Sensorineural Deafness, Distinctive Facial Features and Abnormal Cranial Bones

PubMed Central

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R.; Matsushita, Mark; Raskind, Wendy H.

2008-01-01

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. PMID:18553554

Mutations in IRX5 impair craniofacial development and germ cell migration via SDF1.

PubMed

Bonnard, Carine; Strobl, Anna C; Shboul, Mohammad; Lee, Hane; Merriman, Barry; Nelson, Stanley F; Ababneh, Osama H; Uz, Elif; Güran, Tülay; Kayserili, Hülya; Hamamy, Hanan; Reversade, Bruno

2012-05-13

Using homozygosity mapping and locus resequencing, we found that alterations in the homeodomain of the IRX5 transcription factor cause a recessive congenital disorder affecting face, brain, blood, heart, bone and gonad development. We found through in vivo modeling in Xenopus laevis embryos that Irx5 modulates the migration of progenitor cell populations in branchial arches and gonads by repressing Sdf1. We further found that transcriptional control by Irx5 is modulated by direct protein-protein interaction with two GATA zinc-finger proteins, GATA3 and TRPS1; disruptions of these proteins also cause craniofacial dysmorphisms. Our findings suggest that IRX proteins integrate combinatorial transcriptional inputs to regulate key signaling molecules involved in the ontogeny of multiple organs during embryogenesis and homeostasis.

Case Report: Congenital Erythroleukemia in a Premature Infant with Dysmorphic Features.

PubMed

Helin, Heidi; van der Walt, Jon; Holder, Muriel; George, Simi

2016-01-01

We present a case of pure erythroleukemia, diagnosed at autopsy, in a dysmorphic premature infant who died of multiorgan failure within 24 hours of birth. Dysmorphic features included facial and limb abnormalities with long philtrum, microagnathia, downturned mouth, short neck as well as abnormal and missing nails, missing distal phalanx from the second toe, and overlapping toes. Internal findings included gross hepatomegaly and patchy hemorrhages in the liver, splenomegaly, and cardiomegaly; and subdural, intracerebral, and intraventricular hemorrhages. Histology revealed infiltration of bone marrow, kidney, heart, liver, adrenal, lung, spleen, pancreas, thyroid, testis, thymus, and placenta by pure erythroleukemia. Only 6 cases of congenital erythroleukemia have been previously reported with autopsy findings similar to those of this case. The dysmorphic features, although not fitting any specific syndrome, make this case unique. Congenital erythroleukemia and possible syndromes suggested by the dysmorphic features are discussed.

Dysmorphic features and developmental outcome of 2-year-old children.

PubMed

Seggers, Jorien; Haadsma, Maaike L; Bos, Arend F; Heineman, Maas Jan; Middelburg, Karin J; van den Heuvel, Edwin R; Hadders-Algra, Mijna

2014-11-01

The aim of this study was to assess the associations between dysmorphic features and neurological, mental, psychomotor, and behavioural development in order to improve our understanding of aetiological pathways leading to minor developmental problems. In our cross-sectional study, 272 generally healthy 2-year-olds (143 males, 129 females; median gestational age 39 weeks, [range 30-43wks]), born after a parental history of subfertility either with or without fertility treatment, were examined. Dysmorphic features were classified as abnormalities (clinically relevant or not), minor anomalies, or common variants according to Merks' classification system. Hempel's neurological assessment resulted in a neurological optimality score (NOS) and fluency score. Mental and psychomotor development were assessed with the Dutch version of the Bayley Scales of Infant Development and behavioural development with the Achenbach Child Behaviour Checklist. Of the different types of dysmorphic feature, clinically relevant abnormalities were most strongly associated with a lower NOS (difference -2.53, 95% confidence interval [CI] -4.23 to -0.83) and fluency score (difference -0.62, 95% CI -1.1 to -0.15). The presence of one or more abnormalities (clinically relevant or not) or one or more common variants was significantly associated with a lower NOS, and the presence of three or more minor anomalies was associated with lower fluency scores. Dysmorphic features were not associated with mental, psychomotor, or behavioural development. As dysmorphic features originate during the first trimester of pregnancy, the association between dysmorphic features and minor alterations in neurodevelopment may suggest an early ontogenetic origin of subtle neurological deviations. © 2014 Mac Keith Press.

Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation.

PubMed

Burdon, Kathryn P; McKay, James D; Sale, Michèle M; Russell-Eggitt, Isabelle M; Mackey, David A; Wirth, M Gabriela; Elder, James E; Nicoll, Alan; Clarke, Michael P; FitzGerald, Liesel M; Stankovich, James M; Shaw, Marie A; Sharma, Shiwani; Gajovic, Srecko; Gruss, Peter; Ross, Shelley; Thomas, Paul; Voss, Anne K; Thomas, Tim; Gécz, Jozef; Craig, Jamie E

2003-11-01

Nance-Horan syndrome (NHS) is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, mental retardation. NHS has been mapped to a 1.3-Mb interval on Xp22.13. We have confirmed the same localization in the original, extended Australian family with NHS and have identified protein-truncating mutations in a novel gene, which we have called "NHS," in five families. The NHS gene encompasses approximately 650 kb of genomic DNA, coding for a 1,630-amino acid putative nuclear protein. NHS orthologs were found in other vertebrates, but no sequence similarity to known genes was identified. The murine developmental expression profile of the NHS gene was studied using in situ hybridization and a mouse line containing a lacZ reporter-gene insertion in the Nhs locus. We found a complex pattern of temporally and spatially regulated expression, which, together with the pleiotropic features of NHS, suggests that this gene has key functions in the regulation of eye, tooth, brain, and craniofacial development.

Mutations in a Novel Gene, NHS, Cause the Pleiotropic Effects of Nance-Horan Syndrome, Including Severe Congenital Cataract, Dental Anomalies, and Mental Retardation

PubMed Central

Burdon, Kathryn P.; McKay, James D.; Sale, Michèle M.; Russell-Eggitt, Isabelle M.; Mackey, David A.; Wirth, M. Gabriela; Elder, James E.; Nicoll, Alan; Clarke, Michael P.; FitzGerald, Liesel M.; Stankovich, James M.; Shaw, Marie A.; Sharma, Shiwani; Gajovic, Srecko; Gruss, Peter; Ross, Shelley; Thomas, Paul; Voss, Anne K.; Thomas, Tim; Gécz, Jozef; Craig, Jamie E.

2003-01-01

Nance-Horan syndrome (NHS) is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, mental retardation. NHS has been mapped to a 1.3-Mb interval on Xp22.13. We have confirmed the same localization in the original, extended Australian family with NHS and have identified protein-truncating mutations in a novel gene, which we have called “NHS,” in five families. The NHS gene encompasses ∼650 kb of genomic DNA, coding for a 1,630–amino acid putative nuclear protein. NHS orthologs were found in other vertebrates, but no sequence similarity to known genes was identified. The murine developmental expression profile of the NHS gene was studied using in situ hybridization and a mouse line containing a lacZ reporter-gene insertion in the Nhs locus. We found a complex pattern of temporally and spatially regulated expression, which, together with the pleiotropic features of NHS, suggests that this gene has key functions in the regulation of eye, tooth, brain, and craniofacial development. PMID:14564667

Role of Imaging and Cytogenetics in Evaluation of DiGeorge Syndrome - A Rare Entity in Clinical Practice.

