tumour on EUS and this was confirmed in all 9 either by oesophagectomy, OGD and oncology follow up, or by endoscopic mucosal resection. Eight patients underwent oesophagectomy, 5 for invasive tumour and 3 for dysplasia only, with pathological agreement with EUS findings in 7 out of 8 cases. The one discrepancy was a EUS case of mucosal thickening only with no invasion, but pathology showed a T1 lesion. Thirteen patients with no evidence of invasion were managed conservatively, with 11 patients being followed up for 6-12 months with serial OGD and biopsy, and no cases of more invasive disease occurring. Therefore, in our experience the sensitivity, specificity and positive predictive value of EUS in complex Barrett's is 90%, 100% and 100% respectively. Conclusion EUS is valuable in the assessment of high grade dysplasia in cases where conservative therapy is being considered, defining those with more deeply invasive tumour for whom radical treatment is the only option. PMID:23526576

Mechanisms of transcriptional repression of cell-cycle G2/M promoters by p63

PubMed Central

Testoni, Barbara; Mantovani, Roberto

2006-01-01

p63 is a developmentally regulated transcription factor related to p53, which activates and represses specific genes. The human AEC (Ankyloblepharon–Ectodermal dysplasia-Clefting) and EEC (Ectrodactyly–Ectodermal dysplasia–Cleft lip/palate) syndromes are caused by missense mutations of p63, within the DNA-binding domain (EEC) or in the C-terminal sterile alpha motif domain (AEC). We show here that p63 represses transcription of cell-cycle G2/M genes by binding to multiple CCAAT core promoters in immortalized and primary keratinocytes. The CCAAT-activator NF-Y and ΔNp63α are associated in vivo and a conserved α-helix of the NF-YC histone fold is required. p63 AEC mutants, but not an EEC mutant, are incapable to bind NF-Y. ΔNp63α, but not the AEC mutants repress CCAAT-dependent transcription of G2/M genes. Chromatin immunoprecipitation recruitment assays establish that the AEC mutants are not recruited to G2/M promoters, while normally present on 14-3-3σ, which contains a sequence-specific binding site. Surprisingly, the EEC C306R mutant activates transcription. Upon keratinocytes differentiation, NF-Y and p63 remain bound to G2/M promoters, while HDACs are recruited, histones deacetylated, Pol II displaced and transcription repressed. Our data indicate that NF-Y is a molecular target of p63 and that inhibition of growth activating genes upon differentiation is compromised by AEC missense mutations. PMID:16473849

Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation

PubMed Central

Arai, Chieko; Yamada, Aya; Saito, Kan; Ishikawa, Masaki; Xue, Han; Funada, Keita; Haruyama, Naoto; Yamada, Yoshihiko; Fukumoto, Satoshi; Takahashi, Ichiro

2016-01-01

Tooth morphogenesis is initiated by reciprocal interactions between the ectoderm and neural crest-derived mesenchyme, and the Wnt signaling pathway is involved in this process. We found that Plakophilin (PKP)1, which is associated with diseases such as ectodermal dysplasia/skin fragility syndrome, was highly expressed in teeth and skin, and was upregulated during tooth development. We hypothesized that PKP1 regulates Wnt signaling via its armadillo repeat domain in a manner similar to β-catenin. To determine its role in tooth development, we performed Pkp1 knockdown experiments using ex vivo organ cultures and cell cultures. Loss of Pkp1 reduced the size of tooth germs and inhibited dental epithelial cell proliferation, which was stimulated by Wnt3a. Furthermore, transfected PKP1-emerald green fluorescent protein was translocated from the plasma membrane to the nucleus upon stimulation with Wnt3a and LiCl, which required the PKP1 N terminus (amino acids 161 to 270). Localization of PKP1, which is known as an adhesion-related desmosome component, shifted to the plasma membrane during ameloblast differentiation. In addition, Pkp1 knockdown disrupted the localization of Zona occludens 1 in tight junctions and inhibited ameloblast differentiation; the two proteins were shown to directly interact by immunoprecipitation. These results implicate the participation of PKP1 in early tooth morphogenesis as an effector of canonical Wnt signaling that controls ameloblast differentiation via regulation of the cell adhesion complex. PMID:27015268

Spinoff from a Moonsuit

NASA Technical Reports Server (NTRS)

1989-01-01

Hypohidrotic ectodermal dysplasia refers to the absence of sweat glands which allow body heat to escape. Children with the disease become overheated quickly and suffer from a number of related afflictions. Several have been assisted by Life Support Systems, Inc., a NASA spinoff company which manufactures a garment cooled by a heat exchanger powered by a minipump through a network of fluid-filled tubes. The suits are used by firefighters, crop dusting pilots, workers in hazardous industries, etc. The company was founded by a former NASA contractor employee. When Sara Moody, whose nephew Stevie Roper has HED, contacted Langley Research Center, she was referred to LSSI. With help from PoFolks Restaurant Corporation and others, she raised $5,000 for a suit for Stevie. LSSI agreed to manufacture the suit at cost. After receiving the suit, Stevie's life improved dramatically, and Sara Moody established the HED Foundation. Through the foundation, other children have also received cool suits.

An Allelic Series of Trp63 Mutations Defines TAp63 as a Modifier of EEC Syndrome

PubMed Central

Lindahl, Emma Vernersson; Garcia, Elvin L.; Mills, Alea A.

2014-01-01

Human Ectrodactyly, Ectodermal dysplasia, Clefting (EEC) syndrome is an autosomal dominant developmental disorder defined by limb deformities, skin defects, and craniofacial clefting. Although associated with heterozygous missense mutations in TP63, the genetic basis underlying the variable expressivity and incomplete penetrance of EEC is unknown. Here we show that mice heterozygous for an allele encoding the Trp63 p.Arg318His mutation, which corresponds to the human TP63 p.Arg279His mutation found in patients with EEC, have features of human EEC. Using an allelic series, we discovered that whereas clefting and skin defects are caused by loss of Trp63 function, limb anomalies are due to gain- and/or dominant-negative effects of Trp63. Furthermore, we identify TAp63 as a strong modifier of EEC-associated phenotypes with regard to both penetrance and expressivity. PMID:23775923

Mondini dysplasia with recurrent bacterial meningitis caused by three different pathogens.

PubMed

Shikano, Hiroaki; Ohnishi, Hidenori; Fukutomi, Hisashi; Ito, Kimiko; Morimoto, Masahiro; Teramoto, Takahide; Aoki, Mitsuhiro; Nishihori, Takezumi; Akeda, Yukihiro; Oishi, Kazunori; Fukao, Toshiyuki

2015-12-01

Mondini dysplasia is rare, but has an important association with recurrent bacterial meningitis. We herein describe the case of a 3-year-old girl with unilateral sensorineural hearing loss who presented with three independent episodes of bacterial meningitis within 8 months. Temporal bone computed tomography indicated the characteristic features of Mondini dysplasia in the right inner ear. This was treated by surgical closure of the inner ear defect via oval window and additional vaccination was administered. Appropriate vaccination might prevent the recurrent bacterial meningitis associated with Mondini dysplasia. © 2015 Japan Pediatric Society.

Maternal Black Race and Persistent Wheezing Illness in Former Extremely Low Gestational Age Newborns: Secondary Analysis of a Randomized Trial.

PubMed

Wai, Katherine C; Hibbs, Anna M; Steurer, Martina A; Black, Dennis M; Asselin, Jeanette M; Eichenwald, Eric C; Ballard, Philip L; Ballard, Roberta A; Keller, Roberta L

2018-04-04

To evaluate the relationship between maternal self-reported race/ethnicity and persistent wheezing illness in former high-risk, extremely low gestational age newborns, and to quantify the contribution of socioeconomic, environmental, and biological factors on this relationship. We assessed persistent wheezing illness determined at 18-24 months corrected (for prematurity) age in survivors of a randomized trial. Parents/caregivers were surveyed for wheeze and inhaled asthma medication use quarterly to 12 months, and at 18 and 24 months. We used multivariable analysis to evaluate the relationship of maternal race to persistent wheezing illness, and identified mediators for this relationship via formal mediation analysis. Of 420 infants (25.2 ± 1.2 weeks of gestation and 714 ± 166 g at birth, 57% male, 34% maternal black race), 189 (45%) had persistent wheezing illness. After adjustment for gestational age, birth weight, and sex, infants of black mothers had increased odds of persistent wheeze compared with infants of nonblack mothers (OR = 2.9, 95% CI 1.9, 4.5). Only bronchopulmonary dysplasia, breast milk diet, and public insurance status were identified as mediators. In this model, the direct effect of race accounted for 69% of the relationship between maternal race and persistent wheeze, whereas breast milk diet, public insurance status, and bronchopulmonary dysplasia accounted for 8%, 12%, and 10%, respectively. Among former high-risk extremely low gestational age newborns, infants of black mothers have increased odds of developing persistent wheeze. A substantial proportion of this effect is directly accounted for by race, which may reflect unmeasured environmental influences, and acquired and innate biological differences. ClinicalTrials.gov: NCT01022580. Copyright © 2018 Elsevier Inc. All rights reserved.

The role of diclofenack on inducing of aplasia cutis congenita: a case report.

PubMed

Pajaziti, Laura; Rexhepi, Syzana; Shatri-Muça, Ylfete; Ferizi, Mybera

2009-10-12

Aplasia cutis congenita is a disorder where e newborn child is missing skin from certain areas. It is a rare condition with no particular race or sex more at risk. May occur by itself or be associated with other physical syndromes or disorders. A classification system exists for aplasia cutis congenital consisting of 9 groups, based on the number and location of the skin defects and the presence or absence of other malformations. Causes of aplasia congenital could be heredity, teratogenic substances, placental infarcts, intrauterine infections, ectodermal dysplasias etc. Diagnosis is made based on the clinical findings. Prognosis depends of the other organs malfunction level and lesions size. Our case was an 22 months old Albanian girl, who was recommended to dermatology for a consultation by a pediatric surgeon because of the changes she had on her parietal part of the scalp with missing hair areas. The child has stenosis congenita ani and to her was installed stoma. In order to investigate other accompanied anomalies of the disease, there are made specific consults by neurologist, orthopedist, cardiologist, nephrologists and citogenetics. It was found out a minor visual discoordination, Sy Floppy, Digiti V superductus pedis bill. Laxitas articularum generalisata. It was a great challenge for us to find out that during the first trimester of the pregnancy (unplanned pregnancy), her mother used Diclofenac. Since there is limited information regarding to teratogenic effects of diclofenac, we considered it interesting to present this case.

The role of diclofenack on inducing of aplasia cutis congenita: a case report

PubMed Central

2009-01-01

Background Aplasia cutis congenita is a disorder where e newborn child is missing skin from certain areas. It is a rare condition with no particular race or sex more at risk. May occur by itself or be associated with other physical syndromes or disorders. A classification system exists for aplasia cutis congenital consisting of 9 groups, based on the number and location of the skin defects and the presence or absence of other malformations. Causes of aplasia congenital could be heredity, teratogenic substances, placental infarcts, intrauterine infections, ectodermal dysplasias etc. Diagnosis is made based on the clinical findings. Prognosis depends of the other organs malfunction level and lesions size. Case report Our case was an 22 months old Albanian girl, who was recommended to dermatology for a consultation by a pediatric surgeon because of the changes she had on her parietal part of the scalp with missing hair areas. The child has stenosis congenita ani and to her was installed stoma. In order to investigate other accompanied anomalies of the disease, there are made specific consults by neurologist, orthopedist, cardiologist, nephrologists and citogenetics. Conclusion It was found out a minor visual discoordination, Sy Floppy, Digiti V superductus pedis bill. Laxitas articularum generalisata. It was a great challenge for us to find out that during the first trimester of the pregnancy (unplanned pregnancy), her mother used Diclofenac. Since there is limited information regarding to teratogenic effects of diclofenac, we considered it interesting to present this case. PMID:19946521

Genetics Home Reference: cranioectodermal dysplasia

MedlinePlus

... CRANIOECTODERMAL DYSPLASIA 4 Sources for This Page Arts H, Knoers N. Cranioectodermal Dysplasia. 2013 Sep 12. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of ...

Focal cortical dysplasias: surgical outcome in 67 patients in relation to histological subtypes and dual pathology.

PubMed

Fauser, Susanne; Schulze-Bonhage, Andreas; Honegger, Juergen; Carmona, Hans; Huppertz, Hans-Juergen; Pantazis, Georgios; Rona, Sabine; Bast, Thomas; Strobl, Karl; Steinhoff, Bernhard J; Korinthenberg, Rudolf; Rating, Dietz; Volk, Benedikt; Zentner, Josef

2004-11-01

The purpose of this study was to assess whether the histological subtype of focal cortical dysplasia and dual pathology affect surgical outcome in patients with medically intractable epilepsy due to focal cortical dysplasia (FCD). We retrospectively analysed the outcome of 67 patients from 2 to 66 years of age at follow-up periods of 6 to 48 months after epilepsy surgery. Histological subtypes were classified according to Palmini and included a few cases with mild histological abnormalities corresponding to the definition of mild malformations of cortical development. The seizure outcome was classified according to Engel and evaluated at the last follow-up visit as well as at follow-up periods of 12 and 24 months after surgery. The outcome in patients with FCD and additional hippocampal pathology (dual pathology) was analysed separately. Distribution of histological subtypes differed in temporal and extratemporal localization, with a significantly higher extratemporal prevalence of FCD type 2. There was a tendency towards better postsurgical outcome related to the last follow-up visit in patients with more subtle abnormalities classified as mild malformations of cortical development (mMCD) (63% Engel Ia), FCD type 1a (67% Engel Ia) and FCD type 1b (55% Engel Ia) compared with patients with FCD type 2a (43% Engel Ia) and FCD type 2b (Taylor type) (50% Engel Ia). Considering the outcome at follow-up periods over 12 and 24 months, complete seizure-freedom was achieved significantly more often in patients with FCD type 1 and mMCD than with FCD type 2, and seizure reduction by less than 75% (Engel IV) occurred in more patients with FCD type 2a compared with the other subgroups. This tendency was seen in the whole patient group and in the extratemporal subgroup. Patients with dual pathology almost always had temporal lobe epilepsy; the outcome in this patient group was generally favourable (66% complete seizure-freedom at the last follow-up visit). The outcome remained almost constant with longer periods of follow-up. We conclude that patients with FCD type 1 and mMCD had a better outcome compared with those with more severe forms of cortical dysplasia. A higher incidence of FCD type 1 in temporal localization did not allow the effects of histological subtype and localization to be separated. A subanalysis of extratemporal FCDs, however, revealed a similar tendency for a better outcome with FCD type 1, suggesting that the histological subtype itself seems to be at least a relevant cofactor influencing postsurgical outcome.

Retrospective study of the influence of HPV persistence on outcomes among women with high-risk HPV infections and negative cytology.

PubMed

Bogani, Giorgio; Taverna, Francesca; Lombardo, Claudia; Borghi, Chiara; Martinelli, Fabio; Signorelli, Mauro; Leone Roberti Maggiore, Umberto; Chiappa, Valentina; Scaffa, Cono; Ditto, Antonino; Lorusso, Domenica; Raspagliesi, Francesco

2017-07-01

To evaluate the outcomes of women diagnosed with high-risk HPV without cytology evidence of cervical dysplasia. The present retrospective observational study enrolled consecutive women aged at least 18 years diagnosed with high-risk HPV types with negative cytology results at the National Cancer Institute, Milan, Italy, between January 1, 2005, and December 31, 2015. The development of cervical intraepithelial neoplasia (CIN) was assessed. There were 212 patients with high-risk HPV infections with negative cytology included in the analysis. After a mean ± SD follow-up period of 48 ± 33 months, 65 (30.7%) and 26 (12.3%) patients had developed cytologic or histologic cervical dysplasia (low-grade squamous intraepithelial lesion [LSIL]/CIN1+) and high-grade cervical dysplasia (CIN2+), respectively. No patients had invasive cancer. No correlations were observed between type-specific HPV infections and LSIL/CIN1+ and CIN2+. HPV persistence correlated with both LSIL/CIN1+ (P<0.001) and CIN2+ (P<0.001) in univariate analyses; a 6-month increase in HPV persistence was associated with increased risk of developing LSIL/CIN1+ (P=0.010) and CIN2+ (P=0.012) in multivariate analyses. Regardless of cytology findings, patients diagnosed with high-risk HPV types should receive strict colposcopy follow-up, particularly with persistent HPV infections. Further prospective studies are needed to defined optimal surveillance strategies for these patients. © 2017 International Federation of Gynecology and Obstetrics.

Hair follicle nevus occurring in frontonasal dysplasia: an electron microscopic observation.

PubMed

Kuwahara, H; Lao, L M; Kiyohara, T; Kumakiri, M; Igawa, H

2001-06-01

We report a rare hair follicle nevus that occurred in a three-month-old Japanese boy with mild frontonasal dysplasia. It had been present since birth. Histologically, numerous tiny vellus hair follicles were found within the dermis. The constituent cells of these follicles showed the features of follicular germ cells under the electron microscope. The fibroblasts around the follicles were active and merged with the colloid substance. Many myofibroblasts were found in a collagenous stroma in the atrophic lesion of the frontonasal dysplasia.

The functional relationship between ectodermal and mesodermal segmentation in the crustacean, Parhyale hawaiensis.

PubMed

Hannibal, Roberta L; Price, Alivia L; Patel, Nipam H

2012-01-15

In arthropods, annelids and chordates, segmentation of the body axis encompasses both ectodermal and mesodermal derivatives. In vertebrates, trunk mesoderm segments autonomously and induces segmental arrangement of the ectoderm-derived nervous system. In contrast, in the arthropod Drosophila melanogaster, the ectoderm segments autonomously and mesoderm segmentation is at least partially dependent on the ectoderm. While segmentation has been proposed to be a feature of the common ancestor of vertebrates and arthropods, considering vertebrates and Drosophila alone, it is impossible to conclude whether the ancestral primary segmented tissue was the ectoderm or the mesoderm. Furthermore, much of Drosophila segmentation occurs before gastrulation and thus may not accurately represent the mechanisms of segmentation in all arthropods. To better understand the relationship between segmented germ layers in arthropods, we asked whether segmentation is an intrinsic property of the ectoderm and/or the mesoderm in the crustacean Parhyale hawaiensis by ablating either the ectoderm or the mesoderm and then assaying for segmentation in the remaining tissue layer. We found that the ectoderm segments autonomously. However, mesoderm segmentation requires at least a permissive signal from the ectoderm. Although mesodermal stem cells undergo normal rounds of division in the absence of ectoderm, they do not migrate properly in respect to migration direction and distance. In addition, their progeny neither divide nor express the mesoderm segmentation markers Ph-twist and Ph-Even-skipped. As segmentation is ectoderm-dependent in both Parhyale and holometabola insects, we hypothesize that segmentation is primarily a property of the ectoderm in pancrustacea. Copyright © 2011 Elsevier Inc. All rights reserved.

Non-neural ectoderm is really neural: evolution of developmental patterning mechanisms in the non-neural ectoderm of chordates and the problem of sensory cell homologies.

PubMed

Holland, Linda Z

2005-07-15

In chordates, the ectoderm is divided into the neuroectoderm and the so-called non-neural ectoderm. In spite of its name, however, the non-neural ectoderm contains numerous sensory cells. Therefore, the term "non-neural" ectoderm should be replaced by "general ectoderm." At least in amphioxus and tunicates and possibly in vertebrates as well, both the neuroectoderm and the general ectoderm are patterned anterior/posteriorly by mechanisms involving retinoic acid and Hox genes. In amphioxus and tunicates the ectodermal sensory cells, which have a wide range of ciliary and microvillar configurations, are mostly primary neurons sending axons to the CNS, although a minority lack axons. In contrast, vertebrate mechanosensory cells, called hair cells, are all secondary neurons that lack axons and have a characteristic eccentric cilium adjacent to a group of microvilli of graded lengths. It has been highly controversial whether the ectodermal sensory cells in the oral siphons of adult tunicates are homologous to vertebrate hair cells. In some species of tunicates, these cells appear to be secondary neurons, and microvillar and ciliary configurations of some of these cells approach those of vertebrate hair cells. However, none of the tunicate cells has all the characteristics of a hair cell, and there is a high degree of variation among ectodermal sensory cells within and between different species. Thus, similarities between the ectodermal sensory cells of any one species of tunicate and craniate hair cells may well represent convergent evolution rather than homology. Copyright 2005 Wiley-Liss, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calderon-Garciduenas, L.; Roy-Ocotla, G.

Southwest metropolitan Mexico City (SWMMC) inhabitants have been exposed several hours per day for the last 6 years to photochemical smog, ozone being the most important oxidant pollutant. Subjects exposed to the SWMMC atmosphere develop several histopathological changes in their nasal mucosa: dysplasia is the most significant, affecting 78.72% of adult individuals within 60 or more days of residence in SWMMC. This study was originally designed to explore whether chemical intervention could modify nasal dysplasia, as determined by nasal cytology, in a defined adult population. In a placebo-controlled, randomized, double-blind trial, 177 healthy male subjects were divided into 5 groupsmore » to whom 5000 IU of vitamin A, 100 IU of vitamin E, a combination of vitamins A and E (5000 IU + 100 IU), 16 mg of beta-carotene, or placebo were administered daily for 4 months. Sixteen clinical and cytological variables were monitored. No effect on dysplasia was seen at the end of the 4-month trial; however, an apparent reversibility as well as progression of the dysplastic nasal lesions and high correlation coefficients between dysplasia and nasal cytology of polymorphonuclear leukocytes (PMNs; 0.85), squamous metaplasia (SM; 0.50), and nasal mucosa atrophy (NMA; 0.41) were found. A mathematical theoretical nasal dysplasia (tD) predictor equation for SWMMC adult male inhabitants is proposed (tD = 0.85 delta PMNs + 0.50 delta SM + 0.41 delta NMA + 0.98), in which PMNs are the best single dysplasia predictor, and all variables are independent.« less

Quality-of-Life Outcomes of Patients following Patellofemoral Stabilization Surgery: The Influence of Trochlear Dysplasia.

PubMed

Hiemstra, Laurie Anne; Kerslake, Sarah; Lafave, Mark R

2017-11-01

Trochlear dysplasia is a well-described risk factor for recurrent patellofemoral instability. Despite its clear association with the incidence of patellofemoral instability, it is unclear whether the presence of high-grade trochlear dysplasia influences clinical outcome after patellofemoral stabilization. The purpose of this study was to assess whether trochlear dysplasia influenced patient-reported, disease-specific outcomes in surgically treated patellar instability patients, when risk factors were addressed in accordance with the à la carte surgical approach to the treatment of patellofemoral instability. The study design is of a case series. A total of 318 patellar stabilization procedures were performed during the study period. Of these procedures, 260 had adequate lateral radiographs and complete Banff Patellar Instability Instrument (BPII) scores available for assessment. A Pearson r correlation was calculated between four characteristics of trochlear dysplasia, the BPII total and the BPII symptoms, and physical complaints scores, a mean of 24 months following patellofemoral stabilization. Independent t -tests were performed between stratified trochlear dysplasia groups (no/low grade and high grade) and all BPII measures. There was a statistically significant correlation between measures of trochlear dysplasia and quality-of-life physical symptoms scores, an average of 2 years following patellofemoral stabilization surgery. The BPII symptoms and physical complaints domain score, as well as the individual weakness and stiffness questions, correlated with the classification of trochlear dysplasia as well as the presence of a trochlear bump ( p  < 0.05). Independent t -tests demonstrated statistically significant differences between the no/low-grade and high-grade dysplasia groups for the BPII stiffness ( p  = 0.002), BPII weakness ( p  = 0.05) and BPII symptom, and physical complaints values ( p  = 0.04). Two additional measures-the 24-month postoperative total BPII score ( p  = 0.11) and BPII pain score ( p  = 0.07)-demonstrated trends toward statistical significance. This research has established a statistically significant correlation between trochlear dysplasia and disease-specific quality-of-life outcomes following patellofemoral stabilization surgery. There was a significant correlation between patient-reported physical symptoms after surgery and high-grade trochlear dysplasia. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neonatal cholestasis and focal medullary dysplasia of the kidneys in a case of microcephalic osteodysplastic primordial dwarfism.

PubMed Central

Berger, A; Haschke, N; Kohlhauser, C; Amman, G; Unterberger, U; Weninger, M

1998-01-01

We report on a male infant who presented with intrauterine growth retardation, severe postnatal failure to thrive, microcephaly, facial dysmorphism, and skeletal dysplasia. The clinical and radiological findings are consistent with former descriptions of microcephalic osteodysplastic primordial dwarfism (MOPD) type I/III. In addition to previously published features, multiple fractures of the long bones, severe neonatal cholestasis, and histological dysplasia of the kidneys were found. The boy died at the age of 8 months. The new finding of focal renal medullary dysplasia further supports the hypothesis of a basic defect in tissue differentiation in the pathogenesis of this rare condition. Images PMID:9475098

Imaging diagnosis--temporomandibular joint dysplasia in a Basset Hound.

PubMed

Lerer, Assaf; Chalmers, Heather J; Moens, Noel M M; Mackenzie, Shawn D; Kry, Kristin

2014-01-01

A 5-month-old intact male Basset Hound presented for evaluation of pain and crepitation during manipulation of the temporomandibular joint, worse on the right side. A computed tomography (CT) scan of the head was performed. The CT images demonstrated the osseous features of temporomandibular joint dysplasia and facilitated a 3D reconstruction, which allowed better visualization of the dysplastic features. The patient responded to conservative management with a tape muzzle with no recurrence reported by the owner 6 months after presentation. © 2013 American College of Veterinary Radiology.

Transcriptional Profiling of Ectoderm Specification to Keratinocyte Fate in Human Embryonic Stem Cells

PubMed Central

Tadeu, Ana Mafalda Baptista; Lin, Samantha; Hou, Lin; Chung, Lisa; Zhong, Mei; Zhao, Hongyu; Horsley, Valerie

2015-01-01

In recent years, several studies have shed light into the processes that regulate epidermal specification and homeostasis. We previously showed that a broad-spectrum γ–secretase inhibitor DAPT promoted early keratinocyte specification in human embryonic stem cells triggered to undergo ectoderm specification. Here, we show that DAPT accelerates human embryonic stem cell differentiation and induces expression of the ectoderm protein AP2. Furthermore, we utilize RNA sequencing to identify several candidate regulators of ectoderm specification including those involved in epithelial and epidermal development in human embryonic stem cells. Genes associated with transcriptional regulation and growth factor activity are significantly enriched upon DAPT treatment during specification of human embryonic stem cells to the ectoderm lineage. The human ectoderm cell signature identified in this study contains several genes expressed in ectodermal and epithelial tissues. Importantly, these genes are also associated with skin disorders and ectodermal defects, providing a platform for understanding the biology of human epidermal keratinocyte development under diseased and homeostatic conditions. PMID:25849374

A rare case of malignant pediatric ectomesenchymoma arising from the cerebrum.

PubMed

Kun, Yao; Duan, Zejun; Mei, Xi; Xu, Ying; Li, Jiuzhou; Li, Shouwei; Qi, Xueling

2015-01-01

Malignant ectomesenchymoma is a rare tumor that contains both ectodermal and mesenchymal elements. So far, only 7 patients with a manifestation in the cerebrum (with confirmed clinicopathological data) have been reported. A 4-year-old girl was present at our hospital with a 3-week history of intermittent sudden dizzy with no apparent cause. MRI showed an irregular enhanced lesion in the left frontal-parietal lobe and lateral ventricle with peripheral gadolinium-enhancement with a significant surrounding edema. Total removal of the tumor was performed. Histological examination of the resected tumor revealed a mixed astrocytoma and anaplastic ependymoma component with undifferentiated mesenchymal spindle cell component. Generally speaking, the main malignant part in most cases of malignant ectomesenchymoma (MEM) is the mesenchymal component. In the present case, the malignant component was both in the mesenchymal and ectodermal part. In particular, the mesenchymal part was mainly composed of spindle cells, and the ectodermal part primarily consisted of gliomatous component and anaplastic ependymoma component. The patient was then treated with chemotherapy and as regard to the prognosis, there was no evidence of tumor recurrence at the 5 months' follow-up. The long term follow-up is still in progress.

Nasal cytology in southwest metropolitan Mexico City inhabitants: a pilot intervention study.

PubMed Central

Calderon-Garcidueñas, L; Roy-Ocotla, G

1993-01-01

Southwest metropolitan Mexico City (SWMMC) inhabitants have been exposed several hours per day for the last 6 years to photochemical smog, ozone being the most important oxidant pollutant. Subjects exposed to the SWMMC atmosphere develop several histopathological changes in their nasal mucosa: dysplasia is the most significant, affecting 78.72% of adult individuals within 60 or more days of residence in SWMMC. This study was originally designed to explore whether chemical intervention could modify nasal dysplasia, as determined by nasal cytology, in a defined adult population. In a placebo-controlled, randomized, double-blind trial, 177 healthy male subjects were divided into 5 groups to whom 5000 IU of vitamin A, 100 IU of vitamin E, a combination of vitamins A and E (5000 IU + 100 IU), 16 mg of beta-carotene, or placebo were administered daily for 4 months. Sixteen clinical and cytological variables were monitored. No effect on dysplasia was seen at the end of the 4-month trial; however, an apparent reversibility as well as progression of the dysplastic nasal lesions and high correlation coefficients between dysplasia and nasal cytology of polymorphonuclear leukocytes (PMNs; 0.85), squamous metaplasia (SM; 0.50), and nasal mucosa atrophy (NMA; 0.41) were found. A mathematical theoretical nasal dysplasia (tD) predictor equation for SWMMC adult male inhabitants is proposed (tD = 0.85 delta PMNs + 0.50 delta SM + 0.41 delta NMA + 0.98), in which PMNs are the best single dysplasia predictor, and all variables are independent.(ABSTRACT TRUNCATED AT 250 WORDS) Images p138-a Figure 1. Figure 2. Figure 3. Figure 4. PMID:8354200

IQ Measurement in Children with Skeletal Dysplasia.

ERIC Educational Resources Information Center

Rogers, John G.; And Others

1979-01-01

IQ studies on 68 children (5 months-15 years) with skeletal dysplasia (dwarfism) were reviewed to provide counseling to parents of newborn affected children. Results of the study show that this population performs intellectually in the same range as other children. Journal availability: see EC 115 198. (PHR)

Disease course and management strategy of pouch neoplasia in patients with underlying inflammatory bowel diseases.

PubMed

Wu, Xian-Rui; Remzi, Feza H; Liu, Xiu-Li; Lian, Lei; Stocchi, Luca; Ashburn, Jean; Shen, Bo

2014-11-01

To evaluate the disease course and management strategy for pouch neoplasia. Patients undergoing ileal pouch surgery for underlying ulcerative colitis who developed low-grade dysplasia (LGD), high-grade dysplasia, or adenocarcinoma in the pouch were identified. All eligible 44 patients were evaluated. Of the 22 patients with initial diagnosis of pouch LGD, 6 (27.3%) had persistence or progression after a median follow-up of 9.5 (4.1-17.6) years. Family history of colorectal cancer was shown to be a risk factor associated with persistence or progression of LGD (P = 0.03). Of the 12 patients with pouch high-grade dysplasia, 5 (41.7%) had a history of (n = 2, 16.7%) or synchronous (n = 4, 33.3%) pouch LGD. Pouch high-grade dysplasia either persisted or progressed in 3 patients (25.0%) after the initial management, during a median time interval of 5.4 (2.2-9.2) years. Of the 14 patients with pouch adenocarcinoma, 12 (85.7%) had a history of (n = 2, 14.3%) or synchronous dysplasia (n = 12, 85.7%). After a median follow-up of 2.1 (0.6-5.2) years, 6 patients with pouch cancer (42.9%) died. Comparison of patients with a final diagnosis of pouch adenocarcinoma (14, 32.6%), and those with dysplasia (29, 67.4%) showed that patients with adenocarcinoma were older (P = 0.04) and had a longer duration from IBD diagnosis or pouch construction to the detection of pouch neoplasia (P = 0.007 and P = 0.0013). The risk for progression of pouch dysplasia can be stratified. The presence of family history of colorectal cancer seemed to increase the risk for persistence or progression for patients with pouch LGD. The prognosis for pouch adenocarcinoma was poor.

Associated aneurysmal bone cyst and cemento-osseous dysplasia: a case report and review of the literature.

PubMed

Jacomacci, Willian Pecin; Veloso Perdigão, João Paulo; Veltrini, Vanessa Cristina; Farah, Gustavo Jacobucci; Tolentino, Elen Souza; Vessoni Iwaki, Lilian Cristina; Iwaki Filho, Liogi

2017-01-01

The purpose of this case report is to describe a previously unpublished association between focal cemento-osseous dysplasia (FCOD) and an aneurysmal bone cyst (ABC) and review the literature with regard to associated benign fibro-osseous lesions and cysts. A 41-year-old woman without a history of trauma presented with asymptomatic swelling in the right side of the mandible. Radiographs of the region revealed a unilocular radiolucent area with radiopaque foci. After aspiration of the lesion was positive for serosanguineous fluid, complete excision of the lesion was performed. Microscopic examination revealed a hybrid ABC and FCOD. The 12-month follow-up showed significant bone repair and no signs of recurrence. A review of the English-language literature from 1980 to 2012 revealed 1 retrospective study, 4 case series, and 18 single-case reports on the topic of cemento-osseous dysplasias, fibro-osseous lesions, and aneurysmal bone cysts. Of 59 cases, none reported an association between an ABC and FCOD. Although fibro-osseous lesions do not require intervention, surgical excision is recommended when they are associated with cysts. This case, in which an ABC and FCOD were associated, reinforces the need for a careful diagnostic process in radiographically mixed lesions that respond positively to aspiration biopsy.

Substitution of aspartate for glycine 103 of the type II collagen triple helical domain: Identification of the minimal mutation which can produce Kniest dysplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilkin, D.J.; Rimoin, D.L.; Cohn, D.H.

1994-09-01

Kniest dysplasia is an autosomal dominant chondrodysplasia which results from mutations in the gene for type II collagen, COL2A1. Characteristics of the disorder include a short trunk and extremities, mid-face hypoplasia, cleft palate, myopia, retinal detachment, and hearing loss. Recently, deletions of all or part of exon 12 have been identified in individuals with Kniest dysplasia, suggesting that mutations within this region of the protein may primarily result in the Kniest dysplasia phenotype. We used SSCP to analyze an amplified genomic DNA fragment containing exon 12 from 7 individuals with Kniest dysplasia. An abnormality was identified in one patient. DNAmore » sequence analysis demonstrated that the patient was heterozygous for a G to A transition that implied substitution of glycine{sup 103} of the triple helix by aspartate. The mutation was not observed in DNA from either of the proband`s parents. Protein microsequencing demonstrated expression of the abnormal allele in the proband`s cartilage, indicating that the Kniest phenotype results from the presence of abnormal type II collagen molecules in the extracellular matrix. These data demonstrate the minimal mutation which can produce Kniest dysplasia and further support the hypothesis that alteration of a domain which includes the region encoded by exon 12 in the type II collagen protein leads to this disorder. Experiments designed to identify specific effects that mutations in this region have on intermolecular interactions among abnormal type II collagen molecules and other components of the cartilage extracellular matrix may clarify the underlying pathophysiology of Kniest dysplasia.« less

Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a for cancer of the oral cavity.

PubMed

Rigual, Nestor; Shafirstein, Gal; Cooper, Michele T; Baumann, Heinz; Bellnier, David A; Sunar, Ulas; Tracy, Erin C; Rohrbach, Daniel J; Wilding, Gregory; Tan, Wei; Sullivan, Maureen; Merzianu, Mihai; Henderson, Barbara W

2013-12-01

The primary objective was to evaluate safety of 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Patients with histologically proven oral dysplasia, carcinoma in situ, or early-stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies used an HPPH dose of 4 mg/m(2) and light doses from 50 to 140 J/cm(2). Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of STAT3 were assessed as potential indicators of PDT effective reaction. Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and carcinoma in situ and 82% for squamous cell carcinomas (SCC) lesions at 140 J/cm(2). The responses in the carcinoma in situ/dysplasia cohort are not durable. The PDT-induced STAT3 cross-links is significantly higher (P = 0.0033) in SCC than in carcinoma in situ/dysplasia for all light doses. HPPH-PDT is safe for the treatment of carcinoma in situ/dysplasia and early-stage cancer of the oral cavity. Early-stage oral HNSCC seems to respond better to HPPH-PDT in comparison with premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT-mediated photoreaction. ©2013 AACR.

Ectodermal Wnt6 is an early negative regulator of limb chondrogenesis in the chicken embryo

PubMed Central

2010-01-01

Background Pattern formation of the limb skeleton is regulated by a complex interplay of signaling centers located in the ectodermal sheath and mesenchymal core of the limb anlagen, which results, in the forelimb, in the coordinate array of humerus, radius, ulna, carpals, metacarpals and digits. Much less understood is why skeletal elements form only in the central mesenchyme of the limb, whereas muscle anlagen develop in the peripheral mesenchyme ensheathing the chondrogenic center. Classical studies have suggested a role of the limb ectoderm as a negative regulator of limb chondrogenesis. Results In this paper, we investigated the molecular nature of the inhibitory influence of the ectoderm on limb chondrogenesis in the avian embryo in vivo. We show that ectoderm ablation in the early limb bud leads to increased and ectopic expression of early chondrogenic marker genes like Sox9 and Collagen II, indicating that the limb ectoderm inhibits limb chondrogenesis at an early stage of the chondrogenic cascade. To investigate the molecular nature of the inhibitory influence of the ectoderm, we ectopically expressed Wnt6, which is presently the only known Wnt expressed throughout the avian limb ectoderm, and found that Wnt6 overexpression leads to reduced expression of the early chondrogenic marker genes Sox9 and Collagen II. Conclusion Our results suggest that the inhibitory influence of the ectoderm on limb chondrogenesis acts on an early stage of chondrogenesis upsteam of Sox9 and Collagen II. We identify Wnt6 as a candidate mediator of ectodermal chondrogenic inhibition in vivo. We propose a model of Wnt-mediated centripetal patterning of the limb by the surface ectoderm. PMID:20334703

Correlation of serum KL-6 and CC16 levels with neurodevelopmental outcome in premature infants at 12 months corrected age

PubMed Central

Zhang, Zhiqun; Lu, Hui; Zhu, Yunxia; Xiang, Junhua; Huang, Xianmei

2015-01-01

The aim of this study was to evaluate KL-6 and CC16 levels and their correlation with neurodevelopmental outcome among very low birth weight pre-term infants at 12 months corrected age. This prospective cohort study was performed from 2011 to 2013 by enrolling pre-term neonates of gestational age ≤ 32 weeks and birth weight ≤ 1500 g. Serum KL-6 and CC16 levels were determined 7 days after birth and their correlation with neurodevelopment was evaluated using Gesell Mental Developmental Scales. Of the 86 eligible pre-term infants, 63 completed follow-up, of which 15 had bronchopulmonary dysplasia. At 12 months corrected age, 49 infants had favorable outcomes and 14 infants had poor neurodevelopmental outcome. KL-6 levels were higher and CC16 levels were lower in infants with poor neurodevelopmental outcome compared with those infants who had favourable neurodevelopmental outcome. Serum KL-6 levels less than 90.0 ng/ml and CC16 levels greater than 320.0 pg/ml at 7 days of life were found to be predictive of a favourable outcome at 12 months corrected age. These biological markers could predict neurodevelopmental outcome at 12 months corrected age in very low birth weight premature infants, and help the clinician plan early therapeutic interventions to minimize or avoid poor neurodevelopmental outcome. PMID:25631862

The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men.

PubMed

Burgos, J; Curran, A; Landolfi, S; Navarro, J; Tallada, N; Guelar, A; Crespo, M; Ocaña, I; Ribera, E; Falcó, V

2016-08-01

Electrocautery is one of the main treatment options for high-grade anal intraepithelial neoplasia (HGAIN). However, data regarding its efficacy are scarce. The aim of the study was to evaluate the effectiveness of electrocautery for the treatment of HGAIN. An observational study of HIV-infected men who have sex with men (MSM) who underwent screening for anal dysplasia was carried out. The on-treatment effectiveness of electrocautery was evaluated (according to biopsy findings measured 6-8 weeks after treatment) in patients with HGAIN. A complete response was defined as resolution of anal intraepithelial neoplasia (AIN), a partial response as regression to low-grade AIN and recurrence as biopsy-proven HGAIN during follow-up. From May 2009 to November 2014, 21.9% (126 of 576) of patients screened were found to have HGAIN. Electrocautery effectiveness was evaluated in 83 patients. A complete response was observed in 27 patients [32.5%; 95% confidence interval (CI) 23.4-53.2%], a partial response in 28 patients (33.7%; 95% CI 24.5-44.4%) and persistence in 28 patients (33.7%; 95% CI 24.5-44.4%). The patients with the most successful results (81.8%) required two to four sessions of electrocautery. After a mean follow-up of 12.1 months, 14 of 55 patients with a response (25.4%; 95% CI 15.8-38.3%) developed recurrent HGAIN within a mean time of 29.9 months (95% CI 22-37.7 months). No patient progressed to invasive cancer during the study or developed serious adverse events after treatment. No factors associated with poor response or recurrences were observed. Although electrocautery is the standard treatment for anal dysplasia, almost 50% of patients with HGAIN in our study did not respond or relapsed. New treatment strategies are necessary to optimize the management of anal dysplasia. © 2015 British HIV Association.

EEC- and ADULT-associated TP63 mutations exhibit functional heterogeneity toward P63 responsive sequences.

PubMed

Monti, Paola; Russo, Debora; Bocciardi, Renata; Foggetti, Giorgia; Menichini, Paola; Divizia, Maria T; Lerone, Margherita; Graziano, Claudio; Wischmeijer, Anita; Viadiu, Hector; Ravazzolo, Roberto; Inga, Alberto; Fronza, Gilberto

2013-06-01

TP63 germ-line mutations are responsible for a group of human ectodermal dysplasia syndromes, underlining the key role of P63 in the development of ectoderm-derived tissues. Here, we report the identification of two TP63 alleles, G134V (p.Gly173Val) and insR155 (p.Thr193_Tyr194insArg), associated to ADULT and EEC syndromes, respectively. These alleles, along with previously identified G134D (p.Gly173Asp) and R204W (p.Arg243Trp), were functionally characterized in yeast, studied in a mammalian cell line and modeled based on the crystal structure of the P63 DNA-binding domain. Although the p.Arg243Trp mutant showed both complete loss of transactivation function and ability to interfere over wild-type P63, the impact of p.Gly173Asp, p.Gly173Val, and p.Thr193_Tyr194insArg varied depending on the response element (RE) tested. Interestingly, p.Gly173Asp and p.Gly173Val mutants were characterized by a severe defect in transactivation along with interfering ability on two DN-P63α-specific REs derived from genes closely related to the clinical manifestations of the TP63-associated syndromes, namely PERP and COL18A1. The modeling of the mutations supported the distinct functional effect of each mutant. The present results highlight the importance of integrating different functional endpoints that take in account the features of P63 proteins' target sequences to examine the impact of TP63 mutations and the associated clinical variability. © 2013 Wiley Periodicals, Inc.

Clinical Outcomes among Diagnostic Subgroups of Infants with Severe Bronchopulmonary Dysplasia through 2 Years of Age.

PubMed

Akangire, Gangaram; Manimtim, Winston; Nyp, Michael F; Noel-MacDonnell, Janelle; Kays, Allyssa N; Truog, William E; Taylor, Jane B

2018-05-31

 This article aimed to identify readmission risk factors through 2 years of life for infants with severe bronchopulmonary dysplasia (BPD) who do not require tracheostomy and ventilatory support after neonatal intensive care unit (NICU) discharge. It also aimed to identify if clinical differences exist between the subcategories of severe BPD.  A retrospective chart review was performed on 182 infants with severe BPD born between 2010 and 2015. A total of 130 infants met the inclusion criteria and were stratified into three groups based on their respiratory status at 36 weeks of gestational age: group A-oxygen (O 2 ), group B-assisted ventilation (AV), group C-both O 2 and AV. NICU clinical risk factors for readmission were assessed at set time points (6/12/18/24 months). Reasons for readmission were assessed for the entire cohort and severe BPD subgroups.  An NICU diagnosis of neurologic abnormality, necrotizing enterocolitis, invasive NICU infection, dysphagia, and O 2 at NICU discharge differed between the three subgroups of severe BPD. The most common cause of readmission was viral respiratory tract infection. Inhaled steroid use remained stable over time, while oxygen use and diuretic use declined over time. Risk factors for readmission in the entire cohort included g-tube, O 2 use, and diuretic use at 12 months. There was no significant difference in readmission rates between the three BPD subgroups. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Split-Hand/Split-Foot Malformation Is Caused by Mutations in the p63 Gene on 3q27

PubMed Central

Ianakiev, Peter; Kilpatrick, Michael W.; Toudjarska, Iva; Basel, Donald; Beighton, Peter; Tsipouras, Petros

2000-01-01

Split-hand/split-foot malformation (SHFM), a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals, is phenotypically analogous to the naturally occurring murine Dactylaplasia mutant (Dac). Results of recent studies have shown that, in heterozygous Dac embryos, the central segment of the apical ectodermal ridge (AER) degenerates, leaving the anterior and posterior segments intact; this finding suggests that localized failure of ridge maintenance activity is the fundamental developmental defect in Dac and, by inference, in SHFM. Results of gene-targeting studies have demonstrated that p63, a homologue of the cell-cycle regulator TP53, plays a critically important role in regulation of the formation and differentiation of the AER. Two missense mutations, 724A→G, which predicts amino acid substitution K194E, and 982T→C, which predicts amino acid substitution R280C, were identified in exons 5 and 7, respectively, of the p63 gene in two families with SHFM. Two additional mutations (279R→H and 304R→Q) were identified in families with EEC (ectrodactyly, ectodermal dysplasia, and facial cleft) syndrome. All four mutations are found in exons that fall within the DNA-binding domain of p63. The two amino acids mutated in the families with SHFM appear to be primarily involved in maintenance of the overall structure of the domain, in contrast to the p63 mutations responsible for EEC syndrome, which reside in amino acid residues that directly interact with the DNA. PMID:10839977

Co-occurence of florid cemento-osseous dysplasia and simple bone cyst: a case report.

PubMed

Rao, Kumuda Arvind; Shetty, Shishir Ram; Babu, Subhas G; Castelino, Renita Lorina

2011-01-01

The purpose of this report is to present a rare case of co-occurrence of florid cemento-osseous dysplasia with simple bone cyst in a middle aged Asian woman. Most of the reported cases are isolated cases of simple bone cyst or florid cemento-osseous dysplasia, but co-occurrence of these two entities is extremely rare. The authors report a 41 year old female patient with co-occurrence of mandibular florid cemento-osseous dysplasia with simple bone cyst. A thorough clinical and radiological examination was carried out. It was diagnosed mandibular cyst with possible co-occurrence of florid cemento-osseous dysplasia. Surgical exploration of the multilocular lesion was applied. Since, the patient was symptomatic at the time of presentation utmost caution was taken during the surgical procedure as florid cemento-osseous dysplasia is associated with hypo-vascularity of the affected bone. Based on histopathological, as well as supporting clinico-radiological findings a confirmative diagnosis of florid cemento-osseous dysplasia co-occurring with simple bone cyst was made. Patient was followed-up for a period of six months and was reported to be asymptomatic. Timely diagnosis and well planned treatment is important to obtain a good prognosis when a rare co-occurrence of two or more bone lesions affects the jaws.

Decreased phosphatidyl choline content in bronchoalveolar lavage fluids of children with bronchopulmonary dysplasia: a preliminary investigation.

PubMed

Clement, A; Masliah, J; Housset, B; Just, J; Garcia, J; Grimfeld, A; Tournier, G

1987-01-01

Bronchoalveolar lavage (BAL) was performed on 12 infants who had recovered from neonatal acute respiratory failure and on 12 patients with bronchopulmonary dysplasia (BPD) in order to evaluate the concentration of phosphatidyl choline (PC) in BAL fluid. These two groups were similar at birth (mean birth weight: 1,980 and 1,750 g, respectively; mean gestational age: 33.4 and 32.1 weeks respectively). Mechanical ventilation based on oxygen requirement lasted longer in the group with BPD. BAL was performed at the end of the first year of life (at 8.5 and 10.3 months, respectively) and the results were compared to control values (from infants of the same age without neonatal disease). Whereas the protein concentration in BAL fluid was similar in the two groups, a dramatic decrease of the BAL PC was found in BPD: The mean values of BAL-PC over protein ratio were 0.9 in the group without pulmonary sequelae and 0.3 in the group with BPD. These preliminary results suggest an impairment of the pulmonary surfactant metabolism in this chronic lung disease following neonatal acute respiratory failure.

The origin and evolution of the ectodermal placodes

PubMed Central

Graham, Anthony; Shimeld, Sebastian M

2013-01-01

Many of the features that distinguish the vertebrates from other chordates are found in the head. Prominent amongst these differences are the paired sense organs and associated cranial ganglia. Significantly, these structures are derived developmentally from the ectodermal placodes. It has therefore been proposed that the emergence of the ectodermal placodes was concomitant with and central to the evolution of the vertebrates. More recent studies, however, indicate forerunners of the ectodermal placodes can be readily identified outside the vertebrates, particularly in urochordates. Thus the evolutionary history of the ectodermal placodes is deeper and more complex than was previously appreciated with the full repertoire of vertebrate ectodermal placodes, and their derivatives, being assembled over a protracted period rather than arising collectively with the vertebrates. PMID:22512454

ECTODERMAL WNT/β-CATENIN SIGNALING SHAPES THE MOUSE FACE

PubMed Central

Reid, Bethany S.; Yang, Hui; Melvin, Vida Senkus; Taketo, Makoto M.; Williams, Trevor

2010-01-01

The canonical Wnt/β-catenin pathway is an essential component of multiple developmental processes. To investigate the role of this pathway in the ectoderm during facial morphogenesis, we generated conditional β-catenin mouse mutants using a novel ectoderm-specific Cre recombinase transgenic line. Our results demonstrate that ablating or stabilizing β-catenin in the embryonic ectoderm causes dramatic changes in facial morphology. There are accompanying alterations in the expression of Fgf8 and Shh, key molecules that establish a signaling center critical for facial patterning, the frontonasal ectodermal zone (FEZ). These data indicate that Wnt/β-catenin signaling within the ectoderm is critical for facial development and further suggest that this pathway is an important mechanism for generating the diverse facial shapes of vertebrates during evolution. PMID:21087601

The evolutionary history of vertebrate cranial placodes II. Evolution of ectodermal patterning.