PubMed

Ramachandran, Rajoo; Babu, Sellappan Rajamanickam; Ilanchezhian, Subramanian; Radhakrishnan, Prabhu Radhan

2015-01-01

DiGeorge syndrome is a congenital genetic disorder that affects the endocrine system, mainly the thymus and parathyroid glands. The syndrome produces different symptoms, which vary in severity and character between patients. It manifests with craniofacial dysmorphism and defects in the heart, parathyroid, and thymus. Patients can present with a palatal deformity and nasal speech. This rare entity is caused mainly due to deletion of chromosome 22q11.2. Radiographic evaluation of DiGeorge syndrome is necessary to define aberrant anatomy, evaluate central nervous system, craniofacial abnormalities, musculoskeletal system, and cardiothoracic contents. It also helps in planning surgical procedures and surgical reconstructions. We report a case of DiGeorge syndrome in a 4-month-old neonate and discuss the clinical, imaging, and cytogenetic findings that helped in the diagnosis of this rare entity.

Prevalence of Body Dysmorphic Disorder Symptoms and Associated Clinical Features among Australian University Students

ERIC Educational Resources Information Center

Bartsch, Dianna

2007-01-01

The current study addressed the frequency of body dysmorphic disorder (BDD) symptoms among university students and investigated the predictors of dysmorphic concern. Six hundred and nineteen Australian university students completed measures assessing BDD, dysmorphic concern, self-esteem, depression, life satisfaction, self-oriented and socially…

Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome?

PubMed

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R; Matsushita, Mark; Raskind, Wendy H

2008-07-15

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair, and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. 2008 Wiley-Liss, Inc.

Phenotype in girls and women with Turner syndrome: Association between dysmorphic features, karyotype and cardio-aortic malformations.

PubMed

Noordman, Iris; Duijnhouwer, Anthonie; Kapusta, Livia; Kempers, Marlies; Roeleveld, Nel; Schokking, Michiel; Smeets, Dominique; Freriks, Kim; Timmers, Henri; van Alfen-van der Velden, Janiëlle

2018-06-01

Turner syndrome (TS) is a genetic disorder characterized by the (partial) absence or a structural aberration of the second sex chromosome and is associated with a variety of phenotypes with specific physical features and cardio-aortic malformations. The objective of this study was to gain a better insight into the differences in dysmorphic features between girls and women with TS and to explore the association between these features, karyotype and cardio-aortic malformations. This prospective study investigated 14 dysmorphic features of TS girls and women using a checklist. Three major phenotypic patterns were recognized (severe phenotype, lymphatic phenotype and skeletal phenotype). Patient data including karyotype and cardio-aortic malformations (bicuspid aortic valve (BAV) and aortic coarctation (COA)) were collected. Associations between the prevalence of dysmorphic features, karyotype and cardio-aortic malformations were analysed using chi 2 -test and odds ratios. A total of 202 patients (84 girls and 118 women) were analysed prospectively. Differences in prevalence of dysmorphic features were found between girls and women. A strong association was found between monosomy 45,X and the phenotypic patterns. Furthermore, an association was found between COA and lymphatic phenotype, but no association was found between karyotype and cardio-aortic malformations. This study uncovered a difference in dysmorphic features between girls and women. Monosomy 45,X is associated with a more severe phenotype, lymphatic phenotype and skeletal phenotype. All patients with TS should be screened for cardio-aortic malformations, because in contrast to previous reports, karyotype and cardio-aortic malformations showed no significant association. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A de novo 11q23 deletion in a patient presenting with severe ophthalmologic findings, psychomotor retardation and facial dysmorphism.

PubMed

Şimşek-Kiper, Pelin Özlem; Bayram, Yavuz; Ütine, Gülen Eda; Alanay, Yasemin; Boduroğlu, Koray

2014-01-01

Distal 11q deletion, previously known as Jacobsen syndrome, is caused by segmental aneusomy for the distal end of the long arm of chromosome 11. Typical clinical features include facial dysmorphism, mild-to-moderate psychomotor retardation, trigonocephaly, cardiac defects, and thrombocytopenia. There is a significant variability in the range of clinical features. We report herein a five-year-old girl with severe ophthalmological findings, facial dysmorphism, and psychomotor retardation with normal platelet function, in whom a de novo 11q23 deletion was detected, suggesting that distal 11q monosomy should be kept in mind in patients presenting with dysmorphic facial features and psychomotor retardation even in the absence of hematological findings.

Use of Dysmorphology for Subgroup Classification on Autism Spectrum Disorder in Chinese Children

ERIC Educational Resources Information Center

Wong, Virginia C. N.; Fung, Cecilia K. Y.; Wong, Polly T. Y.

2014-01-01

Data from 1,261 Chinese Autistic Spectrum Disorder (ASD) patients were evaluated and categorized into dysmorphic (10.79%) and non-dysmorphic groups (89.21%) upon physical examination by the presence of dysmorphic features. Abnormal MRI/CT result, IQ scores and epilepsy were significantly associated with the dysmorphic group of ASD children.…

Prenatal diagnosis of isochromosome 20q in a fetus with vertebral anomaly and rocker-bottom feet.

PubMed

Receveur, Aline; Brisset, Sophie; Martinovic, Jelena; Bazin, Anne; Lhomann, Laurence; Colmant, Claire; Pineau, Dominique; Gautier, Valérie; Tosca, Lucie; Tachdjian, Gérard

2017-10-01

Isochromosome of the long arm of chromosome 20 (i(20q)) is a rare structural abnormality in prenatal diagnosis. Thirty prenatal cases of mosaic i(20q) have been reported, among which only four are associated with fetal malformations. We describe a new prenatal case of i(20q) with fetal malformations. We also observed a discrepancy between uncultured and cultured amniotic fluid cells by using conventional cytogenetic, fluorescence in situ hybridization and array-SNP analysis. The short arm deletion of chromosome 20 arising from the isochromosome encompassed two candidate genes PAX1 and JAG1 involved in cranio-facial and vertebral development. The data would allow establishing a phenotype-genotype correlation. Thus, we proposed to define a recognizable syndrome combining cranio-facial dysmorphism, vertebral bodies' anomalies, feet and cerebral malformations. Copyright © 2017. Published by Elsevier B.V.

Fetus with Casamassima-Morton-Nance Syndrome and Limb-Body Wall Defect: Presentation of a Novel Association and Review of the Phenotype.

PubMed

Salinas-Torres, Victor M

2016-01-01

In 1981, Casamassima and colleagues described an autosomal recessive syndrome of spondylocostal dysostosis associated with anal and urogenital anomalies. Here, I describe 1 new fetus who presented with limb-body wall defect as a novel association, compile 7 patients, and review the clinical phenotype of Casamassima-Morton-Nance syndrome. This appears to be the 1st Casamassima-Morton-Nance syndrome fetus with this complex malformation. In light of this manifestation, a detailed comparative phenotypic analysis of published patients revealed a heterogeneous syndrome with significant clinical variability. Accordingly, it is proposed that Casamassima-Morton-Nance syndrome should be considered in those patients with the combination of a short and asymmetric thorax with rib and vertebral anomalies and scoliosis (spondylocostal-like pattern), anal atresia, absent external genitalia, renal and urethral abnormalities (caudal dysgenesis complex), craniofacial dysmorphic features (mainly flat nose with anteverted nares, low-set/abnormal ears, and short neck), hydrops, oligohydramnios, and a poor clinical outcome.

Rubinstein-Taybi Syndrome Associated with Pituitary Macroadenoma: A Case Report.

PubMed

Olyaei, Yasamin; Sarmiento, J Manuel; Bannykh, Serguei I; Drazin, Doniel; Naruse, Robert T; King, Wesley

2017-04-11

Rubinstein-Taybi Syndrome (RSTS) is an autosomal dominant disorder that is classically characterized by prenatal and postnatal growth restriction, microcephaly, dysmorphic craniofacial features, broad thumbs and toes, and intellectual disability. We describe the first reported case of a pituitary macroadenoma associated with RSTS. A 39-year-old Caucasian female with a past medical history of RSTS diagnosed at age two was found to have a gadolinium-enhancing pituitary mass on magnetic resonance imaging (MRI) of the brain three years ago during workup for migraine-like headaches. Subsequent serial imaging showed radiographic evidence of growth up to 11.5 x 14.0 x 10.0 mm in size. The pituitary sellar lesion was resected through an endoscopic transnasal transsphenoidal approach and was found to be a thyrotroph adenoma. RSTS is a rare, neurodevelopmental genetic disease where most patients with disabilities survive into adulthood. The disorder is associated with an increased predisposition for development of nervous system tumors, including pituitary adenomas.

Rubinstein-Taybi Syndrome Associated with Pituitary Macroadenoma: A Case Report

PubMed Central

Olyaei, Yasamin; Bannykh, Serguei I; Drazin, Doniel; Naruse, Robert T; King, Wesley

2017-01-01

Rubinstein-Taybi Syndrome (RSTS) is an autosomal dominant disorder that is classically characterized by prenatal and postnatal growth restriction, microcephaly, dysmorphic craniofacial features, broad thumbs and toes, and intellectual disability. We describe the first reported case of a pituitary macroadenoma associated with RSTS. A 39-year-old Caucasian female with a past medical history of RSTS diagnosed at age two was found to have a gadolinium-enhancing pituitary mass on magnetic resonance imaging (MRI) of the brain three years ago during workup for migraine-like headaches. Subsequent serial imaging showed radiographic evidence of growth up to 11.5 x 14.0 x 10.0 mm in size. The pituitary sellar lesion was resected through an endoscopic transnasal transsphenoidal approach and was found to be a thyrotroph adenoma. RSTS is a rare, neurodevelopmental genetic disease where most patients with disabilities survive into adulthood. The disorder is associated with an increased predisposition for development of nervous system tumors, including pituitary adenomas. PMID:28503387

Oral manifestations and dental management of a child with Zellweger syndrome.

PubMed

Lertsirivorakul, Jinda; Wongswadiwat, Malinee; Treesuwan, Panta

2014-01-01

Zellweger syndrome (ZS) is a rare autosomal recessive disorder, resulting from an impairment in peroxisome function. It is characterized by craniofacial dysmorphism and neurological abnormalities, and involves several systems, which may complicate dental and anesthesia management. The case of a 7-year-old girl diagnosed with ZS is described with emphasis on oral manifestations, oral rehabilitation under general anesthesia (GA), and home oral care. Apart from the unique features of ZS, she presented with clinodactyly, distinctive palatal vault, Class III malocclusion, missing teeth, microdontia, and delayed dental formation. Dental treatment under GA was conducted with concerns of risk of respiratory insufficiency. Oral home care by the parent and regular recall visits were essential to maintain good oral health. Children with ZS may survive into late childhood. They, however, present multiple health problems that are of special concern for not only the pediatric dentist but also the anesthesiologist. Collaboration with the medical team is essential for optimal care of these patients. ©2012 Special Care Dentistry Association and Wiley Periodicals, Inc.

Microcephalic osteodysplastic primordial dwarfism, with the fascinating history of "Mademoiselle Crachami".

PubMed

Bozkaya, O Giray

2013-01-01

This review critically examines the findings which characterize the dysmorphic, radiologic and behavioral phenotype of Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) and has an historical perspective on it. MOPD is a group of primordial dwarfism syndromes with prenatal onset growth retardation, a typical craniofacial appearance and behavioral phenotype. In 1959, Mann and Russell have described the first case in a detailed report, and named "microcephalic midget of extreme type". In their report; based on historical records and a small painting, they pointed "Mademoiselle Crachami" as the oldest known case.

Novel compound heterozygous DPH1 mutations in a patient with the unique clinical features of airway obstruction and external genital abnormalities.

PubMed

Nakajima, Junya; Oana, Shingo; Sakaguchi, Tomohiro; Nakashima, Mitsuko; Numabe, Hironao; Kawashima, Hisashi; Matsumoto, Naomichi; Miyake, Noriko

2018-04-01

The diphthamide biosynthesis 1 (DPH1) gene encodes one of the essential components of the enzyme catalyzing the first step of diphthamide formation on eukaryotic elongation factor 2 (EEF2). Diphthamide is the posttranslationally modified histidine residue on EEF2 that promotes protein chain elongation in the ribosome. DPH1 defects result in a failure of protein synthesis involving EEF2, leading to growth defects, embryonic lethality, and cell death. In humans, DPH1 mutations cause developmental delay with a short stature, dysmorphic features, and sparse hair, and are inherited in an autosomal recessive manner (MIM#616901). To date, only two homozygous missense mutations in DPH1 (c.17T>A, p.Met6Lys and c.701T>C, p.Leu234Pro) have been reported. We used WES to identify novel compound heterozygous mutations in DPH1 (c.289delG, p.Glu97Lysfs*8 and c.491T>C, p.Leu164Pro) in a patient from a nonconsanguineous family presenting with intellectual disability, a short stature, craniofacial abnormalities, and external genital abnormalities. The clinical phenotype of all patients with DPH1 mutations, including the current patient, revealed core features, although the external genital anomaly was newly recognized in our case.

Congenital oculomotor nerve synkinesis associated with fetal retinoid syndrome.

PubMed

Morrison, David G; Elsas, Frederick J; Descartes, Maria

2005-04-01

Isotretinoin (RA), used for the treatment of cystic acne, is a powerful teratogen, causing craniofacial dysmorphisms and neural tube defects. We present two patients with RA embryopathy and oculomotor nerve synkinesis. Retrospective review of patient records. Two patients presented with third nerve synkinesis and fetal RA exposure. Both had marked elevation of the upper eyelids on adduction such that the lid fissures alternately opened and closed on gaze from side to side. Both patients showed typical dysmorphisms of RA embryopathy. The first patient had complete agenesis of the cerebellar vermix and died at 2 years. The second patient had restricted extraocular muscles in one eye and was exotropic and hypotropic. Both patients demonstrated simultaneous innervation of the medial rectus and levator palpebrae muscles causing coincident lid elevation in adduction. This evidence of oculomotor nerve synkinesis is consistent with animal studies showing abnormalities in the formation of cranial nerve ganglia following fetal RA exposure. RA is a powerful teratogen. These patients provide additional clinical evidence of its influence on neural migration during early development.

A t(5;16) translocation is the likely driver of a syndrome with ambiguous genitalia, facial dysmorphism, intellectual disability, and speech delay.