PubMed

Schlosser, Gerhard; Patthey, Cedric; Shimeld, Sebastian M

2014-05-01

Cranial placodes are evolutionary innovations of vertebrates. However, they most likely evolved by redeployment, rewiring and diversification of preexisting cell types and patterning mechanisms. In the second part of this review we compare vertebrates with other animal groups to elucidate the evolutionary history of ectodermal patterning. We show that several transcription factors have ancient bilaterian roles in dorsoventral and anteroposterior regionalisation of the ectoderm. Evidence from amphioxus suggests that ancestral chordates then concentrated neurosecretory cells in the anteriormost non-neural ectoderm. This anterior proto-placodal domain subsequently gave rise to the oral siphon primordia in tunicates (with neurosecretory cells being lost) and anterior (adenohypophyseal, olfactory, and lens) placodes of vertebrates. Likewise, tunicate atrial siphon primordia and posterior (otic, lateral line, and epibranchial) placodes of vertebrates probably evolved from a posterior proto-placodal region in the tunicate-vertebrate ancestor. Since both siphon primordia in tunicates give rise to sparse populations of sensory cells, both proto-placodal domains probably also gave rise to some sensory receptors in the tunicate-vertebrate ancestor. However, proper cranial placodes, which give rise to high density arrays of specialised sensory receptors and neurons, evolved from these domains only in the vertebrate lineage. We propose that this may have involved rewiring of the regulatory network upstream and downstream of Six1/2 and Six4/5 transcription factors and their Eya family cofactors. These proteins, which play ancient roles in neuronal differentiation were first recruited to the dorsal non-neural ectoderm in the tunicate-vertebrate ancestor but subsequently probably acquired new target genes in the vertebrate lineage, allowing them to adopt new functions in regulating proliferation and patterning of neuronal progenitors. Copyright © 2014 Elsevier Inc. All rights reserved.

Anterior segment dysgenesis correlation with epithelial-mesenchymal transition in Smad4 knockout mice.

PubMed

Li, Jing; Qin, Yu; Zhao, Fang-Kun; Wu, Di; He, Xue-Fei; Liu, Jia; Zhao, Jiang-Yue; Zhang, Jin-Song

2016-01-01

To explore the molecular mechanisms in lens development and the pathogenesis of Peters anomaly in Smad4 defective mice. Le-Cre transgenic mouse line was employed to inactivate Smad4 in the surface ectoderm selectively. Pathological techniques were used to reveal the morphological changes of the anterior segment in Smad4 defective eye. Immunohistochemical staining was employed to observe the expression of E-cadherin, N-cadherin and α-SMA in anterior segment of Smad4 defective mice and control mice at embryonic (E) day 16.5. Real-time quantitative polymerase chain reaction (qPCR) was performed to detect the expression of Snail, Zeb1, Zeb2 and Twist2 in lens of Smad4 defective mice and control mice at E16.5. Statistical evaluations were performed using the unpaired Student's t-test (two-tailed) by SPSS 11.0 software. Conditional deletion of Smad4 on eye surface ectoderm resulted in corneal dysplasia, iridocorneal angle closure, corneolenticular adhesions and cataract resembling Peters anomaly. Loss of Smad4 function inhibited E-cadherin expression in the lens epithelium cells and corneal epithelium cells in Smad4 defective eye. Expression of N-cadherin was up-regulated in corneal epithelium and corneal stroma. Both E-cadherin and N-cadherin were down-regulated at the future trabecular meshwork region in mutant eye. The qPCR results showed that the expression of Twist2 was increased significantly in the mutant lens (P<0.01). Smad4 is essential to eye development and likely a candidate pathogenic gene to Peters anomaly by regulating epithelial-mesenchymal transition. Twist2 can be regulated by Smad4 and plays an essential role in lens development.

Successful implant placement in a Case of Florid Cemento-osseous Dysplasia: a case report and literature review.

PubMed

Esfahanizadeh, Nasrin; Yousefi, Hila

2018-02-06

Florid cemento-osseus dysplasia (FCOD) has been described as a reactive process in which normal bone is replaced by fibrous connective tissues and cementum-like materials. Radiographically it appears as dense, lobulated masses, often occurring bilaterally with symmetric involvement. In this case report a successful implant placement has been reported in a 62-year-old Caucasian woman with a chief complaint of mandibular partial edentulous. Radiographic images showed the bilateral radio-opaque lesions in edentulous regions of mandible, and mandibular anterior teeth alike. All mandibular teeth were vital and no root resorption was detected. The findings of X-ray images were attributable to FCOD. A highly conservative step-by-step two-stage implant surgery was performed. After 6 months the implants loaded with fixed prosthesis. 2, 4,6,12 and 18 months after the surgery radiographic images were taken, which revealed an optimal functional rehabilitation and complete integration of implants. This report confirms that treating the edentulous area near the FCOD lesions could be planned, if conservative and step-by-step implant placement been considered. To the best of our knowledge, a case of FCOD with successful implant placement has not been reported previously. More studies in more patients are needed to confirm results of such a therapeutic modality.

[Effect of parents' occupational and life environment exposure during six months before pregnancy on executive function of preschool children].

PubMed

Ni, Lingling; Shao, Ting; Tao, Huihui; Sun, Yanli; Yan, Shuangqin; Gu, Chunli; Cao, Hui; Huang, Kun; Tao, Fangbiao; Tong, Shilu

2016-02-01

To examine the effect of parents' occupational and life exposure during six months before pregnancy on executive function of preschool children. Pregnant women involved in the study came from the Ma'anshan Birth Cohort Study,a part of the China-Anhui Birth Cohort Study. Between October 2008 and October 2010, pregnant women who accepted pregnancy care in four municipal medical and health institutions in Ma'anshan city were recruited as study objects. A total of 5,084 pregnant women and 4,669 singleton live births entered in this cohort. Between April 2014 and April 2015, a total of 3,803 pre-school children were followed up. Finally, except 32 preschool children did not have EF evaluation result, there were 3,771 children included in this study. By using self-designed " Maternal health handbook", we researched parents' general demographic characteristics, and life and occupational exposure during six months before pregnancy. To research preschool children's executive function, we used the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Univariate and multivariate statistical method was used to analyze the association of parents' life and occupational exposure during six months before pregnancy and preschool children's EF. 3,771 preschool children's detected rate of inhibitory self-control index (ISCI), flexibility index (FI), emergent metacognition index (EMI) and global executive composite (GEC) dysplasia were 4.8% (182), 2.3% (88), 16.5% (623) and 8.6% (324) respectively. During six months before pregnancy, children whose parents were lived in a noise environment (OR=1.86, 95% CI: 1.36-2.54), whose maternal were exposed to pesticides were the risk of ISCI dysplasia(OR=3.60, 95% CI: 1.45-8.95). During six months before pregnancy, children whose maternal were exposed to pesticides (OR=6.72, 95% CI: 2.50-18.07) and whose father were exposed to occupational lead (OR=2.10, 95% CI: 1.25-3.54) were the risk of FI dysplasia. During six months before pregnancy, children whose parents were lived in a noise environment (OR=1.42, 95%CI: 1.18-1.71) and whose father were exposed to occupational lead (OR=1.30, 95%CI: 1.02-1.65) were the risk of EMI dysplasia. During six months before pregnancy, children whose parents were lived in a noise environment (OR=1.58, 95% CI: 1.24-2.01) and whose maternal were exposed to pesticides (OR=2.39, 95% CI: 1.02-5.58) were the risk of GEC dysplasia. The development of executive function is worse among preschool children whose parents live in noise environment, mother exposed to pesticides, and father exposed to occupational lead during six months before pregnancy.

Photodynamic therapy for Barrett's esophagus using a 20-mm diameter light-delivery balloon

NASA Astrophysics Data System (ADS)

Panjehpour, Masoud; Overholt, Bergein F.; Phan, Mary N.; Haydek, John M.; Robinson, Amy R.

2002-06-01

Background and Objective: Patients with high grade dysplasia (HGD) in Barrett's esophagus are at a high risk for developing esophageal adenocarcinoma. Esophagectomy is the standard treatment for such patients. The objective of this study was to evaluate the safety and efficacy of photodynamic therapy (PDT) using an improved light delivery balloon for ablation of Barrett's esophagus with high grade dysplasia and/or early cancer. Materials and Methods: 20 patients with HGD or early cancer (19 with HGD, 1 with T1 cancer) received 2 mg/kg of porfimer sodium, intravenously. Two to three days after the injection, laser light was delivered using a cylindrical diffuser inserted inside a 20-mm diameter reflective esophageal PDT balloon. Initially, the balloon was inflated to a pressure of 80 mm Hg. The balloon pressure was gradually reduced to 30 mm Hg. A KTP/dye laser at 630 nm was used as the light source. Light dose of 115 J/cm was delivered at an intensity of 270 mw/cm. Nodules were pre- treated with an extra 50 J/cm using a short diffuser inserted through the scope. Patients were maintained on PPI therapy to keep the gastric pH higher than 4. Eighteen patients required one treatment, while two patients were treated twice. Follow-up consisted of endoscopy with four quadrant biopsies at every 2 cm of the treated area. Thermal ablation was used to treat small residual islands on the follow-ups. The follow-up endoscopies ranged from 6 to 17 months. Results: On follow-up endoscopy, 12 patients had complete replacement of their Barrett's mucosa with neosquamous mucosa. Five patients had residual non-dysplastic Barrett's mucosa, one had indefinite dysplasia, two had low grad dysplasia. There were no residual HGD or cancers. The average length of Barrett's was reduced from 5.4 cm to 1.2 cm. High balloon pressure resulted in wide variation in PDT response among patients. Lower balloon pressures resulted in more consistent destruction of Barrett's mucosa among patients. Five patients developed strictures which responded well to dilations. One patient developed atrial fibrillation which responded to medications. Conclusions: Photodynamic therapy using a 20 mm diameter balloon was effective for ablation of high grade dysplasia and early cancer in Barrett's esophagus. Low balloon inflation pressure was a critical parameter in producing consistent tissue destruction.

Photodynamic Therapy with 3-(1’-hexyloxyethyl) pyropheophorbide a (HPPH) for Cancer of the Oral Cavity

PubMed Central

Rigual, Nestor; Shafirstein, Gal; Cooper, Michele T.; Baumann, Heinz; Bellnier, David A.; Sunar, Ulas; Tracy, Erin C.; Rohrbach, Daniel J.; Wilding, Gregory; Tan, Wei; Sullivan, Maureen; Merzianu, Mihai; Henderson, Barbara W.

2013-01-01

Purpose The primary objective was to evaluate safety of 3-(1’-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Experimental Design Patients with histologically proven oral dysplasia, carcinoma in situ (CiS ) or early stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies employed an HPPH dose of 4 mg/m2 and light doses from 50 to 140 J/cm2. Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of signal transducer and activator of transcription 3 (STAT3) were assessed as potential indicators of PDT effective reaction. Results Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and CiS, and 82% for SCCs lesions at 140 J/cm2. The responses in the CiS/dysplasia cohort are not durable. The PDT induced STAT3 cross-links is significantly higher (P=0.0033) in SCC than in CiS/dysplasia for all light-doses. Conclusion HPPH-PDT is safe for the treatment of CiS/dysplasia and early stage cancer of the oral cavity. Early stage oral HNSCC appears to respond better to HPPH-PDT in comparison to premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT mediated photoreaction. PMID:24088736

Different clinical presentation and management of temporal bone fibrous dysplasia in children.

PubMed

Mierzwiński, Józef; Kosowska, Justyna; Tyra, Justyna; Haber, Karolina; Drela, Maria; Paczkowski, Dariusz; Burduk, Paweł

2018-01-15

Fibrous dysplasia is a slowly progressive benign fibro-osseous disorder that involves one or multiple bones with a unilateral distribution in most cases. It is a lesion of unknown etiology, uncertain pathogenesis, and diverse histopathology. Temporal bone involvement is the least frequently reported type, especially in children. We reviewed available articles regarding fibrous dysplasia with temporal bone involvement in children and added four patients aged 7 to 17 years who were diagnosed and treated in our institution from 2006 to 2017. The patients' clinical picture comprised head deformity, external canal stenosis, headache, progressive conductive and/or sensorineural hearing loss, tinnitus, and sudden deafness. Two patients had experienced severe episodic vertigo with nausea and vomiting. Two were referred to us with external canal obstruction and secondary cholesteatoma formation with broad middle ear destruction. One was diagnosed with acute mastoiditis and intracranial complications. Optimal management of fibrous dysplasia is unclear and can be challenging, especially in children. In our two patients with disease expansion and involvement of important structures, surgical treatment was abandoned and a "wait-and-scan" policy was applied. The other two were qualified for surgical treatment. One patient underwent two surgeries: modified lateral petrosectomy (canal left open) with pathological tissue removal, cavity obliteration, and subsequent tympanoplasty. Another patient with extensive destruction of the left temporal bone underwent canal wall down mastoidectomy with perisinus abscess drainage and revision 12 months later. Tympanoplasty was unsatisfactory in both patients because of slow progression of the middle ear pathology. None of our patients underwent pharmacological treatment. In younger patients, observation and a "wait-and-scan" protocol is relevant until significant function, or cosmetic deficits are obvious. Surgery is not preferred and should be delayed until puberty because fibrous dysplasia has a tendency to stabilize after adolescence. In patients with severe symptoms medical treatment can be implemented, but safety of this treatment in children remain controversial.

Clinical Outcomes After Isolated Medial Patellofemoral Ligament Reconstruction for Patellar Instability Among Patients With Trochlear Dysplasia.

PubMed

Liu, Joseph N; Brady, Jacqueline M; Kalbian, Irene L; Strickland, Sabrina M; Ryan, Claire Berdelle; Nguyen, Joseph T; Shubin Stein, Beth E

2018-03-01

Medial patellofemoral ligament (MPFL) reconstruction has become one of the most common and widely used procedures to regain stability among patients with recurrent lateral patellar dislocation. While recent studies demonstrated low recurrence rates, improved patient-reported outcome measures, and a high rate of return to sports, limited literature explored its effectiveness as an isolated intervention in the context of trochlear dysplasia. To determine the efficacy of isolated MPFL reconstruction in treating patellar instability in the setting of trochlear dysplasia. Case series; Level of evidence, 4. This was a retrospective review of consecutive patients who underwent uni- or bilateral medial patellofemoral ligament reconstruction for patellofemoral instability with a minimum 2-year follow-up. No osteotomies were included. Pre- and postoperative assessment included ligamentous laxity, patellar crepitus, tilt, translation, apprehension, and radiographic features, including tibial tubercle-trochlear groove (TT-TG) distance, Dejour classification, and Caton-Deschamps index. A total of 121 MPFL reconstructions were included. Mean age at surgery was 23.8 years, and 4.4 dislocation events occurred before surgery. Mean follow-up was 44 months; 76% of patients were female. Mean preoperative TT-TG ratio was 13.5, and mean Caton-Deschamps ratio was 1.2; 92% of patients had Dejour B, C, or D trochlear dysplasia. Kujala score improved from 55.0 preoperatively to 90.0 ( P < .001). Almost all patients (94.5%) were able to return to sports at 1 year, with 74% returning to the same or higher level of play. Only 3 patients reported a postoperative dislocation or subluxation event. For patients without significantly elevated TT-TG distances or significant patella alta, isolated MPFL reconstruction provides a safe and effective treatment for patellofemoral instability, despite the presence of trochlear dysplasia. Most patients are able to return to sports by 1 year postoperatively at the same or higher level of play.

Growth-sparing spinal instrumentation in skeletal dysplasia.

PubMed

Karatas, Ali F; Dede, Ozgur; Rogers, Kenneth; Ditro, Colleen P; Holmes, Laurens; Bober, Michael; Shah, Suken A; Mackenzie, William G

2013-11-15

Retrospective case series. To report the outcomes of distraction-based, growth-sparing spinal instrumentation in patients with skeletal dysplasia. Patients with skeletal dysplasia with spinal deformity often undergo early fusion, further compromising an already small chest. Nonfusion techniques may provide a safe alternative and allow for thoracic growth. Between 2004 and 2010, 12 children with a diagnosis of various types of skeletal dysplasia underwent growth-sparing spinal instrumentation for severe spinal deformities. The mean duration of treatment with growing rods was 57 months (42-84 mo). Nine patients were treated with growing rods (8 dual, 1 single), and 3 were treated with vertical expandable prosthetic titanium rib (VEPTR; Synthes). Preoperative, initial postoperative, and final follow-up anteroposterior and lateral spine radiographs were measured for magnitude of deformity, junctional kyphosis, and implant failure. The major curve Cobb angle improved from a mean of 79° preoperatively to a mean of 41° at the last follow-up (52%). There was a decrease in mean thoracic kyphosis from 77° preoperatively to 64° at final follow-up and an increase in mean lumbar lordosis from 58° preoperatively to 63° at final follow-up. The mean space available for the lungs increased by 26 mm on the concave and 24 mm on the convex side. Six patients required revision surgery for proximal junctional kyphosis. There were 4 rod failures and 6 hook and 8 screw dislodgements. One patient with vertical expandable prosthetic titanium rib had failed rib fixation that required revision. Growth-sparing spinal instrumentation in patients with skeletal dysplasia and severe spinal deformity has a high complication and revision rate, and surgeons should closely monitor these patients. The complication rate is comparable with previous reports on patients with other diagnoses. However, deformities were well controlled, some trunk growth was achieved, and fusion surgery was delayed in all cases. 4.

Photodynamic therapy with Photofrin followed by thermal ablation for elimination of dysplasia and early cancer in Barrett's esophagus: follow-up in 100 patients

NASA Astrophysics Data System (ADS)

Panjehpour, Masoud; Overholt, Bergein F.; Haydek, John M.

1998-05-01

Photodynamic therapy (PDT) using Photofrin and 630 nm laser light was used to treat 100 Barrett's esophagus patients with dysplasia and early cancer. Twelve patients had superficial esophageal cancers (T1-T2, NO, MO). Laser light was delivered to the esophageal mucosa by cylindrical diffuser inserted through the endoscope or via a 3, 5 or 7 cm windowed esophageal centering balloons. Nd:YAG laser ablation was used on small residual islands of Barrett's mucosa during long term follow-up after PDT. Patients were maintained on omeprazole and were followed for 6 - 84 months following photodynamic therapy. Photodynamic therapy produced destruction of normal, dysplastic and malignant mucosa in treated areas. Approximately 75 - 80% of treated Barrett's mucosa healed as normal squamous epithelium in all patients. Complete elimination of Barrett's epithelium was found in 43 patients. Nd:YAG laser was required to ablate small residual areas of Barrett's mucosa in 35 of these patients. Dysplasia was eliminated in 77 patients. Ten of the 12 malignancies were ablated with no recurrence being found during follow-up. Healing was associated with esophageal strictures in 34% but after using the 5 and 7 cm balloons, the incidence of strictures decreased to 18%. All strictures were treated successfully by dilation. In summary, PDT alone or combined with Nd:YAG laser ablation, in conjunction with long-term acid inhibition provides an effective endoscopic treatment to eliminate dysplasia and superficial cancer in Barrett's patients, and reduce the amount of or eliminate Barrett's mucosa completely.

Distinct requirements for cranial ectoderm and mesenchyme-derived wnts in specification and differentiation of osteoblast and dermal progenitors.

PubMed

Goodnough, L Henry; Dinuoscio, Gregg J; Ferguson, James W; Williams, Trevor; Lang, Richard A; Atit, Radhika P

2014-02-01

The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme, to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation.

Evaluation and Referral for Developmental Dysplasia of the Hip in Infants.

PubMed

Shaw, Brian A; Segal, Lee S

2016-12-01

Developmental dysplasia of the hip (DDH) encompasses a wide spectrum of clinical severity, from mild developmental abnormalities to frank dislocation. Clinical hip instability occurs in 1% to 2% of full-term infants, and up to 15% have hip instability or hip immaturity detectable by imaging studies. Hip dysplasia is the most common cause of hip arthritis in women younger than 40 years and accounts for 5% to 10% of all total hip replacements in the United States. Newborn and periodic screening have been practiced for decades, because DDH is clinically silent during the first year of life, can be treated more effectively if detected early, and can have severe consequences if left untreated. However, screening programs and techniques are not uniform, and there is little evidence-based literature to support current practice, leading to controversy. Recent literature shows that many mild forms of DDH resolve without treatment, and there is a lack of agreement on ultrasonographic diagnostic criteria for DDH as a disease versus developmental variations. The American Academy of Pediatrics has not published any policy statements on DDH since its 2000 clinical practice guideline and accompanying technical report. Developments since then include a controversial US Preventive Services Task Force "inconclusive" determination regarding usefulness of DDH screening, several prospective studies supporting observation over treatment of minor ultrasonographic hip variations, and a recent evidence-based clinical practice guideline from the American Academy of Orthopaedic Surgeons on the detection and management of DDH in infants 0 to 6 months of age. The purpose of this clinical report was to provide literature-based updated direction for the clinician in screening and referral for DDH, with the primary goal of preventing and/or detecting a dislocated hip by 6 to 12 months of age in an otherwise healthy child, understanding that no screening program has eliminated late development or presentation of a dislocated hip and that the diagnosis and treatment of milder forms of hip dysplasia remain controversial. Copyright © 2016 by the American Academy of Pediatrics.

Clonal and molecular analysis of the prospective anterior neural boundary in the mouse embryo

PubMed Central

Cajal, Marieke; Lawson, Kirstie A.; Hill, Bill; Moreau, Anne; Rao, Jianguo; Ross, Allyson; Collignon, Jérôme; Camus, Anne

2012-01-01

In the mouse embryo the anterior ectoderm undergoes extensive growth and morphogenesis to form the forebrain and cephalic non-neural ectoderm. We traced descendants of single ectoderm cells to study cell fate choice and cell behaviour at late gastrulation. In addition, we provide a comprehensive spatiotemporal atlas of anterior gene expression at stages crucial for anterior ectoderm regionalisation and neural plate formation. Our results show that, at late gastrulation stage, expression patterns of anterior ectoderm genes overlap significantly and correlate with areas of distinct prospective fates but do not define lineages. The fate map delineates a rostral limit to forebrain contribution. However, no early subdivision of the presumptive forebrain territory can be detected. Lineage analysis at single-cell resolution revealed that precursors of the anterior neural ridge (ANR), a signalling centre involved in forebrain development and patterning, are clonally related to neural ectoderm. The prospective ANR and the forebrain neuroectoderm arise from cells scattered within the same broad area of anterior ectoderm. This study establishes that although the segregation between non-neural and neural precursors in the anterior midline ectoderm is not complete at late gastrulation stage, this tissue already harbours elements of regionalisation that prefigure the later organisation of the head. PMID:22186731

Diffuse Palmoplantar Keratoderma, Onychodystrophy, universal Hypotrichosis and Cysts.

PubMed

Arif, Tasleem; Amin, Syed Suhail; Adil, Mohammad; Mohtashim, Mohd

2017-07-01

Dear Editor, Clouston syndrome, also called hidrotic ectodermal dysplasia (HED), is an autosomal dominant ectodermal dysplasia characterized by a clinical triad of onychodystrophy, generalized hypotrichosis, and palmoplantar keratoderma (1). Herein we report the case of a 24-year-old male with the distinctive clinical triad associated with multiple epidermoid cysts, which probably reflects the phenotype of Clouston syndrome. A 24-year-old male presented to our Department with diffuse thickening of the skin of his palms and soles since infancy. He also complained of sparsity to near absence of body hair and also reported thickening of the nails and multiple swellings involving the genitals and head since childhood. There was no history of consanguinity or of recurrent painful paronychia or abnormality in sweating. The patient denied any history of deafness, diminution of vision, redness, or watering of the eyes. On examination, diffuse hyperkeratosis of the palms and soles was observed (Figure 1 a, b) However, there was no extension of this hyperkeratosis to the dorsal aspects of the hands and feet or any proximal extension to the forearms or legs. Extensor aspects of the elbows and knees did not reveal any hyperkeratotic skin lesions. The nails were yellowish-brown, thickened, and hyperconvex, which was more pronounced in the finger nails than the toe nails (Figure 1 c, d). There was no associated paronychia. The scalp hair was very sparse, fine, and pale in color, reaching just a length of 3-4 mm in some places while totally absent in other places. The hair from the beard, eyebrows, eyelashes, moustaches, and pubic and axillary regions was very sparse to nearly absent (Figure 2 a, b, c). General body hair was also absent. In the left pre-auricular area there was a 3×2.5 cm swelling, soft to firm in consistency, non-tender, and non-pulsatile with no sinus or scar over it (Figure 2c). Multiple similar swellings of variable size measuring 0.6 to 1.3 cm were present over the scrotum (Figure 2 d). Systemic examination including oro-dental and ophthalmological examination was unremarkable. Physical tests for hearing were normal. Nail clippings for KOH examination did not reveal any fungal components. Fine needle aspiration from the pre-auricular swelling was consistent with epidermoid cyst. The classical triad of onychodystrophy, universal hypotrichosis, and palmoplantar hyperkeratosis with normal sweating and teeth indicated a diagnosis of Clouston syndrome. Hidrotic ectodermal dysplasia was first described in a French-Canadian kindred (2). However, it has subsequently been described in other ethnic and geographical areas. There is a mutation in the β gap junction protein gene which codes for the protein connexin 30 (Cx30) (3). This condition primarily affects the hair, nails, and skin, while sparing the teeth and sweat glands. The hair is sparse and pale, and the alopecia can be patchy or total. Hair loss may lead to total alopecia by puberty. The eyelashes are short and sparse, and the eyebrows as well as axillary and pubic hair are also sparse or absent (1), as in our case. During infancy, the nails are typically milky white, gradually thickening throughout childhood. The nail plate is short, thick, slow-growing, and discolored, which was consistent with our patient's nail changes. Diffuse palmoplantar hyperkeratosis is a characteristic sign which may extend to the dorsum of the hands and feet (4). However, our case had no transgradient component. There are other less common abnormalities reported in Clouston syndrome, which include conjunctivitis, strabismus, congenital cataract, oral leucoplakia, diffuse eccrine poromatosis, sensorineural hearing loss, thickened skull bones, and tufting of the terminal phalanges (2,5-8). However, to the best of our knowledge, the presence of epidermoid cysts in Clouston syndrome has not been previously reported, making our case a unique clinical presentation. Pachyonychia congenita is a very close differential diagnosis for this entity. However, universal hypotrichosis and the lack of oral leukokeratosis were the differentiating features in our case. Additionally, palmoplantar keratoderma in pachyonychia congenita is mainly focal rather than diffuse, as in our case. However, genetic studies are needed to establish such a diagnosis.

Fatal complication from a balloon-expandable tracheal stent in a child: a case report.

PubMed

Stotz, William H; Berkowitz, Ivor D; Hoehner, Jeff C; Tunkel, David E

2003-01-01

The use of airway stents in the pediatric population is uncommon, reflected in the few patient series reported in the literature. We describe a fatal complication of tracheal stent placement in an 18-month-old child with spondylothoracic dysplasia. Case report. Intensive care unit of a tertiary academic pediatric center. An 18-month-old child with spondylothoracic dysplasia who underwent tracheal stent placement for tracheomalacia. Management of an acute upper-airway hemorrhage. The patient died, despite aggressive interventions. Use of tracheal stents in pediatric patients with tracheomalacia is not without risks; tracheal erosion with severe hemoptysis is an infrequent but devastating complication of this intervention.

Osseous dysplasia (cemento-osseous dysplasia) of the jaw bones in western Pennsylvania patients: analysis of 35 cases.

PubMed

Owosho, Adepitan A; Potluri, Anitha; Bilodeau, Elizabeth A

2013-01-01

The purpose of this study is to analyze the demographic, clinical, and radiographic presentations of osseous dysplasia of the jaws in western Pennsylvania patients and its associated complications. The clinical records and radiographs of patients diagnosed with osseous (cement-osseous) dysplasia were retrieved from the electronic health record of the University of Pittsburgh, School of Dental Medicine from 2007 to 2012. All cases were reviewed; the WHO criteria and classification for osseous dysplasia was used. Clinical and demographic data, radiographic findings, and final diagnoses were collected and analyzed. 35 cases of osseous dysplasia were retrieved over the six-year period.The majority (33) were females [94.3%], with ages ranging from 26 to 89 years, with a mean age of 53.9 years +/- standard deviation of 15.6 years, 32 [91.4%] were African Americans and 3 [8.6%] were Caucasians. 17 [48.6%] were florid osseous dysplasia, 13 [37.1%] periapical osseous dysplasia and 5 [14.3%] focal osseous dysplasia. Of the 35 patients only 8 [22.9%] patients were symptomatic. All florid osseous dysplasia patients were African American females, with 7 of the patients being symptomatic and the commonest symptom being pain. Also, all periapical osseous dysplasia patients were African Americans (12 females and 1 male), with 1 of the patients presenting with widening of the diastema. Of the focal osseous dysplasia patients, 3 were Caucasians and 2 African American (4 females and 1 male). The cases occurred mostly in African American females with a peak incidence in the fifth and sixth decades of life; most cases occurred in the mandible. The commonest form of osseous dysplasias was the florid osseous dysplasia which is most likely to present with symptoms.

Pamidronic acid and cabergoline as effective long-term therapy in a 12-year-old girl with extended facial polyostotic fibrous dysplasia, prolactinoma and acromegaly in McCune-Albright syndrome: a case report

PubMed Central

2012-01-01

Introduction McCune-Albright syndrome is a complex inborn disorder due to early embryonal postzygotic somatic activating mutations in the GNAS1 gene. The phenotype is very heterogeneous and includes polyostotic fibrous dysplasia, typically involving the facial skull, numerous café-au-lait spots and autonomous hyperfunctions of several endocrine systems, leading to hyperthyroidism, hypercortisolism, precocious puberty and acromegaly. Case presentation Here, we describe a 12-year-old Caucasian girl with severe facial involvement of fibrous dysplasia, along with massive acromegaly due to growth hormone excess and precocious puberty, with a prolactinoma. Our patient was treated with a bisphosphonate and the prolactin antagonist, cabergoline, resulting in the inhibition of fibrous dysplasia and involution of both the prolactinoma and growth hormone excess. During a follow-up of more than two years, no severe side effects were noted. Conclusion Treatment with bisphosphonates in combination with cabergoline is a suitable option in patients with McCune-Albright syndrome, especially in order to circumvent surgical interventions in patients suffering from polyostotic fibrous dysplasia involving the skull base. PMID:22273876

Bronchopulmonary Dysplasia and Perinatal Characteristics Predict 1-Year Respiratory Outcomes in Newborns Born at Extremely Low Gestational Age: A Prospective Cohort Study.

PubMed

Keller, Roberta L; Feng, Rui; DeMauro, Sara B; Ferkol, Thomas; Hardie, William; Rogers, Elizabeth E; Stevens, Timothy P; Voynow, Judith A; Bellamy, Scarlett L; Shaw, Pamela A; Moore, Paul E

2017-08-01

To assess the utility of clinical predictors of persistent respiratory morbidity in extremely low gestational age newborns (ELGANs). We enrolled ELGANs (<29 weeks' gestation) at ≤7 postnatal days and collected antenatal and neonatal clinical data through 36 weeks' postmenstrual age. We surveyed caregivers at 3, 6, 9, and 12 months' corrected age to identify postdischarge respiratory morbidity, defined as hospitalization, home support (oxygen, tracheostomy, ventilation), medications, or symptoms (cough/wheeze). Infants were classified as having postprematurity respiratory disease (PRD, the primary study outcome) if respiratory morbidity persisted over ≥2 questionnaires. Infants were classified with severe respiratory morbidity if there were multiple hospitalizations, exposure to systemic steroids or pulmonary vasodilators, home oxygen after 3 months or mechanical ventilation, or symptoms despite inhaled corticosteroids. Mixed-effects models generated with data available at 1 day (perinatal) and 36 weeks' postmenstrual age were assessed for predictive accuracy. Of 724 infants (918 ± 234 g, 26.7 ± 1.4 weeks' gestational age) classified for the primary outcome, 68.6% had PRD; 245 of 704 (34.8%) were classified as severe. Male sex, intrauterine growth restriction, maternal smoking, race/ethnicity, intubation at birth, and public insurance were retained in perinatal and 36-week models for both PRD and respiratory morbidity severity. The perinatal model accurately predicted PRD (c-statistic 0.858). Neither the 36-week model nor the addition of bronchopulmonary dysplasia to the perinatal model improved accuracy (0.856, 0.860); c-statistic for BPD alone was 0.907. Both bronchopulmonary dysplasia and perinatal clinical data accurately identify ELGANs at risk for persistent and severe respiratory morbidity at 1 year. ClinicalTrials.gov: NCT01435187. Copyright © 2017 Elsevier Inc. All rights reserved.

Ectoderm exerts the driving force for gastrulation in the sand dollar Scaphechinus mirabilis.

PubMed

Takata, H; Kominami, T

2001-06-01

How the ectodermal layer relates to the invagination processes was examined in the sand dollar Scaphechinus mirabilis. When the turgor pressure of blastocoele was increased, invagination was completely blocked. In contrast, an increase in turgor pressure did not affect elongation of the gut rudiment in the regular echinoid Hemicentrotus pulcherrimus. Rhodamine-phalloidin staining showed that the distribution of actin filaments was different between two species of embryos. In S. mirabilis gastrulating embryos, abundant actin filaments were seen at the basal cortex of ectoderm in addition to archenteron cells, while the intense signal was restricted to the archenteron in H. pulcherrimus. To investigate whether actin filaments contained in the ectodermal layer exert the force of invagination, a small part of the ectodermal layer was aspirated with a micropipette. If S. mirabilis embryos were aspirated from the onset of gastrulation, invagination did not occur at all, irrespective of the suction site. Even after the archenteron had invaginated to one-half of its full length, further elongation of the archenteron was severely blocked by suction of the lateral ectoderm. In contrast, suction of the ectodermal layer did not affect the elongation processes in H. pulcherrimus. These results strongly suggest that the ectodermal layer, especially in the vegetal half, exerts the driving force of invagination in S. mirabilis.

Eph and Ephrin function in dispersal and epithelial insertion of pigmented immunocytes in sea urchin embryos

PubMed Central

Krupke, Oliver A; Zysk, Ivona; Mellott, Dan O; Burke, Robert D

2016-01-01

The mechanisms that underlie directional cell migration are incompletely understood. Eph receptors usually guide migrations of cells by exclusion from regions expressing Ephrin. In sea urchin embryos, pigmented immunocytes are specified in vegetal epithelium, transition to mesenchyme, migrate, and re-enter ectoderm, distributing in dorsal ectoderm and ciliary band, but not ventral ectoderm. Immunocytes express Sp-Eph and Sp-Efn is expressed throughout dorsal and ciliary band ectoderm. Interfering with expression or function of Sp-Eph results in rounded immunocytes entering ectoderm but not adopting a dendritic form. Expressing Sp-Efn throughout embryos permits immunocyte insertion in ventral ectoderm. In mosaic embryos, immunocytes insert preferentially in ectoderm expressing Sp-Efn. We conclude that Sp-Eph signaling is necessary and sufficient for epithelial insertion. As well, we propose that immunocytes disperse when Sp-Eph enhances adhesion, causing haptotactic movement to regions of higher ligand abundance. This is a distinctive example of Eph/Ephrin signaling acting positively to pattern migrating cells. DOI: http://dx.doi.org/10.7554/eLife.16000.001 PMID:27474796

Low-grade central osteosarcoma of distal femur, resembling fibrous dysplasia

PubMed Central

Vasiliadis, Haris S; Arnaoutoglou, Christina; Plakoutsis, Sotiris; Doukas, Michalis; Batistatou, Anna; Xenakis, Theodoros A

2013-01-01

We report a case of a 32 year-old male, admitted for a lytic lesion of the distal femur. One month after the first X-ray, clinical and imaging deterioration was evident. Open biopsy revealed fibrous dysplasia. Three months later, the lytic lesion had spread to the whole distal third of the femur reaching the articular cartilage. The malignant clinical and imaging features necessitated excision of the lesion and reconstruction with a custom-made total knee arthroplasty. Intra-operatively, no obvious soft tissue infiltration was evident. Nevertheless, an excision of the distal 15.5 cm of the femur including 3.0 cm of the surrounding muscles was finally performed. The histological examination of the excised specimen revealed central low-grade osteosarcoma. Based on the morphological features of the excised tumor, allied to the clinical findings, the diagnosis of low-grade central osteosarcoma was finally made although characters of a fibrous dysplasia were apparent. Central low-grade osteosarcoma is a rare, well-differentiated sub-type of osteosarcoma, with clinical, imaging, and histological features similar to benign tumours. Thus, initial misdiagnosis is usual with the condition commonly mistaken for fibrous dysplasia. Central low-grade osteosarcoma is usually treated with surgery alone, with rare cases of distal metastases. However, regional recurrence is quite frequent after close margin excision. PMID:24147271

Protein-losing enteropathy with intestinal lymphangiectasia in skeletal dysplasia with Lys650Met mutation.

PubMed

Yang, Chen; Dehner, Louis P

2016-11-01

Protein-losing enteropathy is a primary or secondary manifestation of a group of conditions, and etiologies which are broadly divisible into those with mucosal injury on the basis of inflammatory and ulcerative conditions, mucosal injury without erosions or ulcerations, and lymphatic abnormalities. We describe the first case of protein-losing enteropathy in a pediatric patient, with severe skeletal dysplasia consistent with thanatophoric dysplasia type I and DNA analysis that revealed a c.1949A>T (p.Lys650Met) in exon 15 of the FGFR3 gene. She presented with protein-losing enteropathy in her 6th month. Post-mortem examination revealed lymphangiectasia in the small intestine. To our knowledge, this is the first report of intestinal lymphangiectasia as a complication of skeletal dysplasia resulting in severe protein-losing enteropathy. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Dlx proteins position the neural plate border and determine adjacent cell fates.

PubMed

Woda, Juliana M; Pastagia, Julie; Mercola, Mark; Artinger, Kristin Bruk

2003-01-01

The lateral border of the neural plate is a major source of signals that induce primary neurons, neural crest cells and cranial placodes as well as provide patterning cues to mesodermal structures such as somites and heart. Whereas secreted BMP, FGF and Wnt proteins influence the differentiation of neural and non-neural ectoderm, we show here that members of the Dlx family of transcription factors position the border between neural and non-neural ectoderm and are required for the specification of adjacent cell fates. Inhibition of endogenous Dlx activity in Xenopus embryos with an EnR-Dlx homeodomain fusion protein expands the neural plate into non-neural ectoderm tissue whereas ectopic activation of Dlx target genes inhibits neural plate differentiation. Importantly, the stereotypic pattern of border cell fates in the adjacent ectoderm is re-established only under conditions where the expanded neural plate abuts Dlx-positive non-neural ectoderm. Experiments in which presumptive neural plate was grafted to ventral ectoderm reiterate induction of neural crest and placodal lineages and also demonstrate that Dlx activity is required in non-neural ectoderm for the production of signals needed for induction of these cells. We propose that Dlx proteins regulate intercellular signaling across the interface between neural and non-neural ectoderm that is critical for inducing and patterning adjacent cell fates.

Fatty metamorphosis and other patterns in fibrous dysplasia

PubMed Central

Shidham, Vinod B; Chavan, Ashwini; Rao, R Nagarjun; Komorowski, Richard A; Asma, Zeenath

2003-01-01

Background Interpretation of small biopsy fragments from suspected lesions of fibrous dysplasia with unusual clinical and / or radiological features may be challenging due to wide histomorphological spectrum of stromal appearances. Awareness of these variations should improve diagnostic confidence. Methods We retrospectively studied 26 cases of fibrous dysplasia (F- 19, M- 7; Ages ranged from 10 to 53 years) with confirmed diagnosis. The sites of the lesions were skull bones (9), humerus (1), femur (8), tibia (2), fibula (3), talus (1), mandible (1), and maxilla (1). Results Different stromal patterns, variably admixed with the classical pattern, were observed in 58%(15/26) of the cases. 20%(3/15) of these had more than one pattern. Focal fatty metamorphosis as groups of fat cells in the central portion of the lesion in the stroma of fibrous dysplasia between osseous trabeculae was observed in 23%(6/26) cases. Other patterns included myxoid stroma in 16%(4/26), collagenization of stroma in 12%(3/26), stroma rich pattern (with paucity of trabeculae) in 12%(3/26), foci of few foam cells in 23% (6/26), and calcified spherules in 12%(3/26). Focal osteoblastic rimming of trabeculae was observed only in 4%(1/26). Conclusions Various stromal variations and previously unreported fatty metamorphosis were frequently observed in fibrous dysplasia. PMID:12946277

Effect of a commercially available fish-based dog food enriched with nutraceuticals on hip and elbow dysplasia in growing Labrador retrievers.

PubMed

Manfredi, Sabrina; Di Ianni, Francesco; Di Girolamo, Nicola; Canello, Sergio; Gnudi, Giacomo; Guidetti, Gianandrea; Miduri, Francesca; Fabbi, Martina; Daga, Eleonora; Parmigiani, Enrico; Centenaro, Sara; Volta, Antonella

2018-04-01

The aim of this study was to evaluate the prevalence of hip and elbow dysplasia in a group of growing Labrador retrievers fed a fish-based diet enriched with nutraceuticals with chondroprotective properties. The puppies ranged from 3 to 12 mo of age and were divided into 2 groups, each fed a different diet. The control diet consisted of a high quality, chicken-based dog food, while the test diet was a fish-based dog food, enriched with nutraceuticals. Hip and elbow joints were radiographed and scored at 6 and 12 mo of age. Overall, 42 dogs completed the study. At 12 mo of age, no differences were found between the groups in the prevalence of hip and elbow dysplasia, although dogs fed the fish-based food enriched with nutraceuticals had a less severe grade of osteoarthritis at 12 mo. It was concluded that the fish-based diet with nutraceuticals did have beneficial effects on the development of severe osteoarthritis.

Bronchial dysplasia induced by radiation in miners exposed to 222Rn progeny.

PubMed Central

Michaylov, M A; Pressyanov, D S; Kalinov, K B

1995-01-01

OBJECTIVES--To investigate whether sputum cytology can be used to monitor epithelial cell changes in groups at high risk of lung cancer from exposure to radiation. METHODS--Dysplasia of bronchial cells was investigated by means of sputum cytology in a group of 434 underground miners. 100 of them were not exposed, and 334 were exposed to 222Rn progeny at cumulative exposures < 450 working level months. RESULTS--The frequency of dysplasia in the exposed group was significantly higher than that in the not exposed group (P < 0.0001), and an exposure-response relation was found. This relation was different for smokers and non-smokers. CONCLUSIONS--Possibly the frequencies of dysplasia could be used to assess past exposures of groups of miners. This approach could be applied to cases where data on radiation monitoring are not available or are very scarce. Images p82-a PMID:7757171

Evaluation of articular cartilage following rotational acetabular osteotomy for hip dysplasia using T2 mapping MRI.

PubMed

Shoji, Takeshi; Yamasaki, Takuma; Izumi, Soutaro; Sawa, Mikiya; Akiyama, Yuji; Yasunaga, Yuji; Adachi, Nobuo

2018-04-27

Rotational acetabular osteotomy (RAO) is one of the surgical treatments for acetabular dysplasia, and satisfactory results have been reported. We evaluated the postoperative changes of articular cartilage and whether the pre-operative condition of the articular cartilage influences the clinical results using T2 mapping MRI. We reviewed 31 hips with early stage osteoarthritis in 31 patients (mean age, 39.6 years), including three men and 28 women who underwent RAO for hip dysplasia. Clinical evaluations including Japanese Orthopedic Association (JOA) score and Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ), and radiographical evaluations on X-ray were performed. Longitudinal qualitative assessment of articular cartilage was also performed using 3.0-T MRI with T2 mapping technique preoperatively, 6 months, and at 1 and 2 years postoperatively. There was no case with progression of osteoarthritis. The mean JOA score improved from 70.1 to 93.4 points, the mean postoperative JHEQ score was 68.8 points, and radiographical data also improved postoperatively. We found that the T2 values of the cartilage at both femoral head and acetabulum increased at 6 months on coronal and sagittal views. However, they significantly decreased 1 and 2 years postoperatively. The T2 values of the center to anterolateral region of acetabulum negatively correlated with postoperative JHEQ score, particularly in pain score. This study suggests that biomechanical and anatomical changes could apparently cause decreased T2 values 1-2 years postoperatively compared with those preoperatively. Furthermore, preoperative T2 values of the acetabulum can be prognostic factors for the clinical results of RAO.

Dlx proteins position the neural plate border and determine adjacent cell fates

PubMed Central

Woda, Juliana M.; Pastagia, Julie; Mercola, Mark; Artinger, Kristin Bruk

2014-01-01

Summary The lateral border of the neural plate is a major source of signals that induce primary neurons, neural crest cells and cranial placodes as well as provide patterning cues to mesodermal structures such as somites and heart. Whereas secreted BMP, FGF and Wnt proteins influence the differentiation of neural and non-neural ectoderm, we show here that members of the Dlx family of transcription factors position the border between neural and non-neural ectoderm and are required for the specification of adjacent cell fates. Inhibition of endogenous Dlx activity in Xenopus embryos with an EnR-Dlx homeodomain fusion protein expands the neural plate into non-neural ectoderm tissue whereas ectopic activation of Dlx target genes inhibits neural plate differentiation. Importantly, the stereotypic pattern of border cell fates in the adjacent ectoderm is re-established only under conditions where the expanded neural plate abuts Dlx-positive non-neural ectoderm. Experiments in which presumptive neural plate was grafted to ventral ectoderm reiterate induction of neural crest and placodal lineages and also demonstrate that Dlx activity is required in non-neural ectoderm for the production of signals needed for induction of these cells. We propose that Dlx proteins regulate intercellular signaling across the interface between neural and non-neural ectoderm that is critical for inducing and patterning adjacent cell fates. PMID:12466200

Effect of month of birth on hip dysplasia in labrador retrievers and Gordon setters.

PubMed

Wood, J L N; Lakhani, K H

2003-01-18

Recent studies have proposed selective breeding policies for preventing or controlling hip dysplasia, based upon the relationships between the hip scores of the offspring and their parents. However, these studies have ignored the possible effects on an animal's hip score of its age when it was examined and the month in which it was born. This paper describes the results of statistical analyses of large data sets of Kennel Club-registered labrador retrievers and Gordon setters. Regression modelling showed that an animal's hip score depended significantly upon the hip score of its sire and dam, and upon its month of birth. Enlarging the model by including its age when examined made it possible to quantify the significant genetic parental effects and the effects of the animal's month of birth and its age when examined.

Sessile serrated adenomas with dysplasia: morphological patterns and correlations with MLH1 immunohistochemistry.

PubMed

Liu, Cheng; Walker, Neal I; Leggett, Barbara A; Whitehall, Vicki Lj; Bettington, Mark L; Rosty, Christophe

2017-12-01

Sessile serrated adenomas are the precursor polyp of approximately 20% of colorectal carcinomas. Sessile serrated adenomas with dysplasia are rarely encountered and represent an intermediate step to malignant progression, frequently associated with loss of MLH1 expression. Accurate diagnosis of these lesions is important to facilitate appropriate surveillance, particularly because progression from dysplasia to carcinoma can be rapid. The current World Health Organization classification describes two main patterns of dysplasia occurring in sessile serrated adenomas, namely, serrated and conventional. However, this may not adequately reflect the spectrum of changes seen by pathologists in routine practice. Furthermore, subtle patterns of dysplasia that are nevertheless associated with loss of MLH1 expression are not encompassed in this classification. We performed a morphological analysis of 266 sessile serrated adenomas with dysplasia with concurrent MLH1 immunohistochemistry with the aims of better defining the spectrum of dysplasia occurring in these lesions and correlating dysplasia patterns with MLH1 expression. We found that dysplasia can be divided morphologically into four major patterns, comprising minimal deviation (19%), serrated (12%), adenomatous (8%) and not otherwise specified (79%) groups. Minimal deviation dysplasia is defined by minor architectural and cytological changes that typically requires loss of MLH1 immunohistochemical expression to support the diagnosis. Serrated dysplasia and adenomatous dysplasia have distinctive histological features and are less frequently associated with loss of MLH1 expression (13 and 5%, respectively). Finally, dysplasia not otherwise specified encompasses most cases and shows a diverse range of morphological changes that do not fall into the other subgroups and are frequently associated with loss of MLH1 expression (83%). This morphological classification of sessile serrated adenomas with dysplasia may represent an improvement on the current description as it correlates with the underlying mismatch repair protein status of the polyps and better highlights the range of morphologies seen by pathologists.

Comparison of Salter osteotomy and Tonnis lateral acetabuloplasty with simultaneous open reduction for the treatment of developmental dysplasia of the hip: midterm results.

PubMed

Bayhan, Ilhan A; Beng, Kubilay; Yildirim, Timur; Akpinar, Evren; Ozcan, Cagri; Yagmurlu, Firat

2016-11-01

The aim of this study was to compare the midterm clinical and radiological outcomes of the Salter osteotomy (SO) and Tonnis lateral acetabuloplasty (TLA) with concomitant open reduction for the treatment of developmental dysplasia of the hip. Twenty-five hips of 20 patients who underwent SO with open reduction and 26 hips of 23 patients who underwent TLA with open reduction were evaluated retrospectively. The average age of the patients at the time of the operation was 35.6 months in the SO and 36.6 months in the TLA group, without a statistically significant difference (P=0.836). The average follow-up times in the SO and TLA groups were 59.9 and 54.8 months, respectively (P=0.397). Preoperative (40.6° in the SO vs. 42.2° in the TLA, P=0.451) and last follow-up acetabular index (12° in the SO vs. 14° in the TLA, P=0.227) and center-edge angle measurements (30° in the SO vs. 26° in the TLA, P=0.069) did not show a statistically significant difference between the SO and TLA groups; however, early postoperative acetabular index improvement was better in the TLA group than in the SO group (21.2° in the SO vs. 17.2° in the TLA, P=0.014). According to the Severin grading system, both groups showed a similar number of good outcomes without a statistically significant difference (P=0.936). Clinical assessment on the basis of McKay's criteria showed similar good and excellent outcomes (P=0.936). Both osteotomy techniques showed similar satisfactory outcomes for the treatment of DDH in patients older than 18 months of age.

Recession wedge trochleoplasty as an additional procedure in the surgical treatment of patellar instability with major trochlear dysplasia: early results.

PubMed

Thaunat, M; Bessiere, C; Pujol, N; Boisrenoult, P; Beaufils, P

2011-12-01

The importance of a dysplastic trochlea as a component of patellar instability has long been recognized. An original trochleoplasty technique consisting in retro-trochlear recession wedge osteotomy was described by Goutallier et al. The aim is not to fashion a groove but to reduce the bump without modifying patellofemoral congruence. This retrospective study reports the operative technique and short-term outcomes of a consecutive case series of 17 patients (19 knees) who underwent recession wedge trochleoplasty for patellofemoral instability associated with severe trochlear dysplasia. Other contributing factors of patellar instability were also corrected as part of the surgical procedure: tibial tuberosity transfer (n=18), MPFL reconstruction (n=8). Minimum follow-up was 12 months (mean, 34 months; range, 12 to 71 months). The trochlear prominence was reduced from a mean 4.8mm (range, 0 to 8mm) to -0.8mm (range, -8 to 6mm). Patellar tilt was reduced from a mean 14° (range, 6° to 26°) to 6° (range, -1° to 24°). Two cases showed recurrent patellofemoral instability. Mean Kujala, KOOS and IKDC score were respectively 80 (± 17), 70 (± 18) and 67 (± 17) at last follow-up. Three patients required further operations, apart from removal of metal screws: arthroscopic arthrolysis for stiffness (n=1), revision for tibial tuberosity non-union (n=1), and supratrochlear exostosectomy (n=1). Recession wedge trochleoplasty is a feasible additional procedure addressing bony trochlear abnormality in the surgical treatment of patellar instability. Our attitude is to perform it never in isolation but associated to realignment of the extensor apparatus according to the à la carte surgery concept. It seems to be effective in preventing future patellar dislocation and reducing anterior knee pain in case of painful patellofemoral instability with a major dysplastic trochlea, or in revision cases when other realignment procedures have failed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Is atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion clinically significant?

PubMed

McHale, Michael T; Souther, Jessica; Elkas, John C; Monk, Bradley J; Harrison, Terry A

2007-04-01

To determine the cumulative risk of cervical intraepithelial neoplasia (CIN) 2 or 3 in patients with atypical squamous cells, cannot exclude HSIL (ASC-H). A retrospective analysis was performed to identify patients referred to the dysplasia clinic with ASC-H. Initial evaluation included colposcopy, endocervical curettage, and an ectocervical biopsy, when indicated, in all the patients. A follow-up evaluation was performed at 6 and 12 months. Cumulative histological diagnosis of CIN 2 or 3 at 12 months served as the clinical end point. Two hundred twenty-nine patients with ASC-H and with a mean age of 32.8 years were evaluated. At the time of initial colposcopy, only 10.0% (23/229; 95% CI = 6.5%-15%) of the patients had histological evidence of CIN 2 or 3. The cumulative risk of CIN 2 or 3 was 12.2% (95% CI = 8%-17%). Evaluation of patients with ASC-H with colposcopy does lead to the detection of CIN 2 or 3 but perhaps at a rate lower than previously reported.

Morphometric assessment of hip dysplasia in a cat treated by juvenile pubic symphysiodesis.

PubMed

Lai, Alen; Culvenor, John; Bailey, Craig

2016-09-20

To quantitatively evaluate the change of the coxofemoral joints using computed tomography and distraction index in a cat with hip dysplasia treated by juvenile pubic symphysiodesis. Case report. Eighteen-week-old female entire Maine Coon cat. Juvenile pubic symphysiodesis resulted in changes in the distraction index, acetabular angle, dorsal acetabular rim angle, dorsal acetabular sector angle, and clinical improvement at the six month follow-up. No intra-operative or postoperative complications were recorded. Juvenile pubic symphysiodesis performed at 18 weeks of age resulted in improvement in hip joint conformation and hip laxity in a dysplastic cat. Juvenile pubic symphysiodesis may be a promising treatment for feline hip dysplasia and is a safe and technically simple procedure to perform. Further investigations are warranted.

Cemento-osseous dysplasia in an elderly Asian male: a case report.

PubMed

Komabayashi, Takashi; Zhu, Qiang

2011-03-01

Cemento-osseous dysplasia is a disorder typically found in middle-aged black women. However, the present report describes a case in a 61-year-old Vietnamese male. Without proper pulp testing and diagnosis, the radiographic presentation can easily be misdiagnosed as periapical periodontitis. On the basis of pulp vitality, lack of clinical symptoms and radiographic features, the diagnosis in this case was periapical cemento-osseous dysplasia at the mixed stage, which generally requires no treatment. At the 18-month follow-up, the patient was still asymptomatic and none of the clinical signs had changed. This case highlights the importance of careful clinical examination, including a pulp vitality test, and of having an unbiased view of age, gender, and ethnicity when diagnosing this condition.

[Local treatment of cervical intraepithelial neoplasia with a 5 percent fluorouracil ointment].

PubMed

Barten, G

1987-01-01

The results of treatment of histologically proven cervical intraepithelial neoplasia (CIN) in 10 women are described. Two of them had CIN I and 8 CIN III. All patients had a application of 5 g 5 per cent 5-fluorouracil cream in a cervical cup daily over a period of 12 hours for one week. All 10 patients have been examined colposcopically, cytological and by biopsy following therapy. In 8 women cone biopsie were done 6-12 months afterwards for having a final diagnosis 2 patients having CIN I pretherapeutically were follow up for 16 months with cytology, colposcopy and punch biopsy. In 6 cases we found better findings (Twice complete healing, twice only CIN I and twice CIN II as residues). In 4 cases severe dysplasia and carcinoma in situ could be found in endocervix. Based on these results were recommended more (not only one) treatment cycles for local efficient chemotherapy using 5 per cent 5-fluorouracil cream.

McCune Albright syndrome in association with excessive GH secretion: case report.

PubMed

Özsu, Elif; Mutlu, Gül Yeşiltepe; Çizmecioğlu, Filiz Mine; Hatun, Şükrü

2015-06-01

McCune-Albright Syndrome is a rare syndrome characterized with excessive function of peripheral endocrine organs and activating mutations of the stimulatory G protein alpha subunit are involved in the pathogenesis. The three main findings of the disease include hyperpigmented café au lait spots, fibrous dysplasia and increased endocrine functions and excessive secretion of growth hormone is observed in 21% of the patients. Clinical signs may be missed in these patients because of precocious puberty and craniofacial fibrous dysplasia. Since radiotherapy causes to sarcomatous changes and transsphenoidal surgery may cause to severe thickening in the cranial bones, they are not appropriate treatment options and medical treatment is recommended. Bromocriptine, cabergoline and octreotide or different combinations of these drugs are used in treatment and pegvisomant has also been used in recent years. Here, we present a male patient aged 12 years and 7 months to show gigantism as a rare clinical reflection of McCune-Albright Syndrome with an excessive height (197 cm), café au lait spots, growht hormone levels which could not be supressed with oral glucose tolerance test and increased prolactin levels.

Congenital heart defects in oculodentodigital dysplasia: Report of two cases.

PubMed

Izumi, Kosuke; Lippa, Andrew M; Wilkens, Alisha; Feret, Holly A; McDonald-McGinn, Donna M; Zackai, Elaine H

2013-12-01

Oculodentodigital dysplasia is caused by mutations in the GJA1 gene. Oculodentodigital dysplasia presents with a spectrum of clinical features including craniofacial, ocular, dental, and limb anomalies. Although recent findings implicate the major role of GJA1 during cardiac organogenesis, congenital heart defects are infrequently reported in oculodentodigital dysplasia. Here we report on two patients with GJA1 mutations presenting with cardiac malformations and type III syndactyly. Patient 1 presented with pulmonary atresia, an intact septum, right ventricular hypoplasia and tricuspid stenosis. The infant had a small nose, thin columella and bilateral 4-5 syndactyly of the fingers. A de novo c.226C>T (p.Arg76Cys) mutation was identified. Patient 2 presented at 6 months with a ventricular septal defect. The child had hypoplastic alae nasi with a thin columella and bilateral 4-5 syndactyly of the digits. A de novo missense mutation, c.145C>G (p.Gln49Glu) was found. Our two patients underscore the importance of cardiac evaluations as part of the initial workup for patients with findings of oculodentodigital dysplasia. Conversely, those patients with type III syndactyly and congenital heart defect should be screened for GJA1 mutations. © 2013 Wiley Periodicals, Inc.

Spinal Cord Injury After Extremity Surgery in Children With Thoracic Kyphosis.

PubMed

Pruszczynski, Blazej; Mackenzie, William G; Rogers, Kenneth; White, Klane K

2015-10-01

Spinal cord injury is a rare complication after lower extremity surgery in children with skeletal dysplasia and thoracic kyphosis. We encountered two patients who had this complication, from among 51 (39 from Nemours/Alfred I. duPont Hospital for Children and 12 from Seattle Children's Hospital) who underwent lower extremity surgery during an 8.5-year period (June 2004 to December 2012). Because spinal cord injury is a devastating complication likely not known to most physicians treating patients with skeletal dysplasias, we sought to examine factors that may contribute to this rare complication. We performed a retrospective review of two patients with skeletal dysplasia who had paraplegia develop after extremity surgery. Outcome measures included operative time, vital signs, and postsurgery recovery of neurologic deficit. MR images were reviewed. Two patients were found-an 8.5-year-old boy with spondyloepiphyseal dysplasia congenita with a 76°-thoracic kyphosis apex at T4 and a 6.5-year-old boy with mucopolysaccharidosis type 1-H with an 80°-thoracic kyphosis apex at T2. Bilateral proximal femoral osteotomies or bilateral innominate and proximal femoral osteotomies had been performed. The spinal cord injuries occurred at the apex of the kyphosis as determined by clinical examination and MRI assessment. In both patients, the mean arterial blood pressure decreased below 50 mm Hg and might be a factor in the etiology of the paralysis. The first patient recovered motor function in 5 months; the second had no recovery. Paraplegia is extremely rare after nonspine operations. Many factors contribute to the risk for a spinal cord event: low mean arterial pressure, duration of the surgery, position on the operating table, the kyphotic spine deformity, or unappreciated vascular disease. Motor-evoked potentials and somatosensory-evoked potentials together potentially provide high sensitivity and specificity for predicting a postoperative neurologic deficit. Based on our two patients with skeletal dysplasia and a literature review of patients with hyperkyphosis undergoing extremity surgery, the surgeon must be aware of the risk of spinal cord injury. Careful preoperative assessment possibly including MRI of the spine is recommended. Mean arterial pressure should be maintained at a safe level; neuromonitoring should be considered.

Clinical and pathological findings of severe subvalvular aortic stenosis and mitral dysplasia in a rottweiler puppy.

PubMed

Fernández del Palacio, M J; Bayón, A; Bernal, L J; Cerón, J J; Navarro, J A

1998-10-01

Subvalvular aortic stenosis (SAS) and mitral dysplasia were diagnosed in an asymptomatic eight-week-old rottweiler. Clinical and pathological findings were compatible with a fixed and dynamic obstruction of the left ventricular outflow tract. Gross and microscopic pathological findings were consistent with the most severe form of SAS, described previously in Newfoundland dogs over six months of age. These observations demonstrate that very young asymptomatic puppies may suffer a severe complex form of SAS.

Lung volume reduction surgery in bronchopulmonary dysplasia.

PubMed

Siaplaouras, J; Heckmann, M; Reiss, I; Schaible, T; Waag, K L; Gortner, L

2003-06-01

We report on a female preterm infant of 29 wk gestational age, who developed acquired lobar emphysema after prolonged artificial ventilation secondary to respiratory disease syndrome and bronchopulmonary dysplasia. The infant underwent atypical segmentectomy at the age of 12 mo because of life-threatening hypoxaemia with pulmonary hypertension and failure of conservative treatment. Lung volume reduction surgery (LVRS) dramatically improved the respiratory function and resulted in adequate weight gain and psychomotor development. In selected cases LVRS can be an option for lobar emphysema in premature infants with severe bronchopulmonary dysplasia.

Early diagnosis of regional odontodysplasia in an infant.

PubMed

Canela, Alfredo Hiram Carrillo; Rezende, Karla Mayra Pinto E Carvalho; Benitez, Mirtha; Bönecker, Marcelo

2012-03-01

Regional odontodysplasia is a rare and significant dental malformation. It is a dental alteration of unknown etiology, involving both mesodermal and ectodermal dental components, which present clinical, radiographic, and histologic features. This article reports a clinical case of a 10-month-old child who was diagnosed with regional odontodysplasia in the maxilla, confirmed by radiographic examination, with a follow-up of 5 years. The clinical, radiographic, and histologic features were reviewed.

A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates.

PubMed

Plouhinec, Jean-Louis; Medina-Ruiz, Sofía; Borday, Caroline; Bernard, Elsa; Vert, Jean-Philippe; Eisen, Michael B; Harland, Richard M; Monsoro-Burq, Anne H

2017-10-01

During vertebrate neurulation, the embryonic ectoderm is patterned into lineage progenitors for neural plate, neural crest, placodes and epidermis. Here, we use Xenopus laevis embryos to analyze the spatial and temporal transcriptome of distinct ectodermal domains in the course of neurulation, during the establishment of cell lineages. In order to define the transcriptome of small groups of cells from a single germ layer and to retain spatial information, dorsal and ventral ectoderm was subdivided along the anterior-posterior and medial-lateral axes by microdissections. Principal component analysis on the transcriptomes of these ectoderm fragments primarily identifies embryonic axes and temporal dynamics. This provides a genetic code to define positional information of any ectoderm sample along the anterior-posterior and dorsal-ventral axes directly from its transcriptome. In parallel, we use nonnegative matrix factorization to predict enhanced gene expression maps onto early and mid-neurula embryos, and specific signatures for each ectoderm area. The clustering of spatial and temporal datasets allowed detection of multiple biologically relevant groups (e.g., Wnt signaling, neural crest development, sensory placode specification, ciliogenesis, germ layer specification). We provide an interactive network interface, EctoMap, for exploring synexpression relationships among genes expressed in the neurula, and suggest several strategies to use this comprehensive dataset to address questions in developmental biology as well as stem cell or cancer research.

A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates

PubMed Central

Borday, Caroline; Bernard, Elsa; Vert, Jean-Philippe; Eisen, Michael B.; Harland, Richard M.

2017-01-01

During vertebrate neurulation, the embryonic ectoderm is patterned into lineage progenitors for neural plate, neural crest, placodes and epidermis. Here, we use Xenopus laevis embryos to analyze the spatial and temporal transcriptome of distinct ectodermal domains in the course of neurulation, during the establishment of cell lineages. In order to define the transcriptome of small groups of cells from a single germ layer and to retain spatial information, dorsal and ventral ectoderm was subdivided along the anterior-posterior and medial-lateral axes by microdissections. Principal component analysis on the transcriptomes of these ectoderm fragments primarily identifies embryonic axes and temporal dynamics. This provides a genetic code to define positional information of any ectoderm sample along the anterior-posterior and dorsal-ventral axes directly from its transcriptome. In parallel, we use nonnegative matrix factorization to predict enhanced gene expression maps onto early and mid-neurula embryos, and specific signatures for each ectoderm area. The clustering of spatial and temporal datasets allowed detection of multiple biologically relevant groups (e.g., Wnt signaling, neural crest development, sensory placode specification, ciliogenesis, germ layer specification). We provide an interactive network interface, EctoMap, for exploring synexpression relationships among genes expressed in the neurula, and suggest several strategies to use this comprehensive dataset to address questions in developmental biology as well as stem cell or cancer research. PMID:29049289

A unique case of intracorneal aberrant lenticular rest.

PubMed

Adulkar, Namrata; Santhi, R; Kim, Usha

2013-06-01

Phakomatous chorsitomas are rare congenital tumors of lenticular anlage believed to be caused by invagination of surface ectoderm into the mesoderm. They may present as a mass lesion in the eyelid or in the orbit. We report a rare case of lenticular anlage occurring within the corneal stroma in a 6-month-old boy. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Specific NEMO mutations impair CD40-mediated c-Rel activation and B cell terminal differentiation

PubMed Central

Jain, Ashish; Ma, Chi A.; Lopez-Granados, Eduardo; Means, Gary; Brady, William; Orange, Jordan S.; Liu, Shuying; Holland, Steven; Derry, Jonathan M.J.

2004-01-01

Hypomorphic mutations in the zinc finger domain of NF-κB essential modulator (NEMO) cause X-linked hyper-IgM syndrome with ectodermal dysplasia (XHM-ED). Here we report that patient B cells are characterized by an absence of Ig somatic hypermutation (SHM) and defective class switch recombination (CSR) despite normal induction of activation-induced cytidine deaminase (AID) and Iε-Cε transcripts. This indicates that AID expression alone is insufficient to support neutralizing antibody responses. Furthermore, we show that patient B cells stimulated with CD40 ligand are impaired in both p65 and c-Rel activation, and whereas addition of IL-4 can enhance p65 activity, c-Rel activity remains deficient. This suggests that these NF-κB components have different activation requirements and that IL-4 can augment some but not all NEMO-dependent NF-κB signaling. Finally, using microarray analysis of patient B cells we identified downstream effects of impaired NF-κB activation and candidate factors that may be necessary for CSR and SHM in B cells. PMID:15578091

Two sibs who are double heterozygotes for achondroplasia and pseudoachondroplastic dysplasia.

PubMed Central

Woods, C G; Rogers, J G; Mayne, V

1994-01-01

We report a family in which two sibs have both achondroplasia and pseudoachondroplastic dysplasia. The mother has achondroplasia and the father has pseudoachondroplastic dysplasia, which he had inherited from his father. Both children appeared typical of achondroplasia at birth. By 1 1/2 years they had developed a fixed lumbar kyphosis with gibbus and had additional x ray changes unusual for just achondroplasia and suggestive of pseudoachondroplastic dysplasia. Subsequently both children have shown characteristic features of both conditions and have grown less well than expected for achondroplasia. Radiographs show the striking synergistic effects of the two conditions. MRI in both sibs confirmed brain stem compression at the foramen magnum. This may be an important complication and should be actively sought in any double heterozygote. Images PMID:7966194

Comparisons and Limitations of Current Definitions of Bronchopulmonary Dysplasia for the Prematurity and Respiratory Outcomes Program.

PubMed

Poindexter, Brenda B; Feng, Rui; Schmidt, Barbara; Aschner, Judy L; Ballard, Roberta A; Hamvas, Aaron; Reynolds, Anne Marie; Shaw, Pamela A; Jobe, Alan H

2015-12-01

Bronchopulmonary dysplasia is the most common morbidity of prematurity, but the validity and utility of commonly used definitions have been questioned. To compare three commonly used definitions of bronchopulmonary dysplasia in a contemporary prospective, multicenter observational cohort of extremely preterm infants. At 36 weeks postmenstrual age, the following definitions of bronchopulmonary dysplasia were applied to surviving infants with and without imputation: need for supplemental oxygen (Shennan definition), National Institutes of Health Workshop definition, and "physiologic" definition after a room-air challenge. Of 765 survivors assessed at 36 weeks, bronchopulmonary dysplasia was diagnosed in 40.8, 58.6, and 32.0% of infants, respectively, with the Shennan, workshop and physiologic definitions. The number of unclassified infants was lowest with the workshop definition (2.1%) and highest with the physiologic definition (16.1%). After assigning infants discharged home in room air before 36 weeks as no bronchopulmonary dysplasia, the modified Shennan definition compared favorably to the workshop definition, with 2.9% unclassified infants. Newer management strategies with nasal cannula flows up to 4 L/min or more and 0.21 FiO2 at 36 weeks obscured classification of bronchopulmonary dysplasia status in 12.4% of infants. Existing definitions of bronchopulmonary dysplasia differ with respect to ease of data collection and number of unclassifiable cases. Contemporary changes in management of infants, such as use of high-flow nasal cannula, limit application of existing definitions and may result in misclassification. A contemporary definition of bronchopulmonary dysplasia that correlates with respiratory morbidity in childhood is needed. Clinical trial registered with www.clinicaltrials.gov (NCT01435187).

Lineage specific expression of Polycomb Group Proteins in human embryonic stem cells in vitro.

PubMed

Pethe, Prasad; Pursani, Varsha; Bhartiya, Deepa

2015-05-01

Human embryonic (hES) stem cells are an excellent model to study lineage specification and differentiation into various cell types. Differentiation necessitates repression of specific genes not required for a particular lineage. Polycomb Group (PcG) proteins are key histone modifiers, whose primary function is gene repression. PcG proteins form complexes called Polycomb Repressive Complexes (PRCs), which catalyze histone modifications such as H2AK119ub1, H3K27me3, and H3K9me3. PcG proteins play a crucial role during differentiation of stem cells. The expression of PcG transcripts during differentiation of hES cells into endoderm, mesoderm, and ectoderm lineage is yet to be shown. In-house derived hES cell line KIND1 was differentiated into endoderm, mesoderm, and ectoderm lineages; followed by characterization using RT-PCR for HNF4A, CDX2, MEF2C, TBX5, SOX1, and MAP2. qRT-PCR and western blotting was performed to compare expression of PcG transcripts and proteins across all the three lineages. We observed that cells differentiated into endoderm showed upregulation of RING1B, BMI1, EZH2, and EED transcripts. Mesoderm differentiation was characterized by significant downregulation of all PcG transcripts during later stages. BMI1 and RING1B were upregulated while EZH2, SUZ12, and EED remained low during ectoderm differentiation. Western blotting also showed distinct expression of BMI1 and EZH2 during differentiation into three germ layers. Our study shows that hES cells differentiating into endoderm, mesoderm, and ectoderm lineages show distinct PcG expression profile at transcript and protein level. © 2015 International Federation for Cell Biology.

A novel FGFR3-binding peptide inhibits FGFR3 signaling and reverses the lethal phenotype of mice mimicking human thanatophoric dysplasia

PubMed Central

Jin, Min; Yu, Ying; Qi, Huabing; Xie, Yangli; Su, Nan; Wang, Xiaofeng; Tan, Qiaoyan; Luo, Fengtao; Zhu, Ying; Wang, Quan; Du, Xiaolan; Xian, Cory J.; Liu, Peng; Huang, Haiyang; Shen, Yue; Deng, Chu-Xia; Chen, Di; Chen, Lin

2012-01-01

Gain-of-function mutations in fibroblast growth factor receptor-3 (FGFR3) lead to several types of human skeletal dysplasia syndromes including achondroplasia, hypochondroplasia and thanatophoric dysplasia (TD). Currently, there are no effective treatments for these skeletal dysplasia diseases. In this study, we screened, using FGFR3 as a bait, a random 12-peptide phage library and obtained 23 positive clones that share identical amino acid sequences (VSPPLTLGQLLS), named as peptide P3. This peptide had high binding specificity to the extracellular domain of FGFR3. P3 inhibited tyrosine kinase activity of FGFR3 and its typical downstream molecules, extracellular signal-regulated kinase/mitogen-activated protein kinase. P3 also promoted proliferation and chondrogenic differentiation of cultured ATDC5 chondrogenic cells. In addition, P3 alleviated the bone growth retardation in bone rudiments from mice mimicking human thanatophoric dysplasia type II (TDII). Finally, P3 reversed the neonatal lethality of TDII mice. Thus, this study identifies a novel inhibitory peptide for FGFR3 signaling, which may serve as a potential therapeutic agent for the treatment of FGFR3-related skeletal dysplasia. PMID:23014564

A randomized, prospective cross-over trial comparing methylene blue-directed biopsy and conventional random biopsy for detecting intestinal metaplasia and dysplasia in Barrett's esophagus.

PubMed

Ragunath, K; Krasner, N; Raman, V S; Haqqani, M T; Cheung, W Y

2003-12-01

The value of methylene blue-directed biopsies (MBDB) in detecting specialized intestinal metaplasia and dysplasia in Barrett's esophagus remains unclear. The aim of this study was to compare the accuracy of MBDB with random biopsy in detecting intestinal metaplasia and dysplasia in patients with Barrett's esophagus. A prospective, randomized, cross-over trial was undertaken to compare MBDB with random biopsy in patients with Barrett's esophagus segments 3 cm or more in length without macroscopic evidence of dysplasia or cancer. Dysplasia was graded as: indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, or carcinoma, and was reported in a blinded fashion. Fifty-seven patients were recruited, 44 of whom were male. A total of 1,269 biopsies were taken (MBDB-651, random biopsie-618). Analysis of the results by per-biopsy protocol showed that the MBDB technique diagnosed significantly more specialized intestinal metaplasia (75 %) compared to the random biopsy technique (68 %; P = 0.032). The sensitivity and specificity rates of MBDB for diagnosing specialized intestinal metaplasia were 91 % (95 % CI, 88 - 93 %) and 43 % (95 % CI, 36 - 51 %), respectively. The sensitivity and specificity rates of MBDB for diagnosing dysplasia or carcinoma were 49 % (95 % CI, 38 - 61 %) and 85 % (95 % CI, 82 - 88 %), respectively. There were no significant differences in the diagnosis of dysplasia and carcinoma - MBDB 12 %, random biopsy 10 %. The methylene blue staining pattern appeared to have an influence on the detection of specialized intestinal metaplasia and dysplasia/carcinoma. Dark blue staining was associated with increased detection of specialized intestinal metaplasia (P < 0.0001), and heterogeneous staining (P = 0.137) or no staining (P = 0.005) were associated with dysplasia and/or carcinoma detection. The MBDB technique prolonged the endoscopy examination by an average of 6 min. The diagnostic accuracy of the MBDB technique was superior to that of the random biopsy technique for identifying specialized intestinal metaplasia, but not dysplasia or carcinoma. The intensity of methylene blue staining has an influence on the detection of specialized intestinal metaplasia and dysplasia or carcinoma, which may help in targeting the biopsies. Although MBDB prolongs the endoscopy procedure slightly, it is a safe and well-tolerated procedure. Further clinical studies on the MBDB technique exclusively in endoscopically normal dysplastic Barrett's esophagus are needed.

Phenotype in a patient with p.D50N mutation in GJB2 gene resemble both KID and Clouston syndromes.

PubMed

Markova, T G; Brazhkina, N B; Bliznech, E A; Bakhshinyan, V V; Polyakov, A V; Tavartkiladze, G A

2016-02-01

Keratitis-ichthyosis-deafness (KID) syndrome (OMIM 148210) is a rare ectodermal dysplasia syndrome characterized by vascularizing keratitis, congenital profound sensorineural hearing loss, and progressive erythrokeratoderma. We have found a 148G-A transition in the GJB2 gene, resulting in an asp50-to-asn (D50N) substitution in a girl with congenital deafness. This finding allowed us to diagnose а KID syndrome. But clinical features were uncommon because of a mild skin manifestation, lack of keratitis and unusual appearance resembling Clouston syndrome. Molecular genetic tests showed that it was de novo mutation because parents have normal genotype. Several autosomal dominant mutations in the GJB2 gene (сonnexin 26) now established to underlie many of the affected cases, with the majority of patients harboring the p.D50N mutation. Skin disease-associated mutation of connexin proteins can cause functional disturbances in gap junction intercellular conductance. It is likely that multiple disease mechanisms are involved across the wide spectrum of hereditary diseases relating to connexin proteins. The clinical data may provide additional insights into the dysregulation mechanisms of mutations result in the disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ectodermal Wnt signaling regulates abdominal myogenesis during ventral body wall development.

PubMed

Zhang, Lingling; Li, Hanjun; Yu, Jian; Cao, Jingjing; Chen, Huihui; Zhao, Haixia; Zhao, Jianzhi; Yao, Yiyun; Cheng, Huihui; Wang, Lifang; Zhou, Rujiang; Yao, Zhengju; Guo, Xizhi

2014-03-01

Defects of the ventral body wall are prevalent birth anomalies marked by deficiencies in body wall closure, hypoplasia of the abdominal musculature and multiple malformations across a gamut of organs. However, the mechanisms underlying ventral body wall defects remain elusive. Here, we investigated the role of Wnt signaling in ventral body wall development by inactivating Wls or β-catenin in murine abdominal ectoderm. The loss of Wls in the ventral epithelium, which blocks the secretion of Wnt proteins, resulted in dysgenesis of ventral musculature and genito-urinary tract during embryonic development. Molecular analyses revealed that the dermis and myogenic differentiation in the underlying mesenchymal progenitor cells was perturbed by the loss of ectodermal Wls. The activity of the Wnt-Pitx2 axis was impaired in the ventral mesenchyme of the mutant body wall, which partially accounted for the defects in ventral musculature formation. In contrast, epithelial depletion of β-catenin or Wnt5a did not resemble the body wall defects in the ectodermal Wls mutant. These findings indicate that ectodermal Wnt signaling instructs the underlying mesodermal specification and abdominal musculature formation during ventral body wall development, adding evidence to the theory that ectoderm-mesenchyme signaling is a potential unifying mechanism for the origin of ventral body wall defects. Copyright © 2013 Elsevier Inc. All rights reserved.

Tooth, hair and claw: comparing epithelial stem cell niches of ectodermal appendages

PubMed Central

Naveau, Adrien; Seidel, Kerstin; Klein, Ophir D.

2014-01-01

The vertebrate ectoderm gives rise to organs that produce mineralized or keratinized substances, including teeth, hair, and claws. Most of these ectodermal derivatives grow continuously throughout the animal’s life and have active pools of adult stem cells that generate all the necessary cell types. These organs provide powerful systems for understanding the mechanisms that enable stem cells to regenerate or renew ectodermally derived tissues, and remarkable progress in our understanding of these systems has been made in recent years using mouse models. We briefly compare what is known about stem cells and their niches in incisors, hair follicles, and claws, and we examine expression of Gli1 as a potential example of a shared stem cell marker. We summarize some of the features, structures, and functions of the stem cell niches in these ectodermal derivatives; definition of the basic elements of the stem cell niches in these organs will provide guiding principles for identification and characterization of the niche in similar systems. PMID:24530577

3D-printed navigation template in proximal femoral osteotomy for older children with developmental dysplasia of the hip

PubMed Central

Zheng, Pengfei; Xu, Peng; Yao, Qingqiang; Tang, Kai; Lou, Yue

2017-01-01

To explore the feasibility of 3D-printed navigation template in proximal femoral varus rotation and shortening osteotomy for older children with developmental dysplasia of the hip (DDH). Between June 2014 and May 2015, navigation templates were designed and used for 12 DDH patients. Surgical information and outcomes were compared to 13 patients undergoing the same surgery but without navigation template. In template-guided patient group, operation time (21.08 min vs. 46.92 min), number of X-ray exposures (3.92 vs. 6.69), and occurrence of femoral epiphysis damage (0 vs. 0.92) were significantly decreased (P < 0.05). Furthermore, after 12–18 months follow-up, 66.7% and 16.7% of the hips in template-guided group were rated as excellent or good, respectively, according to the McKay criteria; 83.3% and 16.7% by using the Severin criteria respectively. By contrast, 46.2% and 23.1% of the hips in traditional operation group were classed as excellent or good, respectively, using the McKay criteria; 46.2% and 30.8% by using the Severin criteria respectively. The template-guided group achieved a better outcome; however, there was no significant difference. Application of the navigation template for older DDH children can reduce the operation time, radiation exposure, and epiphysis damage, which also simplifies surgery and improves precision. PMID:28322290

Longitudinal outcomes of radiofrequency ablation versus surveillance endoscopy for Barrett's esophagus with low-grade dysplasia.

PubMed

Kahn, A; Al-Qaisi, M; Kommineni, V T; Callaway, J K; Boroff, E S; Burdick, G E; Lam-Himlin, D M; Temkit, M; Vela, M F; Ramirez, F C

2018-04-01

Radiofrequency ablation of Barrett's esophagus with low-grade dysplasia is recommended in recent American College of Gastroenterology guidelines, with endoscopic surveillance considered a reasonable alternative. Few studies have directly compared outcomes of radiofrequency ablation to surveillance and those that have are limited by short duration of follow-up. This study aims to compare the long-term effectiveness of radiofrequency ablation versus endoscopic surveillance in a large, longitudinal cohort of patients with Barrett's esophagus, and low-grade dysplasia.We conducted a retrospective analysis of patients with confirmed low-grade dysplasia at a single academic medical center from 1991 to 2014. Patients progressing to high-grade dysplasia or esophageal adenocarcinoma within one year of index LGD endoscopy were defined as missed dysplasia and excluded. Risk factors for progression were assessed via Cox proportional hazards model. Comparison of progression risk was conducted using a Kaplan-Meier analysis. Subset analyses were conducted to examine the effect of reintroducing early progressors and excluding patients diagnosed prior to the advent of ablative therapy. Of 173 total patients, 79 (45.7%) underwent radiofrequency ablation while 94 (54.3%) were untreated, with median follow up of 90 months. Seven (8.9%) patients progressed to high-grade dysplasia or adenocarcinoma despite ablation, compared with 14 (14.9%) undergoing surveillance (P = 0.44). This effect was preserved when patients diagnosed prior to the introduction of radiofrequency ablation were excluded (8.9% vs 13%, P = 0.68). Reintroduction of patients progressing within the first year of follow-up resulted in a trend toward significance for ablation versus surveillance (11.1% vs 23.8%, P = 0.053).In conclusion, progression to high-grade dysplasia or adenocarcinoma was not significantly reduced in the radiofrequency ablation cohort when compared to surveillance. Despite recent studies suggesting the superiority of radiofrequency ablation in reducing progression, diligent endoscopic surveillance may provide similar long-term outcomes.

Incidence, Risk Factors, and Outcomes of Colorectal Cancer in Patients With Ulcerative Colitis With Low-Grade Dysplasia: A Systematic Review and Meta-analysis.

PubMed

Fumery, Mathurin; Dulai, Parambir S; Gupta, Samir; Prokop, Larry J; Ramamoorthy, Sonia; Sandborn, William J; Singh, Siddharth

2017-05-01

Little is known about outcomes of patients with ulcerative colitis with low-grade dysplasia (UC-LGD). We estimated the incidence of and risk factors for progression to colorectal cancer (CRC) in cohorts of patients with UC-LGD who underwent surveillance (surveillance cohort), and the prevalence of dysplasia-related findings among patients who underwent colectomy for UC-LGD (surgical cohort). We performed a systematic literature review through June 1, 2016, to identify cohort studies of adults with UC-LGD. We estimated pooled incidence rates of CRC and risk factors associated with dysplasia progression in surveillance cohorts, and prevalence of synchronous advanced neoplasia (CRC and/or high-grade dysplasia) in surgical cohorts. In 14 surveillance cohort studies of 671 patients with UC-LGD (52 developed CRC), the pooled annual incidence of CRC was 0.8% (95% confidence interval [CI], 0.4-1.3); the pooled annual incidence of advanced neoplasia was 1.8% (95% CI, 0.9-2.7). Risk of CRC was higher when LGD was diagnosed by expert gastrointestinal pathologist (1.5%) than by community pathologists (0.2%). Factors significantly associated with dysplasia progression were concomitant primary sclerosing cholangitis (odds ratio [OR], 3.4; 95% CI, 1.5-7.8), invisible dysplasia (vs visible dysplasia; OR, 1.9; 95% CI, 1.0-3.4), distal location (vs proximal location; OR, 2.0; 95% CI, 1.1-3.7), and multifocal dysplasia (vs unifocal dysplasia; OR, 3.5; 95% CI, 1.5-8.5). In 12 surgical cohort studies of 450 patients who underwent colectomy for UC-LGD, 34 patients had synchronous CRC (pooled prevalence, 17%; 95% CI, 8-33). In a systematic review of the literature, we found that among patients with UC-LGD under surveillance, the annual incidence of progression to CRC was 0.8%; differences in rates of LGD diagnosis varied with pathologists' level of expertise. Concomitant primary sclerosing cholangitis, invisible dysplasia, distal location, and multifocal LGD are high-risk features associated with dysplasia progression. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Treatment of Crowe Type-IV Hip Dysplasia Using Cementless Total Hip Arthroplasty and Double Chevron Subtrochanteric Shortening Osteotomy: A 5- to 10-Year Follow-Up Study.

PubMed

Li, Xigong; Lu, Yang; Sun, Junying; Lin, Xiangjin; Tang, Tiansi

2017-02-01

The purpose of this study was to evaluate the functional and radiographic results of patients with Crowe type-IV hip dysplasia treated by cementless total hip arthroplasty and double chevron subtrochanteric osteotomy. From January 2000 to February 2006, cementless total hip arthroplasty with a double chevron subtrochanteric shortening osteotomy was performed on 18 patients (22 hips) with Crowe type-IV dysplasia. The acetabular cup was placed in the position of the anatomic hip center, and subtrochanteric femoral shortening osteotomy was performed with the use of a double chevron design. The clinical and radiographic outcomes were reviewed with a mean follow-up of 6.5 years (5-10 years). The mean amount of femoral subtrochanteric shortening was 38 mm (25-60 mm). All osteotomy sites were healed by 3-6 months without complications. The mean Harris Hip Score improved significantly from 47 points (35-65 points) preoperatively to 88 points (75-97 points) at the final follow-up. The Trendelenburg sign was corrected from a positive preoperative status to a negative postoperative status in 12 of 22 hips. No acetabular and femoral components have loosened or required revision during the period of follow-up. Cementless total hip arthroplasty using double chevron subtrochanteric osteotomy allowed for restoration of anatomic hip center with safely functional limb lengthening, achieved correction of preoperative limp, and good functional and radiographic outcomes for 22 Crowe type-IV dislocation hips at the time of the 5- to 10-year follow-up. Copyright © 2016 Elsevier Inc. All rights reserved.

Phenotypic Variation in Patients with Homozygous c.1678G>T Mutation in EVC Gene: Report of Two Mexican Families with Ellis-van Creveld Syndrome

PubMed Central

Ibarra-Ramirez, Marisol; Campos-Acevedo, Luis Daniel; Lugo-Trampe, Jose; Martínez-Garza, Laura E.; Martinez-Glez, Víctor; Valencia-Benitez, María; Lapunzina, Pablo; Ruiz-Peréz, Víctor

2017-01-01

Case series Patient: — Final Diagnosis: Ellis van Creveld syndrome Symptoms: Conical teeth • polydactyly • short stature Medication: — Clinical Procedure: — Specialty: Pediatrics and Neonatology Objective: Rare disease Background: Ellis-van Creveld syndrome is an autosomal recessive chondro-ectodermal dysplasia characterized by disproportionate short stature, limb shortening, narrow chest, postaxial polydactyly and dysplastic nails and teeth. In addition, 60% of cases present congenital heart defects. Ellis-van Creveld syndrome is predominantly caused by mutations in the EVC or EVC2 (4p16) genes, with only a few cases caused by mutations in WDR35. Case Report: Here, we report on two Mexican families with patients diagnosed with Ellis-van Creveld syndrome. Family 1 includes four patients: three females of 15, 18, and 23 years of age and a 7-year old male. Family 2 has only one affected newborn male. All patients exhibited multiple features including hypodontia, dysplastic teeth, extra frenula, mild short stature, distal limb shortening, postaxial polydactyly of hands and feet, nail dystrophy, and knee joint abnormalities. Only two patients had an atrial septal defect. In all cases, molecular analysis by Sanger sequencing identified the same homozygous mutation in exon 12 of EVC, c.1678G>T, which leads to a premature stop codon. Conclusions: The mutation c.1678G>T has been previously reported in another Mexican patient and it appears to be a recurrent mutation in Mexico which could represent a founder mutation. The large number of patients in this case allows the clinical variability and spectrum of manifestations present in individuals with Ellis-van Creveld syndrome even if they carry the same homozygous mutation in a same family. PMID:29229899

Ultrasound diagnosis of fetal thanatophoric skeletal dysplasia: Three cases report and a brief review.

PubMed

Zhao, Qing-Hong; Shi, Hua; Hu, Jia-Qi; Wang, Dan; Fang, Gui; Zhang, Yu-Guo; Wang, Yan-Qing; Yang, Jing

2017-02-01

Congenital skeletal deformity of fetus varies and may be attributed to a range of reasons. Congenital skeletal deformity seriously affects body function or even leads to neonatal death directly. The disease brings great pain to victim and their family. We reviewed the fetal prenatal ultrasonic data conducted during period from Jan. 2013 to June 2016, and there were 84 fetuses with skeletal abnormalities among 12 000 cases, and 3 fetuses with thanatophoric dysplasia. Our report described and reviewed three common types of thanatophoric dysplasia, aiming to explore the value of standardized prenatal ultrasonic diagnosis of fetal abnormalities in the skeletal system.

Tissue distribution of cells derived from the area opaca in heterospecific quail-chick blastodermal chimeras

PubMed Central

Karagenç, Levent; Sandikci, Mustafa

2010-01-01

The objective of the current study was to determine the tissue distribution of cells derived from the area opaca in heterospecific quail-chick blastodermal chimeras. Quail-chick chimeras were constructed by transferring dissociated cells from the area opaca of the stage X–XII (EG&K) quail embryo into the subgerminal cavity of the unincubated chick blastoderm. The distribution of quail cells in embryonic as well as extra-embryonic tissues of the recipient embryo were examined using the QCPN monoclonal antibody after 6 days of incubation in serial sections taken at 100-μm intervals. Data gathered in the present study demonstrated that, when introduced into the subgerminal cavity of a recipient embryo, cells of the area opaca are able to populate not only extra-embryonic structures such as the amnion and the yolk sac, but also various embryonic tissues derived from the ectoderm and less frequently the mesoderm. Ectodermal chimerism was confined mainly to the head region and was observed in tissues derived from the neural ectoderm and the surface ectoderm, including the optic cup, diencephalon and lens. Although the possibility of random incorporation of transplanted cells into these embryonic structures cannot be excluded, these results would suggest that area opaca, a peripheral ring of cells in the avian embryo destined to form the extra-embryonic ectoderm and endoderm of the yolk sac, might harbor cells that have the potential to give rise to various cell types in the recipient chick embryo, including those derived from the surface ectoderm and neural ectoderm. PMID:19900180

Candidate EDA targets revealed by expression profiling of primary keratinocytes from Tabby mutant mice

PubMed Central

Esibizione, Diana; Cui, Chang-Yi; Schlessinger, David

2009-01-01

EDA, the gene mutated in anhidrotic ectodermal dysplasia, encodes ectodysplasin, a TNF superfamily member that activates NF-kB mediated transcription. To identify EDA target genes, we have earlier used expression profiling to infer genes differentially expressed at various developmental time points in Tabby (Eda-deficient) compared to wild-type mouse skin. To increase the resolution to find genes whose expression may be restricted to epidermal cells, we have now extended studies to primary keratinocyte cultures established from E19 wild-type and Tabby skin. Using microarrays bearing 44,000 gene probes, we found 385 preliminary candidate genes whose expression was significantly affected by Eda loss. By comparing expression profiles to those from Eda-A1 transgenic skin, we restricted the list to 38 “candidate EDA targets”, 14 of which were already known to be expressed in hair follicles or epidermis. We confirmed expression changes for 3 selected genes, Tbx1, Bmp7, and Jag1, both in keratinocytes and in whole skin, by Q-PCR and Western blotting analyses. Thus, by the analysis of keratinocytes, novel candidate pathways downstream of EDA were detected. PMID:18848976

Ectoderm gene activation in sea urchin embryos mediated by the CCAAT-binding factor.

PubMed

Li, Xiaotao; Bhattacharya, Chitralekha; Dayal, Sandeep; Maity, Sankar; Klein, William H

2002-05-01

Transcriptional enhancers are short stretches of DNA that function to achieve highly specific patterns of gene expression. To identify the mechanisms by which enhancers achieve their specificity, we made use of an enhancer from the aboral ectoderm-specific spec2a gene of the sea urchin Strongylocentrotus purpuratus. The spec2a enhancer contains five cis-regulatory elements within 78 base pairs that interact with five distinct DNA-binding proteins to confer aboral ectoderm expression. Here, we present an analysis of the sea urchin CCAAT binding factor (CBF), which binds to a CCAAT motif within the spec2a enhancer. S. purpuratus CBF and SpOtx, a ubiquitously expressed factor, act together at closely placed cis-regulatory elements to mediate spec2a transcription in the ectoderm. SpCBF was the sole factor that bound to the spec2a CCAAT element, and two of the three subunits that make up the CBF holoprotein were cloned and shown to have high sequence conservation with their vertebrate orthologs. Based on its involvement in the regulation of several other sea urchin genes, SpCBF appears to be a major transcription factor in the sea urchin embryo for positive regulation of ectoderm gene expression. In addition to its role in vertebrate cell growth and proliferation, our results indicate that CBF also functions at the early stages of germ layer formation, namely ectoderm differentiation.

Abnormal primary and permanent dentitions with ectodermal symptoms predict WNT10A deficiency.

PubMed

Bergendal, Birgitta; Norderyd, Johanna; Zhou, Xiaolei; Klar, Joakim; Dahl, Niklas

2016-11-24

The WNT10A protein is critical for the development of ectodermal appendages. Variants in the WNT10A gene may be associated with a spectrum of ectodermal abnormalities including extensive tooth agenesis. In seven patients with severe tooth agenesis we identified anomalies in primary dentition and additional ectodermal symptoms, and assessed WNT10A mutations by genetic analysis. Investigation of primary dentition revealed peg-shaped crowns of primary mandibular incisors and three individuals had agenesis of at least two primary teeth. The permanent dentition was severely affected in all individuals with a mean of 21 missing teeth. Primary teeth were most often present in positions were succedaneous teeth were missing. Furthermore, most existing molars had taurodontism. Light, brittle or coarse hair was reported in all seven individuals, hyperhidrosis of palms and soles in six individuals and nail anomalies in two individuals. The anomalies in primary dentition preceded most of the additional ectodermal symptoms. Genetic analysis revealed that all seven individuals were homozygous or compound heterozygous for WNT10A mutations resulting in C107X, E222X and F228I. We conclude that tooth agenesis and/or peg-shaped crowns of primary mandibular incisors, severe oligodontia of permanent dentition as well as ectodermal symptoms of varying severity may be predictors of bi-allelic WNT10A mutations of importance for diagnosis, counselling and follow-up.

K-ras mutations and HLA-DR expression in large bowel adenomas.

PubMed Central

Norheim Andersen, S.; Breivik, J.; Løvig, T.; Meling, G. I.; Gaudernack, G.; Clausen, O. P.; Schjölberg, A.; Fausa, O.; Langmark, F.; Lund, E.; Rognum, T. O.

1996-01-01

A total of 72 sporadic colorectal adenomas in 56 patients were studied for the presence of point mutations in codons 12 and 13 of the K-ras gene and for HLA-DR antigen expression related to clinicopathological variables. Forty K-ras mutations in 39 adenomas were found (54%): 31 (77%) in codon 12 and nine (23%) in codon 13. There was a strong relationship between the incidence of K-ras mutations and adenoma type, degree of dysplasia and sex. The highest frequency of K-ras mutations was seen in large adenomas of the villous type with high-grade dysplasia. Fourteen out of 15 adenomas obtained from 14 women above 65 years of age carried mutations. HLA-DR positivity was found in 38% of the adenomas, large tumours and those with high-grade dysplasia having the strongest staining. Coexpression of K-ras mutations and HLA-DR was found significantly more frequently in large and highly dysplastic adenomas, although two-way analysis of variance showing size and grade of dysplasia to be the most important variable. None of the adenomas with low-grade dysplasia showed both K-ras mutation and HLA-DR positivity (P = 0.004). K-ras mutation is recognised as an early event in colorectal carcinogenesis. The mutation might give rise to peptides that may be presented on the tumour cell surface by class II molecules, and thereby induce immune responses against neoplastic cells. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:8679466

Cementless total hip arthroplasty with a double chevron subtrochanteric shortening osteotomy in patients with Crowe type-IV hip dysplasia.

PubMed

Li, Xigong; Sun, Junying; Lin, Xiangjin; Xu, Sanzhong; Tang, Tiansi

2013-06-01

The authors describe a modified double chevron subtrochanteric shortening osteotomy combined with cementless total hip arthroplasty for Crowe type-IV hip dysplasia. Shortening the femur allows to relax the shortened musculature. This operation was performed in 18 patients (22 hips) between January 2000 and February 2006. The mean follow-up period was 5.6 years (range: 3 to 8 years). The mean amount of femoral subtrochanteric shortening was 38 mm (range: 25 to 60 mm). The mean Harris hip score improved from 47 (range: 35 to 65) preoperatively to 88 points (range: 75 to 97) at final follow-up. The Trendelenburg sign was corrected from positive to negative in 12 of 22 hips. No acetabular or femoral components loosened or required revision during the follow-up period. All osteotomy sites healed in 3 to 6 months without complications. Cementless total hip arthroplasty using the modified double chevron subtrochanteric osteotomy provided good short- to midterm results in all 22 Crowe type-IV hip dislocations. Moreover, it restored the anatomic hip center and the limb length, which contributed to correction of the preoperative limp.