PubMed

Ozantürk, Ayşegül; Davis, Erica E; Sabo, Aniko; Weiss, Marjan M; Muzny, Donna; Dugan-Perez, Shannon; Sistermans, Erik A; Gibbs, Richard A; Özgül, Köksal R; Yalnızoglu, Dilek; Serdaroglu, Esra; Dursun, Ali; Katsanis, Nicholas

2016-03-01

Genetic studies grounded on monogenic paradigms have accelerated both gene discovery and molecular diagnosis. At the same time, complex genomic rearrangements are also appreciated as potent drivers of disease pathology. Here, we report two male siblings with a dysmorphic face, ambiguous genitalia, intellectual disability, and speech delay. Through quad-based whole-exome sequencing and concomitant molecular cytogenetic testing, we identified two copy-number variants (CNVs) in both affected individuals likely arising from a balanced translocation: a 13.5-Mb duplication on Chromosome 16 (16q23.1 → 16qter) and a 7.7-Mb deletion on Chromosome 5 (5p15.31 → 5pter), as well as a hemizygous missense variant in CXorf36 (also known as DIA1R). The 5p terminal deletion has been associated previously with speech delay, whereas craniofacial dysmorphia and genital/urinary anomalies have been reported in patients with a terminal duplication of 16q. However, dosage changes in either genomic region alone could not account for the overall clinical presentation in our family; functional testing of CXorf36 in zebrafish did not induce defects in neurogenesis or the craniofacial skeleton. Notably, literature and database analysis revealed a similar dosage disruption in two siblings with extensive phenotypic overlap with our patients. Taken together, our data suggest that dosage perturbation of genes within the two chromosomal regions likely drives the syndromic manifestations of our patients and highlight how multiple genetic lesions can contribute to complex clinical pathologies.

A deletion and a duplication in distal 22q11.2 deletion syndrome region. Clinical implications and review

PubMed Central

Fernández, Luis; Nevado, Julián; Santos, Fernando; Heine-Suñer, Damià; Martinez-Glez, Victor; García-Miñaur, Sixto; Palomo, Rebeca; Delicado, Alicia; Pajares, Isidora López; Palomares, María; García-Guereta, Luis; Valverde, Eva; Hawkins, Federico; Lapunzina, Pablo

2009-01-01

Background Individuals affected with DiGeorge and Velocardiofacial syndromes present with both phenotypic diversity and variable expressivity. The most frequent clinical features include conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial dysmorphism. The etiology in most patients is a 3 Mb recurrent deletion in region 22q11.2. However, cases of infrequent deletions and duplications with different sizes and locations have also been reported, generally with a milder, slightly different phenotype for duplications but with no clear genotype-phenotype correlation to date. Methods We present a 7 month-old male patient with surgically corrected ASD and multiple VSDs, and dysmorphic facial features not clearly suggestive of 22q11.2 deletion syndrome, and a newborn male infant with cleft lip and palate and upslanting palpebral fissures. Karyotype, FISH, MLPA, microsatellite markers segregation studies and SNP genotyping by array-CGH were performed in both patients and parents. Results Karyotype and FISH with probe N25 were normal for both patients. MLPA analysis detected a partial de novo 1.1 Mb deletion in one patient and a novel partial familial 0.4 Mb duplication in the other. Both of these alterations were located at a distal position within the commonly deleted region in 22q11.2. These rearrangements were confirmed and accurately characterized by microsatellite marker segregation studies and SNP array genotyping. Conclusion The phenotypic diversity found for deletions and duplications supports a lack of genotype-phenotype correlation in the vicinity of the LCRC-LCRD interval of the 22q11.2 chromosomal region, whereas the high presence of duplications in normal individuals supports their role as polymorphisms. We suggest that any hypothetical correlation between the clinical phenotype and the size and location of these alterations may be masked by other genetic and/or epigenetic modifying factors. PMID:19490635

The first Korean patient with Potocki-Shaffer syndrome: a rare cause of multiple exostoses.

PubMed

Sohn, Young Bae; Yim, Shin-Young; Cho, Eun-Hae; Kim, Ok-Hwa

2015-02-01

Potocki-Shaffer syndrome (PSS, OMIM #601224) is a rare contiguous gene deletion syndrome caused by haploinsufficiency of genes located on the 11p11.2p12. Affected individuals have a number of characteristic features including multiple exostoses, biparietal foramina, abnormalities of genitourinary system, hypotonia, developmental delay, and intellectual disability. We report here on the first Korean case of an 8-yr-old boy with PSS diagnosed by high resolution microarray. Initial evaluation was done at age 6 months because of a history of developmental delay, hypotonia, and dysmorphic face. Coronal craniosynostosis and enlarged parietal foramina were found on skull radiographs. At age 6 yr, he had severe global developmental delay. Multiple exostoses of long bones were detected during a radiological check-up. Based on the clinical and radiological features, PSS was highly suspected. Subsequently, chromosomal microarray analysis identified an 8.6 Mb deletion at 11p11.2 [arr 11p12p11.2 (Chr11:39,204,770-47,791,278)×1]. The patient continued rehabilitation therapy for profound developmental delay. The progression of multiple exostosis has being monitored. This case confirms and extends data on the genetic basis of PSS. In clinical and radiologic aspect, a patient with multiple exostoses accompanying with syndromic features, including craniofacial abnormalities and mental retardation, the diagnosis of PSS should be considered.

Familial cardiofaciocutaneous syndrome in a father and a son with a novel MEK2 mutation.

PubMed

Karaer, Kadri; Lissewski, Christina; Zenker, Martin

2015-02-01

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder belonging to the group of RASopathies. It is typically characterized by congenital heart defects, short stature, dysmorphic craniofacial features, intellectual disability, failure to thrive, and ectodermal abnormalities such as hyperkeratosis and sparse, brittle, curly hair. CFC syndrome is caused by dominant mutations in one of the four genes BRAF, MEK1, MEK2, and KRAS. Only three familial cases of CFC syndrome have been reported to date, whereas the vast majorities are sporadic cases due to de novo mutations. We report on a fourth familial case with transmission of CFC syndrome from father to son due to a novel heterozygous sequence change c.376A>G (p.N126D) in exon 3 of MEK2 gene. This observation further documents the possibility of vertical transmission of CFC syndrome, which appears to be associated with rare mutations and relatively mild intellectual disability in affected individual. The hypomorphic effect of specific mutations particularly regarding neurocognitive issues may be related to the variable fertility of affected individuals. © 2014 Wiley Periodicals, Inc.

An atypical 7q11.23 deletion in a normal IQ Williams–Beuren syndrome patient

PubMed Central

Ferrero, Giovanni Battista; Howald, Cédric; Micale, Lucia; Biamino, Elisa; Augello, Bartolomeo; Fusco, Carmela; Turturo, Maria Giuseppina; Forzano, Serena; Reymond, Alexandre; Merla, Giuseppe

2010-01-01

Williams–Beuren syndrome (WBS; OMIM no. 194050) is a multisystemic neurodevelopmental disorder caused by a hemizygous deletion of 1.55 Mb on chromosome 7q11.23 spanning 28 genes. Haploinsufficiency of the ELN gene was shown to be responsible for supravalvular aortic stenosis and generalized arteriopathy, whereas LIMK1, CLIP2, GTF2IRD1 and GTF2I genes were suggested to be linked to the specific cognitive profile and craniofacial features. These insights for genotype–phenotype correlations came from the molecular and clinical analysis of patients with atypical deletions and mice models. Here we report a patient showing mild WBS physical phenotype and normal IQ, who carries a shorter 1 Mb atypical deletion. This rearrangement does not include the GTF2IRD1 and GTF2I genes and only partially the BAZ1B gene. Our results are consistent with the hypothesis that hemizygosity of the GTF2IRD1 and GTF2I genes might be involved in the facial dysmorphisms and in the specific motor and cognitive deficits observed in WBS patients. PMID:19568270

Monosomy1p36.3 and trisomy 19p13.3 in a child with periventricular nodular heterotopia.