Clinical and neuropathological study about the neurotization of the suprascapular nerve in obstetric brachial plexus lesions

PubMed Central

2009-01-01

Background The lack of recovery of active external rotation of the shoulder is an important problem in children suffering from brachial plexus lesions involving the suprascapular nerve. The accessory nerve neurotization to the suprascapular nerve is a standard procedure, performed to improve shoulder motion in patients with brachial plexus palsy. Methods We operated on 65 patients with obstetric brachial plexus palsy (OBPP), aged 5-35 months (average: 19 months). We assessed the recovery of passive and active external rotation with the arm in abduction and in adduction. We also looked at the influence of the restoration of the muscular balance between the internal and the external rotators on the development of a gleno-humeral joint dysplasia. Intraoperatively, suprascapular nerve samples were taken from 13 patients and were analyzed histologically. Results Most patients (71.5%) showed good recovery of the active external rotation in abduction (60°-90°). Better results were obtained for the external rotation with the arm in abduction compared to adduction, and for patients having only undergone the neurotization procedure compared to patients having had complete plexus reconstruction. The neurotization operation has a positive influence on the glenohumeral joint: 7 patients with clinical signs of dysplasia before the reconstructive operation did not show any sign of dysplasia in the postoperative follow-up. Conclusion The neurotization procedure helps to recover the active external rotation in the shoulder joint and has a good prevention influence on the dysplasia in our sample. The nerve quality measured using histopathology also seems to have a positive impact on the clinical results. PMID:19744351

Wnt ligands from the embryonic surface ectoderm regulate ‘bimetallic strip’ optic cup morphogenesis in mouse

PubMed Central

Carpenter, April C.; Smith, April N.; Wagner, Heidi; Cohen-Tayar, Yamit; Rao, Sujata; Wallace, Valerie; Ashery-Padan, Ruth; Lang, Richard A.

2015-01-01

The Wnt/β-catenin response pathway is central to many developmental processes. Here, we assessed the role of Wnt signaling in early eye development using the mouse as a model system. We showed that the surface ectoderm region that includes the lens placode expressed 12 out of 19 possible Wnt ligands. When these activities were suppressed by conditional deletion of wntless (Le-cre; Wlsfl/fl) there were dramatic consequences that included a saucer-shaped optic cup, ventral coloboma, and a deficiency of periocular mesenchyme. This phenotype shared features with that produced when the Wnt/β-catenin pathway co-receptor Lrp6 is mutated or when retinoic acid (RA) signaling in the eye is compromised. Consistent with this, microarray and cell fate marker analysis identified a series of expression changes in genes known to be regulated by RA or by the Wnt/β-catenin pathway. Using pathway reporters, we showed that Wnt ligands from the surface ectoderm directly or indirectly elicit a Wnt/β-catenin response in retinal pigment epithelium (RPE) progenitors near the optic cup rim. In Le-cre; Wlsfl/fl mice, the numbers of RPE cells are reduced and this can explain, using the principle of the bimetallic strip, the curvature of the optic cup. These data thus establish a novel hypothesis to explain how differential cell numbers in a bilayered epithelium can lead to shape change. PMID:25715397

Height outcome of short children with hypochondroplasia after recombinant human growth hormone treatment: a meta-analysis.

PubMed

Massart, Francesco; Miccoli, Mario; Baggiani, Angelo; Bertelloni, Silvano

2015-11-01

Hypochondroplasia (HCH) is a genetic skeletal dysplasia, characterized by rhizomelic short height (Ht) with facial dysmorphology and lumbar hyperlordosis. Albeit there are concerns that HCH children may not achieve optimal long-term outcome in response to recombinant human growth hormone (rhGH), anecdotal experiences suggested at least short-term Ht improvement. After thorough search of published studies, meta-analysis of rhGH use in HCH children was performed. In 113 HCH children, rhGH administration (median 0.25 mg/kg/week) progressively improved Ht pattern with 12 months catch-up growth (p < 0.0001). Then, Ht improvement resulted constant until 36 months (p < 0.0001), but stature remained subnormal. While bone age chronologically progressed, no serious adverse events were reported. In conclusion, our meta-analysis indicates that rhGH treatment progressively improved Ht outcome of HCH subjects.

CSF otorhinorrhea in a child with inner ear dysplasia: diagnosis with T2-weighted and intrathecal contrast-enhanced MR cisternography.

PubMed

Mehdi, Elnur; Alkan, Alpay; Yetis, Huseyin; Aralasmak, Ayse; Ozdemir, Huseyin

2014-07-01

During the follow-up of recurrent pneumonia in a 9-month-old girl, rhinorrhea with discharge of a positional and intermittent nature was discovered. Radiological assessment was requested to detect any skull base openings and cerebrospinal fluid (CSF) leakage. T2-weighted MR cisternography showed bilateral inner ear dysplasia, communication of the internal auditory canal with the vestibule, and effusion in the right middle ear. Intrathecal contrast-enhanced MR cisternography revealed a CSF fistula from the right internal auditory canal to the Eustachian tube. The patient was operated upon on the right side, and the presence of a CSF leak near the oval window was confirmed. No adverse effects were seen during the short-term and long-term follow-up. Diagnosing this case required special attention, careful examination, and relevant investigations to find the site of CSF leakage in this patient with bilateral inner ear dysplasia.

Lung Volume Reduction Surgery for Respiratory Failure in Infants With Bronchopulmonary Dysplasia.

PubMed

Sohn, Bongyeon; Park, Samina; Park, In Kyu; Kim, Young Tae; Park, June Dong; Park, Sung-Hye; Kang, Chang Hyun

2018-04-01

Lung volume reduction surgery (LVRS) can be performed in patients with severe emphysematous disease. However, LVRS in pediatric patients has not yet been reported. Here, we report our experience with 2 cases of pediatric LVRS. The first patient was a preterm infant girl with severe bronchopulmonary dysplasia, pulmonary hypertension, and hypothyroidism. The emphysematous portion of the right lung was removed via sternotomy and right hemiclamshell incision. The patient was discharged on full-time home ventilator support for 3 months after the surgery. Since then, her respiratory function has improved continuously. She no longer needs oxygen supplementation or ventilator care. Her T-cannula was removed recently. The second patient was also a preterm infant girl with bronchopulmonary dysplasia. She was born with pulmonary hypertension and multiple congenital anomalies, including an atrial septal defect. Despite receiving the best supportive care, she could not be taken off the mechanical ventilator because of severe hypercapnia. We performed LVRS on the right lung via thoracotomy. She was successfully weaned off the mechanical ventilator 1 month after the surgery. She was discharged without severe complications at 3 months after the operation. At present, she is growing well with the help of intermittent home ventilator support. She can now tolerate an oral diet. Our experience shows that LVRS can be considered as a treatment option for pediatric patients with severe emphysematous lung. It is especially helpful for discontinuing prolonged mechanical ventilator care for patients with respiratory failure. Copyright © 2018 by the American Academy of Pediatrics.

Long-term follow-up results of stepwise radical endoscopic resection for Barrett's esophagus with early neoplasia.

PubMed

Belghazi, Kamar; van Vilsteren, Frederike G I; Weusten, Bas L A M; Meijer, Sybren L; Bergman, Jacques J G H M; Pouw, Roos E

2018-01-01

Stepwise radical endoscopic resection (SRER) has shown to be effective in eradicating Barrett's esophagus (BE) and its associated dysplasia. The aim of this study was to assess the long-term durability after successful SRER for early Barrett's neoplasia. Patients treated with SRER for BE ≤5 cm with high-grade dysplasia (HGD) or early cancer (EC) and who had reached complete eradication of intestinal metaplasia (CE-IM) and neoplasia (CE-neo) were included. Primary outcomes were recurrence of neoplasia (HGD/EC), recurrence of dysplasia (indefinite for dysplasia included), and recurrence of endoscopically visible BE. Secondary outcomes were buried Barrett's glands, IM in biopsy specimens obtained distal to a normal-appearing neo-squamocolumnar junction (neo-SCJ), need for retreatment, and sustained CE-IM and CE-neo at the last follow-up endoscopy. Seventy-three patients were included (64 men; mean age, 66 years; median BE, C2M3). Median follow-up was 76 months. Recurrence of neoplasia was observed in 1 patient (T1bN0M0) after 129 months of follow-up and was treated with curative surgery (annual incidence of .22% per patient-year of follow-up). In 4 patients, recurrence of dysplasia was found (.87% per patient-year of follow-up). Twelve patients had recurrent endoscopically visible BE after a median follow-up of 22 months (2.6% per patient-year of follow-up), mostly small islands or tongues. Five patients had a single finding of buried Barrett's glands (1.1% per patient-year of follow-up), and 27 patients (5.9% per patient-year of follow-up) showed IM in biopsy specimens just distal to the neo-SCJ, which was not reproduced in 56%. Retreatment was performed in 9 patients. CE-IM and CE-neo (excluding IM in the neo-SCJ) at the last follow-up endoscopy was seen in 95% and 97% of patients, respectively. This study presents the longest published follow-up data on SRER to date. The 6-year outcomes show that successful SRER is a durable treatment for BE ≤5 cm with HGD/EC. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

MURCS association.

PubMed

Balasubramanian, S; Muralinath, S; Shivbalan, So; Sripathi, V; Shivakumar, S

2004-07-01

The MURCS association i.e. MUllerian duct aplasia, Renal aplasia, Cervicothoracic Somite dysplasia is a rare developmental disorder. The authors report a case of MURCS association with supernumerary ribs in a 7-month-old infant who presented with failure to thrive.

Topically applied 1% voriconazole induces dysplastic changes on the ocular surface: animal study.

PubMed

Arikan, Gul; Karatas, Ezgi; Lebe, Banu; Ayhan, Ziya; Utine, Canan Asli; Kutsoylu, Oya Eren; Gunenc, Uzeyir; Yilmaz, Osman

2018-04-26

To identify the risk of inducing ocular surface dysplasia following topical administration of 1% voriconazole eye drop. Fourteen noninflamed healthy eyes of 14 white adult New Zealand rabbits were included in the study. The rabbits were randomly divided into two groups comprised of 7 rabbits each. Group 1 received topical 1% voriconazole and Group 2 received topical saline as the control group. In all animals, right eye was selected for the study. In Group 1 (Voriconazole Group), single drop of voriconazole was instilled every 10 min consecutively for 17 times a day for 60 days. In Group 2 (Control Group), single drop of saline was instilled every 10 min consecutively for 17 times a day for 60 days. At two months, animals were sacrificed and study eyes were enucleated with the eyelids. The specimens were stained with hematoxylin-eosin and histopathologic changes in cornea, bulbar and palpebral conjunctiva were evaluated under light microscope. There were no macroscopically visible lesions on the ocular surface of any rabbits. Histopathological evaluation showed mild to moderate dysplasia localized mainly in the limbus and extending to the adjacent cornea and bulbar conjunctiva in all rabbits in Voriconazole Group. Severe dysplasia or carcinoma in situ was not observed. In the Control Group, dysplasia was not observed, at all. This animal study provides a possible relationship between topically administered 1% voriconazole and ocular surface dysplasia. We recommend ophthalmologists to be aware of the risk of ocular surface dysplasia in patients received voriconazole eye drop.

In situ hybridization analysis of the temporospatial expression of the midkine/pleiotrophin family in rat embryonic pituitary gland.

PubMed

Fujiwara, Ken; Maliza, Rita; Tofrizal, Alimuddin; Batchuluun, Khongorzul; Ramadhani, Dini; Tsukada, Takehiro; Azuma, Morio; Horiguchi, Kotaro; Kikuchi, Motoshi; Yashiro, Takashi

2014-07-01

Pituitary gland development is controlled by numerous signaling molecules, which are produced in the oral ectoderm and diencephalon. A newly described family of heparin-binding growth factors, namely midkine (MK)/pleiotrophin (PTN), is involved in regulating the growth and differentiation of many tissues and organs. Using in situ hybridization with digoxigenin-labeled cRNA probes, we detected cells expressing MK and PTN in the developing rat pituitary gland. At embryonic day 12.5 (E12.5), MK expression was localized in Rathke's pouch (derived from the oral ectoderm) and in the neurohypophyseal bud (derived from the diencephalon). From E12.5 to E19.5, MK mRNA was expressed in the developing neurohypophysis, and expression gradually decreased in the developing adenohypophysis. To characterize MK-expressing cells, we performed double-staining of MK mRNA and anterior pituitary hormones. At E19.5, no MK-expressing cells were stained with any hormone. In contrast, PTN was expressed only in the neurohypophysis primordium during all embryonic stages. In situ hybridization clearly showed that MK was expressed in primitive (immature/undifferentiated) adenohypophyseal cells and neurohypophyseal cells, whereas PTN was expressed only in neurohypophyseal cells. Thus, MK and PTN might play roles as signaling molecules during pituitary development.

Radiographic Prevalence of Dysplasia, Cam, and Pincer Deformities in Elite Ballet.

PubMed

Harris, Joshua D; Gerrie, Brayden J; Varner, Kevin E; Lintner, David M; McCulloch, Patrick C

2016-01-01

The demands of hip strength and motion in ballet are high. Hip disorders, such as cam and pincer deformities or dysplasia, may affect dance performance. However, the prevalence of these radiographic findings is unknown. To determine the prevalence of radiographic cam and pincer deformities, borderline dysplasia, and dysplasia in a professional ballet company. Cross-sectional study; Level of evidence, 3. An institutional review board-approved cross-sectional investigation of a professional ballet company was undertaken. Male and female adult dancers were eligible for inclusion. Four plain radiographs were obtained (standing anteroposterior pelvis, bilateral false profile, and supine Dunn 45°) and verified for adequacy. Cam and pincer deformities, dysplasia, borderline dysplasia, and osteoarthritis were defined. All plain radiographic parameters were measured and analyzed on available radiographs. Student t test, chi-square test (and Fisher exact test), and Spearman correlation analyses were performed to compare sexes, groups, and the effect of select radiographic criteria. A total of 47 dancers were analyzed (21 males, 26 females; mean age (±SD), 23.8 ± 5.4 years). Cam deformity was identified in 25.5% (24/94) of hips and 31.9% (15/47) of subjects, with a significantly greater prevalence in male dancers than females (48% hips and 57% subjects vs 8% hips and 12% subjects; P < .001 and P = .001, respectively). Seventy-four percent of subjects had at least 2 of 6 radiographic signs of pincer deformity. Male dancers had a significantly greater prevalence of both prominent ischial spine and posterior wall signs (P = .001 and P < .001, respectively), while female dancers had a significantly greater prevalence of coxa profunda (85% female hips vs 26% male hips; P < .001). Eighty-nine percent of subjects had dysplasia or borderline dysplasia in at least 1 hip (37% dysplastic), with a significantly greater prevalence of dysplasia or borderline dysplasia in female versus male dancers (92% female hips vs 74% male hips; P < .022). Further, in those with dysplasia or borderline dysplasia, 92% of female and 82% of male dancers had bilateral findings. In this professional ballet company, a high prevalence of radiographic abnormalities was found, including cam and pincer deformity and dysplasia. The results also revealed several sex-related differences of these abnormalities in this unique population. The long-term implications of these findings in this group of elite athletes remain unknown, and this issue warrants future investigation. © 2015 The Author(s).

Tooth eruption in a patient with craniometaphyseal dysplasia: case report.

PubMed

Hayashibara, T; Komura, T; Sobue, S; Ooshima, T

2000-10-01

Craniometaphyseal dysplasia (CMD) is a very rare genetic disorder of bone remodeling caused by osteoclast dysfunction. The clinical and radiographical features of oral findings are presented in a sporadic case of CMD in a child (age 10 years, 7 months). An intraoral examination showed severe malocclusions, including anterior crossbite and deep bite. Furthermore, a radiographic examination showed increased radiopacity of the maxilla and mandibular bones due to hyperostosis and sclerosis of the jaw. There was no root resorption of the canines or molars in the primary dentition, although root formation of the permanent teeth was proceeding. Dental age was calculated to be approximately 1 year, 4 months younger than his chronological age. The eruption speed of the permanent lateral incisors after the gingival emergence was shown to be within normal values, and we discuss whether the canines and premolars in the permanent dentition could erupt or not.

Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation.

PubMed

Romaniello, Romina; Arrigoni, Filippo; Panzeri, Elena; Poretti, Andrea; Micalizzi, Alessia; Citterio, Andrea; Bedeschi, Maria Francesca; Berardinelli, Angela; Cusmai, Raffaella; D'Arrigo, Stefano; Ferraris, Alessandro; Hackenberg, Annette; Kuechler, Alma; Mancardi, Margherita; Nuovo, Sara; Oehl-Jaschkowitz, Barbara; Rossi, Andrea; Signorini, Sabrina; Tüttelmann, Frank; Wahl, Dagmar; Hehr, Ute; Boltshauser, Eugen; Bassi, Maria Teresa; Valente, Enza Maria; Borgatti, Renato

2017-12-01

To determine the neuroimaging pattern of cerebellar dysplasia (CD) and other posterior fossa morphological anomalies associated with mutations in tubulin genes and to perform clinical and genetic correlations. Twenty-eight patients harbouring 23 heterozygous pathogenic variants (ten novel) in tubulin genes TUBA1A (n = 10), TUBB2B (n = 8) or TUBB3 (n = 5) were studied by a brain MRI scan performed either on a 1.5 T (n = 10) or 3 T (n = 18) MR scanner with focus on the posterior fossa. Cerebellar anomalies were detected in 24/28 patients (86%). CD was recognised in 19/28 (68%) including cortical cerebellar dysplasia (CCD) in 18/28, either involving only the cerebellar hemispheres (12/28) or associated with vermis dysplasia (6/28). CCD was located only in the right hemisphere in 13/18 (72%), including four TUBB2B-, four TUBB3- and five TUBA1A-mutated patients, while in the other five TUBA1A cases it was located only in the left hemisphere or in both hemispheres. The postero-superior region of the cerebellar hemispheres was most frequently affected. The cerebellar involvement in tubulinopathies shows specific features that may be labelled as 'tubulin-related CD'. This pattern is unique and differs from other genetic causes of cerebellar dysplasia. • Cortical cerebellar dysplasia without cysts is suggestive of tubulin-related disorder. • Cerebellar dysplasia in tubulinopathies shows specific features labelled as 'tubulin-related CD'. • Focal and unilateral involvement of cerebellar hemispheres has important implications for counselling.

[Renal dysplasia: clinico-pathologic review].

PubMed

Cunha, A S; de Sousa, J F; Garcia, C

1992-05-01

Histology records from 63 nephrectomies were reviewed; 22 patients had unilateral totally dysplastic kidneys and 5 had polar or segmental dysplasia. A clinicopathological study of these cases was undertaken. In the first group, there was a slight male preponderance and 75% of the patients presented were under two years of age. Urinary tract infection was the most common complaint. 4 patients were diagnosed in utero by ultrasound and 5 infants presented an abdominal mass. Hypertension was documented in a newborn baby. Ipsilateral lower urinary tract anomalies were found in 12 patients and those of the contralateral kidney in 2 children. There were 3 cases of extrarenal anomalies. Histological examination revealed 13 cases of multicystic dysplasia and 9 of solid dysplasia. Metaplastic cartilage was found in 1 case. In the group of segmental dysplasia, age ranging from 27 weeks' gestation to 8 years, at the time of the diagnosis. They all had duplex kidneys and 4 had ureterocele. Histological study in these cases was similar to the one found in the previous series, although superimposed inflammatory changes were more pronounced. Some of the theories regarding the pathogenesis of this disorder are reviewed and the importance of its diagnosis is emphasised.

Ewing's Sarcoma of the Adrenal Gland.

PubMed

Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

2016-01-01

Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.

Computer-assisted brush-biopsy analysis for the detection of dysplasia in a high-risk Barrett's esophagus surveillance population.

PubMed

Anandasabapathy, Sharmila; Sontag, Stephen; Graham, David Y; Frist, Stephen; Bratton, Joan; Harpaz, Noam; Waye, Jerome D

2011-03-01

Barrett's epithelial dysplasia, the direct precursor to esophageal adenocarcinoma, is often unapparent and frequently missed during surveillance of Barrett's esophagus with four-quadrant forceps biopsy protocol. To determine whether the detection of dysplasia is improved by adding computer-assisted brush biopsy (EndoCDx©) to four-quadrant biopsy protocol. Patients with a history of Barrett's esophagus with dysplasia scheduled for endoscopic surveillance were recruited from four academic medical centers. Patients underwent brush biopsy followed by four-quadrant biopsy every 1-2 cm. The results from brush and forceps biopsy were reviewed independently by pathologists blinded to the other's results. Among 151 patients enrolled (124 men, 27 women; mean age: 65), 117 (77.5%) had forceps and brush-biopsy specimens adequate for interpretation. The mean number of forceps biopsies was 11.9 (median 10, range 2-40) and brush biopsies was 2.0 (median 2, range 1-4). The overall yield of forceps alone was 25.2% (n = 38). Brush biopsy added an additional 16 positive cases increasing the yield of dysplasia detection by 42% (95% CI: 20.7-72.7). The number needed to test (NNT) to detect one additional case of dysplasia was 9.4 (95% CI: 6.4-17.7). There were no significant differences in results among different centers, between standard versus jumbo forceps, or between forceps biopsies taken every 1 cm versus every 2 cm. These data suggest that computer-assisted brush biopsy is a useful adjunct to standard endoscopic surveillance regimens for the identification of dysplasia in Barrett's esophagus.

High-dose docosahexaenoic acid supplementation of preterm infants: respiratory and allergy outcomes.

PubMed

Manley, Brett J; Makrides, Maria; Collins, Carmel T; McPhee, Andrew J; Gibson, Robert A; Ryan, Philip; Sullivan, Thomas R; Davis, Peter G

2011-07-01

Docosahexaenoic acid (DHA) has been associated with downregulation of inflammatory responses. To report the effect of DHA supplementation on long-term atopic and respiratory outcomes in preterm infants. This study is a multicenter, randomized controlled trial comparing the outcomes for preterm infants <33 weeks' gestation who consumed expressed breast milk from mothers taking either tuna oil (high-DHA diet) or soy oil (standard-DHA) capsules. Data collected included incidence of bronchopulmonary dysplasia (BPD) and parental reporting of atopic conditions over the first 18 months of life. Six hundred fifty-seven infants were enrolled (322 to high-DHA diet, 335 to standard), and 93.5% completed the 18-month follow-up. There was a reduction in BPD in boys (relative risk [RR]: 0.67 [95% confidence interval (CI): 0.47-0.96]; P=.03) and in all infants with a birth weight of <1250 g (RR: 0.75 [95% CI: 0.57-0.98]; P=.04). There was no effect on duration of respiratory support, admission length, or home oxygen requirement. There was a reduction in reported hay fever in all infants in the high-DHA group at either 12 or 18 months (RR: 0.41 [95% CI: 0.18-0.91]; P=.03) and at either 12 or 18 months in boys (RR: 0.15 [0.03-0.64]; P=.01). There was no effect on asthma, eczema, or food allergy. DHA supplementation for infants of <33 weeks' gestation reduced the incidence of BPD in boys and in all infants with a birth weight of <1250 g and reduced the incidence of reported hay fever in boys at either 12 or 18 months. Copyright © 2011 by the American Academy of Pediatrics.

Outcomes after liquid nitrogen spray cryotherapy in Barrett's esophagus-associated high-grade dysplasia and intramucosal adenocarcinoma: 5-year follow-up.

PubMed

Ramay, Fariha H; Cui, Qingping; Greenwald, Bruce D

2017-10-01

Liquid nitrogen spray cryotherapy (LNSCT) has been shown to be a safe, well-tolerated, and effective therapy for Barrett's esophagus (BE)-associated high-grade dysplasia (BE-HGD) and intramucosal adenocarcinoma (IMC). Long-term follow-up is lacking. The aim of this study was to assess the efficacy, durability, and rate of neoplastic progression after LNSCT in BE-HGD/IMC at 3 and 5 years. In this single-center, retrospective study drawn from a prospective database, patients with BE-HGD/IMC of any length treated with LNSCT were followed with surveillance endoscopy with biopsy for 3 to 5 years. Patients with IMC completely removed by endoscopic resection were included. Outcome measures included complete eradication of HGD (CE-HGD), dysplasia, and intestinal metaplasia; incidence rates; durability of response; location of recurrent intestinal metaplasia and dysplasia; and rate of disease progression. A total of 50 and 40 patients were included in 3-year and 5-year analyses. Initial CE-HGD, dysplasia, and intestinal metaplasia achieved in 98%, 90%, and 60%, respectively. Overall CE-HGD, dysplasia, and intestinal metaplasia at 3 years were 96% (48/50), 94% (47/50), and 82% (41/50), and at 5 years were 93% (37/40), 88% (35/40), and 75% (30/40). Incidence rates of recurrent intestinal metaplasia, dysplasia, and HGD/esophageal adenocarcinoma per person-year of follow-up after initial complete eradication of intestinal metaplasia (CE-IM) were 12.2%, 4.0%, and 1.4% per person-year for the 5-year cohort. Most recurrences were found immediately below the neosquamocolumnar junction. Two of 7 HGD recurrences occurred later than 4 years after initial eradication, and 2 patients (4%) progressed to adenocarcinoma despite treatment. In patients with BE-HGD/IMC, LNSCT is effective in eliminating dysplasia and intestinal metaplasia. Progression to adenocarcinoma was uncommon, and recurrence of dysplasia was successfully treated in most cases. Long-term surveillance is necessary to detect late recurrence of dysplasia. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Holoprosencephaly with caudal dysplasia. Pseudo-trisomy 13 or a distinct entity?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hicks, R.P.B.; Aylsworth, A.S.; Timmons, M.C.

1994-09-01

We have studied three chromosomally normal patients with multiple anomalies that include holoprosencephaly and caudal dysplasia. Each has features found in patients with pseudo-trisomy 13, though each lacks malformations common in that syndrome. Patients 1 and 2 did not have polydactyly and patients 2 and 3 had no congenital heart malformation. Patient 1 is also unusual in that he does not have typical holoprosencephalic facies and is alive at age 25 months. We have also identified two other similar patients in the London Dysmorphology Database, each of which had holoprosencephaly, congenital heart malformation, and imperforate anus. Isolated caudal dysplasia andmore » holoprosencephaly are both causally heterogeneous. They have been reported together rarely in patients with several different syndromes including chromosomal abnormalities, monogenic syndromes, teratogenic insults, and syndromes of unknown cause. Over thirty cases of {open_quotes}pseudo-trisomy 13{close_quotes} have now been reported and eight of these have had features of caudal dysplasia. There have been four with imperforate anus or anal stenosis, one with lumbosacral vertebral anomaly, and three others with bilateral renal agenesis or hypoplasia. Based on our patients and this review of other reported and unreported cases, we suggest that caudal dysplasia may be a significant clinical feature of pseudo-trisomy 13. Alternatively, holoprosencephaly and caudal dysplasia with a normal karyotype may represent a similar though distinct entity. Some may have submicroscopic chromosomal deletions. Molecular studies of regions known to be associated with holoprosencephaly are currently in progress on tissue from Patient 1. We hope these observations will stimulate reports of similarly affected patients to allow better definition of pseudo-trisomy 13 and other overlap syndromes.« less

Epileptogenicity of cortical dysplasia in temporal lobe dual pathology: an electrophysiological study with invasive recordings.

PubMed

Fauser, Susanne; Schulze-Bonhage, Andreas

2006-01-01

Hippocampal sclerosis is often associated with macroscopic or microscopic dysplasia in the temporal neocortex (TN). The relevance of such a dual pathology with regard to epileptogenesis is unclear. This study investigates the role of both pathologies in the generation of ictal and interictal activity. Ictal (113 seizures) and interictal data from invasive EEG recordings with simultaneous depth electrodes in the hippocampus and subdural electrodes over the TN were analysed retrospectively in 12 patients with variable degrees of hippocampal sclerosis and different types of histologically confirmed temporal cortical dysplasia [all male, age at epilepsy onset <1-29 years (mean 9.6 years), age when invasive recordings were performed 6-50 years (mean 28.2 years)]. Of the seizures 41.3% arose from the amygdala/hippocampus complex (AHC), 34.7% from the TN, 22% were simultaneously recorded from AHC and TN (indeterminate seizure onset), and 2% from other regions. In three patients, seizure onset was recorded only from the AHC. In patients with severe hippocampal sclerosis only 12% of the seizures arose from the TN, whereas in patients with mild hippocampal sclerosis 58% arose from the TN. The type of cortical dysplasia, however, did not predict seizure onset in the AHC or TN. Propagation time from the TN to the AHC tended to be shorter (mean 7.4 s) than vice versa (mean 13.7 s). The most common initial ictal patterns in the AHC were rhythmic beta activity (<25 Hz) and repetitive sharp waves, and in the TN were fast activity (>25 Hz) and repetitive sharp waves. The interictal patterns over the TN were similar to those seen over extratemporal focal cortical dysplasias. Simultaneous recordings from the hippocampus and the TN strongly suggest that dysplastic tissue in the TN is often epileptogenic. The quantitative contribution of the hippocampus to seizure generation corresponded with the degree of hippocampal pathology, whereas different subtypes of cortical dysplasia did not affect its relative contribution to seizure generation and even mild forms of dysplasia were epileptogenic.

A combined procedure with Bereiter-type trochleoplasty leads to a stable patellofemoral joint at 5-year follow-up.

PubMed

Wind, Rutger J P; Heesterbeek, Petra J C; Wymenga, Ate B

2018-06-11

Trochlear dysplasia is a major risk factor predisposing to patellar instability and has been reported to occur in up to 85% of patients with recurrent patellar dislocation. Different operative techniques have been described to correct trochlear dysplasia, including the Bereiter technique, in which subchondral bone is removed and the cartilage can be compressed into a U-shaped groove. The hypothesis was that after a Bereiter-type trochleoplasty combined with medialisation of the tibial tubercle and MPFL reconstruction, patellar pain and instability decreased and anatomic reconstruction can be seen radiographically after 5-year follow-up. Between 2004 and 2011, a combined procedure including Bereiter-type trochleoplasty was performed on 21 consecutively included patients (22 knees) with objective patellar instability and severe trochlear dysplasia. Instability and pain were assessed preoperatively and 3, 6, 12, 24 and 60 months postoperatively with the visual analogue scale (VAS) for pain and instability, Kujala, International Knee Documentation Committee Subjective Knee Evaluation (IKDC SKE) and Short Form Health Survey (SF-36). Pre- and postoperatively, a true lateral radiograph was made to investigate the presence of the crossing sign and to measure the trochlear bump and trochlear depth, as well as a sunrise patella view to measure the sulcus angle. VAS pain and instability, Kujala and IKDC SKE improved significantly 5 years after trochleoplasty (p < 0.05). SF-36 showed no significant improvement. None of the patients reported patellar dislocations postoperatively. Sport activities remained limited. Postoperative radiographs showed no crossing sign. There was a significant increase in trochlear depth (p < 0.0001) and also a significant decrease in trochlear bump and sulcus angle (both p < 0.0001). A combined procedure consisting of Bereiter-type trochleoplasty, medialisation of the tibial tubercle and MPFL reconstruction in patients with objective patellar instability and severe trochlear dysplasia resulted in a clear decrease of pain and instability. Radiological assessment showed anatomical reconstruction. Nevertheless, residual symptoms remain and the possibility of future cartilage damage is uncertain. IV.

erbB expression changes in ethanol and 7, 12- dimethylbenz (a) anthracene-induced oral carcinogenesis

PubMed Central

Jacinto-Alemán, Luis F.; García-Carrancá, Alejandro; Leyba-Huerta, Elba R.; Zenteno-Galindo, Edgar; Jiménez-Farfán, María D.

2013-01-01

Objetive: The aim of this study was to determine erbB expression in normal mucosa, oral dysplasia, and invasive carcinomas developed in the hamster’s buccal pouch chemical carcinogenesis model. Study design: Fifty Syrian golden hamsters were equally divided in five groups (A-E); two controls and three experimental group exposed to alcohol, DMBA, or both for 14 weeks. Number of tumors per cheek, volume, histological condition, erbB expression were determined and results were analyzed by the Mann–Whitney U and Dunn’s test. Results: Control groups and those exposed to alcohol (A, B and C respectively) only presented clinical and histological normal mucosa; while those exposed to DMBA or DMBA plus alcohol (D and E groups) developed dysplasia and invasive carcinomas. erbB2, erbB3, and erbB4 increased their expression in alcohol-exposed mucosa, dysplasia, and invasive carcinomas. We observed a similar expression level for erbB2 in dysplasia and carcinomas; while, erbB3 and erbB4 were similar only in carcinomas. Conclusion: The DMBA and alcohol can be considered as carcinogen and promoter for oral carcinogenesis. The erbB expression is different according to their histological condition, suggesting differential participation of the erbB family in oral carcinogenesis induced by alcohol and DMBA. Key words:erbB, 7,12- dimethylbenz(a)anthracene, oral squamous cell carcinoma. PMID:23229248

[Ectodermal Capdepont syndrome and oral prosthetic rehabilitation. About a clinical case].

PubMed

Kumpanya, P; Matshumba, M; Sekele, I B; Mayunga, M; Lutula, P S; Ntumba, M K

2015-03-01

The authors describe the ectodermal Capdepont syndrome as an anomaly characterized by anhidrosis, hypotrichosis and anodontia diagnosed in a 22 year-old adult. In front of this anodontia, oral prosthetic rehabilitation remains the only solution.

Hairless mutation: a driving force of humanization from a human–ape common ancestor by enforcing upright walking while holding a baby with both hands

PubMed Central

Sutou, Shizuyo

2012-01-01

Three major characteristics distinguish humans from other primates: bipedality, practical nakedness, and the family as a social unit. A hairless mutation introduced into the chimpanzee/human last common ancestor (CLCA) 6 million years ago (Mya) diverged hairless human and hairy chimpanzee lineages. All primates except humans can carry their babies without using their hands. A hairless mother would be forced to stand and walk upright. Her activities would be markedly limited. The male partner would have to collect food and carry it to her by hand to keep her and their baby from starving; irresponsible and selfish males could not have left their offspring. The mother would have sexually accepted her partner at any time as a reward for food. Sexual relations irrespective of estrus cycles might have strengthened the pair bond. Molecular and paleontological dating indicates that CLCA existed 6 Mya, and early hominin fossils show that they were bipeds, indicating that humanization from CLCA occurred rapidly. A single mutation in animals with scalp hair is known to induce hairless phenotype (ectodermal dysplasia). Bipedalism and hairlessness are disadvantageous traits; only those who could survive trials and tribulations in cooperation with family members must have been able to evolve as humans. PMID:22404045

Aberrant connexin26 hemichannels underlying keratitis-ichthyosis-deafness syndrome are potently inhibited by mefloquine

PubMed Central

Levit, Noah A.; Sellitto, Caterina; Wang, Hong-Zhan; Li, Leping; Srinivas, Miduturu; Brink, Peter R.; White, Thomas W.

2014-01-01

Keratitis-ichthyosis-deafness (KID) syndrome is an ectodermal dysplasia caused by dominant mutations of connexin26 (Cx26). Loss of Cx26 function causes non-syndromic sensorineural deafness, without consequence in the epidermis. Functional analyses have revealed that a majority of KID-causing mutations confer a novel expansion of hemichannel activity, mediated by connexin channels in a non-junctional configuration. Inappropriate Cx26 hemichannel opening is hypothesized to compromise keratinocyte integrity and epidermal homeostasis. Pharmacological modulators of Cx26 are needed to assess the pathomechanistic involvement of hemichannels in the development of hyperkeratosis in KID syndrome. We have used electrophysiological assays to evaluate small molecule analogs of quinine for suppressive effects on aberrant hemichannel currents elicited by KID mutations. Here, we show that mefloquine inhibits several mutant hemichannel forms implicated in KID syndrome when expressed in Xenopus laevis oocytes (IC50≈16µM), using an extracellular divalent cation, zinc (Zn++), as a non-specific positive control for comparison (IC50≈3µM). Furthermore, we used freshly isolated transgenic keratinocytes to show that micromolar concentrations of mefloquine attenuated increased macroscopic membrane currents in primary mouse keratinocytes expressing human Cx26-G45E, a mutation causing a lethal form of KID syndrome. PMID:25229253

Gastric intestinal metaplasia with basal gland atypia: a morphological and biologic evaluation in a large Chinese cohort.

PubMed

Li, Yuan; Chang, Xiaoyan; Zhou, Weixun; Xiao, Yu; Nakatsuka, Laura N; Chen, Jie; Lauwers, Gregory Y

2013-04-01

Gastric intestinal metaplasia can display cytoarchitectural atypia that falls short of qualifying for dysplasia but can be classified as indefinite for dysplasia. Yet few studies have evaluated the prevalence, the morphologic, and biologic characteristics of this variant. Out of a cohort of 554 biopsies with chronic atrophic gastritis and/or dysplasia, we categorized the cases as either (1) simple intestinal metaplasia; (2) intestinal metaplasia with hyperplasia; (3) intestinal metaplasia with basal gland atypia; and (4) gastric dysplasia. The relationship between the subtypes and various clinicopathologic features, mucin immunophenotypes, and biologic characteristics was evaluated. The final cohort consisted of 424 cases of simple intestinal metaplasia, 93 intestinal metaplasia with hyperplasia, 16 intestinal metaplasia with basal gland atypia, and 21 gastric dysplasia. Intestinal metaplasia with basal gland atypia had a prevalence of 2.8% and similar to gastric dysplasia, 3.7%. Both of these lesions were similar in body/fundus distribution (12.5%) and paucity of goblet cells (68.8%). Intestinal metaplasia with basal gland atypia and gastric dysplasia seem to share some biologic similarities but with a lower frequency of alpha-methylacyl-CoA racemase expression (25% versus 62%), p53 expression (6.3% versus 47.6%), and increased Ki-67 index on surface/pit and isthmus in intestinal metaplasia with basal gland atypia. Alternatively, simple intestinal metaplasia and intestinal metaplasia with hyperplasia did not differ statistically with regard to the various characteristics evaluated. We concluded that gastric intestinal metaplasia can be divided into 2 broad categories that are readily defined by cytoarchitectural and biologic characteristics. Based on the characteristics of intestinal metaplasia with basal gland atypia and in keeping with others, we confirm that this subtype could represent a preneoplastic lesion that needs further evaluation. Copyright © 2013 Elsevier Inc. All rights reserved.

The development of the eyelids. Part I. External features.

PubMed Central

Pearson, A A

1980-01-01

The sequence of developmental events leading to the formation of the eyelids is described in staged human embryos. By the end of the fourth week the optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode (Stage 13). A few days later (about 32 days, Stage 14) the lens placode is indented by the lens pit. A day or two later (about 33 days, Stage 15) the lens pit is closed: however, the lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface. Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it (stage 16, 37 days). As these grooves deepen, in Stages 17--19, eyelid folds develop, first below, and then above, the eye. In Stages 19--22 the eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19. The inner canthus is established a few days later in Stage 20. Closure of the eyelids is complete in Stage 23. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 PMID:7364662

[Partial regression of Barret esophagus with high grade dysplasia and adenocarcinoma after photocoagulation and endocurietherapy under antisecretory treatment].

PubMed

Fremond, L; Bouché, O; Diébold, M D; Demange, L; Zeitoun, P; Thiefin, G

1995-01-01

Barrett's oesophagus is a premalignant condition. The possibility of eradicating at least partially the metaplastic epithelium has been reported recently. In this case report, a patient with Barrett's oesophagus complicated by high grade dysplasia and focal adenocarcinoma was treated by Nd:Yag laser then high dose rate intraluminal irradiation while on omeprazole 40 mg/day. A partial eradication of Barrett's oesophagus and a transient tumoural regression were obtained. Histologically, residual specialized-type glandular tissue was observed beneath regenerative squamous epithelium. Four months after intraluminal irradiation, a local tumoural recurrence was detected while the area of restored squamous epithelium was unchanged on omeprazole 40 mg/day. This indicates that physical destruction of Barrett's oesophagus associated with potent antisecretory treatment can induce a regression of the metaplastic epithelium, even in presence of high grade dysplasia. The persistence of specialized-type glands beneath the squamous epithelium raises important issues about its potential malignant degeneration.

Immune status does not predict high-risk HPV in anal condyloma.

PubMed

Lee, Janet T; Goldberg, Stanley M; Madoff, Robert D; Tawadros, Patrick S

2016-03-01

More than 90% of anal condyloma is attributed to nonhigh risk strains of human papillomavirus (HPV), thus patients with anal condyloma do not necessarily undergo HPV serotyping unless they are immunocompromised (IC). We hypothesized that IC patients with anal condyloma have a higher risk of high-risk HPV and dysplasia than nonimmunocompromised (NIC) patients. We performed a retrospective chart review of patients who underwent surgical treatment by a single surgeon for anal condyloma from 1/2000 to 1/2012. HPV serotyping was performed on all patient samples. We compared incidence of high-risk HPV and dysplasia in condyloma specimens from IC and NIC patients. High-risk HPV was identified in 14 specimens with serotypes 16, 18, 31, 33, 51, 52, and 67. Twenty-two cases (18.3%) had dysplasia. Invasive carcinoma was identified in one IC patient. The prevalence of dysplasia or high-risk HPV was not significantly different between IC and NIC groups. High-risk HPV was a significant independent predictor of dysplasia (odds ratio [OR] = 5.2; 95% CI = 1.24-21.62). Immune status, however, was not a significant predictor of high-risk HPV (OR = 1.11; 95% CI = 0.16-5.12) nor dysplasia (OR = 0.27; 95% CI = 0.037-1.17). IC patients did not have a significantly higher prevalence or risk of high-risk HPV or dysplasia in our study. HPV typing of all condylomata, regardless of immune status, should be considered as it may help predict risk of neoplastic transformation or identify NIC patients with an increased risk of developing anal intraepithelial neoplasia. Copyright © 2016 Elsevier Inc. All rights reserved.

Sox5 is a DNA binding co-factor for BMP R-Smads that directs target specificity during patterning of the early ectoderm

PubMed Central

Nordin, Kara; LaBonne, Carole

2014-01-01

SUMMARY The SoxD factor, Sox5, is expressed in ectodermal cells at times and places where BMP signaling is active, including the cells of the animal hemisphere at blastula stages, and the neural plate border (NPB) and neural crest (NC) at neurula stages. Sox5 is required for proper ectoderm development, and deficient embryos display patterning defects characteristic of perturbations of BMP signaling, including loss of neural crest and epidermis and expansion of the neural plate. We show that Sox5 is essential for activation of BMP target genes in embryos and explants, that it physically interacts with BMP R-Smads, and that it is essential for recruitment of Smad1/4 to BMP regulatory elements. Our findings identify Sox5 as the long sought DNA binding partner for BMP R-Smads essential to plasticity and pattern in the early ectoderm. PMID:25453832

Developmental dysplasia of the hip: addressing evidence gaps with a multicentre prospective international study.

PubMed

Schaeffer, Emily K; Study Group, Ihdi; Mulpuri, Kishore

2018-05-07

There is a lack of high quality evidence available to guide clinical practice in the treatment and management of developmental dysplasia of the hip (DDH). Evidence has been limited by persistent confusion on diagnostic and classification terminology, variability in surgeon decision making and a reliance on single centre, retrospective studies with small patient numbers. To address gaps in knowledge regarding screening, diagnosis and management of DDH, the International Hip Dysplasia Institute began a multicentre, international prospective study on infants with hips dislocated at rest. This review discusses the current state of screening, diagnostic and management practices in DDH and addresses important unanswered questions that will be critical in identifying best practices and optimising patient outcomes. There is insufficient evidence to support universal ultrasound screening; instead, selective screening should be performed by 6-8 weeks of age on infants with risk factors of breech presentation, family history, or history of clinical hip instability. Follow-up of infants with risk factors and normal initial screening should be considered to at least 6 months of age. Brace treatment is a sensible first-line treatment for management of dislocated hips at rest in infants < 6 months of age. Early operative reduction may be considered as there is insufficient evidence to support a protective role for the ossific nucleus in the development of avascular necrosis.

Deletion of OTX2 in neural ectoderm delays anterior pituitary development

PubMed Central

Mortensen, Amanda H.; Schade, Vanessa; Lamonerie, Thomas; Camper, Sally A.

2015-01-01

OTX2 is a homeodomain transcription factor that is necessary for normal head development in mouse and man. Heterozygosity for loss-of-function alleles causes an incompletely penetrant, haploinsufficiency disorder. Affected individuals exhibit a spectrum of features that range from developmental defects in eye and/or pituitary development to acephaly. To investigate the mechanism underlying the pituitary defects, we used different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. Mice homozygous for Otx2 deficiency in early head development and pituitary oral ectoderm exhibit craniofacial defects and pituitary gland dysmorphology, but normal pituitary cell specification. The morphological defects mimic those observed in humans and mice with OTX2 heterozygous mutations. Mice homozygous for Otx2 deficiency in the pituitary neural ectoderm exhibited altered patterning of gene expression and ablation of FGF signaling. The posterior pituitary lobe and stalk, which normally arise from neural ectoderm, were extremely hypoplastic. Otx2 expression was intact in Rathke's pouch, the precursor to the anterior lobe, but the anterior lobe was hypoplastic. The lack of FGF signaling from the neural ectoderm was sufficient to impair anterior lobe growth, but not the differentiation of hormone-producing cells. This study demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe and pituitary stalk, and it has significant extrinsic effects on anterior pituitary growth. Otx2 expression early in head development is important for establishing normal craniofacial features including development of the brain, eyes and pituitary gland. PMID:25315894

Periapical cemento-osseous dysplasia: a case report with twelve-year follow-up and review of literature.

PubMed

Senia, E S; Sarao, M S

2015-11-01

To present a case report describing the long-term behaviour of periapical cemento-osseous dysplasia by observing the radiographic changes that took place over a period of 12 years. A review of the pertinent literature is also presented. A healthy 26-year-old white female was referred to the Wilford Hall USAF Medical Center Endodontic Department for evaluation of an asymptomatic radiolucency at the apex of the right mandibular lateral incisor. Following a clinical evaluation that included pulp testing, a diagnosis of periapical cemento-osseous dysplasia (PCOD) was made. No treatment was rendered but follow-up visits were recommended. The patient was subsequently re-evaluated 8 times over a period of 12 years. During that time the lesion changed in appearance, displaying the various phases of PCOD. At the same time, lesions affecting the three adjoining incisors appeared and behaved in a similar manner. At the 12-year recall, the right lateral and both central incisors revealed no evidence of PCOD and an almost normal trabecular pattern of bone could be seen. Misdiagnosis and unnecessary treatment of PCOD may be avoided with careful pulp testing and knowledge of its most common locations of occurrence, radiographic appearances (phases) and benign behaviour. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Cellular basis of gastrulation in the sand dollar Scaphechinus mirabilis.

PubMed

Kominami, T; Takata, H

2000-12-01

The processes of gastrulation in the sand dollar Scaphechinus mirabilis are quite different from those in regular echinoids. In this study, we explored the cellular basis of gastrulation in this species with several methods. Cell-tracing experiments revealed that the prospective endodermal cells were convoluted throughout the invagination processes. Histological observation showed that the ectodermal layer remained thickened, and the vegetal cells retained an elongated shape until the last step of invagination. Further, most of the vegetal ectodermal cells were skewed or distorted. Wedge-shaped cells were common in the vegetal ectoderm, especially at the subequatorial region. In these embryos, unlike the embryos of regular echinoids, secondary mesenchyme cells did not seem to exert the force to pull up the archenteron toward the inner surface of the apical plate. In fact, the archenteron cells were not stretched along the axis of elongation and were in close contact with each other. Here we found that gastrulation was completely blocked when the embryos were attached to a glass dish coated with poly-L-lysine, in which the movement of the ectodermal layer was inhibited. These results suggest that a force generated by the thickened ectoderm, rather than rearrangement of the archenteron cells, may play a key role in the archenteron elongation in S. mirabilis embryos.

Sleep Quality, Stress, Caregiver Burden, and Quality Of Life in Maternal Caregivers of Young Children With Bronchopulmonary Dysplasia

PubMed Central

Feeley, Christine A.; Turner-Henson, Anne; Christian, Becky J.; Avis, Kristin T.; Heaton, Karen; Lozano, David; Su, Xiaogang

2014-01-01

Little is known about the influence of sleep quality, stress, and caregiver burden on quality of life in maternal caregivers of young children with bronchopulmonary dysplasia (BPD). In 61 maternal caregivers (mean age 29.59 years) of young children with BPD (mean age 13.93 months), caregivers reported sleeping a mean of 5.8 hours, and significant correlations were found between sleep quality and depressive symptoms and stress, as well as an inverse correlation with quality of life. Sleep quality was found to be the most significant predictor of quality of life in maternal caregivers. PMID:23999065

Short stature/short limb skeletal dysplasia with severe combined immunodeficiency and bowing of the femora: report of two patients and review.

PubMed Central

MacDermot, K D; Winter, R M; Wigglesworth, J S; Strobel, S

1991-01-01

We report two patients with severe combined immunodeficiency and short stature/short limb skeletal dysplasia. Case 1 presented at birth with rhizomelic shortening of the extremities and bowing of the femora. She developed clinical signs of severe combined immunodeficiency at 13 months and died at 21 months. Case 2 had severe prenatal shortening and bowing of the extremities and a small, malformed chest. Symptoms of severe combined immunodeficiency and severe failure to thrive developed soon after birth and she died at 5 months. The diagnosis of severe combined immunodeficiency in our patients was based on their clinical course and necropsy findings, supported in case 1 by the results of immune function tests. The results of investigation of immune function (immunoglobulins, lymphocyte subpopulations, lymphocyte function) are very variable in this syndrome as in other variants of severe combined immunodeficiency. Bone histopathology in both patients showed grossly irregular costochondral junctions, but normal transition of proliferating to hypertrophic chondrocytes. These cases belong to early lethal type 1 short limb skeletal dysplasia with severe combined immunodeficiency. Review of previously published cases with severe combined immunodeficiency and well documented skeletal findings show eight patients with prenatal onset of bowing and shortening of the extremities and metaphyseal abnormalities. These include two sib pairs concordant for the skeletal changes. In these cases, adenosine deaminase levels were not reported. An additional four published cases with associated adenosine deaminase deficiency had only mild metaphyseal abnormalities, but subsequently showed no linear growth.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:1999827

Lesion guided stereotactic radiofrequency thermocoagulation for palliative, in selected cases curative epilepsy surgery.

PubMed

Wellmer, Jörg; Parpaley, Yaroslav; Rampp, Stefan; Popkirov, Stoyan; Kugel, Harald; Aydin, Ümit; Wolters, Carsten H; von Lehe, Marec; Voges, Jürgen

2016-03-01

Resective epilepsy surgery is an established treatment option in patients with pharmacoresistant, lesion related epilepsy. Yet, if the presurgical work-up proves multi-focal organization of the epileptogenic zone, or the area of intended resection is close to eloquent brain areas, patients may decide against resections because of an unfavorable risk-benefit-ratio. We assess if lesion guided cortical stereotactic radiofrequency thermocoagulation (L-RFTC) is a potential surgical alternative in these patients. We performed seven procedures of L-RFTC. Three patients had monofocal epilepsy arising close to eloquent structures; in four, invasive pre-surgical workup documented monofocal seizure onset but strong interictal epileptic activity also independent and distant from the seizure onset zone. L-RFTC was restricted to the lesional area (=seizure onset site). 12 to 37 months after RFTC worthwhile seizure improvement was achieved in 6 patients. One patient became seizure free following complete coagulation of a focal cortical dysplasia, two had had 1-2 auras under tapered but not under continued medication. In one patient only subclinical seizures persisted. In one patient hypermotor seizures were transformed into milder short tonic seizures and another one had a seizure reduction by 50%. Only one patient did not profit at all. One patient developed a persisting neurological deficit. In patients with complex epileptogenic zones L-RFTC can lead to worthwhile seizure reduction. This qualifies this procedure as a palliative surgical technique with potential good risk-benefit ratio. In patients with small focal cortical dysplasias L-RFTC may even allow minimal-invasive surgery with curative intention. Copyright © 2016 Elsevier B.V. All rights reserved.

Surgical management of an infected aggressive florid cemento-osseous dysplasia. Report of a case.

PubMed

Martini, M Zillo; de Carvalho Júnior, J Pereira; Soares, H Arid

2006-09-01

Florid cemento-osseous dysplasia (FCOD) is a quite rare condition presenting in the jaws and is most seen in middle-aged black women, from the 4th decade of life on. The pathogenesis of the cemento-osseous dysplasias remains unknown; however, they seem to represent some kind of reactional or dysplastic process. We describe an aggressive case of infected florid cemento-osseous dysplasia (IFCOD) in a 47-year-old black woman. Extensive dysplastic lesions affected all jaw quadrants and radiographic features showed images of irregular radiopaque multilobular masses, peripherally lined by a radiolucent layer. We decided to keep the patient in the hospital in order to perform endovenous medication, hydration, drainage and general care. The surgery planning would be started as soon as regression of the acute feature was observed. Histopathologic analysis revealed the lesion was composed by osseous and cementoid tissues, being its diagnosis compatible with FCOD. The surgical procedure was accomplished with the patient under general anesthesia. It was opted for the excision of the lesion in all quadrants, with sequestrectomy and total dental extraction and remodelling of the alveolar ridges. After 9 months of follow-up the patient is still undergoing clinical control, presenting healing within the expected patterns. Symptomatic cases follow-up should be lasting and periodical, since there are reports of recurrence.

Quantitative Analysis of the Area of the Apical Ectodermal Ridge in Chick Appendages Using Image-J.

PubMed

Syed, Hamd Binte Shahab; Khan, Muhammad Yunus

2018-06-01

To determine the effect of sodium phenytoin on the apical ectodermal ridges (AER) of chick wing buds by using the software program Image-J. An experimental study. Department of Anatomy, Regional Center, College of Physicians and Surgeons Pakistan (CPSP), Islamabad, from January 2014 to January 2015. Sixty fertilised chicken eggs of 'Egyptian fayoumi' breed were selected and separated into experimental (B) and control (A) groups, each having 30 eggs. A single dose of 3.5 mg sodium phenytoin was injected into each egg of the experimental group. The controls were injected with the same volume of normal saline. Developing embryos were extracted 96 hours (day 4) after incubation and histological sections were cut at 5 μm thickness. These sections were stained with Feulgen Nuclear and Light Green. The area of apical ectodermal ridges of chick wing buds was calculated by employing Image-J and subjected to statistical analysis. The difference between the mean values of the area of apical ectodermal ridges of experimental and control groups, as calculated by Image-J, was found to be statistically insignificant. Change in the area of the apical ectodermal ridges in experimental chicks, following phenytoin exposure, was insignificant as proven on the basis of quantification by Image-J.

Vojta method in the treatment of developmental hip dysplasia – a case report

PubMed Central

Kiebzak, Wojciech; Żurawski, Arkadiusz; Dwornik, Michał

2016-01-01

Background Developmental dysplasia of the hip joint is one of the most common congenital defects and often results in functional and structural disorders. Such cases particularly demand optimizing therapeutic effects and maximally reducing the duration of therapy. Purpose The aim of this case report is to present the therapeutic process in a child with developmental hip dysplasia. Case report This is a case report of a female child with a birth weight of 2,800 g and an Apgar score of 9 points born to a gravida 3 para 3 mother at 37 weeks. The child was delivered by cesarean section, and the pregnancy was complicated by oligohydramnios. Subluxation of the left hip joint was diagnosed by an orthopedist in the third month of life. The treatment followed was the Vojta method (the first phase of reflex turning and reflex crawling). Results During the 6 weeks of the Vojta treatment, the left half of the femoral head was centralized, and the process of formation of the hip joint acetabulum was influenced effectively enough to change the acetabulum’s Graff type from the baseline D to IIb after 41 days of treatment. Conclusion The diagnostic work-up of congenital hip joint dysplasia should involve a physiotherapist who will investigate the child’s neuromuscular coordination, in addition to a neonatologist and a pediatrician. The therapy for a disorder of hip joint development of neuromotor origin should involve the application of global patterns according to Vojta. Children with congenital dysplasia of the hip joint should commence rehabilitation as early as possible. PMID:27578980

Height outcome of the recombinant human growth hormone treatment in patients with SHOX gene haploinsufficiency: a meta-analysis.

PubMed

Massart, Francesco; Bizzi, Martina; Baggiani, Angelo; Miccoli, Mario

2013-04-01

Patients with mutations or deletions of the SHOX gene present variable growth impairment, with or without mesomelic skeletal dysplasia. If untreated, short patients with SHOX haplodeficiency (SHOXD) remain short into adulthood. Although recombinant human growth hormone (rhGH) treatment improves short-term linear growth, there are episodic data on the final height of treated SHOXD subjects. After a thorough search of the published literature for pertinent studies, we undertook a meta-analysis evaluation of the efficacy and safety of rhGH treatment in SHOXD patients. In SHOXD patients, administration of rhGH progressively improved the height deficit from baseline to 24 months, although the major catch-up growth was detected after 12 months. The rhGH-induced growth appeared constant until final height. Our meta-analysis suggested rhGH therapy improves height outcome of SHOXD patients, though future studies using carefully titrated rhGH protocols are needed. Original submitted 29 October 2012; Revision submitted 22 February 2013.

Case report: imaging and treatment of ophthalmic manifestations in oculodentodigital dysplasia.

PubMed

Mosaed, Sameh; Jacobsen, Bradley H; Lin, Ken Young

2016-01-07

Diagnostic and surgical management of severe chronic angle- closure glaucoma secondary to ciliary body cysts can be difficult to manage in a patient with oculodentodigital dysplasia. A 6-year old girl with oculodentodigital dysplasia, with progressive chronic angle- closure glaucoma secondary to ciliary body cysts presented to our clinic. The initial examination revealed counting fingers vision in the left eye. Intraocular pressure (IOP), as assessed by tonopen, was 31 mm Hg. Ultrasound biomicroscopy revealed ciliary body cysts in the left eye, and gonioscopy confirmed chronic angle closure. A tube shunt was placed to control the elevated IOP. A year after her tube shunt placement in the left eye, ultrasound biomiscropy was performed on her right eye and showed no ciliary body cysts. Gonioscopy in the right eye revealed an open angle to the ciliary body band. Subsequent serial gonioscopy every 3 months showed gradual narrowing of the right eye angle and finally three-and-a-half years after tube placement of the left eye, her right eye IOP became uncontrolled with medications alone and a tube shunt was similarly placed in the right eye. Intraoperative ultrasound biomicroscopy performed at the time of the right eye tube shunt revealed extensive ciliary body cysts in the right eye. Her IOP in both eyes have been well controlled since the placement of tube shunts. This is one of the first reported cases of severe chronic angle- closure glaucoma secondary to ciliary body cysts in a patient with oculodentodigital dysplasia. We believe that early screening for ciliary body cysts is important in patients with oculodentodigital dysplasia.

[Application of computer-aided osteotomy template design in treatment of developmental dysplasia of the hip with steel osteotomy].

PubMed

Tong, Kuang; Zhang, Yuanzhi; Zhang, Sheng; Yu, Bin

2013-06-01

To provide an accurate method for osteotomy in the treatment of developmental dysplasia of the hip with steel osteotomy by three-dimensional reconstruction and Reverse Engineering technique. Between January 2011 and December 2012, 13 children with developmental dysplasia of the hip underwent steel osteotomy. 3D CT scan pelvic images were obtained and transferred via a DICOM network into a computer workstation to construct 3D models of the hip using Materialise Mimics 14.1 software in STL format. These models were imported into Imageware 12.0 software for steel osteotomy simulation until a stable hip was attained in the anatomical position for dislocation or subluxation of the hip in older children. The osteotomy navigational templates were designed according to the anatomical features after a stable hip was reconstructed. These navigational templates were manufactured using a rapid prototyping technique. The reconstruction hips in these children show good matching property and acetabulum cover. The computer-aided design of osteotomy template provides personalized and accurate solutions in the treatment of developmental dysplasia of the hip with steel osteotomy in older children.

Developmental Dysplasia of the Hip

MedlinePlus

... look for DDH. Identifying and treating the problem early will help a child avoid muscle, joint, and skeletal problems down the ... is needed for several months, depending on the child's condition. Outlook When DDH is recognized early and treated appropriately, most children develop normally and ...

Mutational spectrum of intraepithelial neoplasia in pancreatic heterotopia.

PubMed

Ma, Changqing; Gocke, Christopher D; Hruban, Ralph H; Belchis, Deborah A

2016-02-01

Heterotopic pancreatic parenchyma recapitulates the normal pancreas in extrapancreatic locations and, on rare occasions, can even give rise to pancreatic adenocarcinoma. The genetic signatures of pancreatic adenocarcinoma and its precursor lesions are well characterized. We explored the genetic alterations in precursor lesions (intraductal papillary mucinous neoplasms [IPMN], pancreatic intraepithelial neoplasia [PanIN]) in patients with pancreatic heterotopias but without concomitant pancreatic ductal adenocarcinomas. This allowed us to determine whether the stereotypical dysplasia--infiltrating carcinoma sequence also occurs in these extrapancreatic foci. Seven cases of heterotopic pancreas with ductal precursor lesions were identified. These included 2 IPMNs with focal high-grade dysplasia and 5 PanINs with low- to moderate-grade dysplasia (PanIN grades 1-2). Neoplastic epithelium was microdissected and genomic DNA was extracted. Sequencing of commonly mutated hotspots (KRAS, TP53, CDKN2A, SMAD4, BRAF, and GNAS) in pancreatic ductal adenocarcinoma and its precursor lesions was performed. Both IPMNs were found to have KRAS codon 12 mutations. The identification of KRAS mutations suggests a genetic pathway shared with IPMN of the pancreas. No mutations were identified in our heterotopic PanINs. One of the possible mechanisms for the development of dysplasia in these lesions is field effect. At the time of these resections, there was no clinical or pathologic evidence of a prior or concomitant pancreatic lesion. However, a clinically undetectable lesion is theoretically possible. Therefore, although a field effect cannot be excluded, there was no evidence for it in this study. Copyright © 2015 Elsevier Inc. All rights reserved.

EDARV370A associated facial characteristics in Uyghur population revealing further pleiotropic effects.

PubMed

Peng, Qianqian; Li, Jinxi; Tan, Jingze; Yang, Yajun; Zhang, Manfei; Wu, Sijie; Liu, Yu; Zhang, Juan; Qin, Pengfei; Guan, Yaqun; Jiao, Yi; Zhang, Zhaoxia; Sabeti, Pardis C; Tang, Kun; Xu, Shuhua; Jin, Li; Wang, Sijia

2016-01-01

An adaptive variant of human Ectodysplasin receptor, EDARV370A, had undergone strong positive selection in East Asia. In mice and humans, EDARV370A was found to affect ectodermal-derived characteristics, including hair thickness, hair shape, active sweat gland density and teeth formation. Facial characteristics are also largely ectodermal derived. In this study, taking advantage of an admixed population of East Asian and European ancestry-the Uyghur, we aim to test whether EDARV370A is affecting facial characteristics and to investigate its pleiotropic nature and genetic model. In a sample of 1027 Uyghurs, we discover that EDARV370A is significantly associated with several facial characteristics, in particular shape of earlobe (P = 3.64 × 10 (-6) ) and type of chin (P = 9.23 × 10 (-5) ), with successful replication in other East Asian populations. Additionally, in this Uyghur population, we replicate previous association findings of incisors shoveling (P = 1.02 × 10 (-7) ), double incisors shoveling (P = 1.86 × 10 (-12) ) and hair straightness (P = 3.99 × 10 (-16) ), providing strong evidence supporting an additive model for the EDARV370A associations. Partial least square path model confirms EDARV370A systematically affect these weakly related ectodermal-derived characteristics, suggesting the pleiotropic effect of EDARV370A mainly plays roles in early embryo development. This study extends our knowledge about the pleiotropic nature of EDARV370A and provides potential clues to its adaptation fitness in human evolution.

Presence or absence of intestinal metaplasia but not its burden is associated with prevalent high-grade dysplasia and cancer in Barrett's esophagus.

PubMed

Bansal, A; McGregor, D H; Anand, O; Singh, M; Rao, D; Cherian, R; Wani, S B; Rastogi, A; Singh, V; House, J; Jones, P G; Sharma, P

2014-01-01

Universal agreement on the inclusion of intestinal metaplasia to diagnose Barrett's esophagus (BE) is lacking. Our aim was to determine the association of intestinal metaplasia and its density with the prevalence of dysplasia/cancer in columnar lined esophagus (CLE). Patients with CLE but no intestinal metaplasia (CLE-no IM) were identified by querying the clinical pathology database using SNOMED codes for distal esophageal biopsies. CLE-IM patients were identified from a prospectively maintained database of BE patients. Subsequently, relative risks for prevalent dysplasia and cancer were calculated. Since patients with CLE-no IM are not usually enrolled in surveillance, only prevalent dysplasia/cancer on index endoscopy was analyzed. Goblet cell density and percent intestinal metaplasia were estimated. All biopsy slides were reviewed for dysplasia by two experienced gastrointestinal pathologists. Two hundred sixty-two CLE-IM and 260 CLE-no IM patients were included (age 64±12 vs. 60±11 years, P=0.001; whites 92% vs. 82%, P=0.001; males 99.7% vs. 99.3%, P=NS; CLE length 3.4±3.2 vears 1.4±0.4 cm, P=0.001 and hiatus hernia 64% vs. 56%, P=0.013). The odds of finding low-grade dysplasia and of high-grade dysplasia (HGD)/cancer were 12.5-fold (2.9-53.8, P=0.007) and 4.2-fold (95% CI 1.4-13, P=0.01) higher, respectively, in the CLE-IM group. Reanalysis after controlling for important variables of age, race, and length did not significantly alter the overall results. In CLE-IM group, when patients with high (>50/LPF) versus low goblet cell density (<50/LPF) and <10% versus >10% intestinal metaplasia were compared, the odds of HGD/cancer, OR 1.5 (0.5-4.9, P=0.5) and 1.97 (0.54-7.22), respectively, were not significantly higher. Demonstration of intestinal metaplasia continues to be an essential element in the definition of BE, but its quantification may not be useful for risk stratification of HGD/cancer in BE. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Long-term clinical and radiographic outcome of the PPF system in ceramic-on-polyethylene hip bearings.

PubMed

Legenstein, R; Huber, W; Ungersboeck, A; Boesch, P

2006-01-01

From 1990 to 1991 we implanted 176 non-cemented proximal press-fit (PPF) total hip arthroplasties (THA) with ceramic-on-polyethylene articulation in 170 patients. Of these, 119 patients (122 THA) were followed from 104 to 129 months. Four cups have been revised for aseptic loosening, but revealed no radiolucencies of the stem. Two infections and two dislocations occurred. The median postoperative Harris hip score was 91. Ninety-eight per cent of the patients were satisfied with the outcome, 83% were free of pain and 67% walked without a limp. Serial radiographs showed stable fixation with bone ongrowth in nearly all arthroplasties except for four cups. Stem radiolucencies were first seen within 12 months, but were of no clinical relevance. Proximal periprosthetic bone resorption of the stem was seen in 18%. Radiolucencies occurred because of polyethylene debris-induced granulomas. The PPF system yields satisfactory long-term results in patients with primary and secondary hip osteoarthritis and dysplasia.

Recurrence of Esophageal Intestinal Metaplasia After Endoscopic Mucosal Resection and Radiofrequency Ablation of Barrett’s Esophagus: Results From a US Multicenter Consortium Recurrence of Barrett’s Esophagus after EMR and RFA

PubMed Central

Gupta, Milli; Iyer, Prasad G.; Lutzke, Lori; Gorospe, Emmanuel C.; Abrams, Julian A.; Falk, Gary W.; Ginsberg, Gregory G.; Rustgi, Anil K.; Lightdale, Charles J.; Wang, Timothy C.; Fudman, David I.; Poneros, John M.; Wang, Kenneth K.

2013-01-01

BACKGROUND & AIMS Radiofrequency ablation (RFA) is an established treatment for dysplastic Barrett’s esophagus (BE). Although short-term endpoints of ablation have been ascertained, there have been concerns about recurrence of intestinal metaplasia (IM) after ablation. We aimed to estimate the incidence and identify factors that predicted the recurrence of IM after successful RFA. METHODS We analyzed data from 592 patients with BE treated with RFA from 2003 through 2011 at 3 tertiary referral centers. Complete remission of intestinal metaplasia (CRIM) was defined as eradication of IM (in esophageal and gastro esophageal junction biopsies), documented by 2 consecutive endoscopies. Recurrence was defined as presence of IM or dysplasia after CRIM in surveillance biopsies. Two experienced gastrointestinal pathologists confirmed pathology findings. RESULTS Based on histology analysis, before RFA, 71% of patients had high-grade dysplasia or esophageal adenocarcinoma, 15% had low-grade dysplasia, and 14% had non-dysplastic BE. Of patients treated, 448 (76%) were assessed following RFA. 55% of patients underwent endoscopic mucosal resection before RFA. The median time to CRIM was 22 months, with 56% of patients in CRIM by 24 months. Increasing age and length of BE segment were associated with a longer times to CRIM. Twenty-four months after CRIM, the incidence of recurrence was 33%; 22% of all recurrences observed were dysplastic BE. There were no demographic or endoscopic factors associated with recurrence. Complications developed in 6.5% of subjects treated with RFA; strictures were the most common complication. CONCLUSION Of patients with BE treated by RFA, 56% are in complete remission after 24 months. However, 33% of these patients have disease recurrence within the next 2 years. Most recurrences were non-dysplastic and endoscopically manageable, but continued surveillance after RFA is essential. PMID:23499759

75 FR 58404 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... sclerosis, CD74 deficiency, Ehlers Danlos syndrome (EDS), Marfan/Loewe Dietz syndrome, fibromuscular dysplasia, Kawasaki syndrome, pseudoxanthoma elasticum, and premature placental calcification. Applications... component of the addictive syndrome, with approximately two-thirds of patients relapsing within three months...

Planar induction of anteroposterior pattern in the developing central nervous system of Xenopus laevis

NASA Technical Reports Server (NTRS)

Doniach, T.; Phillips, C. R.; Gerhart, J. C.

1992-01-01

It has long been thought that anteroposterior (A-P) pattern in the vertebrate central nervous system is induced in the embryo's dorsal ectoderm exclusively by signals passing vertically from underlying, patterned dorsal mesoderm. Explants from early gastrulae of the frog Xenopus laevis were prepared in which vertical contact between dorsal ectoderm and mesoderm was prevented but planar contact was maintained. In these, four position-specific neural markers (engrailed-2, Krox-20, XlHbox 1, and XlHbox 6) were expressed in the ectoderm in the same A-P order as in the embryo. Thus, planar signals alone, following a path available in the normal embryo, can induce A-P neural pattern.

Visual rehabilitation in end-stage inflammatory ocular surface disease with the osteo-odonto-keratoprosthesis: results from the UK.

PubMed

Liu, C; Okera, S; Tandon, R; Herold, J; Hull, C; Thorp, S

2008-09-01

To report the long-term results of osteo-odonto-keratoprosthesis (OOKP) surgery in the visual rehabilitation of patients with corneal blindness from end-stage inflammatory ocular surface disease. A non-comparative retrospective case series of 36 consecutive patients treated at the National OOKP referral centre in Brighton, UK, between November 1996 and March 2006. A total of 36 patients, with age ranging from 19 to 87 years (mean 51 (SD 19) years), were included in the analysis. The main preoperative diagnoses were Stevens-Johnson syndrome (n = 16, or 44%), severe thermal or chemical burns (n = 6, or 17%), and mucous membrane pemphigoid (n = 5, or 14%). The remainder of the cases comprised miscellaneous causes of dry eye (n = 9, or 25%), which included one each of graft versus host disease, ectodermal dysplasia, ionising radiation damage, cicatrising conjunctivitis from topical medication, trachoma, congenital trigeminal nerve hypoplasia, linear IgA disease, Sjögren syndrome and nutritional deficiency. Follow-up ranged from 6 months to 9 years (mean 3.9 (SD 2.5) years). Anatomical retention during the entirety of the follow-up period was seen in 72% of patients. The main factor resulting in anatomical failure was resorption of the OOKP lamina, which occurred in seven cases (or 19%). Predicted resorption in three cases resulted in successful planned exchange of the lamina, but two cases underwent emergency removal of the OOKP, and two cases developed endophthalmitis. Human leucocyte antigen-matched allografts suffered a higher rate of laminar resorption. Out of the entire cohort, 30 patients (or 83%) had some improvement in vision, 28 (or 78%) achieved vision of 6/60 or better, and 19 (or 53%) achieved 6/12 or better. The best-achieved vision was retained throughout the follow-up period in 61% of cases. Survival analysis suggested that the probability of retaining vision >6/60 5 years after surgery was 53 (10)%. Vision-threatening complications occurred in nine cases (or 25%) and included endophthalmitis, retinal detachment and glaucoma. De novo glaucoma occurred in six patients (or 24%) but was seen overall in 17 patients (or 47%), 10 of whom required surgical treatment. OOKP surgery can restore useful and lasting vision in patients suffering from end-stage ocular surface disease, for whom conventional corneal surgery is not possible. The main problems seen in this study were laminar resorption, particularly in allografts, and glaucoma.

Cell tracking supports secondary gastrulation in the moon jellyfish Aurelia.

PubMed

Gold, David A; Nakanishi, Nagayasu; Hensley, Nicholai M; Hartenstein, Volker; Jacobs, David K

2016-11-01

The moon jellyfish Aurelia exhibits a dramatic reorganization of tissue during its metamorphosis from planula larva to polyp. There are currently two competing hypotheses regarding the fate of embryonic germ layers during this metamorphosis. In one scenario, the original endoderm undergoes apoptosis and is replaced by a secondary endoderm derived from ectodermal cells. In the second scenario, both ectoderm and endoderm remain intact through development. In this study, we performed a pulse-chase experiment to trace the fate of larval ectodermal cells. We observed that prior to metamorphosis, ectodermal cells that proliferated early in larval development concentrate at the future oral end of the polyp. During metamorphosis, these cells migrate into the endoderm, extending all the way to the aboral portion of the gut. We therefore reject the hypothesis that larval endoderm remains intact during metamorphosis and provide additional support for the "secondary gastrulation" hypothesis. Aurelia appears to offer the first and only described case where a cnidarian derives its endoderm twice during normal development, adding to a growing body of evidence that germ layers can be dramatically reorganized in cnidarian life cycles.

Gigantism treated by pure endoscopic endonasal approach in a case of McCune-Albright syndrome with sphenoid fibrous dysplasia: a case report.

PubMed

Sharifi, Guive; Jalessi, Maryam; Sarvghadi, Farzaneh; Farhadi, Mohammad

2013-12-01

McCune-Albright syndrome (MAS) is an uncommon polyostotic manifestation of fibrous dysplasia in association with at least one endocrinopathy that is mostly associated with precocious puberty and hyperpigmented skin macules named café-au-lait spots. We present an atypical manifestation of McCune-Albright syndrome in a 19-year-old man with the uncommon association of polyostotic fibrous dysplasia and gigantism in the absence of café-au-lait spots and precocious puberty. He presented with a height increase to 202 cm in the previous 3 years, which had become more progressive in the few months prior. Physical examination revealed only a mild facial asymmetry; however, a computed tomography (CT) scan discovered vast areas of voluminous bones with ground-glass density and thickening involving the craniofacial bones and skull base. Magnetic resonance imaging (MRI) found a right stalk shift of the pituitary with a 20 mm pituitary adenoma. We describe the diagnostic and endoscopic endonasal transsphenoidal approach for excision of the tumor. Georg Thieme Verlag KG Stuttgart · New York.

Single Stage Treatment of Non - Union of Transcervical Neck Femur Fracture with Shepherd Crook Deformity of Proximal Femur in A Case of Fibrous Dysplasia using Dynamic Hip Screw Fixation.

PubMed

Vk, Kandhari; Ss, Bava; Mm, Desai; Rn, Wade

2015-01-01

Fibrous dysplasia is a rare benign disorder of the skeletal system characterized by fibro osseous proliferation with intervening areas of normal or immature bone in the intramedullary region. It can either be a monostotic (involves one bone) or a polyostotic (involves more than one bone) presentation and usually occurs equally in males and females. Deformities like scoliosis and shepherd's crook deformity are frequently encountered in the polyostotic form. We report a rare managed case of bilateral non-union of the pathological fracture of femur neck with shepherd's crook deformity of the proximal femur in a case of polyostotic fibrous dysplasia. A 16 years old female case of polyostotic fibrous dysplasia had bilateral Shepherd's crook deformity of the proximal femur with bilateral non - union of pathological fracture of neck femur. We managed each side in one stage with two osteotomies. On the right side, first oblique osteotomy was done from just distal to the greater trochanter up to the level of the neck and the second; lateral closing wedge abduction osteotomy was done at the subtrochanteric level. 2 months later on the left side double lateral closing wedge abduction osteotomies were performed both at the subtrochanteric level. Fixation of both the sides was done using a 135° Dynamic Richard's screw with a long side plate to span the osteotomy sites and the lesion. Post - operatively we achieved a neck shaft angle of 135° on right side and 133° on the left side. Follow up imaging showed union at both the osteotomy sites bilaterally and also at the site of the pathological fracture of neck femur. Presently, at 18 months post - operatively, patient is walking full weight bearing without support and there are no signs of recurrence of lesions of fibrous dysplasia or the deformity. Double osteotomy is an easy and effective method to correct the shepherd's crook deformity and achieve correct mechanical alignment. Dynamic hip screw with long side plate is a versatile implant to tackle the proximal femur deformity. Double osteotomy corrects the deformity and tackles the associated problems like non - union of the pathological neck femur fracture in one stage.

Single Stage Treatment of Non – Union of Transcervical Neck Femur Fracture with Shepherd Crook Deformity of Proximal Femur in A Case of Fibrous Dysplasia using Dynamic Hip Screw Fixation

PubMed Central

VK, Kandhari; SS, Bava; MM, Desai; RN, Wade

2015-01-01

Introduction: Fibrous dysplasia is a rare benign disorder of the skeletal system characterized by fibro osseous proliferation with intervening areas of normal or immature bone in the intramedullary region. It can either be a monostotic (involves one bone) or a polyostotic (involves more than one bone) presentation and usually occurs equally in males and females. Deformities like scoliosis and shepherd’s crook deformity are frequently encountered in the polyostotic form. We report a rare managed case of bilateral non-union of the pathological fracture of femur neck with shepherd’s crook deformity of the proximal femur in a case of polyostotic fibrous dysplasia. Case Report: A 16 years old female case of polyostotic fibrous dysplasia had bilateral Shepherd’s crook deformity of the proximal femur with bilateral non – union of pathological fracture of neck femur. We managed each side in one stage with two osteotomies. On the right side, first oblique osteotomy was done from just distal to the greater trochanter up to the level of the neck and the second; lateral closing wedge abduction osteotomy was done at the subtrochanteric level. 2 months later on the left side double lateral closing wedge abduction osteotomies were performed both at the subtrochanteric level. Fixation of both the sides was done using a 135° Dynamic Richard’s screw with a long side plate to span the osteotomy sites and the lesion. Post – operatively we achieved a neck shaft angle of 135° on right side and 133° on the left side. Follow up imaging showed union at both the osteotomy sites bilaterally and also at the site of the pathological fracture of neck femur. Presently, at 18 months post – operatively, patient is walking full weight bearing without support and there are no signs of recurrence of lesions of fibrous dysplasia or the deformity. Conclusion: Double osteotomy is an easy and effective method to correct the shepherd’s crook deformity and achieve correct mechanical alignment. Dynamic hip screw with long side plate is a versatile implant to tackle the proximal femur deformity. Double osteotomy corrects the deformity and tackles the associated problems like non - union of the pathological neck femur fracture in one stage. PMID:27299066

The incidence of avascular necrosis and the radiographic outcome following medial open reduction in children with developmental dysplasia of the hip: a systematic review.

PubMed

Gardner, R O E; Bradley, C S; Howard, A; Narayanan, U G; Wedge, J H; Kelley, S P

2014-02-01

The incidence of clinically significant avascular necrosis (AVN) following medial open reduction of the dislocated hip in children with developmental dysplasia of the hip (DDH) remains unknown. We performed a systematic review of the literature to identify all clinical studies reporting the results of medial open reduction surgery. A total of 14 papers reporting 734 hips met the inclusion criteria. The mean follow-up was 10.9 years (2 to 28). The rate of clinically significant AVN (types 2 to 4) was 20% (149/734). From these papers 221 hips in 174 children had sufficient information to permit more detailed analysis. The rate of AVN increased with the length of follow-up to 24% at skeletal maturity, with type 2 AVN predominating in hips after five years' follow-up. The presence of AVN resulted in a higher incidence of an unsatisfactory outcome at skeletal maturity (55% vs 20% in hips with no AVN; p < 0.001). A higher rate of AVN was identified when surgery was performed in children aged < 12 months, and when hips were immobilised in ≥ 60° of abduction post-operatively. Multivariate analysis showed that younger age at operation, need for further surgery and post-operative hip abduction of ≥ 60° increased the risk of the development of clinically significant AVN.

Outcome of oral dysplasia: a retrospective hospital-based study of 207 patients with a long follow-up.

PubMed

Arduino, Paolo G; Surace, Antonio; Carbone, Mario; Elia, Alessandra; Massolini, Gianluca; Gandolfo, Sergio; Broccoletti, Roberto

2009-07-01

The aim of this retrospective hospital-based study was to review and evaluate the long-term outcome of patients with oral epithelial dysplasia (OED), with or without surgical intervention, to identify factors affecting clinical course and malignant evolution. Patients with a follow-up of at least 12 months were included. Data collected were statistically analyzed. The mean age was 63.58 years for women (n = 100) and 64.17 years for men (n = 107). One hundred and thirty-five of the patients had lesions with histopathological features of mild OED, 50 had moderate OED and 22 had severe OED. Gender and risk factors seemed not to be related with the development of OED. One hundred and thirty-three patients underwent active treatment. During the period considered, 39.4% of the 207 lesions disappeared; 19.66% remained stable and 33.7% of the total cases showed a new dysplastic event after treatment. Fifteen (7.24%) out of 207 developed a squamous cell carcinoma during follow-up. Our data showed that speckled lesions are more often associated with high histological grade. The risk of malignant development does not seem to be predictable. Surrounded by the limitations of the retrospective designs, we have showed that there is no eminent benefit of surgical intervention of OED in preventing recurrences and malignant development.

Limited hair cell induction from human induced pluripotent stem cells using a simple stepwise method.

PubMed

Ohnishi, Hiroe; Skerleva, Desislava; Kitajiri, Shin-ichiro; Sakamoto, Tatsunori; Yamamoto, Norio; Ito, Juichi; Nakagawa, Takayuki

2015-07-10

Disease-specific induced pluripotent stem cells (iPS) cells are expected to contribute to exploring useful tools for studying the pathophysiology of inner ear diseases and to drug discovery for treating inner ear diseases. For this purpose, stable induction methods for the differentiation of human iPS cells into inner ear hair cells are required. In the present study, we examined the efficacy of a simple induction method for inducing the differentiation of human iPS cells into hair cells. The induction of inner ear hair cell-like cells was performed using a stepwise method mimicking inner ear development. Human iPS cells were sequentially transformed into the preplacodal ectoderm, otic placode, and hair cell-like cells. As a first step, preplacodal ectoderm induction, human iPS cells were seeded on a Matrigel-coated plate and cultured in a serum free N2/B27 medium for 8 days according to a previous study that demonstrated spontaneous differentiation of human ES cells into the preplacodal ectoderm. As the second step, the cells after preplacodal ectoderm induction were treated with basic fibroblast growth factor (bFGF) for induction of differentiation into otic-placode-like cells for 15 days. As the final step, cultured cells were incubated in a serum free medium containing Matrigel for 48 days. After preplacodal ectoderm induction, over 90% of cultured cells expressed the genes that express in preplacodal ectoderm. By culture with bFGF, otic placode marker-positive cells were obtained, although their number was limited. Further 48-day culture in serum free media resulted in the induction of hair cell-like cells, which expressed a hair cell marker and had stereocilia bundle-like constructions on their apical surface. Our results indicate that hair cell-like cells are induced from human iPS cells using a simple stepwise method with only bFGF, without the use of xenogeneic cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction

PubMed Central

Jin, Yong-Ri; Turcotte, Taryn J.; Crocker, Alison L.; Han, Xiang Hua; Yoon, Jeong Kyo

2011-01-01

R-spondins are a recently characterized family of secreted proteins that activate Wnt/β-catenin signaling. Herein, we determine R-spondin2 (Rspo2) function in craniofacial development in mice. Mice lacking a functional Rspo2 gene exhibit craniofacial abnormalities such as mandibular hypoplasia, maxillary and mandibular skeletal deformation, and cleft palate. We found that loss of the mouse Rspo2 gene significantly disrupted Wnt/β-catenin signaling and gene expression within the first branchial arch (BA1). Rspo2, which is normally expressed in BA1 mesenchymal cells, regulates gene expression through a unique ectoderm-mesenchyme interaction loop. The Rspo2 protein, potentially in combination with ectoderm-derived Wnt ligands, up-regulates Msx1 and Msx2 expression within mesenchymal cells. In contrast, Rspo2 regulates expression of the Dlx5, Dlx6, and Hand2 genes in mesenchymal cells via inducing expression of their upstream activator, Endothelin1 (Edn1), within ectodermal cells. Loss of Rspo2 also causes increased cell apoptosis, especially within the aboral (or caudal) domain of the BA1, resulting in hypoplasia of the BA1. Severely reduced expression of Fgf8, a survival factor for mesenchymal cells, in the ectoderm of Rspo2−/− embryos is likely responsible for increased cell apoptosis. Additionally, we found that cleft palate in Rspo2−/− mice is not associated with defects intrinsic to the palatal shelves. A possible cause of cleft palate is a delay of proper palatal shelf elevation that may result from the small mandible and a failure of lowering the tongue. Thus, our study identifies Rspo2 as a mesenchyme-derived factor that plays critical roles in regulating BA1 patterning and morphogenesis through ectodermal-mesenchymal interaction and a novel genetic factor for cleft palate. PMID:21237142

Regional differences in BMP-dependence of dorsoventral patterning in the leech Helobdella.

PubMed

Kuo, Dian-Han; Shankland, Marty; Weisblat, David A

2012-08-01

In the leech Helobdella, the ectoderm exhibits a high degree of morphological homonomy between body segments, but pattern elements in lateral ectoderm arise via distinct cell lineages in the segments of the rostral and midbody regions. In each of the four rostral segments, a complete set of ventrolateral (O fate) and dorsolateral (P fate) ectodermal pattern elements arises from a single founder cell, op. In the 28 midbody and caudal segments, however, there are two initially indeterminate o/p founder cells; the more dorsal of these is induced to adopt the P fate by BMP5-8 emanating from the dorsalmost ectoderm, while the more ventral cell assumes the O fate. Previous work has suggested that the dorsoventral patterning of O and P fates differs in the rostral region, but the role of BMP signaling in those segments has not been investigated. We show here that suppression of dorsal BMP5-8 signaling (which effects a P-to-O fate change in the midbody) has no effect on the patterning of O and P fates in the rostral region. Furthermore, ectopic expression of BMP5-8 in the ventral ectoderm (which induces an O-to-P fate change in the midbody) has no effect in the rostral region. Finally, expression of a dominant-negative BMP receptor (which induces a P-to-O fate change in the midbody) fails to affect O/P patterning in the rostral region. Thus, the rostral segments appear to use some mechanism other than BMP signaling to pattern O and P cell fates along the dorsoventral axis. From a mechanistic standpoint, the OP lineage of the rostral segments and the O-P equivalence group of the midbody and caudal segments constitute distinct developmental modules that rely to differing degrees on positional cues from surrounding ectoderm in order to specify homonomous cell fates. Copyright © 2012 Elsevier Inc. All rights reserved.

HPV prevalence and HPV-related dysplasia in elderly women

PubMed Central

Hermansson, Ruth S.; Olovsson, Matts; Hoxell, Emelie

2018-01-01

Introduction In Sweden, where screening ends at the age of 60, about 30% of the cervical cancer cases occur in women older than 60. The aim of the present study was to investigate the prevalence of HPV and cervical dysplasia in women of 60 years and above. Patients and methods From September 2013 until June 2015, 1051 women aged 60–89 years (mean 68 years) were sampled for an HPV test when attending an outpatient gynecology clinic. Women with positive results had a second HPV test and liquid based cytology (LBC), after 3.5 months on average. Those with a positive second HPV test were examined by colposcopy, and biopsy and a sample for LBC was obtained. Results The prevalence of HPV was 4.1%, (95%CI 3.0–5.5, n = 43) at the first test, and at the second test 2.6% remained positive (95%CI 1.7–3.8, n = 27). The majority of women positive in both HPV tests, had dysplasia in histology, 81.5% (22/27) (4 CIN 2–0.4%, 18 CIN 1–1.7%). HPV-related dysplasia was found in 2.1%, (95%CI 1.3–3.2, n = 22) of the 1051 women. Four of the 22 women with positive HPV tests also had abnormal cytology, one ASCUS and three CIN 1. No cancer or glandular dysplasia was detected. Conclusion A significant proportion of elderly women were found to have a persistent cervical HPV infection. Among them there was a high prevalence of CIN diagnosed by histology. The HPV test showed high sensitivity and specificity in detecting CIN in elderly women, while cytology showed extremely low sensitivity. PMID:29320507

Evaluation of the Reliability and Validity of the Crawford Classification of Congenital Tibial Dysplasia

DTIC Science & Technology

2007-12-01

Month 1): a. Train a research coordinator to identify potential radiographs at pediatric orthopedic hospital. b. Have conference call with...JR. Delayed autogenous bone graft in the treatment of congenital pseudarthrosis. J Bone Joint Surg Am 1949;31:23. 8. Rudicel S. The orthopaedic

Staphyloma in a cat.

PubMed

Skorobohach, Brian J; Hendrix, Diane V H

2003-06-01

A unilateral scleral staphyloma in an 18-month-old, female spayed Domestic Short-haired cat was treated with excision, primary closure and fascial graft. Other ocular abnormalities noted on examination included iris coloboma, anterior cortical cataract, focal lens equator flattening and retinal dysplasia. The staphyloma was presumed to be congenital in origin.

Identification of a spatially specific enhancer element in the chicken Msx-2 gene that regulates its expression in the apical ectodermal ridge of the developing limb buds of transgenic mice.

PubMed

Sumoy, L; Wang, C K; Lichtler, A C; Pierro, L J; Kosher, R A; Upholt, W B

1995-07-01

Msx-2 is a member of the Msx family of homeobox-containing genes expressed in a variety of embryonic tissues involved in epithelial-mesenchymal interactions and pattern formation. In the developing chick limb bud, Msx-2 is expressed in the apical ectodermal ridge, which plays a crucial role in directing the growth and patterning of limb mesoderm. In addition, Msx-2 is expressed in the anterior nonskeletal-forming mesoderm of the limb bud, in the posterior necrotic zone, and in the interdigital mesenchyme. Studies of the altered expression patterns of Msx-2 in amelic and polydactylous mutant chick limbs have suggested that the apical ectodermal ridge and mesodermal domains of Msx-2 expression are independently regulated and that there might be separate cis-regulatory elements in the Msx-2 gene controlling its spatially distinct domains of expression. To test this hypothesis, we have isolated the chicken Msx-2 gene and have tested the ability of various regions of the gene to target expression of LacZ reporter gene to specific regions of the limbs of transgenic mice. A variety of these constructs are consistently expressed only in the apical ectodermal ridge and the ectoderm of the genital tubercle and are not expressed in the mesoderm of the limb bud or in other regions of the embryo where the endogenous Msx-2 gene is expressed. These results suggest the presence of spatially specific cis-regulatory elements in the Msx-2 gene. We identified a 348-bp region in the 5' flanking region of the Msx-2 gene which can act as an apical ectodermal ridge enhancer element when placed in reverse orientation in front of the reporter gene with transcription initiation directed by the minimal hsp68 promoter.

Natural and Artificial Intelligence, Language, Consciousness, Emotion, and Anticipation

NASA Astrophysics Data System (ADS)

Dubois, Daniel M.

2010-11-01

The classical paradigm of the neural brain as the seat of human natural intelligence is too restrictive. This paper defends the idea that the neural ectoderm is the actual brain, based on the development of the human embryo. Indeed, the neural ectoderm includes the neural crest, given by pigment cells in the skin and ganglia of the autonomic nervous system, and the neural tube, given by the brain, the spinal cord, and motor neurons. So the brain is completely integrated in the ectoderm, and cannot work alone. The paper presents fundamental properties of the brain as follows. Firstly, Paul D. MacLean proposed the triune human brain, which consists to three brains in one, following the species evolution, given by the reptilian complex, the limbic system, and the neo-cortex. Secondly, the consciousness and conscious awareness are analysed. Thirdly, the anticipatory unconscious free will and conscious free veto are described in agreement with the experiments of Benjamin Libet. Fourthly, the main section explains the development of the human embryo and shows that the neural ectoderm is the whole neural brain. Fifthly, a conjecture is proposed that the neural brain is completely programmed with scripts written in biological low-level and high-level languages, in a manner similar to the programmed cells by the genetic code. Finally, it is concluded that the proposition of the neural ectoderm as the whole neural brain is a breakthrough in the understanding of the natural intelligence, and also in the future design of robots with artificial intelligence.

The evaluation of lumbosacral dysplasia in young patients with lumbosacral spondylolisthesis: comparison with controls and relationship with the severity of slip.

PubMed

Pawar, Abhijit; Labelle, Hubert; Mac-Thiong, Jean-Marc

2012-11-01

Comparison of lumbosacral dysplasia between normal individuals and patients with low and high grade spondylolisthesis has not been done previously. The objective of this study is to evaluate the relationship between lumbosacral dysplasia and severity of slip in young patients with lumbosacral spondylolisthesis. Postero-anterior and lateral radiographs of 120 normal individuals and 131 patients with developmental spondylolisthesis (91 low and 40 high grades) were reviewed. Quantitative evaluation of lumbosacral dysplasia was done using 6 criteria involving the degree of laminar dysplasia, degree of facet dysplasia, size of L5 transverse processes, L5/S1 disc height, type of sacral doming and L5 lumbar index. Subjects were categorized as having no/low, moderate or severe dysplasia based on the total dysplasia score. Comparisons in total dysplasia score between normal, low grade and high grade groups were performed and the correlation between degree of dysplasia and percentage of slip was assessed. Most normal individuals (88.3%) had no/low dysplasia; most patients with low grade spondylolisthesis (61.5%) had moderate dysplasia, while most patients with high grade spondylolisthesis (72.5%) had severe dysplasia. There was a significant difference in dysplasia between normal individuals and patients with spondylolisthesis. Dysplasia also varied significantly between low and high grade spondylolisthesis. There was a strong positive correlation (r = 0.63) between severity of dysplasia and percentage of slip. There is a significant relationship between the severity of spondylolisthesis and lumbosacral dysplasia, with mainly no/low dysplasia observed in controls and increasing total dysplasia scores in higher grades of spondylolisthesis. In addition, a variable degree of dysplasia was found within groups with low or high grade spondylolisthesis, suggesting that different subgroups of patients exist with regard to dysplasia. Thus the degree of dysplasia varies in spondylolisthesis and it is possible that different grades of dysplasia could relate to different prognoses or outcomes with treatment.

High prevalence of genital HPV infection among long-term monogamous partners of women with cervical dysplasia or genital warts-Another reason for HPV vaccination of boys.

PubMed

Rob, Filip; Tachezy, Ruth; Pichlík, Tomáš; Rob, Lukáš; Kružicová, Zuzana; Hamšíková, Eva; Šmahelová, Jana; Hercogová, Jana

2017-01-01

We conducted a cross-sectional study on the occurrence of a specific type of genital human papillomavirus (HPV) among long-term monogamous male partners of women with cervical dysplasia and genital warts. The purpose of the study was to improve knowledge with regards to the management of these couples. The presence of genital HPV-DNA was detected by PCR with broad spectrum primers followed by hybridization. 82 males met the study criteria, 41 in each group. Genital HPV-DNA prevalence was 67.5% in the genital warts group and 72.2% in the cervical dysplasia group. The prevalence of high risk HPVs was higher in the cervical dysplasia group, while low risk HPVs were more prevalent in the genital warts group (p < .05). The prevalence of HPV in males was independent of the duration of the relationship (73.5% for 6-24 months and 66.7% for longer relationships). In conclusion, our results suggest that the prevalence of the genital HPV infection in both groups of male partners is comparable and very high, but the spectrum of HPV types varies significantly. The presence of the genital HPV infection in male sexual partners seems to be independent of the duration of the relationship. Applying the HPV vaccination to boys may prevent this phenomenon. © 2016 Wiley Periodicals, Inc.

Barrett's esophagus: photodynamic therapy for ablation of dysplasia, reduction of specialized mucosa and treatment of superficial esophageal cancer

NASA Astrophysics Data System (ADS)

Overholt, Bergein F.; Panjehpour, Masoud

1995-03-01

Fifteen patients with Barrett's esophagus and dysplasia were treated with photodynamic therapy. Four patients also had early, superficial esophageal cancers and 5 had esophageal polyps. Light was delivered via a standard diffuser or a centering esophageal balloon. Eight patients maintained on omeprazole and followed for 6 - 54 months are the subject of this report. Photodynamic therapy ablated dysplastic or malignant mucosa in patients with superficial cancer. Healing and partial replacement of Barrett's mucosa with normal squamous epithelium occurred in all patients and complete replacement with squamous epithelium was found in two. Side effects included photosensitivity and mild-moderate chest pain and dysphagia for 5 - 7 days. In three patients with extensive circumferential mucosal ablation in the proximal esophagus, healing was associated with esophageal strictures which were treated successfully by esophageal dilation. Strictures were not found in the distal esophagus. Photodynamic therapy combined with long-term acid inhibition provides effective endoscopic therapy of Barrett's mucosal dysplasia and superficial (Tis-T1) esophageal cancer. The windowed centering balloon improves delivery of photodynamic therapy to diffusely abnormal esophageal mucosa.

DNA methylation as an adjunct to histopathology to detect prevalent, inconspicuous dysplasia and early-stage neoplasia in Barrett’s esophagus

PubMed Central

Alvi, Muhammad A; Liu, Xinxue; O’Donovan, Maria; Newton, Richard; Wernisch, Lorenz; Shannon, Nicholas B; Shariff, Kareem; di Pietro, Massimiliano; Bergman, Jacques J G H M; Ragunath, Krish; Fitzgerald, Rebecca C

2016-01-01

Purpose Endoscopic surveillance of Barrett’s esophagus (BE) is problematic because dysplasia/early-stage neoplasia are frequently invisible and likely to be missed due to sampling bias. Molecular abnormalities may be more diffuse than dysplasia. The aim was therefore to test whether DNA methylation; especially on imprinted and X-chromosome genes; is able to detect dysplasia/early-stage neoplasia. Experimental design 27K methylation arrays were used to find genes best able to differentiate between 22 BE and 24 esophageal adenocarcinoma (EAC) samples. These were validated using pyrosequencing on a retrospective cohort (60 BE, 36 dysplastic and 90 EAC) and then in a prospective multicenter study (98 BE patients, including 28 dysplastic and 9 early EAC) designed to utilize biomarkers to stratify patients according to their prevalent dysplasia/EAC status. Results 23% genes on the array, including 7% of X-linked and 69% of imprinted genes, demonstrated statistically significant changes in methylation in EAC vs. BE (Wilcoxon P<0.05). 6/7 selected candidate genes were successfully internally (Pearson’s P<0.01) and externally validated (ANOVA P<0.001). Four genes (SLC22A18, PIGR, GJA12 and RIN2) showed the greatest area under curve (0.988) to distinguish between BE and dysplasia/EAC in the retrospective cohort. This methylation panel was able to stratify patients from the prospective cohort into three risk groups based on the number of genes methylated (low risk: <2 genes, intermediate: 2 and high: >2). Conclusion Widespread DNA methylation changes were observed in Barrett’s carcinogenesis including ≈70% of known imprinted genes. A four-gene methylation panel stratified BE patients into three risk groups with potential clinical utility. PMID:23243219

Intraoperative MRI-guided resection of focal cortical dysplasia in pediatric patients: technique and outcomes.