PubMed

Descartes, Maria; Mikhail, Fady M; Franklin, Judith C; McGrath, Tony M; Bebin, Martina

2011-10-01

Monosomy 1p36 is a clinically recognizable syndrome that is considered to be the most common terminal deletion syndrome. It has characteristic clinical features that include craniofacial dysmorphism, congenital anomalies, hearing deficits, developmental delay, mental retardation, hypotonia, seizures, and brain anomalies. Brain anomalies in patients with 1p36 deletion are frequent but inconsistent. To date, 2 cases with monosomy 1p36 associated with periventricular nodular heterotopia (PNH) have been reported. We report a 2-month-old boy with multiple congenital anomalies; brain magnetic resonance imaging revealed PNH. The first 2 described cases were pure terminal deletions, whereas our patient carried unbalanced translocation due to an adjacent 1 segregation of a balanced maternal translocation, resulting in monosomy 1p36.3 and trisomy 19p13.3 identified by whole-genome array comparative genomic hybridization analysis. Our patient, with a smaller deletion that the 2 previously reported cases, can help narrow the critical region for PNH in association with the 1p36 deletion. Several potential candidate genes are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Say-Meyer syndrome: additional manifestations in a new patient and phenotypic assessment.

PubMed

Salinas-Torres, Victor M

2015-07-01

In 1981, Say and Meyer described a seemingly X-linked recessive syndrome of trigonocephaly, short stature, and developmental delay. Here, I present a new patient and review eight patients from the literature examining the nature and phenotypic differences. A Mexican 10-year-old boy with Say-Meyer syndrome is described. Additionally, he had C6 vertebral right pedicle agenesis, brachymesophalangy of the fifth fingers, bilateral widening of Sylvian fissure, and white matter amplitude as novel observed findings of the syndrome. This appears to be the first Say-Meyer syndrome patient with extracranial skeletal anomalies. In light of these manifestations, a detailed comparative phenotypic analysis of published patients revealed a heterogeneous syndrome with a significant clinical variability. Moreover, increasing evidence points to a variable expressivity of the same autosomal dominant mutation. Accordingly, it is proposed that Say-Meyer syndrome should be considered in those patients with the combination of trigonocephaly/metopic synostosis, short stature, developmental delay including prenatal and postnatal growth disorders, craniofacial dysmorphic features (especially hypotelorism), structural CNS anomalies (mainly white matter involvement), conductive hearing loss, seizures, and cardiovascular abnormalities.

The novel RAF1 mutation p.(Gly361Ala) located outside the kinase domain of the CR3 region in two patients with Noonan syndrome, including one with a rare brain tumor.

PubMed

Harms, Frederike L; Alawi, Malik; Amor, David J; Tan, Tiong Y; Cuturilo, Goran; Lissewski, Christina; Brinkmann, Julia; Schanze, Denny; Kutsche, Kerstin; Zenker, Martin

2018-02-01

Noonan syndrome is characterized by typical craniofacial dysmorphism, postnatal growth retardation, congenital heart defect, and learning difficulties and belongs to the RASopathies, a group of neurodevelopmental disorders caused by germline mutations in genes encoding components of the RAS-MAPK pathway. Mutations in the RAF1 gene are associated with Noonan syndrome, with a high prevalence of hypertrophic cardiomyopathy (HCM). RAF1 mutations cluster in exons encoding the conserved region 2 (CR2), the kinase activation segment of the CR3 domain, and the C-terminus. We present two boys with Noonan syndrome and the identical de novo RAF1 missense variant c.1082G>C/p.(Gly361Ala) affecting the CR3, but located outside the kinase activation segment. The p.(Gly361Ala) mutation has been identified as a RAF1 allele conferring resistance to RAF inhibitors. This amino acid change favors a RAF1 conformation that allows for enhanced RAF dimerization and increased intrinsic kinase activity. Both patients with Noonan syndrome showed typical craniofacial dysmorphism, macrocephaly, and short stature. One individual developed HCM and was diagnosed with a disseminated oligodendroglial-like leptomeningeal tumor (DOLT) of childhood at the age of 9 years. While there is a well-established association of NS with malignant tumors, especially childhood hemato-oncological diseases, brain tumors have rarely been reported in Noonan syndrome. Our data demonstrate that mutation scanning of the entire coding region of genes associated with Noonan syndrome is mandatory not to miss rare variants located outside the known mutational hotspots. © 2017 Wiley Periodicals, Inc.

Pathogenesis of Germline and Somatic NF1 Rearrangements

DTIC Science & Technology

1999-10-01

de novo DNA deletion in a patient with sporadic neurofibromatosis 1, mental retardation, and dysmorphism . J Med Genet 29:686-90. Leppig, K., Kaplan...a patient with sporadic neurofibromatosis 1, mental retardation, and dysmorphism . J. Med. Genet., 29, 686-690. 13. Kayes, L.M., Burke, W., Riccardi...gene are predominantly of maternal origin and commonly associated with a learning disability, dysmorphic features and developmental delay. Hum. Genet

Axenfeld-Rieger syndrome.

PubMed

Seifi, M; Walter, M A

2018-06-01

Axenfeld-Rieger syndrome (ARS) is a clinically and genetically heterogeneous group of developmental disorders affecting primarily the anterior segment of the eye, often leading to secondary glaucoma. Patients with ARS may also present with systemic changes, including dental defects, mild craniofacial dysmorphism, and umbilical anomalies. ARS is inherited in an autosomal-dominant fashion; the underlying defect in 40% of patients is mutations in PITX2 or FOXC1. Here, an overview of the clinical spectrum of ARS is provided. As well, the known underlying genetic defects, clinical diagnostic possibilities, genetic counseling and treatments of ARS are discussed in detail. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

K-RasV14I recapitulates Noonan syndrome in mice

PubMed Central

Hernández-Porras, Isabel; Fabbiano, Salvatore; Schuhmacher, Alberto J.; Aicher, Alexandra; Cañamero, Marta; Cámara, Juan Antonio; Cussó, Lorena; Desco, Manuel; Heeschen, Christopher; Mulero, Francisca; Bustelo, Xosé R.; Guerra, Carmen; Barbacid, Mariano

2014-01-01

Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. NS also is associated with a risk for developing myeloproliferative disorders (MPD), including juvenile myelomonocytic leukemia (JMML). Mutations responsible for NS occur in at least 11 different loci including KRAS. Here we describe a mouse model for NS induced by K-RasV14I, a recurrent KRAS mutation in NS patients. K-RasV14I–mutant mice displayed multiple NS-associated developmental defects such as growth delay, craniofacial dysmorphia, cardiac defects, and hematologic abnormalities including a severe form of MPD that resembles human JMML. Homozygous animals had perinatal lethality whose penetrance varied with genetic background. Exposure of pregnant mothers to a MEK inhibitor rescued perinatal lethality and prevented craniofacial dysmorphia and cardiac defects. However, Mek inhibition was not sufficient to correct these defects when mice were treated after weaning. Interestingly, Mek inhibition did not correct the neoplastic MPD characteristic of these mutant mice, regardless of the timing at which the mice were treated, thus suggesting that MPD is driven by additional signaling pathways. These genetically engineered K-RasV14I–mutant mice offer an experimental tool for studying the molecular mechanisms underlying the clinical manifestations of NS. Perhaps more importantly, they should be useful as a preclinical model to test new therapies aimed at preventing or ameliorating those deficits associated with this syndrome. PMID:25359213

Prevalence and correlates of body dysmorphic disorder in a community sample of adolescents.