PubMed

Sacino, Matthew F; Ho, Cheng-Ying; Murnick, Jonathan; Tsuchida, Tammy; Magge, Suresh N; Keating, Robert F; Gaillard, William D; Oluigbo, Chima O

2016-06-01

OBJECTIVE Previous meta-analysis has demonstrated that the most important factor in seizure freedom following surgery for focal cortical dysplasia (FCD) is completeness of resection. However, intraoperative detection of epileptogenic dysplastic cortical tissue remains a challenge, potentially leading to a partial resection and the need for reoperation. The objective of this study was to determine the role of intraoperative MRI (iMRI) in the intraoperative detection and localization of FCD as well as its impact on surgical decision making, completeness of resection, and seizure control outcomes. METHODS The authors retrospectively reviewed the medical records of pediatric patients who underwent iMRI-assisted resection of FCD at the Children's National Health System between January 2014 and April 2015. Data reviewed included demographics, length of surgery, details of iMRI acquisition, postoperative seizure freedom, and complications. Postsurgical seizure outcome was assessed utilizing the Engel Epilepsy Surgery Outcome Scale. RESULTS Twelve consecutive pediatric patients (8 females and 4 males) underwent iMRI-guided resection of FCD lesions. The mean age at the time of surgery was 8.8 years ± 1.6 years (range 0.7 to 18.8 years), and the mean duration of follow up was 3.5 months ± 1.0 month. The mean age at seizure onset was 2.8 years ± 1.0 year (range birth to 9.0 years). Two patients had Type 1 FCD, 5 patients had Type 2A FCD, 2 patients had Type 2B FCD, and 3 patients had FCD of undetermined classification. iMRI findings impacted intraoperative surgical decision making in 5 (42%) of the 12 patients, who then underwent further exploration of the resection cavity. At the time of the last postoperative follow-up, 11 (92%) of the 12 patients were seizure free (Engel Class I). No patients underwent reoperation following iMRI-guided surgery. CONCLUSIONS iMRI-guided resection of FCD in pediatric patients precluded the need for repeat surgery. Furthermore, it resulted in the achievement of complete resection in all the patients, leading to a high rate of postoperative seizure freedom.

Morphology of isolated mouse inner cell masses developing in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiley, L.M.; Spindle, A.I.; Pedersen, R.A.

1978-01-01

The purpose of this study was to examine the developmental capacity of the mouse inner cell mass (ICM) in the absence of the trophoblast. ICMs were isolated from blastocysts by immunosurgery and cultured under conditions that support egg cylinder formation by intact blastocysts. After 2 or 3 days of culture, the ICMs consisted of an outer layer of endoderm and an inner layer of ectoderm that had cavitated centrally. By 4 or 5 days of culture, 25 to 60% of these ICMs had developed into paired cysts, apparently by secondary cavity formation. The inner cell layer surrounding this secondary cavitymore » resembled the extraembryonic ectoderm of cultured egg cylinders. By 6 days of culture, 60% of the ICMs had expanded into yolk sac-like structures that subsequently produced capillaries containing blood cells. The ICMs appeared to develop mesoderm in two distinct ways. A few of them developed mesoderm as a third layer of cells in the cleft separating endoderm and ectoderm, presumably by migrating from the inner, ectodermal layer, through the primitive streak, as in the intact egg cylinder. In the rest of the ICMs the embryonic ectoderm gradually differentiated into mesoderm while still in the inner layer, without primitive streak formation. We suggest, therefore, that the continuous presence of the trophoblast or of its derivatives is not required for the cytodifferentiation of mesoderm although it may be important in establishing embryonic polarity or in providinginductive signals necessary for the morphogenetic aspects of mesoderm differentiation, specifically primitive streak formation.« less

The incidence of malignancy in heart transplant recipients.

PubMed

Garlicki, M; Wierzbicki, K; Przybyłowski, P; Drop, D; Biernat, M; Rudziński, P; Olszewska, B; Dziatkowiak, A

1998-01-01

219 heart transplant recipients with survival over 3 months were retro- and prospectively analysed for the incidence of primary neoplasms. Patients received immunosuppressive drugs (cyclosporine A, azathioprine, steroids) with a 4-5 days induction course of Rabbit Anti-Thymocyte Immunoglobulin (RATG) or monoclonal antibodies induction /OKT3/ in some cases. Anti-rejection treatment consisted of pulse doses of methyloprednisolon or RATG. 9 cases of malignancy (4.1%) with one case of pre-malignant liver condition (dysplasia gigantocellulare, 0.45%) were found (8M; 1F; age: 45-67 y.o., x57.7). Symptoms of neoplasms occurred 7-79 months (x31.4) postoperatively. Skin carcinomas: planoepitheliale, spinocellulare, soft tissue neoplasms/mesenchymal sarcoma, larynx Ca planoepitheliale, lung: adenocarcinoma and Ca microcellulare, kidney Ca clarocellulare and post transplant non-Hodgkin lymphoma were diagnosed. Chemo- and radiotherapy, surgery and reduction of immunosuppression did not change the outcome of malignancy in 6 pts.; (regression-1 pt was., remission-2 pts). Patients died 7-86 months after Htx (x41), 4-25 mos. (x12.5) after suffering from first symptoms and 0-10 months (x4.9) after pathology-based diagnosis of neoplasm. Heart transplant recipients have an increased risk of carcinogenesis. The incidence of malignancies in the studied group is similar or even lower than in other reports.

Histological comparison of long-bone cortex between 11-year-old giant cow with dermal dysplasia and the child cow aged 8.5 years.

PubMed

Mori, Ryoichi; Kodaka, Tetsuo; Naito, Yoshihisa

2012-02-01

Young calves are known to be formed with laminar bone in long-bone cortex during growing periods and the osteon formation begins later. Previously, we reported that an 11-year-old giant Holstein cow with dermal dysplasia showed a delayed osteon formation. An 8.5-year-old cow, born from the giant Holstein cow, also showed some dermal dysplasia and the outer-half layer of the child almost retained laminar bone similar to that of the mother, although the body weight was approximately normal. The mother had formed the inner circumferential lamella and the child was going to form the inner circumferential lamella, but their outer circumferential lamellas were not formed yet in both of them, when compared with a 12-years-old cow as a control of the mother. Therefore, we suggest on long-bone formation pattern that the child resembled the mother rather than the control, and that the child had more or less succeeded to the mother genes of delayed osteon formation as well as dermal dysplasia which seemed to be genetic collagen disorder, although there were mild gene appearances.

Sequential occurrence of preneoplastic lesions and accumulation of loss of heterozygosity in patients with gallbladder stones suggest causal association with gallbladder cancer.

PubMed

Jain, Kajal; Mohapatra, Trilochan; Das, Prasenjit; Misra, Mahesh Chandra; Gupta, Siddhartha Datta; Ghosh, Manju; Kabra, Madhulika; Bansal, Virinder Kumar; Kumar, Subodh; Sreenivas, Vishnubhatla; Garg, Pramod Kumar

2014-12-01

Causal association of gallbladder stones with gallbladder cancer (GBC) is not yet well established. To study the frequency of occurrence of preneoplastic histological lesions and loss of heterozygosity (LOH) of tumor suppressor genes in patients with gallstones. All consecutive patients with gallstones undergoing cholecystectomy from 2007-2011 were included prospectively. Histological examination of the gallbladder specimens was done for preneoplastic lesions. LOH at 8 loci, that is 3p12, 3p14.2, 5q21, 9p21, 9q, 13q, 17p13, and 18q for tumor suppressor genes (DUTT1, FHIT, APC, p16, FCMD, RB1, p53, and DCC genes) that are associated with GBC was tested from microdissected preneoplastic lesions using microsatellite markers. These LOH were also tested in 30 GBC specimens. Of the 350 gallbladder specimens from gallstone patients, hyperplasia was found in 32%, metaplasia in 47.8%, dysplasia in 15.7%, and carcinoma in situ in 0.6%. Hyperplasia, metaplasia, and dysplasia alone were found in 11.7%, 24.6%, and 1.4% of patients, respectively. A combination of hyperplasia and dysplasia, metaplasia and dysplasia, and hyperplasia, metaplasia, and dysplasia was found in 3.4%, 6.3%, and 4.3% of patients, respectively. LOH was present in 2.1% to 47.8% of all the preneoplastic lesions at different loci. Fractional allelic loss was significantly higher in those with dysplasia compared with other preneoplastic lesions (0.31 vs 0.22; P = 0.042). No preneoplastic lesion or LOH was found in normal gallbladders. Patients with gallstones had a high frequency of preneoplastic lesions and accumulation of LOH at various tumor suppressor genes, suggesting a possible causal association of gallstones with GBC.

Monosodium glutamate (MSG): a villain and promoter of liver inflammation and dysplasia.

PubMed

Nakanishi, Yuko; Tsuneyama, Koichi; Fujimoto, Makoto; Salunga, Thucydides L; Nomoto, Kazuhiro; An, Jun-Ling; Takano, Yasuo; Iizuka, Seiichi; Nagata, Mitsunobu; Suzuki, Wataru; Shimada, Tsutomu; Aburada, Masaki; Nakano, Masayuki; Selmi, Carlo; Gershwin, M Eric

2008-01-01

Chronic inflammation is a common theme in a variety of disease pathways, including autoimmune diseases. The pathways of chronic inflammation are well illustrated by nonalcoholic steatohepatitis (NASH), which is of a serious concern due to its increasing prevalence in the westernized world and its direct correlation with lifestyle factors, particularly diet. Importantly, NASH may ultimately lead to the development of hepatocellular carcinoma. We previously reported that injection of monosodium glutamate (MSG) in ICR mice leads to the development of significant inflammation, central obesity, and type 2 diabetes. To directly address the long-term consequences of MSG on inflammation, we have performed serial analysis of MSG-injected mice and focused in particular on liver pathology. By 6 and 12 months of age, all MSG-treated mice developed NAFLD and NASH-like histology, respectively. In particular, the murine steatohepatitis at 12 months was virtually undistinguishable from human NASH. Further, dysplastic nodular lesions were detected in some cases within the fibrotic liver parenchyma. We submit that MSG treatment of mice induces obesity and diabetes with steatosis and steatohepatitis resembling human NAFLD and NASH with pre-neoplastic lesions. These results take on considerable significance in light of the widespread usage of dietary MSG and we suggest that MSG should have its safety profile re-examined and be potentially withdrawn from the food chain.

The effect of orbital implantation on peripheral blood melatonin and sex hormone levels in child patients with congenital eyeball dysplasia.

PubMed

Ma, Junze; Liu, Tao; Qu, Jianqiang

2017-09-01

The aim of the study was to examine the effect of orbital implantation on peripheral blood melatonin and sex hormone levels in pediatric patients with congenital eyeball dysplasia. A total of 28 cases of pediatric patients with congenital eyeball dysplasia diagnosed in the Second Affiliated Hospital of Xi'an Jiaotong University from June 2014 to December 2014 were selected for the study. The patients included those that received orbital implantation, and the melatonin levels in the peripheral blood in patients before and after operation was observed. In addition, the sex hormone levels and T lymphocytes, plasma reactive oxygen species (ROS) and VEGF levels, urine 8-OHdG and 8-isoPGF2α levels in patients before and after treatment were detected, followed by statistical analysis. As a result, after 3 months of orbital implantation, the sex hormone levels in peripheral blood in child patients fluctuated significantly, and differences were not statistically significant (P>0.05). The peripheral blood T lymphocytes and ROS levels were significantly lower than those before treatment, and the differences were statistically significant (P<0.05). The correlation analysis revealed that the peripheral blood melatonin levels were negatively related to ROS levels; the correlation coefficient was rs = -0.481 and P<0.05. In conclusion, orbital implantation does not have significant impact on sex hormone levels in child patients with congenital eyeball dysplasia. The hydroxyapatite orbital implantation can achieve more satisfactory curative effects, and there are fewer postoperative complications. It does not affect the appearance of the eye, and therefore, it is suitable for patients with congenital eyeball dysplasia.

Kindler syndrome protein Kindlin-1 is mainly expressed in adult tissues originating from ectoderm/endoderm.

PubMed

Zhan, Jun; Yang, Mei; Zhang, Jing; Guo, YongQing; Liu, Wei; Zhang, HongQuan

2015-05-01

Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related diseases are confined in limited tissue types. However, Kindlin-1 tissue distribution and the dogma that governs Kindlin-1 expression in normal human body are elusive. This study examined Kindlin-1 expression in normal human adult organs, human and mouse embryonic organs by immunohistochemical analyses. We identified a general principle that the level of Kindlin-1 expression in tissues is tightly correlated with the corresponding germ layers from which these tissues originate. We compared the expression of Kindlin-1 with Kindlin-2 and found that Kindlin-1 is highly expressed in epithelial tissues derived from ectoderm and endoderm, whereas Kindlin-2 is mainly expressed in mesoderm-derived tissues. Likewise, Kindlin-1 was also found highly expressed in endoderm/ectoderm-derived tissues in human and mouse embryos. Our findings indicate that Kindlin-1 may play an importance role in the development of endoderm/ectoderm related tissues.

Kidney Dysplasia

MedlinePlus

... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes.

PubMed

Marchegiani, Shannon; Davis, Taylor; Tessadori, Federico; van Haaften, Gijs; Brancati, Francesco; Hoischen, Alexander; Huang, Haigen; Valkanas, Elise; Pusey, Barbara; Schanze, Denny; Venselaar, Hanka; Vulto-van Silfhout, Anneke T; Wolfe, Lynne A; Tifft, Cynthia J; Zerfas, Patricia M; Zambruno, Giovanna; Kariminejad, Ariana; Sabbagh-Kermani, Farahnaz; Lee, Janice; Tsokos, Maria G; Lee, Chyi-Chia R; Ferraz, Victor; da Silva, Eduarda Morgana; Stevens, Cathy A; Roche, Nathalie; Bartsch, Oliver; Farndon, Peter; Bermejo-Sanchez, Eva; Brooks, Brian P; Maduro, Valerie; Dallapiccola, Bruno; Ramos, Feliciano J; Chung, Hon-Yin Brian; Le Caignec, Cédric; Martins, Fabiana; Jacyk, Witold K; Mazzanti, Laura; Brunner, Han G; Bakkers, Jeroen; Lin, Shuo; Malicdan, May Christine V; Boerkoel, Cornelius F; Gahl, William A; de Vries, Bert B A; van Haelst, Mieke M; Zenker, Martin; Markello, Thomas C

2015-07-02

Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families. Moreover, a genotype-phenotype correlation was observed, because the two syndromes differed based solely upon the nature of the substituting amino acid: a lysine at TWIST2 residue 75 resulted in AMS, whereas a glutamine or alanine yielded BSS. TWIST2 encodes a basic helix-loop-helix transcription factor that regulates the development of mesenchymal tissues. All identified mutations fell in the basic domain of TWIST2 and altered the DNA-binding pattern of Flag-TWIST2 in HeLa cells. Comparison of wild-type and mutant TWIST2 expressed in zebrafish identified abnormal developmental phenotypes and widespread transcriptome changes. Our results suggest that autosomal-dominant TWIST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor's DNA binding. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

WNT/β-catenin signaling mediates human neural crest induction via a pre-neural border intermediate.

PubMed

Leung, Alan W; Murdoch, Barbara; Salem, Ahmed F; Prasad, Maneeshi S; Gomez, Gustavo A; García-Castro, Martín I

2016-02-01

Neural crest (NC) cells arise early in vertebrate development, migrate extensively and contribute to a diverse array of ectodermal and mesenchymal derivatives. Previous models of NC formation suggested derivation from neuralized ectoderm, via meso-ectodermal, or neural-non-neural ectoderm interactions. Recent studies using bird and amphibian embryos suggest an earlier origin of NC, independent of neural and mesodermal tissues. Here, we set out to generate a model in which to decipher signaling and tissue interactions involved in human NC induction. Our novel human embryonic stem cell (ESC)-based model yields high proportions of multipotent NC cells (expressing SOX10, PAX7 and TFAP2A) in 5 days. We demonstrate a crucial role for WNT/β-catenin signaling in launching NC development, while blocking placodal and surface ectoderm fates. We provide evidence of the delicate temporal effects of BMP and FGF signaling, and find that NC development is separable from neural and/or mesodermal contributions. We further substantiate the notion of a neural-independent origin of NC through PAX6 expression and knockdown studies. Finally, we identify a novel pre-neural border state characterized by early WNT/β-catenin signaling targets that displays distinct responses to BMP and FGF signaling from the traditional neural border genes. In summary, our work provides a fast and efficient protocol for human NC differentiation under signaling constraints similar to those identified in vivo in model organisms, and strengthens a framework for neural crest ontogeny that is separable from neural and mesodermal fates. © 2016. Published by The Company of Biologists Ltd.

Retrospective study of congenital heart defects in 151 dogs.

PubMed

Tidholm, A

1997-03-01

The case records of 151 dogs diagnosed with congenital heart disease were reviewed retrospectively. The most common defect was aortic stenosis, accounting for 35 per cent of all cases, followed by pulmonic stenosis (20 per cent), ventricular septal defect (12 per cent), patent ductus arteriosus (11 per cent), mitral valve dysplasia (8 per cent), tricuspid valve dysplasia (7 per cent), endocardial fibroelastosis (1.9 per cent) and tetralogy of Fallot (0.6 per cent). Fifty-one breeds were represented, with golden retrievers, German shepherd dogs and boxers predominating. No overall sex predilection was obvious. Seventy-five per cent of the dogs were asymptomatic at presentation. The defects most often associated with presenting symptoms, such as dyspnoea, syncope, ascites, failure to grow and depression, were mitral valve dysplasia, atrial septal defect, tricuspid valve dysplasia and endocardial fibroelastosis. The latter presented with the most severe signs of heart failure. In some cases of aortic stenosis and pulmonic stenosis, where the defect could not be accurately visualised with two-dimensional echocardiography, Doppler echocardiographic examination was needed for definitive diagnosis.

Incident anal human papillomavirus and human papillomavirus-related sequelae in HIV-infected versus HIV-uninfected adolescents in the United States.

PubMed

Mullins, Tanya L Kowalczyk; Wilson, Craig M; Rudy, Bret J; Sucharew, Heidi; Kahn, Jessica A

2013-09-01

Little is known about the incidence of anal human papillomavirus (HPV) infection and related sequelae, as well as factors associated with these outcomes, among adolescents who are HIV infected versus HIV uninfected but at risk. We analyzed the data from a multisite US study, the Reaching for Excellence in Adolescent Care and Health Project. Adolescents aged 12 to 18 years who were behaviorally HIV infected (n = 319) or HIV uninfected but at risk (n = 177) were recruited. Incidence rates for anal HPV, high-risk anal HPV, anogenital warts, and anal dysplasia were calculated using Poisson modeling. Factors associated with these outcomes were examined using Cox proportional hazards modeling. Mean age at entry was 16.8 years; mean (SD) follow-up time for detection of anal HPV was 22.4 (10.8) months. Most participants (76%) were female; 70% were black non-Hispanic. HIV-infected (vs. HIV-uninfected) women had a significantly higher incidence of anal HPV (30 vs. 14 per 100 person-years; P = 0.002), high-risk anal HPV (12 vs. 5.3 per 100 person-years; P = 0.04), and anogenital warts (6.7 vs. 1.6 per 100 person-years; P = 0.002) but not anal dysplasia. Although incidence rates were higher for these outcomes among HIV-infected versus HIV-uninfected men, the differences were not statistically significant. Among women, factors associated with anal HPV and related sequelae differed by HIV status and included biological, behavioral, and HIV-related factors. No factors were associated with outcomes in men. HIV-infected versus HIV-uninfected adolescent women had higher rates of anal HPV and anogenital warts. Because HIV-infected youth are at increased risk of these outcomes, enhanced HPV prevention efforts such as vaccination are warranted for this group.

Growth, nutritional, and gastrointestinal aspects of ankyloblepharon-ectodermal defect-cleft lip and/or palate (AEC) syndrome

USDA-ARS?s Scientific Manuscript database

Ankyloblepharon-ectodermal defect-cleft lip and/or palate (AEC), is a rare genetic disorder due to mutations in the TP63 gene. In the present study, we characterized the pattern of growth and body composition, and the nutritional and gastrointestinal aspects of children and adults (n = 18) affected ...

Detailed evaluation of the upper urinary tract in patients with prune belly syndrome using magnetic resonance urography.

PubMed

Garcia-Roig, M L; Grattan-Smith, J D; Arlen, A M; Smith, E A; Kirsch, A J

2016-04-01

Magnetic resonance urography (MRU) has proven to be useful in the setting of complex urologic anatomy. Prune belly syndrome (PBS) patients are known to have malformed and highly variable urinary tract anatomy due to significant dilation and renal dysplasia. To further characterize the renal and ureteral anatomy and renal function in patients with PBS via MRU. Children with PBS undergoing MRU (2006-2011) were identified. Studies were performed to evaluate severe hydronephrosis in all patients. Demographics, previous imaging, and MRU findings were collected. A single radiologist reviewed all studies. MRU was performed on 13 boys, with a median age of 29.3 months (IQR 6-97). Two patients underwent >1 study for ureteropelvic junction obstruction (UPJ obstruction) and calyceal diverticulum with a solitary kidney, respectively. Hydroureteronephrosis (HUN) was identified in 12 boys (92%), while one (8%) did not have ureteral dilation. All patients demonstrated morphologic abnormalities beyond HUN as follows: five (38%) renal dysplasia; five (38%) scarring; four (31%) calyceal diverticula; and three (23%) thickened bladder. The median renal transit time (RTT) was 6 min (IQR 3.5-10.5), and >8 min (range 8.5-35) in six patients; one patient was ultimately diagnosed with obstruction. The mean serum creatinine was 0.5 ± 0.3 mg/dl. This summary figure is a coronal excretory phase T1 MRU image demonstrating absence of well-defined calyces and a 5-cm calyceal diverticulum (white arrow). This study reports significant anatomic and functional findings on MRU that were not readily apparent when using standard imaging for children with PBS. The high-resolution images and functional data obtained with MRU allowed for visualization of calyceal diverticula and abnormal renal pelvic anatomy not previously described in PBS. In addition, renal dysplasia could be identified with MRU, which is badly characterized in the PBS population outside of renal biopsy studies. Potential limitations of the study included its nature as a small retrospective case series, which limited the ability to compare imaging modalities. Imaging modalities were based on individual clinical needs; therefore, comparison with diuretic renal scintigraphy was limited. MRU provided anatomic and functional details of the urinary tract in children with PBS that allowed for characterization of new renal anatomic abnormalities, including the incidence of calyceal diverticula and renal dysplasia, which have not been previously described. While renal scarring, dysplasia and calyceal diverticula were easily discerned on MRU in ten patients, their clinical significance requires longer follow-up in a larger patient population. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Genetics Home Reference: ALG12-congenital disorder of glycosylation

MedlinePlus

... CDG are likely due to impaired glycosylation of proteins and lipids that are needed for normal function of many organs and tissues, ... R, Gibbs RA, Lee BH, Cohn D, Campeau PM. Diagnosis of ALG12-CDG by exome sequencing in a case of severe skeletal dysplasia. Mol ...

Multicystic dysplastic kidney: a retrospective study.

PubMed

Sharada, Sathish; Vijayakumar, Mahalingam; Nageswaran, Prahlad; Ekambaram, Sudha; Udani, Amish

2014-08-01

To report the renal structural and functional anomalies in children with multicystic dysplastic kidneys. Retrospective descriptive analysis of 47 children with multicystic dysplastic kidney seen in a pediatric nephrology unit over a period of 6 years. Antenatal diagnosis of multicystic dysplastic kidney was made in 34 (72.3%) patients. On follow up of 31 children for more than 12 months, 21 (68%) had involution, 4 [13%] had non-regression, and 4 (13%) were nephrectomized. Vesico-ureteric reflux (n=13; 28%) was the commonest renal abnormality. The serum creatinine values were higher (P=0.006) in children with contralateral reflux. Sub-nephrotic proteinuria was noted in 9 (29%) and was significantly associated with complete involution (P=<0.023). None of the patients developed hypertension and 2 (6.4%) had renal failure. Close nephrological follow-up is needed in children with multicystic dysplasia of kidneys.

Oxygen saturation target range for extremely preterm infants: a systematic review and meta-analysis.

PubMed

Manja, Veena; Lakshminrusimha, Satyan; Cook, Deborah J

2015-04-01

The optimal oxygen saturation (SpO2) target for extremely preterm infants is unknown. To systematically review evidence evaluating the effect of restricted vs liberal oxygen exposure on morbidity and mortality in extremely preterm infants. MEDLINE, PubMed, CENTRAL, and CINAHL databases from their inception to March 31, 2014, and abstracts submitted to Pediatric Academic Societies from 2000 to 2014. All published randomized trials evaluating the effect of restricted (SpO2, 85%-89%) vs liberal (SpO2, 91%-95%) oxygen exposure in preterm infants (<28 weeks' gestation at birth). All meta-analyses were performed using Review Manager 5.2. The Cochrane risk-of-bias tool was used to assess study quality. The summary of the findings and the level of confidence in the estimate of effect were assessed using GRADEpro. Treatment effect was analyzed using a random-effects model. Death before hospital discharge, death or severe disability before 24 months, death before 24 months, neurodevelopmental outcomes, hearing loss, bronchopulmonary dysplasia, necrotizing enterocolitis, and severe retinopathy of prematurity. Five trials were included in the final synthesis. These studies had a similar design with a prespecified composite outcome of death/disability at 18 to 24 months corrected for prematurity; however, this outcome has not been reported for 2 of the 5 trials. There was no difference in the outcome of death/disability before 24 months (risk ratio [RR], 1.02 [95% CI, 0.92-1.14]). Mortality before 24 months was not different (RR, 1.13 [95% CI, 0.97-1.33]); however, a significant increase in mortality before hospital discharge was found in the restricted oxygen group (RR, 1.18 [95% CI, 1.03-1.36]). The rates of bronchopulmonary dysplasia, neurodevelopmental outcomes, hearing loss, and retinopathy of prematurity were similar between the 2 groups. Necrotizing enterocolitis occurred more frequently in infants on restricted oxygen (RR, 1.24 [95% CI, 1.05-1.47]). Using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria, we found that the quality of evidence for these outcomes was moderate to low. Although infants cared for with a liberal oxygen target had significantly lower mortality before hospital discharge than infants cared for with a restricted oxygen target, the quality of evidence for this estimate of effect is low. Necrotizing enterocolitis occurred less frequently in the liberal oxygen group. We found no significant differences in death or disability at 24 months, bronchopulmonary dysplasia, retinopathy of prematurity, neurodevelopmental outcomes, or hearing loss at 24 months.

Successful Treatment of a Drug-Resistant Epilepsy by Long-term Transcranial Direct Current Stimulation: A Case Report.

PubMed

San-Juan, Daniel; Sarmiento, Carlos Ignacio; González, Katia Márquez; Orenday Barraza, José Manuel

2018-01-01

Transcranial direct current stimulation (tDCS) is a reemerged noninvasive cerebral therapy used to treat patients with epilepsy, including focal cortical dysplasia, with controversial results. We present a case of a 28-year-old female with left frontal cortical dysplasia refractory to antiepileptic drugs, characterized by 10-15 daily right tonic hemi-body seizures. The patient received a total of seven sessions of cathodal tDCS (2 mA, 30 min). The first three sessions were applied over three consecutive days, and the remaining four sessions of tDCS were given each at 2-week intervals. At the 1-year follow-up, the patient reported to have a single seizure per month and only mild adverse events.

Successful Treatment of a Drug-Resistant Epilepsy by Long-term Transcranial Direct Current Stimulation: A Case Report

PubMed Central

San-Juan, Daniel; Sarmiento, Carlos Ignacio; González, Katia Márquez; Orenday Barraza, José Manuel

2018-01-01

Transcranial direct current stimulation (tDCS) is a reemerged noninvasive cerebral therapy used to treat patients with epilepsy, including focal cortical dysplasia, with controversial results. We present a case of a 28-year-old female with left frontal cortical dysplasia refractory to antiepileptic drugs, characterized by 10–15 daily right tonic hemi-body seizures. The patient received a total of seven sessions of cathodal tDCS (2 mA, 30 min). The first three sessions were applied over three consecutive days, and the remaining four sessions of tDCS were given each at 2-week intervals. At the 1-year follow-up, the patient reported to have a single seizure per month and only mild adverse events. PMID:29479337

Diagnosis and Management of Low-Grade Dysplasia in Barrett's Esophagus: Expert Review From the Clinical Practice Updates Committee of the American Gastroenterological Association.

PubMed

Wani, Sachin; Rubenstein, Joel H; Vieth, Michael; Bergman, Jacques

2016-11-01

The purpose of this clinical practice update expert review is to define the key principles in the diagnosis and management of low-grade dysplasia (LGD) in Barrett's esophagus patients. The best practices outlined in this review are based on relevant publications, including systematic reviews and expert opinion (when applicable). Practice Advice 1: The extent of Barrett's esophagus should be defined using a standardized grading system documenting the circumferential and maximal extent of the columnar lined esophagus (Prague classification) with a clear description of landmarks and visible lesions (nodularity, ulceration) when present. Practice Advice 2: Given the significant interobserver variability among pathologists, the diagnosis of Barrett's esophagus with LGD should be confirmed by an expert gastrointestinal pathologist (defined as a pathologist with a special interest in Barrett's esophagus-related neoplasia who is recognized as an expert in this field by his/her peers). Practice Advice 3: Expert pathologists should report audits of their diagnosed cases of LGD, such as the frequency of LGD diagnosed among surveillance patients and/or the difference in incidence of neoplastic progression among patients diagnosed with LGD vs nondysplastic Barrett's esophagus. Practice Advice 4: Patients in whom the diagnosis of LGD is downgraded to nondysplastic Barrett's esophagus should be managed as nondysplastic Barrett's esophagus. Practice Advice 5: In Barrett's esophagus patients with confirmed LGD (based on expert gastrointestinal pathology review), repeat upper endoscopy using high-definition/high-resolution white-light endoscopy should be performed under maximal acid suppression (twice daily dosing of proton pump inhibitor therapy) in 8-12 weeks. Practice Advice 6: Under ideal circumstances, surveillance biopsies should not be performed in the presence of active inflammation (erosive esophagitis, Los Angeles grade C and D). Pathologists should be informed if biopsies are obtained in the setting of erosive esophagitis and if pathology findings suggest LGD, or if no biopsies are obtained, surveillance biopsies should be repeated after the anti-reflux regimen has been further intensified. Practice Advice 7: Surveillance biopsies should be performed in a four-quadrant fashion every 1-2 cm with target biopsies obtained from visible lesions taken first. Practice Advice 8: Patients with a confirmed histologic diagnosis of LGD should be referred to an endoscopist with expertise in managing Barrett's esophagus-related neoplasia practicing at centers equipped with high-definition endoscopy and capable of performing endoscopic resection and ablation. Practice Advice 9: Endoscopic resection should be performed in Barrett's esophagus patients with LGD with endoscopically visible abnormalities (no matter how subtle) in order to accurately assess the grade of dysplasia. Practice Advice 10: In patients with confirmed Barrett's esophagus with LGD by expert GI pathology review that persists on a second endoscopy, despite intensification of acid-suppressive therapy, risks and benefits of management options of endoscopic eradication therapy (specifically adverse events associated with endoscopic resection and ablation), and ongoing surveillance should be discussed and documented. Practice Advice 11: Endoscopic eradication therapy should be considered in patients with confirmed and persistent LGD with the goal of achieving complete eradication of intestinal metaplasia. Practice Advice 12: Patients with LGD undergoing surveillance rather than endoscopic eradication therapy should undergo surveillance every 6 months times 2, then annually unless there is reversion to nondysplastic Barrett's esophagus. Biopsies should be obtained in 4-quadrants every 1-2 cm and of any visible lesions. Practice Advice 13: In patients with Barrett's esophagus-related LGD undergoing ablative therapy, radiofrequency ablation should be used. Practice Advice 14: Patients completing endoscopic eradication therapy should be enrolled in an endoscopic surveillance program. Patients who have achieved complete eradication of intestinal metaplasia should undergo surveillance every year for 2 years and then every 3 years thereafter to detect recurrent intestinal metaplasia and dysplasia. Patients who have not achieved complete eradication of intestinal metaplasia should undergo surveillance every 6 months for 1 year after the last endoscopy, then annually for 2 years, then every 3 years thereafter. Practice Advice 15: Following endoscopic eradication therapy, the biopsy protocol of obtaining biopsies in 4 quadrants every 2 cm throughout the length of the original Barrett's esophagus segment and any visible columnar mucosa is suggested. Practice Advice 16: Endoscopists performing endoscopic eradication therapy should report audits of their rates of complete eradication of dysplasia and intestinal metaplasia and adverse events in clinical practice. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Incident Anal HPV and HPV-Related Sequelae in HIV-Infected vs. HIV-Uninfected Adolescents in the United States

PubMed Central

Mullins, Tanya L. Kowalczyk; Wilson, Craig M.; Rudy, Bret J.; Sucharew, Heidi; Kahn, Jessica A.

2015-01-01

Background Little is known about the incidence of anal HPV infection and related sequelae, and factors associated with these outcomes, among adolescents who are HIV-infected vs. uninfected but at-risk. Methods We analyzed data from a multisite U.S. study, the Reaching for Excellence in Adolescent Care and Health Project. Adolescents aged 12–18 years who were behaviorally HIV-infected (n=319) or HIV-uninfected but at-risk (n=177) were recruited. Incidence rates for anal HPV, high-risk anal HPV, anogenital warts, and anal dysplasia were calculated using Poisson modeling. Factors associated with these outcomes were examined using Cox proportional hazards modeling. Results Mean age at entry was 16.8 years; mean follow-up time for detection of anal HPV was 22.4 months (SD 10.8). Most participants (76%) were female; 70% were black non-Hispanic. HIV-infected (vs. –uninfected) women had significantly higher incidence of anal HPV (30 vs. 14 per 100 person-years; p=0.002), high-risk anal HPV (12 vs. 5.3 per 100 person-years; p=0.04), and anogenital warts (6.7 vs. 1.6 per 100 person-years; p=0.002) but not anal dysplasia. Although incidence rates were higher for these outcomes among HIV-infected vs. -uninfected men, the differences were not statistically significant. Among women, factors associated with anal HPV and related sequelae differed by HIV status and included biological, behavioral, and HIV-related factors. No factors were associated with outcomes in men. Conclusions HIV-infected vs. -uninfected adolescent women had higher rates of anal HPV and anogenital warts. Because HIV-infected youth are at increased risk of these outcomes, enhanced HPV prevention efforts, such as vaccination, are warranted for this group. PMID:23949587

Major regulatory factors in the evolution of development: the roles of goosecoid and Msx in the evolution of the direct-developing sea urchin Heliocidaris erythrogramma.

PubMed

Wilson, Keen A; Andrews, Mary E; Rudolf Turner, F; Raff, Rudolf A

2005-01-01

The transcription factors Gsc and Msx are expressed in the oral ectoderm of the indirect-developing sea urchin Heliocidaris tuberculata. Their patterns of expression are highly modified in the direct developer Heliocidaris erythrogramma, which lacks an oral ectoderm. We here test the hypothesis that they are large effect genes responsible for the loss of the oral ectoderm module in the direct-developing larva of H. erythrogramma as well as for the restoration of an overt oral ectoderm in H.e. xH.t. hybrids. We undertook misexpression/overexpression and knockdown assays in the two species and in hybrids by mRNA injection. The results indicate that dramatic changes of function of these transcription factors has occurred. One of these genes, Gsc, has the ability when misexpressed to partially restore oral ectoderm in H. erythrogramma. On the other hand, Msx has lost any oral function and instead has a role in mesoderm proliferation and patterning. In addition, we found that the H. tuberculataGsc is up regulated in H.e. xH.t. hybrids, showing a preferential use of the indirect developing parental gene in the development of the hybrid. We suggest that Gsc qualifies as a gene of large evolutionary effect and is partially responsible for the evolution of direct development of H. erythrogramma. We discuss these results in light of modularity and genetic networks in development, as well as in their implications for the rapid evolution of large morphological changes in development.

Optical biopsy for the diagnosis of dysplasia in Barrett's oesophagus

NASA Astrophysics Data System (ADS)

Pickard, David C. O.; Bigio, Irving J.; Bown, Stephen G.; Lovat, Laurence B.; Ripley, Paul M.; Novelli, Marco

2002-05-01

Several research groups have been developing optical-spectroscopy methods, often mediated by fibre-optic probes, to noninvasively identify dysplasia and cancer in situ and in real time: often called 'optical biopsy'. Researchers at Los Alamos National Laboratory (Los Alamos, New Mexico) have developed the method of elastic-scattering spectroscopy (ESS). ESS is a point measurement that is sensitive to the morphological changes at the cellular and sub-cellular level, including changes in the size and/or density of the nuclei, mitochondria or other organelles. It is therefore sensitive to morphology features that a pathologist looks for during histological examination. We report on the first stages of a clinical study currently under way at the Middlesex Hospital an University College London, designed to test the ESS method for identification of dysplasia in Barrett's oesophagus. Preliminary results using elastic-scattering spectroscopy during endoscopic examination show that this technique has potential as a real-time test for in vivo detection of dysplasia or early cancer within Barrett's mucosa, or at least as a guide to assist in locating optimum sites for biopsy. Initial data sets are encouraging and the randomly chosen testing and training sets give specificities and sensitivities comparable to the accuracy of histology. It is evident that the ESS technique is proving to be convenient for the physicians given its speed and compatibility with endoscopic equipment. It is intended to begin prospective trials in the next few months to assess the systems suitability for general clinical practice.

bicaudal-C is required for the formation of anterior neurogenic ectoderm in the sea urchin embryo.

PubMed

Yaguchi, Shunsuke; Yaguchi, Junko; Inaba, Kazuo

2014-10-31

bicaudal-C (bicC) mRNA encodes a protein containing RNA-binding domains that is reported to be maternally present with deflection in the oocytes/eggs of some species. The translated protein plays a critical role in the regulation of cell fate specification along the body axis during early embryogenesis in flies and frogs. However, it is unclear how it functions in eggs in which bicC mRNA is uniformly distributed, for instance, sea urchin eggs. Here, we show the function of BicC in the formation of neurogenic ectoderm of the sea urchin embryo. Loss-of-function experiments reveal that BicC is required for serotonergic neurogenesis and for expression of ankAT-1 gene, which is essential for the formation of apical tuft cilia in the neurogenic ectoderm of the sea urchin embryo. In contrast, the expression of FoxQ2, the neurogenic ectoderm specification transcription factor, is invariant in BicC morphants. Because FoxQ2 is an upstream factor of serotonergic neurogenesis and ankAT-1 expression, these data indicate that BicC functions in regulating the events that are coordinated by FoxQ2 during sea urchin embryogenesis.

Progressive proliferative and dysplastic typhlocolitis in aging syrian hamsters naturally infected with Helicobacter spp.: a spontaneous model of inflammatory bowel disease.

PubMed

Nambiar, P R; Kirchain, S M; Courmier, K; Xu, S; Taylor, N S; Theve, E J; Patterson, M M; Fox, J G

2006-01-01

Helicobacter spp. have been implicated in a variety of gastrointestinal tract diseases, including peptic ulcer disease, gastric cancer, and inflammatory bowel disease (IBD), in humans and animals. Although most models of IBD are experimentally induced, spontaneous or natural models of IBD are rare. Herein, we describe a long-term study of chronic, progressive lesions that develop in the distal portion of the large bowel of unmanipulated Syrian hamsters naturally infected with Helicobacter spp. Twenty-four Syrian hamsters of three age groups (group A, 1 month [n = 4], group B, 7-12 months [n = 12], group C, 18-24 months [n = 12]), underwent complete postmortem examination. Results of microbial isolation and polymerase chain reaction and restriction fragment length polymorphism analyses confirmed the presence of Helicobacter spp. infection in the distal portion of the large bowel of all animals. Additionally, confounding pathogens, such as Clostridium difficile, Lawsonia intracellularis, and Giardia spp. that can cause proliferative enteritis, were absent in the hamsters of this study. Histopathologic scores for inflammation (P < 0.01), hyperplasia (P < 0.01), and dysplasia (P < 0.05) were significantly higher in the ileocecocolic (ICC) junction of animals in group C, relative to group A. Dysplastic lesions of various grades were detected in 5 of 11 hamsters in group C. Interestingly, the segment of the bowel that is usually colonized by Helicobacter spp. in hamsters had the most severe lesions. One hamster of group C developed a malignant fibrous histiocytoma, whereas another hamster developed a round cell sarcoma originating from the ICC junction. Thus, lesions in the distal portion of the large bowel of aging hamsters naturally colonized with Helicobacter spp. warrants developing the hamster as an animal model of IBD and potentially IBD-related cancer.

Uncoupling neurogenic gene networks in the Drosophila embryo.

PubMed

Rogers, William A; Goyal, Yogesh; Yamaya, Kei; Shvartsman, Stanislav Y; Levine, Michael S

2017-04-01

The EGF signaling pathway specifies neuronal identities in the Drosophila embryo by regulating developmental patterning genes such as intermediate neuroblasts defective ( ind ). EGFR is activated in the ventral midline and neurogenic ectoderm by the Spitz ligand, which is processed by the Rhomboid protease. CRISPR/Cas9 was used to delete defined rhomboid enhancers mediating expression at each site of Spitz processing. Surprisingly, the neurogenic ectoderm, not the ventral midline, was found to be the dominant source of EGF patterning activity. We suggest that Drosophila is undergoing an evolutionary transition in central nervous system (CNS)-organizing activity from the ventral midline to the neurogenic ectoderm. © 2017 Rogers et al.; Published by Cold Spring Harbor Laboratory Press.

Proctoscopy should be mandatory in men that have sex with men with external anogenital warts.

PubMed

Mlakar, Bostjan

2009-03-01

The aim of this study was to evaluate anal pathology in men having sex with men (MSM) seen at our proctology outpatient clinics. The charts of 74 MSM treated by the author between January 2002 and April 2006 were reviewed. Three of 74 patients (4%) had proctitis and 96% had anogenital condylomata acuminata (warts). 49 out of 71 (69%) had external anogenital as well as intra-anal warts and 13 (18%) had only intra-anal warts. In 14 an intra-anal dysplasia and in 2 patients intra-anal verrucous carcinomas were detected. The average duration of disease before referral to our institutions was more than 9 months. Half of the patients were previously treated for anogenital warts with ointments and suppositories at other institutions, including 17 that were "treated" with ointments and/or suppositories for hemorrhoids prescribed by family physicians. The patients mostly had widespread disease and sixty-nine of them required surgery. In the follow-up period there was no recurrence of warts and only itching was observed in 31 (44%) patients. Therapy with imiquimod was introduced for 3 months in twenty-two cases with intra-anal dysplasia. No major side effects were noticed despite intra-anal use. Proctoscopy and histological examination of intra-anal lesions in cases of external anogenital warts should be mandatory in MSM patients. I would like to encourage other physicians to use this approach, which enables detection of intra-anal warts, dysplasia, and even carcinoma in the asymptomatic stage.

The DP-1 transcription factor is required for keratinocyte growth and epidermal stratification.

PubMed

Chang, Wing Y; Bryce, Dawn M; D'Souza, Sudhir J A; Dagnino, Lina

2004-12-03

The epidermis is a stratified epithelium constantly replenished through the ability of keratinocytes in its basal layer to proliferate and self-renew. The epidermis arises from a single-cell layer ectoderm during embryogenesis. Large proliferative capacity is central to ectodermal cell and basal keratinocyte function. DP-1, a heterodimeric partner of E2F transcription factors, is highly expressed in the ectoderm and all epidermal layers during embryogenesis. To investigate the role of DP-1 in epidermal morphogenesis, we inhibited DP-1 activity through exogenous expression of a dominant-negative mutant (dnDP-1). Expression of the dnDP-1 mutant interferes with binding of E2F/DP-1 heterodimers to DNA and inhibits DNA replication, as well as cyclin A mRNA and protein expression. Chromatin immunoprecipitation analysis demonstrated that the cyclin A promoter is predominantly bound in proliferating keratinocytes by complexes containing E2F-3 and E2F-4. Thus, the mechanisms of decreased expression of cyclin A in the presence of dnDP-1 seem to involve inactivation of DP-1 complexes containing E2F-3 and E2F-4. To assess the consequences on epidermal morphogenesis of inhibiting DP-1 activity, we expressed dnDP-1 in rat epithelial keratinocytes in organotypic culture and observed that DP-1 inhibition negatively affected stratification of these cells. Likewise, expression of dnDP-1 in embryonic ectoderm explants produced extensive disorganization of subsequently formed epidermal basal and suprabasal layers, interfering with normal epidermal formation. We conclude that DP-1 activity is required for normal epidermal morphogenesis and ectoderm-to-epidermis transition.

Embryological Development: Evolutionary History, Genetic Bias, and Cellular Environment Control the Flow of Developmental Events, Part II.

ERIC Educational Resources Information Center

Caplan, Arnold I.

1981-01-01

Emphasizes ectodermal-mesodermal interaction but focuses on the genesis of specialized structures like feathers (ectodermal) and muscles, cartilage, and bone. The sum of these interactions and other factors which govern normal development may be important in regulating the regeneration of particular structures in postembryonic individuals.…

Rasmussen encephalitis with dual pathology in a patient without seizures: case report and literature review.

PubMed

Ravindra, Vijay M; Mazur, Marcus D; Mohila, Carrie A; Sweney, Matthew T; Hersh, Aimee; Bollo, Robert J

2015-11-01

Rasmussen encephalitis without seizures is rare. We report a case of Rasmussen encephalitis and cortical dysplasia without epilepsy as well as describe the imaging, pathology, and clinical course and review the literature to investigate whether this may represent a rare subset of Rasmussen encephalitis. We report the case of a 12-year-old girl with a history of cognitive decline and right arm weakness. Magnetic resonance imaging demonstrated diffuse left hemispheric cortical and subcortical atrophy suggestive of Rasmussen encephalitis. The patient had no clinical history of seizures, and electroencephalography did not demonstrate epileptiform abnormalities. Craniotomy for open brain biopsy was performed, and histopathologic evaluation identified Rasmussen encephalitis with cortical dysplasia (dual pathology). To the best of our knowledge, this is the third case of Rasmussen encephalitis diagnosed by both imaging and histopathology that had no clinical or electroencephalographic evidence of seizures and is the only case of Rasmussen encephalitis with cortical dysplasia without epilepsy.

Barrett’s Esophagus: Frequency and Prediction of Dysplasia and Cancer

PubMed Central

Falk, Gary W.

2015-01-01

The incidence of esophageal adenocarcinoma is continuing to increase at an alarming rate in the Western world today. Barrett’s esophagus is a clearly recognized risk factor for the development of esophageal adenocarcinoma, but the overwhelming majority of patients with Barrett’s esophagus will never develop esophageal cancer. A number of endoscopic, histologic and epidemiologic risk factors identify Barrett’s esophagus patients at increased risk for progression to high-grade dysplasia and esophageal adenocarcinoma. Endoscopic factors include segment length, mucosal abnormalities as seemingly trivial as esophagitis and the 12 to 6 o’clock hemisphere of the esophagus. Both intestinal metaplasia and low grade dysplasia, the latter only if confirmed by a pathologist with expertise in Barrett’s esophagus pathologic interpretation are the histologic risk factors for progression. Epidemiologic risk factors include aging, male gender, obesity, and smoking. Factors that may protect against the development of adenocarcinoma include a diet rich in fruits and vegetables, and the use of proton pump inhibitors, aspirin/NSAIDs and statins. PMID:25743461

Barrett's oesophagus: frequency and prediction of dysplasia and cancer.

PubMed

Falk, Gary W

2015-02-01

The incidence of oesophageal adenocarcinoma is continuing to increase at an alarming rate in the Western world today. Barrett's oesophagus is a clearly recognized risk factor for the development of oesophageal adenocarcinoma, but the overwhelming majority of patients with Barrett's oesophagus will never develop oesophageal cancer. A number of endoscopic, histologic and epidemiologic risk factors identify Barrett's oesophagus patients at increased risk for progression to high-grade dysplasia and oesophageal adenocarcinoma. Endoscopic factors include segment length, mucosal abnormalities as seemingly trivial as oesophagitis and the 12 to 6 o'clock hemisphere of the oesophagus. Both intestinal metaplasia and low grade dysplasia, the latter only if confirmed by a pathologist with expertise in Barrett's oesophagus pathologic interpretation are the histologic risk factors for progression. Epidemiologic risk factors include ageing, male gender, obesity, and smoking. Factors that may protect against the development of adenocarcinoma include a diet rich in fruits and vegetables, and the use of proton pump inhibitors, aspirin/NSAIDs and statins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anterior delayed gadolinium-enhanced MRI of cartilage values predict joint failure after periacetabular osteotomy.