PubMed

Schneider, Sophie C; Turner, Cynthia M; Mond, Jonathan; Hudson, Jennifer L

2017-06-01

Body dysmorphic disorder typically begins in adolescence, yet little is known about the prevalence and correlates of the disorder in this age group. The current study aimed to explore the presenting features of adolescents meeting probable criteria for body dysmorphic disorder in a large community sample, and compare levels of comorbid psychopathology, quality of life and mental health service use between adolescents with probable body dysmorphic disorder and those without. Questionnaires were completed at school by 3149 adolescents: 63% male, aged 12-18 years ( M = 14.58). These assessed Diagnostic and Statistical Manual of Mental Disorders (4th ed.) body dysmorphic disorder criteria, past mental health service use and symptoms of body dysmorphic disorder, anxiety, depression, obsessive-compulsive disorder and eating disorders. In male participants, additional measures assessed quality of life, muscularity concerns, emotional symptoms, peer problems, conduct problems and hyperactivity. The prevalence of probable body dysmorphic disorder was 1.7%; there was no sex difference in prevalence, but older adolescents reported higher prevalence than younger adolescents. Probable body dysmorphic disorder participants reported substantially elevated levels of psychopathology, quality of life impairment and mental health service use compared to non-body dysmorphic disorder participants. The prevalence of body dysmorphic disorder in adolescents is similar to adult samples, and probable body dysmorphic disorder is associated with comorbidity, distress and functional impairment in a community sample. Further research is required to better understand the presentation of body dysmorphic disorder in adolescents, and to improve diagnosis and treatment.

ChIP-Chip Identifies SEC23A, CFDP1, and NSD1 as TFII-I Target Genes in Human Neural Crest Progenitor Cells.

PubMed

Makeyev, Aleksandr V; Bayarsaihan, Dashzeveg

2013-05-01

Objectives :  GTF2I and GTF2IRD1 genes located in Williams-Beuren syndrome (WBS) critical region encode TFII-I family transcription factors. The aim of this study was to map genomic sites bound by these proteins across promoter regions of developmental regulators associated with craniofacial development. Design :  Chromatin was isolated from human neural crest progenitor cells and the DNA-binding profile was generated using the human RefSeq tiling promoter ChIP-chip arrays. Results :  TFII-I transcription factors are recruited to the promoters of SEC23A, CFDP1, and NSD1 previously defined as TFII-I target genes. Moreover, our analysis revealed additional binding elements that contain E-boxes and initiator-like motifs. Conclusions :  Genome-wide promoter binding studies revealed SEC23A, CFDP1, and NSD1 linked to craniofacial or dental development as direct TFII-I targets. Developmental regulation of these genes by TFII-I factors could contribute to the WBS-specific facial dysmorphism.

Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects.

PubMed

De Mori, Roberta; Romani, Marta; D'Arrigo, Stefano; Zaki, Maha S; Lorefice, Elisa; Tardivo, Silvia; Biagini, Tommaso; Stanley, Valentina; Musaev, Damir; Fluss, Joel; Micalizzi, Alessia; Nuovo, Sara; Illi, Barbara; Chiapparini, Luisa; Di Marcotullio, Lucia; Issa, Mahmoud Y; Anello, Danila; Casella, Antonella; Ginevrino, Monia; Leggins, Autumn Sa'na; Roosing, Susanne; Alfonsi, Romina; Rosati, Jessica; Schot, Rachel; Mancini, Grazia Maria Simonetta; Bertini, Enrico; Dobyns, William B; Mazza, Tommaso; Gleeson, Joseph G; Valente, Enza Maria

2017-10-05

The Sonic Hedgehog (SHH) pathway is a key signaling pathway orchestrating embryonic development, mainly of the CNS and limbs. In vertebrates, SHH signaling is mediated by the primary cilium, and genetic defects affecting either SHH pathway members or ciliary proteins cause a spectrum of developmental disorders. SUFU is the main negative regulator of the SHH pathway and is essential during development. Indeed, Sufu knock-out is lethal in mice, and recessive pathogenic variants of this gene have never been reported in humans. Through whole-exome sequencing in subjects with Joubert syndrome, we identified four children from two unrelated families carrying homozygous missense variants in SUFU. The children presented congenital ataxia and cerebellar vermis hypoplasia with elongated superior cerebellar peduncles (mild "molar tooth sign"), typical cranio-facial dysmorphisms (hypertelorism, depressed nasal bridge, frontal bossing), and postaxial polydactyly. Two siblings also showed polymicrogyria. Molecular dynamics simulation predicted random movements of the mutated residues, with loss of the native enveloping movement of the binding site around its ligand GLI3. Functional studies on cellular models and fibroblasts showed that both variants significantly reduced SUFU stability and its capacity to bind GLI3 and promote its cleavage into the repressor form GLI3R. In turn, this impaired SUFU-mediated repression of the SHH pathway, as shown by altered expression levels of several target genes. We demonstrate that germline hypomorphic variants of SUFU cause deregulation of SHH signaling, resulting in recessive developmental defects of the CNS and limbs which share features with both SHH-related disorders and ciliopathies. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Analysis of chromosomal abnormalities by CGH-array in patients with dysmorphic and intellectual disability with normal karyotype

PubMed Central

Pratte-Santos, Rodrigo; Ribeiro, Katyanne Heringer; Santos, Thainá Altoe; Cintra, Terezinha Sarquis

2016-01-01

ABSTRACT Objective To investigate chromosomal abnormalities by CGH-array in patients with dysmorphic features and intellectual disability with normal conventional karyotype. Methods Retrospective study, carried out from January 2012 to February 2014, analyzing the CGH-array results of 39 patients. Results Twenty-six (66.7%) patients had normal results and 13 (33.3%) showed abnormal results - in that, 6 (15.4%) had pathogenic variants, 6 (15.4%) variants designated as uncertain and 1 (2.5%) non-pathogenic variants. Conclusion The characterization of the genetic profile by CGH-array in patients with intellectual disability and dysmorphic features enabled making etiologic diagnosis, followed by genetic counseling for families and specific treatment. PMID:27074231

De novo PHIP-predicted deleterious variants are associated with developmental delay, intellectual disability, obesity, and dysmorphic features.

PubMed

Webster, Emily; Cho, Megan T; Alexander, Nora; Desai, Sonal; Naidu, Sakkubai; Bekheirnia, Mir Reza; Lewis, Andrea; Retterer, Kyle; Juusola, Jane; Chung, Wendy K

2016-11-01

Using whole-exome sequencing, we have identified novel de novo heterozygous pleckstrin homology domain-interacting protein ( PHIP ) variants that are predicted to be deleterious, including a frameshift deletion, in two unrelated patients with common clinical features of developmental delay, intellectual disability, anxiety, hypotonia, poor balance, obesity, and dysmorphic features. A nonsense mutation in PHIP has previously been associated with similar clinical features. Patients with microdeletions of 6q14.1, including PHIP , have a similar phenotype of developmental delay, intellectual disability, hypotonia, and obesity, suggesting that the phenotype of our patients is a result of loss-of-function mutations. PHIP produces multiple protein products, such as PHIP1 (also known as DCAF14), PHIP, and NDRP. PHIP1 is one of the multiple substrate receptors of the proteolytic CUL4-DDB1 ubiquitin ligase complex. CUL4B deficiency has been associated with intellectual disability, central obesity, muscle wasting, and dysmorphic features. The overlapping phenotype associated with CUL4B deficiency suggests that PHIP mutations cause disease through disruption of the ubiquitin ligase pathway.

Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing.

PubMed

Hong, Nan; Chen, Yan-hua; Xie, Chen; Xu, Bai-sheng; Huang, Hui; Li, Xin; Yang, Yue-qing; Huang, Ying-ping; Deng, Jian-lian; Qi, Ming; Gu, Yang-shun

2014-08-01

Nance-Horan syndrome (NHS) is a rare X-linked disorder characterized by congenital nuclear cataracts, dental anomalies, and craniofacial dysmorphisms. Mental retardation was present in about 30% of the reported cases. The purpose of this study was to investigate the genetic and clinical features of NHS in a Chinese family. Whole exome sequencing analysis was performed on DNA from an affected male to scan for candidate mutations on the X-chromosome. Sanger sequencing was used to verify these candidate mutations in the whole family. Clinical and ophthalmological examinations were performed on all members of the family. A combination of exome sequencing and Sanger sequencing revealed a nonsense mutation c.322G>T (E108X) in exon 1 of NHS gene, co-segregating with the disease in the family. The nonsense mutation led to the conversion of glutamic acid to a stop codon (E108X), resulting in truncation of the NHS protein. Multiple sequence alignments showed that codon 108, where the mutation (c.322G>T) occurred, was located within a phylogenetically conserved region. The clinical features in all affected males and female carriers are described in detail. We report a nonsense mutation c.322G>T (E108X) in a Chinese family with NHS. Our findings broaden the spectrum of NHS mutations and provide molecular insight into future NHS clinical genetic diagnosis.

[A case of partial 1p36.1 deletion and partial trisomy 6p diagnosed by karyotype].

PubMed

Fernández Pineda, Monica; Ramírez-Cheyne, Julián; Isaza, Carolina; Saldarriaga, Wilmar

The deletion of chromosomal region 1p36 is one of the most common sub-telomeric microdeletion syndromes and has distinctive dysmorphic features. On the other hand, partial trisomy of the short arm of chromosome 6 is a rare chromosomal abnormality with a variable phenotype. To report a case with both chromosome abnormalities, and to highlight the importance of the karyotype as a diagnostic tool in dysmorphology. The case of is presented of a two month-old infant with several craniofacial anomalies, neck haemangioma, sacral pit, rhizomelic shortening, small hands and feet, left unilateral cryptorchidism, and hypotonia. The infant also suffered intrauterine growth restriction and is the product of the eighth pregnancy of a 28 years old woman. Due to the unspecific findings in phenotype, a karyotype was requested, which showed a partial deletion of 1p36.1 and a partial trisomy of chromosome 6. The development of new techniques in molecular biology has improved diagnostic possibilities in medical genetics. However, the traditional karyotype remains as an important diagnostic tool in patients with multiple congenital anomalies. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Dysmorphic Facial Features and Other Clinical Characteristics in Two Patients with PEX1 Gene Mutations

PubMed Central

Gunduz, Mehmet

2016-01-01

Peroxisomal disorders are a group of genetically heterogeneous metabolic diseases related to dysfunction of peroxisomes. Dysmorphic features, neurological abnormalities, and hepatic dysfunction can be presenting signs of peroxisomal disorders. Here we presented dysmorphic facial features and other clinical characteristics in two patients with PEX1 gene mutation. Follow-up periods were 3.5 years and 1 year in the patients. Case I was one-year-old girl that presented with neurodevelopmental delay, hepatomegaly, bilateral hearing loss, and visual problems. Ophthalmologic examination suggested septooptic dysplasia. Cranial magnetic resonance imaging (MRI) showed nonspecific gliosis at subcortical and periventricular deep white matter. Case II was 2.5-year-old girl referred for investigation of global developmental delay and elevated liver enzymes. Ophthalmologic examination findings were consistent with bilateral nystagmus and retinitis pigmentosa. Cranial MRI was normal. Dysmorphic facial features including broad nasal root, low set ears, downward slanting eyes, downward slanting eyebrows, and epichantal folds were common findings in two patients. Molecular genetic analysis indicated homozygous novel IVS1-2A>G mutation in Case I and homozygous p.G843D (c.2528G>A) mutation in Case II in the PEX1 gene. Clinical findings and developmental prognosis vary in PEX1 gene mutation. Kabuki-like phenotype associated with liver pathology may indicate Zellweger spectrum disorders (ZSD). PMID:27882258

pitx2 Deficiency Results in Abnormal Ocular and Craniofacial Development in Zebrafish

PubMed Central

Liu, Yi; Semina, Elena V.

2012-01-01

Human PITX2 mutations are associated with Axenfeld-Rieger syndrome, an autosomal-dominant developmental disorder that involves ocular anterior segment defects, dental hypoplasia, craniofacial dysmorphism and umbilical abnormalities. Characterization of the PITX2 pathway and identification of the mechanisms underlying the anomalies associated with PITX2 deficiency is important for better understanding of normal development and disease; studies of pitx2 function in animal models can facilitate these analyses. A knockdown of pitx2 in zebrafish was generated using a morpholino that targeted all known alternative transcripts of the pitx2 gene; morphant embryos generated with the pitx2ex4/5 splicing-blocking oligomer produced abnormal transcripts predicted to encode truncated pitx2 proteins lacking the third (recognition) helix of the DNA-binding homeodomain. The morphological phenotype of pitx2ex4/5 morphants included small head and eyes, jaw abnormalities and pericardial edema; lethality was observed at ∼6–8-dpf. Cartilage staining revealed a reduction in size and an abnormal shape/position of the elements of the mandibular and hyoid pharyngeal arches; the ceratobranchial arches were also decreased in size. Histological and marker analyses of the misshapen eyes of the pitx2ex4/5 morphants identified anterior segment dysgenesis and disordered hyaloid vasculature. In summary, we demonstrate that pitx2 is essential for proper eye and craniofacial development in zebrafish and, therefore, that PITX2/pitx2 function is conserved in vertebrates. PMID:22303467

Melorheostosis involving the craniofacial skeleton.