PubMed

Kim, Sang Do; Jessel, Rebecca; Zurakowski, David; Millis, Michael B; Kim, Young-Jo

2012-12-01

Several available compositional MRIs seem to detect early osteoarthritis before radiographic appearance. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) has been most frequently used in clinical studies and reportedly predicts premature joint failure in patients undergoing Bernese periacetabular osteotomies (PAOs). We asked, given regional variations in biochemical composition in dysplastic hips, whether the dGEMRIC index of the anterior joint would better predict premature joint failure after PAOs than the coronal dGEMRIC index as previously reported. We retrospectively reviewed 43 hips in 41 patients who underwent Bernese PAO for hip dysplasia. Thirty-seven hips had preserved joints after PAOs and six were deemed premature failures based on pain, joint space narrowing, or subsequent THA. We used dGEMRIC to determine regional variations in biochemical composition. Preoperative demographic and clinical outcome score, radiographic measures of osteoarthritis and severity of dysplasia, and dGEMRIC indexes from different hip regions were analyzed in a multivariable regression analysis to determine the best predictor of premature joint failure. Minimum followup was 24 months (mean, 32 months; range, 24-46 months). The two cohorts were similar in age and sex distribution. Severity of dysplasia was similar as measured by lateral center-edge, anterior center-edge, and Tönnis angles. Preoperative pain, joint space width, Tönnis grade, and coronal and sagittal dGEMRIC indexes differed between groups. The dGEMRIC index in the anterior weightbearing region of the hip was lower in the prematurely failed group and was the best predictor. Success of PAO depends on the amount of preoperative osteoarthritis. These degenerative changes are seen most commonly in the anterior joint. The dGEMRIC index of the anterior joint may better predict premature joint failure than radiographic measures of hip osteoarthritis and coronal dGEMRIC index. Level II, prognostic study. See Instructions for Authors for a complete description of levels of evidence.

Analysis of Msx1; Msx2 double mutants reveals multiple roles for Msx genes in limb development.

PubMed

Lallemand, Yvan; Nicola, Marie-Anne; Ramos, Casto; Bach, Antoine; Cloment, Cécile Saint; Robert, Benoît

2005-07-01

The homeobox-containing genes Msx1 and Msx2 are highly expressed in the limb field from the earliest stages of limb formation and, subsequently, in both the apical ectodermal ridge and underlying mesenchyme. However, mice homozygous for a null mutation in either Msx1 or Msx2 do not display abnormalities in limb development. By contrast, Msx1; Msx2 double mutants exhibit a severe limb phenotype. Our analysis indicates that these genes play a role in crucial processes during limb morphogenesis along all three axes. Double mutant limbs are shorter and lack anterior skeletal elements (radius/tibia, thumb/hallux). Gene expression analysis confirms that there is no formation of regions with anterior identity. This correlates with the absence of dorsoventral boundary specification in the anterior ectoderm, which precludes apical ectodermal ridge formation anteriorly. As a result, anterior mesenchyme is not maintained, leading to oligodactyly. Paradoxically, polydactyly is also frequent and appears to be associated with extended Fgf activity in the apical ectodermal ridge, which is maintained up to 14.5 dpc. This results in a major outgrowth of the mesenchyme anteriorly, which nevertheless maintains a posterior identity, and leads to formation of extra digits. These defects are interpreted in the context of an impairment of Bmp signalling.

Orally administered brown seaweed-derived β-glucan effectively restrained development of gastric dysplasia in A4gnt KO mice that spontaneously develop gastric adenocarcinoma.

PubMed

Desamero, Mark Joseph; Kakuta, Shigeru; Chambers, James Kenn; Uchida, Kazuyuki; Hachimura, Satoshi; Takamoto, Masaya; Nakayama, Jun; Nakayama, Hiroyuki; Kyuwa, Shigeru

2018-07-01

β-Glucan refers to a heterogeneous group of chemically defined storage polysaccharides containing β-(1,3)-d-linked glucose polymers with branches connected by either β-(1,4) or β-(1,6) glycosidic linkage. To date, an extensive amount of scientific evidence supports their multifunctional biological activities, but their potential involvement in the progression of premalignant lesions remains to be clarified. A4gnt KO mice that lack α1,4-N-acetylglucosamine-capped O-glycans in gastric gland mucin are a unique animal model for gastric cancer because the mutant mice spontaneously develop gastric cancer through hyperplasia-dysplasia-adenocarcinoma sequence. In particular, A4gnt KO mice show gastric dysplasia during 10-20 weeks of age. Here we investigated the putative gastro-protective activity of brown seaweed-derived β-glucan (Laminaran) against development of gastric dysplasia, precancerous lesion for gastric cancer in A4gnt KO mice. The mutant mice at 12 weeks of age were randomly assigned into three treatment groups namely, wildtype control + distilled water (normal control), A4gnt KO mice + distilled water (untreated control), and A4gnt KO mice + 100 mg/kg Laminaran. After 3 weeks, the stomach was removed and examined for morphology and gene expression patterns. In contrast to the untreated control group, administration of Laminaran substantially attenuated gastric dysplasia development and counterbalanced the increased induction in cell proliferation and angiogenesis. Furthermore, Laminaran treatment effectively overcame the A4gnt KO-induced alteration in the gene expression profile of selected cytokines as revealed by real-time PCR analysis. Collectively, our present findings indicate that β-glucan can potentially restrain the development of gastric dysplasia to mediate their tissue-preserving activity. Copyright © 2018 Elsevier B.V. All rights reserved.

Columnar Metaplasia in Three Types of Surgical Mouse Models of Esophageal Reflux.

PubMed

Terabe, Fabio; Aikou, Susumu; Aida, Junko; Yamamichi, Nobutake; Kaminishi, Michio; Takubo, Kaiyo; Seto, Yasuyuki; Nomura, Sachiyo

2017-07-01

Esophageal adenocarcinoma develops in the setting of gastroesophageal reflux and columnar metaplasia in distal esophagus. Columnar metaplasia arising in gastroesophageal reflux models has developed in rat; however, gastroesophageal reflux models in mice have not been well-characterized. One hundred thirty-five C57Bl/6J mice aged 8 weeks old were divided into the following operations: esophagogastrojejunostomy (side-to-side) (EGJ), esophageal separation and esophagojejunostomy (end-to-side) (EJ), and EJ and gastrectomy (end-to-side) (EJ/TG). The animals were euthanized after 40 weeks and the histology of the junction was examined. Immunohistochemistry for p53, PDX-1, and CDX-2 was performed. Metaplasia developed in 15/33 (45.5%) of EGJ, 0/38 (0%) of EJ, and 6/39 (15.4%) of EJ/TG ( P < .05) and dysplasia developed 7/33 (21.2%) of EGJ, 0% of EJ, and 1/39 (2.6%) of EJ/TG. p53 was positive in all of the dysplastic regions, 12/15 (80%) metaplasias in the EGJ model, and 1/6 (16.7%) metaplasia in the EJ/TG model. CDX-2 was positive in all cases of metaplasias, but decreased in some cases of dysplasia. PDX-1 was positive in 7/8 (88%) cases of dysplasia and in 15/21 (71%) cases of metaplasia ( P < .05). The EGJ model, which causes reflux of gastric acid and duodenal content, developed metaplasia and dysplasia most frequently. No metaplasia developed in the EJ model in which gastric juice and duodenal content mixed before reflux. Thus, duodenal contents alone can induce columnar metaplasia and dysplasia; however, the combination of gastric acid with duodenal content reflux can cause metaplasia and dysplasia more efficiently.

Utility of immediate postoperative hip MRI in developmental hip dysplasia: closed vs. open reduction.

PubMed

Jadhav, Siddharth P; More, Snehal R; Shenava, Vinitha; Zhang, Wei; Kan, J Herman

2018-04-25

Magnetic resonance imaging (MRI) of the hips is being increasingly used to confirm hip reduction after surgery and spica cast placement for developmental dysplasia of the hip (DDH). To review a single institutional experience with post-spica MRI in children undergoing closed or open hip reduction and describe the utility of MRI in directing the need for re-intervention. Seventy-four patients (52 female, 22 male) who underwent post-spica hip MRI over a 6-year period were retrospectively reviewed. One hundred and seven hips were included. Data reviewed included age at intervention, gender, type of intervention performed, MRI findings, the need for re-intervention and the interval between interventions. Gender was compared between the closed and open reduction groups via the Fisher exact test. Age at the first procedure was compared via the Wilcoxon rank test. Rates of re-intervention after closed and open reduction were calculated and the reasons for re-intervention were reviewed. The mean age at the time of the first intervention was 16.4 months (range: 4 to 63 months). Mean age for the closed reduction group was 10.5 months (range: 4-24 months) and for the open reduction group was 23.7 months (range: 5-63 months), which was significant (P-value <0.0001). Of the 52 hips that underwent closed reduction, 16 (31%) needed re-intervention. Of the 55 hips that underwent open reduction, MRI was useful in deciding re-intervention in only 1 (2%). This patient had prior multiple failed closed and open reductions at an outside institute. Post intervention hip spica MRI is useful in determining the need for re-intervention after closed hip reduction, but its role after open reduction is questionable.

Spontaneous aortic dissecting hematoma in two dogs.

PubMed

Boulineau, Theresa Marie; Andrews-Jones, Lydia; Van Alstine, William

2005-09-01

This report describes 2 cases of spontaneous aortic dissecting hematoma in young Border Collie and Border Collie crossbred dogs. Histology was performed in one of the cases involving an unusual splitting of the elastin present within the wall of the aorta, consistent with elastin dysplasia as described in Marfan syndrome in humans. The first case involved a young purebred Border Collie that died suddenly and the second case involved a Border Collie crossbred dog that died after a 1-month history of seizures. Gross lesions included pericardial tamponade with dissection of the ascending aorta in the former case and thoracic cavity hemorrhage, mediastinal hematoma, and aortic dissection in the latter. Histologic lesions in the case of the Border Collie crossbred dog included a dissecting hematoma of the ascending aorta with elastin dysplasia and right axillary arterial intimal proliferation.

Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett's oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial.

PubMed

van Vilsteren, Frederike G I; Pouw, Roos E; Seewald, Stefan; Alvarez Herrero, Lorenza; Sondermeijer, Carine M T; Visser, Mike; Ten Kate, Fiebo J W; Yu Kim Teng, Karl C; Soehendra, Nib; Rösch, Thomas; Weusten, Bas L A M; Bergman, Jacques J G H M

2011-06-01

After focal endoscopic resection (ER) of high-grade dysplasia (HGD) or early cancer (EC) in Barrett's oesophagus (BO), eradication of all remaining BO reduces the recurrence risk. The aim of this study was to compare the safety of stepwise radical ER (SRER) versus focal ER followed by radiofrequency ablation (RFA) for complete eradication of BO containing HGD/EC. A multicentre randomised clinical trial was carried out in three tertiary centres. Patients with BO ≤ 5 cm containing HGD/EC were randomised to SRER or ER/RFA. Patients in the SRER group underwent piecemeal ER of 50% of BO followed by serial ER. Patients in the ER/RFA group underwent focal ER for visible lesions followed by serial RFA. Follow-up endoscopy with biopsies (four-quadrant/2 cm BO) was performed at 6 and 12 months and then annually. The main outcome measures were: stenosis rate; complications; complete histological response for neoplasia (CR-neoplasia); and complete histological response for intestinal metaplasia (CR-IM). CR-neoplasia was achieved in 25/25 (100%) SRER and in 21/22 (96%) ER/RFA patients. CR-IM was achieved in 23 (92%) SRER and 21 (96%) ER/RFA patients. The stenosis rate was significantly higher in SRER (88%) versus ER/RFA (14%; p<0.001), resulting in more therapeutic sessions in SRER (6 vs 3; p<0.001) due to dilations. After median 24 months follow-up, one SRER patient had recurrence of EC, requiring ER. In patients with BO ≤ 5 cm containing HGD/EC, SRER and ER/RFA achieved comparably high rates of CR-IM and CR-neoplasia. However, SRER was associated with a higher number of complications and therapeutic sessions. For these patients, a combined endoscopic approach of focal ER followed by RFA may thus be preferred over SRER. Clinical trial number NTR1337.

Ectodermal fragments from normal frog gastrulae condition substrata to support normal and hybrid mesodermal cell migration in vitro.

PubMed

Nakatsuji, N; Johnson, K E

1984-06-01

Using time-lapse cinemicrography and scanning electron microscopy, we have shown that normal Rana embryos and gastrulating hybrid embryos have extracellular fibrils on the inner surface of the ectodermal layer. These fibrils are absent prior to gastrulation and appear in increasing numbers during gastrulation. They can also be deposited in vitro where they condition substrata in such a way that normal presumptive mesodermal cells placed on them show extensive attachment and unoriented cell movement. These fibrils are also present in some arrested hybrid embryos, but in reduced numbers, or are lacking in other arrested hybrid embryos. Explanted ectodermal fragments from arrested hybrid embryos fail both to condition culture substrata by the deposition of fibrils and to promote cell attachment and translocation. In contrast, ectodermal fragments from normal embryos can condition culture substrata so as to promote moderate cell attachment and, for one particular gamete combination, even cell translocation of presumptive mesodermal cells taken from arrested hybrid embryos. These results provide new evidence to support the hypothesis that extracellular fibrils represent a system that promotes mesodermal cell migration in amphibian embryos. Differences in the fibrillar system in urodele and anuran embryos are discussed in relation to fundamental differences in the mode of mesodermal cell migration in these two classes of Amphibia.

Postnatal progression of bone disease in the cervical spines of mucopolysaccharidosis I dogs

PubMed Central

Chiaro, Joseph A; Baron, Matthew D; del Alcazar, Chelsea; O’Donnell, Patricia; Shore, Eileen M; Elliott, Dawn M; Ponder, Katherine P; Haskins, Mark E; Smith, Lachlan J

2013-01-01

Introduction Mucopolysaccharidosis I (MPS I) is a lysosomal storage disorder characterized by deficient α-L-iduronidase activity leading to accumulation of poorly degraded dermatan and heparan sulfate glycosaminoglycans (GAGs). MPS I is associated with significant cervical spine disease, including vertebral dysplasia, odontoid hypoplasia, and accelerated disc degeneration, leading to spinal cord compression and kypho-scoliosis. The objective of this study was to establish the nature and rate of progression of cervical vertebral bone disease in MPS I using a canine model. Methods C2 vertebrae were obtained post-mortem from normal and MPS I dogs at 3, 6 and 12 months-of-age. Morphometric parameters and mineral density for the vertebral trabecular bone and odontoid process were determined using micro-computed tomography. Vertebrae were then processed for paraffin histology, and cartilage area in both the vertebral epiphyses and odontoid process were quantified. Results Vertebral bodies of MPS I dogs had lower trabecular bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD) than normals at all ages. For MPS I dogs, BV/TV, Tb.Th and BMD plateaued after 6 months-of-age. The odontoid process appeared morphologically abnormal for MPS I dogs at 6 and 12 months-of-age, although BV/TV and TMD were not significantly different from normals. MPS I dogs had significantly more cartilage in the vertebral epiphyses at both 3 and 6 months-of-age. At 12 months-of-age, epiphyseal growth plates in normal dogs were absent, but in MPS I dogs they persisted. Conclusions In this study we report reduced trabecular bone content and mineralization, and delayed cartilage to bone conversion in MPS I dogs from 3 months-of-age, which may increase vertebral fracture risk and contribute to progressive deformity. The abnormalities of the odontoid process we describe likely contribute to increased incidence of atlanto-axial subluxation observed clinically. Therapeutic strategies that enhance bone formation may decrease incidence of spine disease in MPS I patients. PMID:23563357

Dental abnormalities and preventive oral care in Schimke immuno-osseous dysplasia.

PubMed

Gendronneau, M; Kérourédan, O; Taque, S; Sixou, J L; Bonnaure-Mallet, M

2014-06-01

Schimke immuno-osseous dysplasia (SIOD) is a rare, severe, autosomal recessive disorder that results in spondyloepiphyseal dysplasia, renal dysfunction, immunodeficiency, facial dysmorphism and growth failure. Little is known about oral features associated with SIOD. Some of the dental anomalies encountered are specific to SIOD and have only been reported in individuals with SIOD. This paper describes the clinical and radiographic dental manifestations of SIOD in two Caucasian brothers. Both lived to be about 10 years old. After a variety of symptoms were reported, a diagnosis of SIOD was finally made when the brothers were, respectively, 5 and 8 years old. At that time, dental anomalies, such as dyschromia, bulbous crowns, short and thin roots, had not been taken into account to establish the diagnosis. However, knowledge of the dental features characteristic of this disease could have helped make the diagnosis. Although both were caries- and periodontal disease-free, special attention was focused on prevention, including dietary counselling, plaque control, oral hygiene instructions and the use of fluoridated toothpaste. The two patients were followed every 6 months, for over 2 years (until their death), by both a private dentist and a university hospital dentist, which helped them maintain good oral health. Oral hygiene was assessed at each appointment and fissure sealants were placed by the private practitioner on their first permanent molars. This report describes dental anomalies specific to SIOD that could facilitate diagnosis. Clinicians and dentists should work in collaboration to diagnose and treat children with SIOD. These patients require regular and specific dental management because of their fragile health and their characteristic dental anomalies. Ideally, preventive visits should be scheduled every 6 months in addition to curative visits as needed.

A radiologist's guide to the imaging in the diagnosis and treatment of developmental dysplasia of the hip. I. General considerations, physical examination as applied to real-time sonography and radiography.

PubMed

Gerscovich, E O

1997-07-01

Developmental dysplasia of the hip (DDH) has a broad spectrum of presentation with the minor findings resolving spontaneously and the most severe ones resulting in disability, if not diagnosed early in life. Diagnosis in the first few months of life allows conservative treatment with complete resolution in most cases. Suspicion of DDH is based on ethnic, family, and pregnancy history, and on physical examination of the newborn. Imaging assists in the diagnosis and follows the treatment. Different modalities have their own advantages and disadvantages. This article deals with the description of the disease, risk factors, statistics, the physical examination as applied to real-time sonography, and imaging (plain radiography, arthrography, computed tomography, and magnetic resonance imaging.

A Case of Atypical McCune-Albright Syndrome with Vaginal Bleeding

PubMed Central

Rostampour, Noushin; Hashemipour, Mahin; Kelishadi, Roya; Hovsepian, Silva; Hekmatnia, Ali

2011-01-01

Background McCune-Albright syndrome (MAS) is a rare non-inherited disorder characterized by the clinical triad of precocious puberty, cafe-au-lait skin lesions, and fibrous dysplasia of bone. Case Presentation We report a girl with MAS, presenting initially with vaginal bleeding at the age of 17 months. Ultrasonography revealed unilateral ovarian cysts and ureteral and ovarian enlargement. Considering the clinical and paraclinical findings, the patient diagnosed as a case of gonadotropin-independent precocious puberty was treated with medroxy-progestrone acetate (MPA) for three months. During the follow up, recurrent episodes of bleeding, ovarian activation and cyst formation, as well as breast size development were reported. At the age of 5.5 years, fibrous dysplasia was detected, which in coexistence with precocious puberty confirmed the diagnosis of MAS. The patient had no cafe-au-lait skin macles during follow up. Conclusion Considering that clinical manifestations of MAS appear later in the course of recurrent periods of ovarian activation and cyst formation, a careful clinical observation and follow up of patients is necessary and the diagnosis of MAS must be kept in mind in cases with gonadotropin-independent precocious puberty. PMID:23056821

Quantitative genetics of secondary hip joint osteoarthritis in a Labrador Retriever-Greyhound pedigree.

PubMed

Hays, Laurel; Zhang, Zhiwu; Mateescu, Raluca G; Lust, George; Burton-Wurster, Nancy I; Todhunter, Rory J

2007-01-01

To evaluate the quantitative inheritance of secondary hip joint osteoarthritis in a canine pedigree. 137 Labrador Retrievers, Greyhounds, and mixed-breed dogs. Necropsy scores ranging from 0 to 4 were obtained for each hip joint. Seven unaffected Greyhounds with normal hip joint conformation were also used for genetic modeling, but were not euthanized. Sixty-six male and 71 female dogs were allocated to 2 groups (< or = 12 months of age and > 12 months of age). Statistical models were developed to establish the inheritance pattern of hip joint osteoarthritis that developed secondary to hip dysplasia. 62 dogs had evidence of osteoarthritis in a hip joint, and 75 had no evidence of osteoarthritis. After sex was adjusted for, the necropsy score was found to be inherited additively but without dominance. Each Labrador Retriever allele increased the necropsy score by 0.7 to 0.9 points, compared with the Greyhound allele, and male sex increased the necropsy score 0.74 over female sex. Approximately 10% of the variation in necropsy score was attributable to the litter of puppies' origin. Because secondary hip joint osteoarthritis is inherited additively, selection pressure could be applied to reduce its incidence. Similar statistical models can be used in linkage and association mapping to detect the genes in the underlying quantitative trait loci that contribute to hip joint osteoarthritis.

A novel loss-of-function mutation in Npr2 clarifies primary role in female reproduction and reveals a potential therapy for acromesomelic dysplasia, Maroteaux type.

PubMed

Geister, Krista A; Brinkmeier, Michelle L; Hsieh, Minnie; Faust, Susan M; Karolyi, I Jill; Perosky, Joseph E; Kozloff, Kenneth M; Conti, Marco; Camper, Sally A

2013-01-15

We discovered a new spontaneous mutant allele of Npr2 named peewee (pwe) that exhibits severe disproportionate dwarfism and female infertility. The pwe phenotype is caused by a four base-pair deletion in exon 3 that generates a premature stop codon at codon 313 (L313X). The Npr2(pwe/pwe) mouse is a model for the human skeletal dysplasia acromesomelic dysplasia, Maroteaux type (AMDM). We conducted a thorough analysis of the female reproductive tract and report that the primary cause of Npr2(pwe/pwe) female infertility is premature oocyte meiotic resumption, while the pituitary and uterus appear to be normal. Npr2 is expressed in chondrocytes and osteoblasts. We determined that the loss of Npr2 causes a reduction in the hypertrophic and proliferative zones of the growth plate, but mineralization of skeletal elements is normal. Mutant tibiae have increased levels of the activated form of ERK1/2, consistent with the idea that natriuretic peptide receptor type 2 (NPR2) signaling inhibits the activation of the MEK/ERK mitogen activated protein kinase pathway. Treatment of fetal tibiae explants with mitogen activated protein kinase 1 and 2 inhibitors U0126 and PD325901 rescues the Npr2(pwe/pwe) growth defect, providing a promising foundation for skeletal dysplasia therapeutics.

A novel loss-of-function mutation in Npr2 clarifies primary role in female reproduction and reveals a potential therapy for acromesomelic dysplasia, Maroteaux type

PubMed Central

Geister, Krista A.; Brinkmeier, Michelle L.; Hsieh, Minnie; Faust, Susan M.; Karolyi, I. Jill; Perosky, Joseph E.; Kozloff, Kenneth M.; Conti, Marco; Camper, Sally A.

2013-01-01

We discovered a new spontaneous mutant allele of Npr2 named peewee (pwe) that exhibits severe disproportionate dwarfism and female infertility. The pwe phenotype is caused by a four base-pair deletion in exon 3 that generates a premature stop codon at codon 313 (L313X). The Npr2pwe/pwe mouse is a model for the human skeletal dysplasia acromesomelic dysplasia, Maroteaux type (AMDM). We conducted a thorough analysis of the female reproductive tract and report that the primary cause of Npr2pwe/pwe female infertility is premature oocyte meiotic resumption, while the pituitary and uterus appear to be normal. Npr2 is expressed in chondrocytes and osteoblasts. We determined that the loss of Npr2 causes a reduction in the hypertrophic and proliferative zones of the growth plate, but mineralization of skeletal elements is normal. Mutant tibiae have increased levels of the activated form of ERK1/2, consistent with the idea that natriuretic peptide receptor type 2 (NPR2) signaling inhibits the activation of the MEK/ERK mitogen activated protein kinase pathway. Treatment of fetal tibiae explants with mitogen activated protein kinase 1 and 2 inhibitors U0126 and PD325901 rescues the Npr2pwe/pwe growth defect, providing a promising foundation for skeletal dysplasia therapeutics. PMID:23065701

Malignant transformation of oral epithelial dysplasia: clinicopathological risk factors and outcome analysis in a retrospective cohort of 138 cases.

PubMed

Liu, Wei; Bao, Zhe-Xuan; Shi, Lin-Jun; Tang, Guo-Yao; Zhou, Zeng-Tong

2011-10-01

To explore the usefulness of a new binary system of grading dysplasia proposed by the World Health Organization and to identify significant risk factors for malignant transformation in a long-term follow-up cohort of patients with oral epithelial dysplasia. A total of 138 patients with histologically confirmed oral dysplasia between 1978 and 2008 were reviewed retrospectively in our department. The mean follow-up period was 5.1 years. Of these dysplasias, 37 (26.8%) developed into cancer, with a mean duration of 4.6 years. Cox regression analysis revealed that high-grade dysplasia was an independent risk factor for transition, but age, gender, lesion site, diet habit, smoking and alcohol intake were not risk factors. High-grade dysplasia was associated with a 2.78-fold (95% confidence interval 1.44-5.38; P = 0.002) increased risk of transition, as compared with low-grade dysplasia. Consistently, high-grade dysplasia had a significantly higher incidence of malignancy than low-grade dysplasia by Kaplan-Meier analysis (log-rank test, P = 0.001). The utilization of high-grade dysplasia as a significant indicator for evaluating malignant transformation risk in patients with potentially malignant lesions is suggested; this may be helpful to guide treatment selection in clinical practice. 2011 Blackwell Publishing Limited.

Fibroblast growth factor receptor 2 (FGFR2) is required for corneal epithelial cell proliferation and differentiation during embryonic development.

PubMed

Zhang, Jinglin; Upadhya, Dinesh; Lu, Lin; Reneker, Lixing W

2015-01-01

Fibroblast growth factors (FGFs) play important roles in many aspects of embryonic development. During eye development, the lens and corneal epithelium are derived from the same surface ectodermal tissue. FGF receptor (FGFR)-signaling is essential for lens cell differentiation and survival, but its role in corneal development has not been fully investigated. In this study, we examined the corneal defects in Fgfr2 conditional knockout mice in which Cre expression is activated at lens induction stage by Pax6 P0 promoter. The cornea in LeCre, Fgfr2(loxP/loxP) mice (referred as Fgfr2(CKO)) was analyzed to assess changes in cell proliferation, differentiation and survival. We found that Fgfr2(CKO) cornea was much thinner in epithelial and stromal layer when compared to WT cornea. At embryonic day 12.5-13.5 (E12.5-13.5) shortly after the lens vesicle detaches from the overlying surface ectoderm, cell proliferation (judged by labeling indices of Ki-67, BrdU and phospho-histone H3) was significantly reduced in corneal epithelium in Fgfr2(CKO) mice. At later stage, cell differentiation markers for corneal epithelium and underlying stromal mesenchyme, keratin-12 and keratocan respectively, were not expressed in Fgfr2(CKO) cornea. Furthermore, Pax6, a transcription factor essential for eye development, was not present in the Fgfr2(CKO) mutant corneal epithelial at E16.5 but was expressed normally at E12.5, suggesting that FGFR2-signaling is required for maintaining Pax6 expression in this tissue. Interestingly, the role of FGFR2 in corneal epithelial development is independent of ERK1/2-signaling. In contrast to the lens, FGFR2 is not required for cell survival in cornea. This study demonstrates for the first time that FGFR2 plays an essential role in controlling cell proliferation and differentiation, and maintaining Pax6 levels in corneal epithelium via ERK-independent pathways during embryonic development.

Irregular chiasm-C-roughest, a member of the immunoglobulin superfamily, affects sense organ spacing on the Drosophila antenna by influencing the positioning of founder cells on the disc ectoderm.

PubMed

Venugopala Reddy, G; Reiter, C; Shanbhag, S; Fischbach, K F; Rodrigues, V

1999-10-01

We describe a role for Irregular chiasmC-roughest (IrreC-rst), an immunoglobulin (Ig) superfamily member, in patterning sense organs on the Drosophila antenna. IrreC-rst protein is initially expressed homogeneously on apical profiles of ectodermal cells in regions of the antennal disc. During specification of founder cells (FCs), the intracellular protein distribution changes and becomes concentrated in regions where specific intercellular contacts presumably occur. Loss of function mutations as well as misexpression of irreC-rst results in an altered arrangement of FCs within the disc compared to wildtype. Sense organ development occurs normally, although spacing is affected. Unlike its role in interommatidial spacing, irreC-rst does not affect apoptosis during antennal development. We propose that IrreC-rst affects the spatial relationship between sensory and ectodermal cells during FC delamination.

Evolution of bilaterian central nervous systems: a single origin?

PubMed Central

2013-01-01

The question of whether the ancestral bilaterian had a central nervous system (CNS) or a diffuse ectodermal nervous system has been hotly debated. Considerable evidence supports the theory that a CNS evolved just once. However, an alternative view proposes that the chordate CNS evolved from the ectodermal nerve net of a hemichordate-like ancestral deuterostome, implying independent evolution of the CNS in chordates and protostomes. To specify morphological divisions along the anterior/posterior axis, this ancestor used gene networks homologous to those patterning three organizing centers in the vertebrate brain: the anterior neural ridge, the zona limitans intrathalamica and the isthmic organizer, and subsequent evolution of the vertebrate brain involved elaboration of these ancestral signaling centers; however, all or part of these signaling centers were lost from the CNS of invertebrate chordates. The present review analyzes the evidence for and against these theories. The bulk of the evidence indicates that a CNS evolved just once – in the ancestral bilaterian. Importantly, in both protostomes and deuterostomes, the CNS represents a portion of a generally neurogenic ectoderm that is internalized and receives and integrates inputs from sensory cells in the remainder of the ectoderm. The expression patterns of genes involved in medio/lateral (dorso/ventral) patterning of the CNS are similar in protostomes and chordates; however, these genes are not similarly expressed in the ectoderm outside the CNS. Thus, their expression is a better criterion for CNS homologs than the expression of anterior/posterior patterning genes, many of which (for example, Hox genes) are similarly expressed both in the CNS and in the remainder of the ectoderm in many bilaterians. The evidence leaves hemichordates in an ambiguous position – either CNS centralization was lost to some extent at the base of the hemichordates, or even earlier, at the base of the hemichordates + echinoderms, or one of the two hemichordate nerve cords is homologous to the CNS of protostomes and chordates. In any event, the presence of part of the genetic machinery for the anterior neural ridge, the zona limitans intrathalamica and the isthmic organizer in invertebrate chordates together with similar morphology indicates that these organizers were present, at least in part, at the base of the chordates and were probably elaborated upon in the vertebrate lineage. PMID:24098981

Is There an Association Between Borderline-to-mild Dysplasia and Hip Osteoarthritis? Analysis of CT Osteoabsorptiometry.

PubMed

Irie, Tohru; Takahashi, Daisuke; Asano, Tsuyoshi; Arai, Ryuta; Terkawi, Muhammad Alaa; Ito, Yoichi M; Iwasaki, Norimasa

2018-07-01

The definitive treatment of borderline-to-mild dysplasia remains controversial. A more comprehensive understanding of the etiology of osteoarthritis (OA) and clarification of any possible association between borderline-to-mild dysplasia and the pathogenesis of OA are essential. (1) Does the distribution of acetabular subchondral bone density increase according to dysplasia severity? (2) Is there an association between borderline-to-mild dysplasia and OA pathogenesis? We evaluated bilateral hips of patients with developmental dysplasia of the hip who underwent eccentric rotational acetabular osteotomy (ERAO) for inclusion in the dysplasia group and contralateral hips of patients with unilateral idiopathic osteonecrosis of the femoral head (ONFH) who underwent curved intertrochanteric varus osteotomy (CVO) for the control group. ERAO was performed in 46 patients and CVO was performed in 32 patients between January 2013 and August 2016 at our institution. All patients underwent bilateral hip CT. The study included 55 hips categorized according to dysplasia severity: (1) borderline-mild, 19 hips (15° ≤ lateral center-edge angle [LCEA] < 25°); (2) moderate, 20 hips (5° ≤ LCEA < 15°); (3) severe, 16 hips (LCEA < 5°); and (4) control, 15 hips. Thirty-seven dysplastic hips (age < 15 or > 50 years old, prior hip surgery, subluxation, aspherical femoral head, cam deformity, and radiographic OA) and 17 control hips (age < 15 or > 50 years old, bilateral ONFH, LCEA < 25° or ≥ 35°, cam deformity, and radiographic OA) were excluded. CT-osteoabsorptiometry (OAM) predicts physiologic biomechanical conditions in joints by evaluating subchondral bone density. We evaluated the distribution of subchondral bone densities in the acetabulum with CT-OAM, dividing the stress distribution map into six segments: anteromedial, anterolateral, centromedial, centrolateral, posteromedial, and posterolateral. We calculated the percentage of high-density area, which was defined as the upper 30% of Hounsfield units values in each region and compared least square means difference estimated by the random intercept model among the four groups. In all regions, the percentage of high-density area did not differ between the borderline-mild group and the control (eg, anterolateral, 16.2 ± 5.6 [95% CI, 13.4 to 18.9] versus 15.5 ± 5.7 [95% CI, 12.4 to 18.5, p = 0.984]; centrolateral, 39.1 ± 5.7 [95% CI, 36.4 to 41.8] versus 39.5 ± 4.7 [95% CI, 36.6 to 42.5, p = 0.995]; posterolateral, 10.9 ± 5.2 [95% CI, 8.0 to 13.8] versus 15.1 ± 6.8 [95% CI, 11.7 to 18.5, p = 0.389]). In the anterolateral region, a smaller percentage of high-density area was observed in the borderline-mild group than in both the moderate group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 28.2 ± 5.1 [95% CI, 25.5-30.9], p < 0.001) and the severe group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 22.2 ± 6.8 [95% CI, 19.2-25.2, p = 0.026). Our results suggest that the cumulative hip stress distribution in borderline-to-mild dysplasia was not concentrated on the lateral side of the acetabulum, unlike severe dysplasia. Based on the stress distribution pattern, our results may suggest that there is no association between borderline-to-mild dysplasia and the pathogenesis of OA. Further studies are needed to evaluate the association between borderline-to-mild dysplasia and instability of the hip.

FGFR3-related condition: a skeletal dysplasia with similarities to thanatophoric dysplasia and SADDAN due to Lys650Met.

PubMed

Farmakis, Shannon G; Shinawi, Marwan; Miller-Thomas, Michelle; Radmanesh, Alireza; Herman, Thomas E

2015-03-01

Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene account for six related skeletal dysplasia conditions: achondroplasia, hypochondroplasia, thanatophoric dysplasia types 1 and 2, SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), and platyspondylic lethal skeletal dysplasia, San Diego type. This group of disorders has very characteristic clinical and radiologic features, which distinguish them from other skeletal dysplasias. They display a spectrum of severity in the skeletal findings, ranging from relatively mild hypochondroplasia to lethal thanatophoric dysplasia. We report a patient who has the missense FGFR3 mutation, Lys650Met, previously reported in association only with SADDAN, who exhibits some findings similar to both thanatophoric dysplasia (types 1 and 2) in addition to those findings characteristic of SADDAN.

Outcome of bioprosthetic valve replacement in dogs with tricuspid valve dysplasia.

PubMed

Bristow, P; Sargent, J; Luis Fuentes, V; Brockman, D

2017-04-01

To describe the short-term and long-term outcome in dogs with tricuspid valve dysplasia undergoing tricuspid valve replacement under cardiopulmonary bypass. Data were collected from the hospital records of all dogs that had undergone tricuspid valve replacement under cardiopulmonary bypass between 2006 and 2012. Dogs were considered candidates for tricuspid valve replacement if they had severe tricuspid valve regurgitation associated with clinical signs of cardiac compromise. Nine dogs of six different breeds were presented. Median age was 13 months (range 7 to 61 months), median weight 26·5 kg (range 9·7 to 59 kg). Eight bovine pericardial valves and one porcine aortic valve were used. One non-fatal intraoperative complication occurred. Complications during hospitalisation occurred in six dogs, four of which were fatal. Of the five dogs discharged, one presented dead due to haemothorax after minor trauma seven days later. The four remaining dogs survived a median of 533 days; all of these dogs received a bovine pericardial valve. Based on our results, tricuspid valve replacement with bovine or porcine prosthetic valves is associated with a high incidence of complications. © 2017 British Small Animal Veterinary Association.

Recognition of p63 by the E3 ligase ITCH: Effect of an ectodermal dysplasia mutant.

PubMed

Bellomaria, A; Barbato, Gaetano; Melino, G; Paci, M; Melino, Sonia

2010-09-15

The E3 ubiquitin ligase Itch mediates the degradation of the p63 protein. Itch contains four WW domains which are pivotal for the substrate recognition process. Indeed, this domain is implicated in several signalling complexes crucially involved in human diseases including Muscular Dystrophy, Alzheimer's Disease and Huntington Disease. WW domains are highly compact protein-protein binding modules that interact with short proline-rich sequences. The four WW domains present in Itch belong to the Group I type, which binds polypeptides with a PY motif characterized by a PP xY consensus sequence, where x can be any residue. Accordingly, the Itch-p63 interaction results from a direct binding of Itch-WW2 domain with the PY motif of p63. Here, we report a structural analysis of the Itch-p63 interaction by fluorescence, CD and NMR spectroscopy. Indeed, we studied the in vitro interaction between Itch-WW2 domain and p63(534-551), an 18-mer peptide encompassing a fragment of the p63 protein including the PY motif. In addition, we evaluated the conformation and the interaction with Itch-WW2 of a site specific mutant of p63, I549T, that has been reported in both Hay-Wells syndrome and Rapp-Hodgkin syndrome. Based on our results, we propose an extended PP xY motif for the Itch recognition motif (P-P-P-Y-x(4)-[ST]-[ILV]), which includes these C-terminal residues to the PP xY motif.

Patent Ductus Arteriosus Therapy: Impact on Neonatal and 18-Month Outcome

PubMed Central

Madan, Juliette C.; Kendrick, Douglas; Hagadorn, James I.; Frantz, Ivan D.

2009-01-01

OBJECTIVE The purpose of this work was to evaluate therapy for patent ductus arteri-osus as a risk factor for death or neurodevelopmental impairment at 18 to 22 months, bronchopulmonary dysplasia, or necrotizing enterocolitis in extremely low birth weight infants. METHODS We studied infants in the National Institute of Child Health and Human Development Neonatal Research Network Generic Data Base born between 2000 and 2004 at 23 to 28 weeks’ gestation and at <1000-g birth weight with patent ductus arteriosus. Patent ductus arteriosus therapy was evaluated as a risk factor for outcomes in bivariable and multivariable analyses. RESULTS Treatment for subjects with patent ductus arteriosus (n = 2838) included 403 receiving supportive treatment only, 1525 treated with indomethacin only, 775 with indomethacin followed by secondary surgical closure, and 135 treated with primary surgery. Patients who received supportive therapy for patent ductus arteriosus did not differ from subjects treated with indomethacin only for any of the outcomes of interest. Compared with indomethacin treatment only, patients undergoing primary or secondary surgery were smaller and more premature. When compared with indomethacin alone, primary surgery was associated with increased adjusted odds for neurodevelopmental impairment and bronchopulmonary dysplasia in multivariable logistic regression. Secondary surgical closure was associated with increased odds for neurodevelopmental impairment and increased adjusted odds for bronchopulmonary dysplasia but decreased adjusted odds for death. Risk of necrotizing enterocolitis did not differ among treatments. Indomethacin prophylaxis did not significantly modify these results. CONCLUSIONS Our results suggest that infants treated with primary or secondary surgery for patent ductus arteriosus may be at increased risk for poor short- and long-term outcomes compared with those treated with indomethacin. Prophylaxis with indomethacin in the first 24 hours of life did not modify the subsequent outcomes of patent ductus arteriosus therapy. PMID:19171637

Phenotypic variability in gap junction syndromic skin disorders: experience from KID and Clouston syndromes' clinical diagnostics.

PubMed

Kutkowska-Kaźmierczak, Anna; Niepokój, Katarzyna; Wertheim-Tysarowska, Katarzyna; Giza, Aleksandra; Mordasewicz-Goliszewska, Maria; Bal, Jerzy; Obersztyn, Ewa

2015-08-01

Connexins belong to the family of gap junction proteins which enable direct cell-to-cell communication by forming channels in adjacent cells. Mutations in connexin genes cause a variety of human diseases and, in a few cases, result in skin disorders. There are significant differences in the clinical picture of two rare autosomal dominant syndromes: keratitis-ichthyosis-deafness (KID) syndrome and hidrotic ectodermal dysplasia (Clouston syndrome), which are caused by GJB2 and GJB6 mutations, respectively. This is despite the fact that, in both cases, malfunctioning of the same family proteins and some overlapping clinical features (nail dystrophy, hair loss, and palmoplantar keratoderma) is observed. KID syndrome is characterized by progressive vascularizing keratitis, ichthyosiform erythrokeratoderma, and neurosensory hearing loss, whereas Clouston syndrome is characterized by nail dystrophy, hypotrichosis, and palmoplantar keratoderma. The present paper presents a Polish patient with sporadic KID syndrome caused by the mutation of p.Asp50Asn in GJB2. The patient encountered difficulties in obtaining a correct diagnosis. The other case presented is that of a family with Clouston syndrome (caused by p.Gly11Arg mutation in GJB6), who are the first reported patients of Polish origin suffering from this disorder. Phenotype diversity among patients with the same genotypes reported to date is also summarized. The conclusion is that proper diagnosis of these syndromes is still challenging and should always be followed by molecular verification.

Risk of progression of Barrett's esophagus in patients with cirrhosis

PubMed Central

Apfel, Tehilla; Lopez, Rocio; Sanaka, Madhusudhan R; Thota, Prashanthi N

2017-01-01

AIM To study Barrett’s esophagus (BE) in cirrhosis and assess progression to esophageal adenocarcinoma (EAC) compared to non-cirrhotic BE controls. METHODS Cirrhotic patients who were found to have endoscopic evidence of BE confirmed by the presence of intestinal metaplasia on histology from 1/1/2000 to 12/1/2015 at Cleveland Clinic were included. Cirrhotic patients were matched 1:4 to BE controls without cirrhosis. Age, gender, race, BE length, hiatal hernia size, Child-Pugh (CP) class and histological findings were recorded. Cases and controls without high-grade dysplasia (HGD)/EAC and who had follow-up endoscopies were studied for incidence of dysplasia/EAC and to assess progression rates. Univariable conditional logistic regression was done to assess differences in baseline characteristics between the two groups. RESULTS A total of 57 patients with cirrhosis and BE were matched with 228 controls (BE without cirrhosis). The prevalence of dysplasia in cirrhosis and controls were similar with 8.8% vs 12% with low grade dysplasia (LGD) and 12.3 % vs 19.7% with HGD or EAC (P = 0.1). In the incidence cohort of 44 patients with median follow-up time of 2.7 years [interquartile range 1.0, 4.8], there were 7 cases of LGD, 2 cases of HGD, and 2 cases of EAC. There were no differences in incidence rates of HGD/EAC in nondysplastic BE between cirrhotic cases and noncirrhotic controls (1.4 vs 1.1 per 100 person- years, P = 0.8). In LGD, cirrhotic patients were found to have higher rates of progression to HGD/EAC compared to control group though this did not reach statistical significance (13.7 vs 8.1 per 100 person- years, P = 0.51). A significant association was found between a higher CP class and neoplastic progression of BE in cirrhotic patients (HR =7.9, 95%CI: 2.0-30.9, P = 0.003). CONCLUSION Cirrhotics with worsening liver function are at increased risk of progression of BE. More frequent endoscopic surveillance might be warranted in such patients. PMID:28566888

Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy

NASA Astrophysics Data System (ADS)

Miller, Sharon J.; Lee, Cameron M.; Joshi, Bishnu P.; Gaustad, Adam; Seibel, Eric J.; Wang, Thomas D.

2012-02-01

Gastrointestinal cancers are heterogeneous and can overexpress several protein targets that can be imaged simultaneously on endoscopy using multiple molecular probes. We aim to demonstrate a multispectral scanning fiber endoscope for wide-field fluorescence detection of colonic dysplasia. Excitation at 440, 532, and 635 nm is delivered into a single spiral scanning fiber, and fluorescence is collected by a ring of light-collecting optical fibers placed around the instrument periphery. Specific-binding peptides are selected with phage display technology using the CPC;Apc mouse model of spontaneous colonic dysplasia. Validation of peptide specificity is performed on flow cytometry and in vivo endoscopy. The peptides KCCFPAQ, AKPGYLS, and LTTHYKL are selected and labeled with 7-diethylaminocoumarin-3-carboxylic acid (DEAC), 5-carboxytetramethylrhodamine (TAMRA), and CF633, respectively. Separate droplets of KCCFPAQ-DEAC, AKPGYLS-TAMRA, and LTTHYKL-CF633 are distinguished at concentrations of 100 and 1 μM. Separate application of the fluorescent-labeled peptides demonstrate specific binding to colonic adenomas. The average target/background ratios are 1.71+/-0.19 and 1.67+/-0.12 for KCCFPAQ-DEAC and AKPGYLS-TAMRA, respectively. Administration of these two peptides together results in distinct binding patterns in the blue and green channels. Specific binding of two or more peptides can be distinguished in vivo using a novel multispectral endoscope to localize colonic dysplasia on real-time wide-field imaging.

[Diagnostic values of bronchoscopy and multi-slice spiral CT for congenital dysplasia of the respiratory system in infants: a comparative study].

PubMed

Wang, Xing-Lu; Huang, Ying; Li, Qu-Bei; Dai, Ji-Hong

2013-09-01

To investigate and compare the diagnostic values of bronchoscopy and multi-slice spiral computed tomography (CT) for congenital dysplasia of the respiratory system in infants. Analysis was performed on the clinical data, bronchoscopic findings and multi-slice spiral CT findings of 319 infants (≤1 years old) who underwent bronchoscopy and/or multi-slice spiral CT and were diagnosed with congenital dysplasia of the respiratory system. A total of 476 cases of congenital dysplasia of the respiratory system were found in the 319 infants, including primary dysplasia of the respiratory system (392 cases) and compressive dysplasia of the respiratory system (84 cases). Of the 392 cases of primary dysplasia of the respiratory system, 225 (57.4%) were diagnosed by bronchoscopy versus 167 (42.6%) by multi-slice spiral CT. There were significant differences in etiological diagnosis between bronchoscopy and multi-slice spiral CT in infants with congenital dysplasia of the respiratory system (P<0.05). All 76 cases of primary dysplasia of the respiratory system caused by tracheobronchomalacia were diagnosed by bronchoscopy and all 17 cases of primary dysplasia of the respiratory system caused by lung tissue dysplasia were diagnosed by multi-slice spiral CT. Of the 84 cases of compressive dysplasia of the respiratory system, 74 cases were diagnosed by multi-slice spiral CT and only 10 cases were diagnosed by bronchoscopy. Compared with multi-slice spiral CT, bronchoscopy can detect primary dysplasia of the respiratory system more directly. Bronchoscopy is valuable in the confirmed diagnosis of tracheobronchomalacia. Multi-slice spiral CT has a higher diagnostic value for lung tissue dysplasia than bronchoscopy.

Sclerosing bone dysplasias: genetic, clinical and radiology update of hereditary and non-hereditary disorders

PubMed Central

Boulet, Cedric; Madani, Hardi; Lenchik, Leon; Vanhoenacker, Filip; Amalnath, Deepak S; de Mey, Johan

2016-01-01

There is a wide variety of hereditary and non-hereditary bone dysplasias, many with unique radiographic findings. Hereditary bony dysplasias include osteopoikilosis, osteopathia striata, osteopetrosis, progressive diaphyseal dysplasia, hereditary multiple diaphyseal sclerosis and pyknodysostosis. Non-hereditary dysplasias include melorheostosis, intramedullary osteosclerosis and overlap syndromes. Although many of these dysplasias are uncommon, radiologists should be familiar with their genetic, clinical and imaging findings to allow for differentiation from acquired causes of bony sclerosis. We present an overview of hereditary and non-hereditary bony dysplasias with focus on the pathogenesis, clinical and radiographic findings of each disorder. PMID:26898950

Cranioplasty Using a Modified Split Calvarial Graft Technique in Cleidocranial Dysplasia

PubMed Central

Jung, Young Taek; Cho, Jae Ik

2015-01-01

Cleidocranial dysplasia is a well-documented rare autosomal dominant skeletal dysplasia characterized by hypoplastic/aplastic clavicles, brachycephalic skull, patent sutures and fontanelles, midface hypoplasia, and abnormalities of dentition. Patients with cleidocranial dysplasia often complain about undesirable esthetic appearance of their forehead and skull. Notwithstanding many studies of molecular, genetics and skeletal abnormalities of this congenial disorder, there have been very few written reports of cranioplasty involving cleidocranial dysplasia. Thus, we report a rare case of successful cranioplasty using a modified split calvarial graft technique in patient with cleidocranial dysplasia. PMID:26279819

Trisomy 18 mosaicism in a woman with normal intelligence, pigmentary dysplasia, and an 18 trisomic daughter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ukita, Masahiko; Hasegawa, Masaaki; Nakahori, Takashi

1997-01-20

Survival beyond the age of 10 years is rare among 18-trisomic individuals. Most of these long-term survivors, when more than one tissue is studied, are normal/trisomy mosaics. They are usually mentally severely retarded with a variety of anomalies. There is another group of mosaic individuals: 7 women and a 13-year-old girl, with a low frequency of 18-trisomic cells, normal or mildly retarded intelligence, and minor anomalies. Two of them were diagnosed after delivering malformed stillborn infants. One of them was the mother of a trisomy 18 patient who was coincidentally found to have trisomy 18 mosaicism. Pigmentary dysplasia, previously calledmore » hypomelanosis of Ito, is a disorder with linear, swirly, or patchy, hypo- or hyperpigmented areas of skin, resulting from migration and interaction of melanoblasts of different pigmentary potential. The disorder is often accompanied by mosaic chromosomal abnormalities, including mosaic trisomy 18. Here we report a 26-year-old woman with low frequency trisomy 18 mosaicism, normal intelligence, and pigmentary dysplasia, who gave birth to an 18-trisomic girl. 12 refs., 1 fig.« less

Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma.

PubMed

Kauttu, T; Mustonen, H; Vainionpää, S; Krogerus, L; Ilonen, I; Räsänen, J; Salo, J; Puolakkainen, P

2017-01-01

Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, 'a disintegrin and metalloproteinases'. We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry. EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett's dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA. ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies.

The autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.

PubMed

LeBoeuf, Nicole; Garg, Amit; Worobec, Sophie

2007-01-01

The autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome is characterized by the presence of chronic mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. Almost all patients have skin or nail findings early in the course of the disease. Therefore, the dermatologist is in the unique position of being able to identify patients with this syndrome early in its course and to facilitate careful monitoring of potentially lethal complications.

High-grade dysplasia and adenocarcinoma are frequent in side-branch intraductal papillary mucinous neoplasm measuring less than 3 cm on endoscopic ultrasound.

PubMed

Wong, Joyce; Weber, Jill; Centeno, Barbara A; Vignesh, Shivakumar; Harris, Cynthia L; Klapman, Jason B; Hodul, Pamela

2013-01-01

Surgical resection for intraductal papillary mucinous neoplasm (IPMN) of the pancreas has increased over the last decade. While IPMN with main duct communication are generally recommended for resection, indications for resection of side-branch IPMN (SDIPMN) have been less clear. We reviewed our single institutional experience with SDIPMN and indications for resection. Patients who underwent resection for IPMN were identified from a prospectively maintained IRB-approved database. Patients with main pancreatic duct communication were excluded. Outcome, clinical and pathologic characteristics were correlated with endoscopic ultrasound (EUS) findings. From 2000 to 2010, 105 patients who underwent preoperative EUS evaluation and resection for SDIPMN were identified. The mean age was within the sixth decade of life, and there was a slight female predominance (55 vs. 45 %). The most common presenting symptom was abdominal pain (N = 47, 45 %), followed by jaundice (N = 24, 23 %) and weight loss (N = 24, 23 %). Only ten patients (10 %) were asymptomatic at presentation; seven (70 %) had suspicious features on EUS. Of the total cohort, few patients had intracystic septations (N = 27, 26 %) or presence of mural nodules (N = 2, 2 %) on EUS. Of 39 patients who had invasive pancreatic ductal adenocarcinoma (PDAC) on final pathology, EUS-fine needle aspiration (EUS-FNA) demonstrated malignancy in only 21 (54 %). An additional seven (18 %) had EUS-FNA findings of atypia or concern for mucinous neoplasm. EUS evaluation of cyst size was correlated with final pathology. Of 70 patients with EUS cyst size <3 cm, 12 (17 %) had a preoperative EUS diagnosis of malignancy. Final pathology revealed 24 (34 %) to have PDAC: 1 of 7 (14 %) patients with cyst size <1 cm, 2 of 19 (11 %) with cyst size 1-2 cm, and 21of 44 (48 %) with cyst size 2-3 cm. Fifteen of 35 (43 %) patients with cyst size >3 cm had PDAC on final pathology. Of the patients with cyst size <3 cm, 16 (23 %) had high-grade dysplasia on final pathology: 3 of 7 (43 %) with cyst size <1 cm, 3 of 19 (16 %) with cyst size 1-2 cm, and 10 of 44 (23 %) with cyst size 2-3 cm. Seven of 35 (20 %) patients with cyst size >3 cm had high-grade dysplasia on final pathology. Although overall survival (OS) at 48 months stratified by EUS cyst size did not significantly differ between groups, patients with PDAC on final pathology had significantly worse OS compared to noninvasive pathology. A total of eight patients (8 %) developed recurrent disease, all of whom had PDAC on final pathology. EUS is a helpful modality for the diagnostic evaluation of SDIPMN. Considering the high incidence of malignancy as well as high-grade dysplasia in SDIPMN greater than 2 cm, EUS features should be used in conjunction with other clinical criteria to guide management decisions. Patients with SDIPMN greater than 2 cm that do not undergo surgical resection may benefit from more intensive surveillance.

Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

PubMed

Feldman, C H; Liu, J; Feldman, S; Solomon, D H; Kim, S C

2017-06-01

Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving hydroxychloroquine alone.

DLX3-Dependent Regulation of Ion Transporters and Carbonic Anhydrases is Crucial for Enamel Mineralization.

PubMed

Duverger, Olivier; Ohara, Takahiro; Bible, Paul W; Zah, Angela; Morasso, Maria I

2017-03-01

Patients with tricho-dento-osseous (TDO) syndrome, an ectodermal dysplasia caused by mutations in the homeodomain transcription factor DLX3, exhibit enamel hypoplasia and hypomineralization. Here we used a conditional knockout mouse model to investigate the developmental and molecular consequences of Dlx3 deletion in the dental epithelium in vivo. Dlx3 deletion in the dental epithelium resulted in the formation of chalky hypomineralized enamel in all teeth. Interestingly, transcriptomic analysis revealed that major enamel matrix proteins and proteases known to be involved in enamel secretion and maturation were not affected significantly by Dlx3 deletion in the enamel organ. In contrast, expression of several ion transporters and carbonic anhydrases known to play an important role in enamel pH regulation during maturation was significantly affected in enamel organs lacking DLX3. Most of these affected genes showed binding of DLX3 to their proximal promoter as evidenced by chromatin immunoprecipitation sequencing (ChIP-seq) analysis on rat enamel organ. These molecular findings were consistent with altered pH staining evidenced by disruption of characteristic pH oscillations in the enamel. Taken together, these results show that DLX3 is indispensable for the regulation of ion transporters and carbonic anhydrases during the maturation stage of amelogenesis, exerting a crucial regulatory function on pH oscillations during enamel mineralization. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Obstacles to reduction in infantile developmental dysplasia of the hip.

PubMed

Studer, K; Williams, N; Studer, P; Baker, M; Glynn, A; Foster, B K; Cundy, P J

2017-10-01

Identification of anatomical structures that block -reduction in developmental dysplasia of the hip (DDH) is -important for the management of this challenging condition. Obstacles to reduction seen on arthrogram are well-known. However, despite the increasing use of MRI in the assessment of adequacy of reduction in DDH, the interpretation of MRI patho-anatomy is ill-defined with a lack of relevant literature to guide clinicians. This is a retrospective analysis of the MRI of patients with DDH treated by closed reduction over a five-year period (between 2009 and 2014). Neuromuscular and genetic disorders were excluded. Each MRI was analysed by two orthopaedic surgeons and a paediatric musculoskeletal radiologist to identify the ligamentum teres, pulvinar, transverse acetabular ligament (TAL), capsule, labrum and acetabular roof cartilage hypertrophy. Inter- and intraobserver reliability was calculated. The minimum follow-up was 12 months. A total of 29 patients (38 hips) underwent closed reduction for treatment of DDH. Eight hips showed persistent subluxation on post-operative MRI. Only three of these eight hips showed an abnormality on arthrogram. The pulvinar was frequently interpreted as 'abnormal' on MRI. The main obstacles identified on MRI were the ligamentum teres (15.8%), labrum (13.1%) and acetabular roof cartilage hypertrophy (13.2%). The inter-rater reliability was good for TAL, capsule and pulvinar; moderate for ligamentum teres and labrum; and poor for hypertrophied cartilage. The labrum, ligamentum teres and acetabular roof cartilage hypertrophy are the most important structures seen on MRI preventing complete reduction of DDH. Focused interpretation of these structures may assist in the management of DDH.

Classification of Systemic and Localized Sweating Disorders.

PubMed

Ohshima, Yuichiro; Tamada, Yasuhiko

2016-01-01

Hyperhidrosis can be subdivided into generalized hyperhidrosis, with increased sweating over the entire body, and focal hyperhidrosis, in which the excessive sweating is restricted to specific parts of the body. Generalized hyperhidrosis may be either primary (idiopathic) or secondary. Secondary generalized hyperhidrosis may be caused by infections such as tuberculosis, hyperthyroidism, endocrine and metabolic disturbances such as pheochromocytoma, neurological disorders, or drugs. Focal hyperhidrosis may also be primary (idiopathic) or secondary. Frey's syndrome is one form of secondary focal hyperhidrosis that occurs during eating together with reddening of the area in front of the ear following parotid gland surgery or injury. Primary focal hyperhidrosis is particularly common on the palms and soles of the feet, in the axilla, and on the head. Anhidrosis may be either congenital/genetic or acquired. Some of the most typical forms of congenital/genetic anhidrosis include hypohidrotic ectodermal dysplasia, congenital insensitivity to pain and anhidrosis, and Fabry disease. Acquired anhidrosis is classified as secondary anhidrosis, which may be due to an underlying disorder such as a neurological disorder, an endocrine or metabolic disturbance, or the effect of drugs, or idiopathic anhidrosis for which the pathology, cause, and mechanism are unknown. Idiopathic anhidrosis is classified into acquired idiopathic generalized anhidrosis (AIGA), idiopathic segmental anhidrosis, and Ross syndrome. AIGA is divided into three categories according to differences in the site of disturbance: (1) sudomotor neuropathy, (2) idiopathic pure sudomotor failure, and (3) sweat gland failure. © 2016 S. Karger AG, Basel.

Spondyloenchondrodysplasia: a rare cause of short stature.

PubMed

Yeşiltepe-Mutlu, Gül; Ozsu, Elif; Cizmecioğlu, Filiz Mine; Alanay, Yasemin; Hatun, Sükrü

2011-01-01

Skeletal dysplasias (osteochondrodysplasias) are a group of diseases that must be included in the differential diagnosis of disproportionate short stature. History, clinical and radiologic findings and consanguinity are important features to be considered when a specific diagnosis is investigated. Spondyloenchondrodysplasia is a very rare skeletal dysplasia characterized with enchondromas in the long bones and platyspondyly. Manifestation of the disorder may include neurological involvement (spasticity, intracranial calcifications and mental retardation) and immune dysfunction. Herein, we report a 12-year-old boy who admitted to our clinic with short stature, who was born to consanguineous parents. He presented clinical (significant widening of wrists, ankles and knees) and radiologic (enchondromatous lesions in the metaphysis of long bones) features of spondyloenchondrodysplasia but did not yet have neurologic or immunologic involvement.

Co-ordinated ocular development from human iPS cells and recovery of corneal function.

PubMed

Hayashi, Ryuhei; Ishikawa, Yuki; Sasamoto, Yuzuru; Katori, Ryosuke; Nomura, Naoki; Ichikawa, Tatsuya; Araki, Saori; Soma, Takeshi; Kawasaki, Satoshi; Sekiguchi, Kiyotoshi; Quantock, Andrew J; Tsujikawa, Motokazu; Nishida, Kohji

2016-03-17

The eye is a complex organ with highly specialized constituent tissues derived from different primordial cell lineages. The retina, for example, develops from neuroectoderm via the optic vesicle, the corneal epithelium is descended from surface ectoderm, while the iris and collagen-rich stroma of the cornea have a neural crest origin. Recent work with pluripotent stem cells in culture has revealed a previously under-appreciated level of intrinsic cellular self-organization, with a focus on the retina and retinal cells. Moreover, we and others have demonstrated the in vitro induction of a corneal epithelial cell phenotype from pluripotent stem cells. These studies, however, have a single, tissue-specific focus and fail to reflect the complexity of whole eye development. Here we demonstrate the generation from human induced pluripotent stem cells of a self-formed ectodermal autonomous multi-zone (SEAM) of ocular cells. In some respects the concentric SEAM mimics whole-eye development because cell location within different zones is indicative of lineage, spanning the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium. It thus represents a promising resource for new and ongoing studies of ocular morphogenesis. The approach also has translational potential and to illustrate this we show that cells isolated from the ocular surface ectodermal zone of the SEAM can be sorted and expanded ex vivo to form a corneal epithelium that recovers function in an experimentally induced animal model of corneal blindness.

Developmental outcome after surgery in focal cortical dysplasia patients with early-onset epilepsy.

PubMed

Kimura, Nobusuke; Takahashi, Yukitoshi; Shigematsu, Hideo; Imai, Katsumi; Ikeda, Hiroko; Ootani, Hideyuki; Takayama, Rumiko; Mogami, Yukiko; Kimura, Noriko; Baba, Koichi; Matsuda, Kazumi; Tottori, Takayasu; Usui, Naotaka; Inoue, Yushi

2014-12-01

The purpose of this study was to investigate the developmental outcome after surgery for early-onset epilepsy in patients with focal cortical dysplasia (FCD). Among 108 patients with histopathologically confirmed FCD operated between 1985 and 2008, we selected 17 patients with epilepsy onset up to 3 years of age. Development was evaluated by the developmental quotient or intelligence quotient (DQ-IQ) and mental age was measured by the Mother-Child Counseling baby test or the Tanaka-Binet scale of intelligence. Postsurgical development outcome was evaluated by the changes in DQ-IQ and mental age as well as rate of increase in mental age (RIMA) after surgery. RIMA was calculated as the increase in mental age per chronological year (months/year; normal average rate: 12 months/year). Age at epilepsy onset of 17 patients ranged from 15 days to 36 months (mean±SD, 11.0±10.0 months). Age at surgery ranged from 18 to 145 months (75.1±32.4 months). Evaluation just before surgery showed that 13 of 17 (76.4%) patients had DQ-IQ below 70. Ten patients (58.8%) were seizure-free throughout the postsurgical follow-up period. After surgery, DQ-IQ was maintained within 10 points of the presurgical level in 13 patients (76.4%), and increased by more than 10 points in one patient (5.9%). After surgery, RIMA in patients with Engel's class I (7.5±3.8) was higher than patients with Engel's class II-IV (2.6±3.4) (unpaired t-test with Welch's correction, t=2.99, df=15, p=0.0092). RIMA was particularly low in two patients with spasm. In four patients with presurgical DQ-IQ<70, seizure-free after surgery and without spasm, DQ-IQ did not increase but RIMA improved from 3.6±2.8 before surgery to 6.9±2.5 months/year after surgery. RIMA became better from 2 years after surgery. In four patients with presurgical DQ-IQ≥70 and no spasm, two showed the same or higher RIMA than normal average after surgery. In 58.8% of FCD patients with early onset epilepsy, epilepsy surgery effectively controlled seizures, and in 82.3% of patients, epilepsy surgery preserved or improved development. Residual seizures after surgery and lower DQ-IQ before surgery might be potential risk factors for poor development after surgery. In patients of Engel's class I with lower presurgical DQ-IQ, catch-up increase in mental age was observed after two years following surgery. Copyright © 2014 Elsevier B.V. All rights reserved.

Embryonic wound healing by apical contraction and ingression in Xenopus laevis.

PubMed

Davidson, Lance A; Ezin, Akouavi M; Keller, Ray

2002-11-01

We have characterized excisional wounds in the animal cap of early embryos of the frog Xenopus laevis and found that these wounds close accompanied by three distinct processes: (1) the assembly of an actin purse-string in the epithelial cells at the wound margin, (2) contraction and ingression of exposed deep cells, and (3) protrusive activity of epithelial cells at the margin. Microsurgical manipulation allowing fine control over the area and depth of the wound combined with videomicroscopy and confocal analysis enabled us to describe the kinematics and challenge the mechanics of the closing wound. Full closure typically occurs only when the deep, mesenchymal cell-layer of the ectoderm is left intact; in contrast, when deep cells are removed along with the superficial, epithelial cell-layer of the ectoderm, wounds do not close. Actin localizes to the superficial epithelial cell-layer at the wound margin immediately after wounding and forms a contiguous "purse-string" in those cells within 15 min. However, manipulation and closure kinematics of shaped wounds and microsurgical cuts made through the purse-string rule out a major force-generating role for the purse-string. Further analysis of the cell behaviors within the wound show that deep, mesenchymal cells contract their apical surfaces and ingress from the exposed surface. High resolution time-lapse sequences of cells at the leading edge of the wound show that these cells undergo protrusive activity only during the final phases of wound closure as the ectoderm reseals. We propose that assembly of the actin purse-string works to organize and maintain the epithelial sheet at the wound margin, that contraction and ingression of deep cells pulls the wound margins together, and that protrusive activity of epithelial cells at the wound margin reseals the ectoderm and re-establishes tissue integrity during wound healing in the Xenopus embryonic ectoderm. Copyright 2002 Wiley-Liss, Inc.

Endoscopic screening for synchronous esophageal neoplasia among patients with incident head and neck cancer: Prevalence, risk factors, and outcomes.

PubMed

Wang, Yao-Kuang; Chuang, Yun-Shiuan; Wu, Tzung-Shiun; Lee, Ka-Wo; Wu, Che-Wei; Wang, Hsiang-Chen; Kuo, Chie-Tong; Lee, Chien-Hung; Kuo, Wen-Rei; Chen, Chung-Ho; Wu, Deng-Chyang; Wu, I-Chen

2017-11-15

Esophageal squamous-cell neoplasia (ESCN) is a common second primary neoplasia found in patients with head-and-neck squamous-cell carcinoma (HNSCC). This study sought to identify the risk factors for synchronous ESCN and how they influence survival in HNSCC patient. Eight hundred and fifteen incident HNSCC patients were prospectively recruited for endoscopy screening for ESCN using white-light imaging, narrow-band imaging, Lugol chromoendoscopy, and pathological confirmation. Associated lifestyle and clinicopathological data were collected. The interquartile follow-up period cutoffs were 11.3, 20.5 and 34.9 months. 124 patients (15.2%) were diagnosed as having synchronous ESCN (66 low-grade dysplasia, 29 high-grade dysplasia, and 29 esophageal squamous-cell carcinoma). Consumption of alcohol, but not betel nut or cigarette, was significantly associated with the presence of synchronous ESCN (adjusted odds ratio [aOR] = 7.1 and 10.9 for former and current drinkers, respectively). There was an interaction between cumulative dose of alcohol consumption and alcohol flushing response on the development of ESCN. High-dose drinkers with flush response were 16.9 times more likely to have esophageal high-grade dysplasia/SCC than non-drinkers. Compared with oral cavity cancer patients, those with hypopharyngeal, laryngeal and oropharyngeal cancer were 6.8, 4.6 and 2.8 times more likely to have esophageal high-grade dysplasia/SCC. HNSCC patients with synchronous ESCN had lower overall survival than those without (p < 0.0001). In conclusion, surveillance of ESCN is strongly recommended for the high-risk subpopulation of HNSCC patients, especially drinkers who have a flush response to alcohol, and those with distant metastasis of index cancer and cancers in hypopharynx, oropharynx and larynx. © 2017 UICC.

Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos

NASA Technical Reports Server (NTRS)

Fredieu, J. R.; Cui, Y.; Maier, D.; Danilchik, M. V.; Christian, J. L.

1997-01-01

When Xenopus gastrulae are made to misexpress Xwnt-8, or are exposed to lithium ions, they develop with a loss of anterior structures. In the current study, we have characterized the neural defects produced by either Xwnt-8 or lithium and have examined potential cellular mechanisms underlying this anterior truncation. We find that the primary defect in embryos exposed to lithium at successively earlier stages during gastrulation is a progressive rostral to caudal deletion of the forebrain, while hindbrain and spinal regions of the CNS remain intact. Misexpression of Xwnt-8 during gastrulation produces an identical loss of forebrain. Our results demonstrate that lithium and Wnts can act upon either prospective neural ectodermal cells, or upon dorsal mesodermal cells, to cause a loss of anterior pattern. Specifically, ectodermal cells isolated from lithium- or Wnt-exposed embryos are unable to form anterior neural tissue in response to inductive signals from normal dorsal mesoderm. In addition, although dorsal mesodermal cells from lithium- or Wnt-exposed embryos are specified properly, and produce normal levels of the anterior neural inducing molecules noggin and chordin, they show a greatly reduced capacity to induce anterior neural tissue in conjugated ectoderm. Taken together, our results are consistent with a model in which Wnt- or lithium-mediated signals can induce either mesodermal or ectodermal cells to produce a dominant posteriorizing morphogen which respecifies anterior neural tissue as posterior.

Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration.

PubMed

Ratheesh, Aparna; Biebl, Julia; Vesela, Jana; Smutny, Michael; Papusheva, Ekaterina; Krens, S F Gabriel; Kaufmann, Walter; Gyoergy, Attila; Casano, Alessandra Maria; Siekhaus, Daria E

2018-05-07

Migrating cells penetrate tissue barriers during development, inflammatory responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally confined environments requires changes in the mechanical properties of the surrounding cells using embryonic Drosophila melanogaster hemocytes, also called macrophages, as a model. We find that macrophage invasion into the germband through transient separation of the apposing ectoderm and mesoderm requires cell deformations and reductions in apical tension in the ectoderm. Interestingly, the genetic pathway governing these mechanical shifts acts downstream of the only known tumor necrosis factor superfamily member in Drosophila, Eiger, and its receptor, Grindelwald. Eiger-Grindelwald signaling reduces levels of active Myosin in the germband ectodermal cortex through the localization of a Crumbs complex component, Patj (Pals-1-associated tight junction protein). We therefore elucidate a distinct molecular pathway that controls tissue tension and demonstrate the importance of such regulation for invasive migration in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

p63 protein is essential for the embryonic development of vibrissae and teeth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rufini, Alessandro; Weil, Miguel; McKeon, Frank

2006-02-17

Development of skin appendages strongly depends on epithelial-mesenchymal interactions. One of the genes involved in this process is p63, a member of the p53 family of transcription factors, essential for ectodermal development, as elucidated by the phenotype of p63 knock-out mice. Surprisingly, no information on p63 expression in tooth and hair is yet available. Here, we show p63 expression during teeth and vibrissae morphogenesis in mouse embryos and we also show a correlation with the expression patterns of the epithelial marker keratin 5 and the proliferation marker Ki67. Our results show that p63 colocalizes with both K5 and Ki67 inmore » the epithelium of developing vibrissae, while in teeth p63 is expressed, together with K5, in the undifferentiated ectoderm (enamel organ), and in ameloblasts, a subpopulation of differentiated ectodermal cells. Moreover, p63 expression in tooth seems not to be fully colocalized with nuclear Ki67 expression.« less

Cleidocranial dysplasia

PubMed Central

Dixit, Ramakant; Dixit, Kalpana; Paramez, A. R.

2010-01-01

Cleidocranial dysplasia is a rare autosomal dominant condition with generalized dysplasia of bone, characterized by delayed closer of cranial sutures, hypoplastic or aplastic clavicles, short stature, dental abnormalities and a variety of other skeletal abnormalities. We present a seven-year-old female child presenting with classical features of cleidocranial dysplasia. PMID:20931042

The association between cervical dysplasia, a short cervix, and preterm birth.

PubMed

Miller, Emily S; Sakowicz, Allie; Grobman, William A

2015-10-01

We sought to determine whether cervical dysplasia in the absence of an excisional procedure is associated with an increased risk of preterm birth (PTB) and whether that risk is independent of the presence of a short cervix. This is a cohort study including women with a singleton pregnancy who underwent routine cervical length assessment between 18-23 6/7 weeks of gestation, stratified by cervical dysplasia (ie, no prior dysplasia, prior dysplasia but no excisional procedure, or prior excisional procedure). The frequency of a short cervix (≤2.5 cm) and PTB were compared between groups and multivariable analyses were performed to identify whether: (1) dysplasia alone or a prior excisional procedure was associated with PTB; and (2) whether these factors remained independently associated with PTB after adjusting for the presence of a short cervix. Of the 18,528 women who met inclusion criteria, 3023 (16.3%) had prior dysplasia alone and 1356 (7.3%) had a prior excisional procedure. The frequency of a short cervix for women without dysplasia, with prior dysplasia alone, or with a prior excisional procedure was 0.8%, 1.0%, and 2.2%, respectively (P < .001). The frequency of PTB, respectively, was 6.4%, 6.5%, and 8.4% (P < .001). After adjusting for potential confounding factors, prior excisional procedure but not prior dysplasia alone was associated with PTB. Having a prior cervical excisional procedure but not dysplasia alone is associated with an increased risk of PTB. This association is independent of the presence of a short cervix. Copyright © 2015 Elsevier Inc. All rights reserved.

Prenatal diagnosis of boomerang dysplasia.

PubMed

Wessels, Marja W; Den Hollander, Nicolette S; De Krijger, Ronald R; Bonifé, Luisa; Superti-Furga, Andrea; Nikkels, Peter G; Willems, Patrick J

2003-10-01

Boomerang dysplasia, atelosteogenesis type 1 and Piepkorn dysplasia are bone dysplasias with an overlapping clinical spectrum characterized by deficient formation and ossification of specific elements of the skeleton. Typical symptoms include micromelia with diminished ossification, and a characteristic bowed and boomerang-like aspect of the long tubular bones. We report here a new case of boomerang dysplasia, which was detected prenatally in the 16th week of gestation by ultrasound. Copyright 2003 Wiley-Liss, Inc.

Post-embryonic larval development and metamorphosis of the hydroid Eudendrium racemosum (Cavolini) (Hydrozoa, Cnidaria)

NASA Astrophysics Data System (ADS)

Sommer, C.

1990-09-01

The morphology and histology of the planula larva of Eudendrium racemosum (Cavolini) and its metamorphosis into the primary polyp are described from light microscopic observations. The planula hatches as a differentiated gastrula. During the lecithotrophic larval period, large ectodermal mucous cells, embedded between epitheliomuscular cells, secrete a sticky slime. Two granulated cell types occur in the ectoderm that are interpreted as secretory and sensorynervous cells, but might also be representatives of only one cell type with a multiple function. The entoderm consists of yolk-storing gastrodermal cells, digestive gland cells, interstitial cells, cnidoblasts, and premature cnidocytes. The larva starts metamorphosis by affixing its blunt aboral pole to a substratum. While the planula flattens down, the mucous cells penetrate the mesolamella and migrate through the entoderm into the gastral cavity where they are lysed. Subsequently, interstitial cells, cnidoblasts, and premature cnidocytes migrate in the opposite direction, i.e. from entoderm to ectoderm. Then, the polypoid body organization, comprising head (hydranth), stem and foot, all covered by peridermal secretion, becomes recognisable. An oral constriction divides the hypostomal portion of the gastral cavity from the stomachic portion. Within the hypostomal entoderm, cells containing secretory granules differentiate. Following growth and the multiplication of tentacles, the head periderm disappears. A ring of gland cells differentiates at the hydranth's base. The positioning of cnidae in the tentacle ectoderm, penetration of the mouth opening and the multiplication of digestive gland cells enable the polyp to change from lecithotrophic to planktotrophic nutrition.

Mechanics of Fluid-Filled Interstitial Gaps. II. Gap Characteristics in Xenopus Embryonic Ectoderm.

PubMed

Barua, Debanjan; Parent, Serge E; Winklbauer, Rudolf

2017-08-22

The ectoderm of the Xenopus embryo is permeated by a network of channels that appear in histological sections as interstitial gaps. We characterized this interstitial space by measuring gap sizes, angles formed between adjacent cells, and curvatures of cell surfaces at gaps. From these parameters, and from surface-tension values measured previously, we estimated the values of critical mechanical variables that determine gap sizes and shapes in the ectoderm, using a general model of interstitial gap mechanics. We concluded that gaps of 1-4 μm side length can be formed by the insertion of extracellular matrix fluid at three-cell junctions such that cell adhesion is locally disrupted and a tension difference between cell-cell contacts and the free cell surface at gaps of 0.003 mJ/m 2 is generated. Furthermore, a cell hydrostatic pressure of 16.8 ± 1.7 Pa and an interstitial pressure of 3.9 ± 3.6 Pa, relative to the central blastocoel cavity of the embryo, was found to be consistent with the observed gap size and shape distribution. Reduction of cell adhesion by the knockdown of C-cadherin increased gap volume while leaving intracellular and interstitial pressures essentially unchanged. In both normal and adhesion-reduced ectoderm, cortical tension of the free cell surfaces at gaps does not return to the high values characteristic of the free surface of the whole tissue. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Focal cemento-osseous dysplasia: review and a case report.

PubMed

Salem, Y M Y; Osman, Y I; Norval, E J G

2010-10-01

Focal cemento-osseous dysplasia is a benign fibro-osseous condition that can be seen in dentate and edentulous patients. It is an asymptomatic lesion and needs no treatment; however follow-up is essential due to the possibility that focal cemento-osseous dysplasia can progress to a condition called florid osseous dysplasia that involves multiple sites. A case report is presented here, along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia.

AmphiFoxQ2, a novel winged helix/forkhead gene, exclusively marks the anterior end of the amphioxus embryo

NASA Technical Reports Server (NTRS)

Yu, Jr-Kai; Holland, Nicholas D.; Holland, Linda Z.

2003-01-01

A full-length FoxQ-related gene (AmphiFoxQ2) was isolated from amphioxus. Expression is first detectable in the animal/anterior hemisphere at the mid blastula stage. The midpoint of this expression domain coincides with the anterior pole of the embryo and is offset dorsally by about 20 degrees from the animal pole. During the gastrula stage, expression is limited to the anterior ectoderm. By the early neurula stage, expression remains in the anterior ectoderm and also appears in the adjacent anterior mesendoderm. By the early larval stages, expression is detectable in the anteriormost ectoderm and in the rostral tip of the notochord. AmphiFoxQ2 is never expressed anywhere except at the anterior tip of amphioxus embryos and larvae. This is the first gene known that exclusively marks the anterior pole of chordate embryos. It may, therefore, play an important role in establishing and/or maintaining the anterior/posterior axis.

Regulation of cell protrusions by small GTPases during fusion of the neural folds

PubMed Central

Rolo, Ana; Savery, Dawn; Escuin, Sarah; de Castro, Sandra C; Armer, Hannah EJ; Munro, Peter MG; Molè, Matteo A; Greene, Nicholas DE; Copp, Andrew J

2016-01-01

Epithelial fusion is a crucial process in embryonic development, and its failure underlies several clinically important birth defects. For example, failure of neural fold fusion during neurulation leads to open neural tube defects including spina bifida. Using mouse embryos, we show that cell protrusions emanating from the apposed neural fold tips, at the interface between the neuroepithelium and the surface ectoderm, are required for completion of neural tube closure. By genetically ablating the cytoskeletal regulators Rac1 or Cdc42 in the dorsal neuroepithelium, or in the surface ectoderm, we show that these protrusions originate from surface ectodermal cells and that Rac1 is necessary for the formation of membrane ruffles which typify late closure stages, whereas Cdc42 is required for the predominance of filopodia in early neurulation. This study provides evidence for the essential role and molecular regulation of membrane protrusions prior to fusion of a key organ primordium in mammalian development. DOI: http://dx.doi.org/10.7554/eLife.13273.001 PMID:27114066

Internet search term affects the quality and accuracy of online information about developmental hip dysplasia.

PubMed

Fabricant, Peter D; Dy, Christopher J; Patel, Ronak M; Blanco, John S; Doyle, Shevaun M

2013-06-01

The recent emphasis on shared decision-making has increased the role of the Internet as a readily accessible medical reference source for patients and families. However, the lack of professional review creates concern over the quality, accuracy, and readability of medical information available to patients on the Internet. Three Internet search engines (Google, Yahoo, and Bing) were evaluated prospectively using 3 difference search terms of varying sophistication ("congenital hip dislocation," "developmental dysplasia of the hip," and "hip dysplasia in children"). Sixty-three unique Web sites were evaluated by each of 3 surgeons (2 fellowship-trained pediatric orthopaedic attendings and 1 orthopaedic chief resident) for quality and accuracy using a set of scoring criteria based on the AAOS/POSNA patient education Web site. The readability (literacy grade level) of each Web site was assessed using the Fleisch-Kincaid score. There were significant differences noted in quality, accuracy, and readability of information depending on the search term used. The search term "developmental dysplasia of the hip" provided higher quality and accuracy compared with the search term "congenital hip dislocation." Of the 63 total Web sites, 1 (1.6%) was below the sixth grade reading level recommended by the NIH for health education materials and 8 (12.7%) Web sites were below the average American reading level (eighth grade). The quality and accuracy of information available on the Internet regarding developmental hip dysplasia significantly varied with the search term used. Patients seeking information about DDH on the Internet may not understand the materials found because nearly all of the Web sites are written at a level above that recommended for publically distributed health information. Physicians should advise their patients to search for information using the term "developmental dysplasia of the hip" or, better yet, should refer patients to Web sites that they have personally reviewed for content and clarity. Orthopaedic surgeons, professional societies, and search engines should undertake efforts to ensure that patients have access to information about DDH that is both accurate and easily understandable.

Activation of Wnt signalling promotes development of dysplasia in Barrett's oesophagus.

PubMed

Moyes, Lisa H; McEwan, Hamish; Radulescu, Sorina; Pawlikowski, Jeff; Lamm, Catherine G; Nixon, Colin; Sansom, Owen J; Going, James J; Fullarton, Grant M; Adams, Peter D

2012-09-01

Barrett's oesophagus is a precursor of oesophageal adenocarcinoma, via intestinal metaplasia and dysplasia. Risk of cancer increases substantially with dysplasia, particularly high-grade dysplasia. Thus, there is a clinical need to identify and treat patients with early-stage disease (metaplasia and low-grade dysplasia) that are at high risk of cancer. Activated Wnt signalling is critical for normal intestinal development and homeostasis, but less so for oesophageal development. Therefore, we asked whether abnormally increased Wnt signalling contributes to the development of Barrett's oesophagus (intestinal metaplasia) and/or dysplasia. Forty patients with Barrett's metaplasia, dysplasia or adenocarcinoma underwent endoscopy and biopsy. Mice with tamoxifen- and β-naphthoflavone-induced expression of activated β-catenin were used to up-regulate Wnt signalling in mouse oesophagus. Immunohistochemistry of β-catenin, Ki67, a panel of Wnt target genes, and markers of intestinal metaplasia was performed on human and mouse tissues. In human tissues, expression of nuclear activated β-catenin was found in dysplasia, particularly high grade. Barrett's metaplasia did not show high levels of activated β-catenin. Up-regulation of Ki67 and Wnt target genes was also mostly associated with high-grade dysplasia. Aberrant activation of Wnt signalling in mouse oesophagus caused marked tissue disorganization with features of dysplasia, but only selected molecular indicators of metaplasia. Based on these results in human tissues and a mouse model, we conclude that abnormal activation of Wnt signalling likely plays only a minor role in initiation of Barrett's metaplasia but a more critical role in progression to dysplasia. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Beating heart mitral valve replacement with a bovine pericardial bioprosthesis for treatment of mitral valve dysplasia in a Bull Terrier.

PubMed

Behr, Luc; Chetboul, Valérie; Sampedrano, Carolina Carlos; Vassiliki, Gouni; Pouchelon, Jean-Louis; Laborde, François; Borenstein, Nicolas

2007-04-01

To describe an open, beating heart surgical technique and use of a bovine pericardial prosthetic valve for mitral valve replacement (MVR) in the dog. Clinical case report. Male Bull Terrier (17-month-old, 26 kg) with mitral valve dysplasia and severe regurgitation. A bovine pericardial bioprosthesis was used to replace the mitral valve using an open beating heart surgical technique and cardiopulmonary bypass. Successful MVR was achieved using a beating heart technique. Mitral regurgitation resolved and cardiac performances improved (left ventricular end-diastolic diameter decreased from 57.6 to 48.7 mm, and left atrium/aorta ratio returned to almost normal, from 1.62 to 1.19). Cardiopulmonary by-pass time and total surgical duration were decreased compared with standard cardioplegic techniques. Surgical recovery was uneventful and on echocardiography 6 months later valve function was excellent. Considering the technique advantages (no cardiac arrest, ischemic reperfusion injury, and hypothermia, or the need for aortic dissection and cannulation for administration of cardioplegic solution), short-term mortality and morbidity may be reduced compared with standard cardioplegic techniques. Based on experience in this dog, beating heart mitral valvular replacement is a seemingly safe and viable option for the dog and bovine pericardial prosthesis may provide better long-term survival than mechanical prostheses.

Schimke immuno-osseous dysplasia: case report and review of 25 patients

PubMed Central

Saraiva, J.; Dinis, A.; Resende, C.; Faria, E.; Gomes, C.; Correia, A; Gil, J.; da Fonseca, N.

1999-01-01

Immuno-osseous dysplasia is characterised by spondyloepiphyseal dysplasia, lymphopenia with defective cellular immunity, and progressive renal disease. We describe a patient with a severe form of the disease, review the features of another 24 patients, and discuss the previous classification. The differences between the two groups are not striking, and although similarities are greater between affected sibs, the same diagnosis of Schimke immuno-osseous dysplasia should apply to them all. The aetiology and physiopathology of this rare osteochondrodysplasia of presumed autosomal recessive inheritance remain unknown.


Keywords: osteochondrodysplasia; immuno-osseous dysplasia; spondyloepiphyseal dysplasia; defective cellular immunity PMID:10528861

Transcriptional regulation of cranial sensory placode development

PubMed Central

Moody, Sally A.; LaMantia, Anthony-Samuel

2015-01-01

Cranial sensory placodes derive from discrete patches of the head ectoderm, and give rise to numerous sensory structures. During gastrulation, a specialized “neural border zone” forms around the neural plate in response to interactions between the neural and non-neural ectoderm and signals from adjacent mesodermal and/or endodermal tissues. This zone subsequently gives rise to two distinct precursor populations of the peripheral nervous system: the neural crest and the pre-placodal ectoderm (PPE). The PPE is a common field from which all cranial sensory placodes arise (adenohypophyseal, olfactory, lens, trigeminal, epibranchial, otic). Members of the Six family of transcription factors are major regulators of PPE specification, in partnership with co-factor proteins such as Eya. Six gene activity also maintains tissue boundaries between the PPE, neural crest and epidermis by repressing genes that specify the fates of those adjacent ectodermally-derived domains. As the embryo acquires anterior-posterior identity, the PPE becomes transcriptionally regionalized, and it subsequently subdivides into specific placodes with distinct developmental fates in response to signaling from adjacent tissues. Each placode is characterized by a unique transcriptional program that leads to the differentiation of highly specialized cells, such as neurosecretory cells, somatic sensory receptor cells, chemosensory neurons, peripheral glia and supporting cells. In this review, we summarize the transcriptional and signaling factors that regulate key steps of placode development, influence subsequent sensory neuron specification, and discuss what is known about mutations in some of the essential PPE genes that underlie human congenital syndromes. PMID:25662264

Genipin-crosslinked gelatin-silk fibroin hydrogels for modulating the behaviour of pluripotent cells.

PubMed

Sun, Wei; Incitti, Tania; Migliaresi, Claudio; Quattrone, Alessandro; Casarosa, Simona; Motta, Antonella

2016-10-01

Different hydrogel materials have been prepared to investigate the effects of culture substrate on the behaviour of pluripotent cells. In particular, genipin-crosslinked gelatin-silk fibroin hydrogels of different compositions have been prepared, physically characterized and used as substrates for the culture of pluripotent cells. Pluripotent cells cultured on hydrogels remained viable and proliferated. Gelatin and silk fibroin promoted the proliferation of cells in the short and long term, respectively. Moreover, cells cultured on genipin-crosslinked gelatin-silk fibroin blended hydrogels were induced to an epithelial ectodermal differentiation fate, instead of the neural ectodermal fate obtained by culturing on tissue culture plates. This work confirms that specific culture substrates can be used to modulate the behaviour of pluripotent cells and that our genipin-crosslinked gelatin-silk fibroin blended hydrogels can induce pluripotent cells differentiation to an epithelial ectodermal fate. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Wide-field piecemeal cold snare polypectomy of large sessile serrated polyps without a submucosal injection is safe.

PubMed

Tate, David J; Awadie, Halim; Bahin, Farzan F; Desomer, Lobke; Lee, Ralph; Heitman, Steven J; Goodrick, Kathleen; Bourke, Michael J

2018-03-01

BACKGROUND AND STUDY AIMS : Large series suggest endoscopic mucosal resection is safe and effective for the removal of large (≥ 10 mm) sessile serrated polyps (SSPs), but it exposes the patient to the risks of electrocautery, including delayed bleeding. We examined the feasibility and safety of piecemeal cold snare polypectomy (pCSP) for the resection of large SSPs.  Sequential large SSPs (10 - 35 mm) without endoscopic evidence of dysplasia referred over 12 months to a tertiary endoscopy center were considered for pCSP. A thin-wire snare was used in all cases. Submucosal injection was not performed. High definition imaging of the defect margin was used to ensure the absence of residual serrated tissue. Adverse events were assessed at 2 weeks and surveillance was planned for between 6 and 12 months.  41 SSPs were completely removed by pCSP in 34 patients. The median SSP size was 15 mm (interquartile range [IQR] 14.5 - 20 mm; range 10 - 35 mm). The median procedure duration was 4.5 minutes (IQR 1.4 - 6.3 minutes). There was no evidence of perforation or significant intraprocedural bleeding. At 2-week follow-up, there were no significant adverse events, including delayed bleeding and post polypectomy syndrome. First follow-up has been undertaken for 15 /41 lesions at a median of 6 months with no evidence of recurrence.  There is potential for pCSP to become the standard of care for non-dysplastic large SSPs. This could reduce the burden of removing SSPs on patients and healthcare systems, particularly by avoidance of delayed bleeding. © Georg Thieme Verlag KG Stuttgart · New York.

Angioplasty for Non-arteriosclerotic Renal Artery Stenosis: The Efficacy of Cutting Balloon Angioplasty Versus Conventional Angioplasty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanaka, Ryoichi; Higashi, Masahiro; Naito, Hiroaki

2007-07-15

Purpose. We examined the efficacy of conventional balloon angioplasty and cutting balloon angioplasty (CBA) for the treatment of non-arteriosclerotic renal artery stenosis (RAS). Materials and Methods. From 1993 to 2005, 20 patients underwent 27 percutaneous transluminal renalangioplasty (PTRA) for non-arteriosclerotic RAS (men: 8, women: 12, 25.5 +/- 2 years old; 16 fibromuscular dysplasia (FMD), 4 Takayasu disease). We evaluated the efficacy of CBA by comparing the rate of initial technical success and surgical conversion. Results. Before the clinical authorization of CBA, three of twelve patients (25 %) underwent surgical bypass due to the failure of PTRA due to the hardnessmore » of the lesion. After the approval of cutting balloon, we performed CBA in four cases (2 FMD,2 Takayasu disease) to dilate hard lesions, within which a properly sized balloon could not dilate due to their hardness, or to reduce the risk of local dissection. Initial successes were obtained in all patients (8/8, 100%) and none of the patients underwent surgical conversion. Despite of the good initial result, restenosis was observed in three cases within 6 month (3/4, 75 %). Additional interventions were performed in all patients, then, the severity of the restenotic lesion was found not to be exceeded comparing with the initial lesion. Conclusion. The cutting balloon angioplasty may be safe and useful procedure for hard lesions of RAS caused by non-arteriosclerotic disease? especially fibromuscular dysplasia. The cutting balloon may provide the initial success, but the effect on long-term patency is still controversial.« less

Predicting Factors for High-Grade Cervical Dysplasia in Women With Low-Grade Cervical Cytology and Nonvisible Squamocolumnar Junction.

PubMed

Bogani, Giorgio; Taverna, Francesca; Lombardo, Claudia; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Leone Roberti Maggiore, U; Mosca, Lavinia; Sabatucci, Ilaria; Scaffa, Cono; Lorusso, Domenica; Raspagliesi, Francesco

2018-01-01

To assess the risk of developing high-grade cervical dysplasia among women with low-grade cervical cytology and nonvisible squamocolumnar junction (SCJ) at colposcopic examination. Data of consecutive women with low-grade intraepithelial lesion(≤LSIL) undergoing colposcopic examination, which was unsatisfactory (due to the lack of the visualization of the entire SCJ), were retrospectively reviewed. The risk of developing high-grade cervical intraepithelial neoplasia (CIN2+) was assessed using Kaplan-Meier and Cox models. Data of 86 women were retrieved. Mean (standard deviation [SD]) age was 36.3 (13.4) years. A total of 71 (82.5%) patients had high-risk human papillomavirus (HR-HPV) at the time of diagnosis. Among the 63 patients undergoing repetition of HPV testing, 15 (24%) and 48 (76%) women had positive and negative tests for HR-HPV at 12 months, respectively. We observed that 5 (33%) of 15 patients with HPV persistence developed CIN2+, while only 1 (2%) patient of 48 patients without HPV persistence developed CIN2+ (odds ratio [OR]: 23.5; 95% confidence interval [CI]: 2.46-223.7; P < .001). The length of HR-HPV persistence correlated with an increased risk of developing CIN2+ ( P < .001; P for trend). High-risk HPV persistence is the only factor predicting for CIN2+ (hazard ratio: 3.19; 95% CI: 1.55-6.57; P = .002). High-risk HPV persistence predicts the risk of developing CIN2+ in patients with unsatisfactory colposcopic examination. Further studies are warranted in order to implement the use of HPV testing in patients with unsatisfactory colposcopy.

[CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].

PubMed

Madiyeva, M; Rymbayeva, T

2017-11-01

The frequency of the combination of congenital heart defects (CHD) and connective tissue dysplasia remains poorly understood. And connective tissue dysplasia enhance severity the clinical of CHD. The aim of the study was to conduct a clinical and laboratory analysis of combinations of congenital heart defects and connective tissue dysplasia in children of Semey and to determine the risk for the development of these pathologies. The object of the study is the children of Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with connective tissue dysplasia, healthy children and their mothers. Definition complex clinical and laboratory studies in children with CHD and connective tissue dysplasia, and their mothers. In children with CHD, the frequency of external and visceral signs of dysplasia was high. In 88.1% of cases in children with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the microelement composition of blood serum and of hemostasis in children with CHD were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the frequency of signs of dysplasia in mothers over the control group to consider dysplasia as a factor that influences the clinical of CHD.

Physical and Clinical Evaluation of Hip Spica Cast applied with Three-slab Technique using Fibreglass Material

PubMed Central

Bitar, KM; Ferdhany, ME; Saw, A

2016-01-01

Introduction: Hip spica casting is an important component of treatment for developmental dysplasia of the hip (DDH) and popular treatment method for femur fractures in children. Breakage at the hip region is a relatively common problem of this cast. We have developed a three-slab technique of hip spica application using fibreglass as the cast material. The purpose of this review was to evaluate the physical durability of the spica cast and skin complications with its use. Methodology: A retrospective review of children with various conditions requiring hip spica immobilisation which was applied using our method. Study duration was from 1st of January 2014 until 31st December 2015. Our main outcomes were cast breakage and skin complications. For children with hip instability, the first cast would be changed after one month, and the second cast about two months later. Results: Twenty-one children were included, with an average age of 2.2 years. The most common indication for spica immobilisation was developmental dysplasia of the hip. One child had skin irritation after spica application. No spica breakage was noted. Conclusion: This study showed that the three-slab method of hip spica cast application using fibreglass material was durable and safe with low risk of skin complications. PMID:28553442

Ectodermal Differentiation of Wharton's Jelly Mesenchymal Stem Cells for Tissue Engineering and Regenerative Medicine Applications.

PubMed

Jadalannagari, Sushma; Aljitawi, Omar S

2015-06-01

Mesenchymal stem cells (MSCs) from Wharton's jelly (WJ) of the human umbilical cord are perinatal stem cells that have self-renewal ability, extended proliferation potential, immunosuppressive properties, and are accordingly excellent candidates for tissue engineering. These MSCs are unique, easily accessible, and a noncontroversial cell source of regeneration in medicine. Wharton's jelly mesenchymal stem cells (WJMSCs) are multipotent and capable of multilineage differentiation into cells like adipocytes, bone, cartilage, and skeletal muscle upon exposure to appropriate conditions. The ectoderm is one of the three primary germ layers found in the very early embryo that differentiates into the epidermis, nervous system (spine, peripheral nerves, brain), and exocrine glands (mammary, sweat, salivary, and lacrimal glands). Accumulating evidence shows that MSCs obtained from WJ have an ectodermal differentiation potential. The current review examines this differentiation potential of WJMSC into the hair follicle, skin, neurons, and sweat glands along with discussing the potential utilization of such differentiation in regenerative medicine.

Upper-extremity phocomelia reexamined: a longitudinal dysplasia.

PubMed

Goldfarb, Charles A; Manske, Paul R; Busa, Riccardo; Mills, Janith; Carter, Peter; Ezaki, Marybeth

2005-12-01

In contrast to longitudinal deficiencies, phocomelia is considered a transverse, intercalated segmental dysplasia. Most patients demonstrate severe, but not otherwise classifiable, upper-extremity deformities, which usually cannot be placed into one of three previously described phocomelia groups. Additionally, these phocomelic extremities do not demonstrate true segmental deficits; the limb is also abnormal proximal and distal to the segmental defect. The purpose of this investigation was to present evidence that upper-extremity abnormalities in patients previously diagnosed as having phocomelia in fact represent a proximal continuum of radial or ulnar longitudinal dysplasia. The charts and radiographs of forty-one patients (sixty extremities) diagnosed as having upper-extremity phocomelia were reviewed retrospectively. On the basis of the findings on the radiographs, the disorders were categorized into three groups: (1) proximal radial longitudinal dysplasia, which was characterized by an absent proximal part of the humerus, a nearly normal distal part of the humerus, a completely absent radius, and a radial-sided hand dysplasia; (2) proximal ulnar longitudinal dysplasia, characterized by a short one-bone upper extremity that bifurcated distally and by severe hand abnormalities compatible with ulnar dysplasia; and (3) severe combined dysplasia, with type A characterized by an absence of the forearm segment (i.e., the radius and ulna) and type B characterized by absence of the arm and forearm (i.e., the hand attached to the thorax). Twenty-nine limbs in sixteen patients could be classified as having proximal radial longitudinal dysplasia. Systemic medical conditions such as thrombocytopenia-absent radius syndrome were common in those patients, but additional musculoskeletal conditions were rare. Twenty limbs in seventeen patients could be classified as having proximal ulnar longitudinal dysplasia. Associated musculoskeletal abnormalities, such as proximal femoral focal deficiency, were common in those patients. Eleven limbs in ten patients were identified as having severe combined dysplasia, which was type A in seven of them and type B in four. Four patients with severe combined dysplasia had congenital cardiac anomalies, and four had associated musculoskeletal abnormalities. Three of the four patients with the type-B disorder had a contralateral ulnar longitudinal dysplasia. We propose that cases previously classified as upper-extremity phocomelia represent a spectrum of severe longitudinal dysplasia, as none of the sixty extremities that we studied demonstrated a true intercalary deficiency. These findings have both developmental and genetic implications.