PubMed

Ethunandan, Madanagopalan; Khosla, Nalin; Tilley, Elizabeth; Webb, Andrew

2004-11-01

Melorheostosis is a rare bone disorder, usually affecting the long bones and adjacent soft tissue. It was originally described by Leri and Joanny in 1922, after its classic x-ray features of flowing hyperostosis resembling dripping candle wax. There have been fewer than 10 reported cases of craniofacial involvement, and in most instances these have also involved the appendicular skeleton. The authors report a case of melorheostosis with isolated craniofacial involvement, describe the clinical course and radiologic and histologic features, and review the pertinent literature.

Prevalence of Body Dysmorphic Disorder and its Association With Body Features in Female Medical Students.

PubMed

Shaffi Ahamed, Shaik; Enani, Jawaher; Alfaraidi, Lama; Sannari, Lujain; Algain, Rihaf; Alsawah, Zainah; Al Hazmi, Ali

2016-06-01

Body dysmorphic disorder (BDD) is a distressing psychiatric disorder. So far there have not been any studies on BDD in Saudi Arabia. The aim of this study was to determine the prevalence of body dysmorphic disorder in female medical students and to investigate whether there is an association between BDD and body features of concern, social anxiety and symptoms of BDD. A cross sectional study was carried out on female medical students of the college of medicine, King Saud University, Riyadh, Saudi Arabia during January to April, 2015. Data were collected using the body image disturbance questionnaire, Body dysmorphic disorder symptomatology and social interaction anxiety scale. Descriptive statistics, bivariate and multivariate analysis were used to analyze the results. Out of 365 students who filled out the questionnaire, 4.4% (95% confidence intervals (CI): 2.54% to 7.04%) were positive for BDD with skin (75%) and fat (68.8%) as the most frequent body features of concern. Ten features (skin, fat, chest, hips, buttocks, arms, legs, lips, fingers, and shoulders) out of twenty-six were significantly associated with BDD. Arms and chest were independently associated with BDD. The odds of presence of body concern related to "arms" was 4.3 (95% C.I: 1.5, 12.1) times more in BDD subjects than non-BDD subjects, while concern about "chest" was 3.8 (1.3, 10.9) times more when compared to non-BDD subjects. No statistically significant association was observed between BDD and social anxiety (P = 0.13). This was the first study conducted in Kingdom of Saudi Arabia (KSA) on female medical students, which quantified the prevalence of BDD and identified the body features associated with it. Body dysmorphic disorder is prevalent in female medical students but it is relatively rare and an unnoticed disorder.

Prevalence of Body Dysmorphic Disorder and its Association With Body Features in Female Medical Students

PubMed Central

Shaffi Ahamed, Shaik; Enani, Jawaher; Alfaraidi, Lama; Sannari, Lujain; Algain, Rihaf; Alsawah, Zainah; Al Hazmi, Ali

2016-01-01

Background Body dysmorphic disorder (BDD) is a distressing psychiatric disorder. So far there have not been any studies on BDD in Saudi Arabia. Objectives The aim of this study was to determine the prevalence of body dysmorphic disorder in female medical students and to investigate whether there is an association between BDD and body features of concern, social anxiety and symptoms of BDD. Materials and Methods A cross sectional study was carried out on female medical students of the college of medicine, King Saud University, Riyadh, Saudi Arabia during January to April, 2015. Data were collected using the body image disturbance questionnaire, Body dysmorphic disorder symptomatology and social interaction anxiety scale. Descriptive statistics, bivariate and multivariate analysis were used to analyze the results. Results Out of 365 students who filled out the questionnaire, 4.4% (95% confidence intervals (CI): 2.54% to 7.04%) were positive for BDD with skin (75%) and fat (68.8%) as the most frequent body features of concern. Ten features (skin, fat, chest, hips, buttocks, arms, legs, lips, fingers, and shoulders) out of twenty-six were significantly associated with BDD. Arms and chest were independently associated with BDD. The odds of presence of body concern related to “arms” was 4.3 (95% C.I: 1.5, 12.1) times more in BDD subjects than non-BDD subjects, while concern about “chest” was 3.8 (1.3, 10.9) times more when compared to non-BDD subjects. No statistically significant association was observed between BDD and social anxiety (P = 0.13). Conclusions This was the first study conducted in Kingdom of Saudi Arabia (KSA) on female medical students, which quantified the prevalence of BDD and identified the body features associated with it. Body dysmorphic disorder is prevalent in female medical students but it is relatively rare and an unnoticed disorder. PMID:27803720

Influence of prenatal EGCG treatment and Dyrk1a dosage reduction on craniofacial features associated with Down syndrome.

PubMed

McElyea, Samantha D; Starbuck, John M; Tumbleson-Brink, Danika M; Harrington, Emily; Blazek, Joshua D; Ghoneima, Ahmed; Kula, Katherine; Roper, Randall J

2016-11-15

Trisomy 21 (Ts21) affects craniofacial precursors in individuals with Down syndrome (DS). The resultant craniofacial features in all individuals with Ts21 may significantly affect breathing, eating and speaking. Using mouse models of DS, we have traced the origin of DS-associated craniofacial abnormalities to deficiencies in neural crest cell (NCC) craniofacial precursors early in development. Hypothetically, three copies of Dyrk1a (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), a trisomic gene found in most humans with DS and mouse models of DS, may significantly affect craniofacial structure. We hypothesized that we could improve DS-related craniofacial abnormalities in mouse models using a Dyrk1a inhibitor or by normalizing Dyrk1a gene dosage. In vitro and in vivo treatment with Epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, modulated trisomic NCC deficiencies at embryonic time points. Furthermore, prenatal EGCG treatment normalized some craniofacial phenotypes, including cranial vault in adult Ts65Dn mice. Normalization of Dyrk1a copy number in an otherwise trisomic Ts65Dn mice normalized many dimensions of the cranial vault, but did not correct all craniofacial anatomy. These data underscore the complexity of the gene–phenotype relationship in trisomy and suggest that changes in Dyrk1a expression play an important role in morphogenesis and growth of the cranial vault. These results suggest that a temporally specific prenatal therapy may be an effective way to ameliorate some craniofacial anatomical changes associated with DS.

Case Conceptualization and Treatment of Comorbid Body Dysmorphic Disorder and Bulimia Nervosa

ERIC Educational Resources Information Center

Didie, Elizabeth R.; Reinecke, Mark A.; Phillips, Katharine A.

2010-01-01

Body dysmorphic disorder (BDD) and eating disorders often co-occur and share some clinical features. In addition, the co-occurrence of BDD and an eating disorder may be associated with greater impairment in functioning. Furthermore, clinical impressions suggest that this comorbidity may be more treatment resistant than either disorder alone. The…

Accurate Detection of Dysmorphic Nuclei Using Dynamic Programming and Supervised Classification.

PubMed

Verschuuren, Marlies; De Vylder, Jonas; Catrysse, Hannes; Robijns, Joke; Philips, Wilfried; De Vos, Winnok H

2017-01-01

A vast array of pathologies is typified by the presence of nuclei with an abnormal morphology. Dysmorphic nuclear phenotypes feature dramatic size changes or foldings, but also entail much subtler deviations such as nuclear protrusions called blebs. Due to their unpredictable size, shape and intensity, dysmorphic nuclei are often not accurately detected in standard image analysis routines. To enable accurate detection of dysmorphic nuclei in confocal and widefield fluorescence microscopy images, we have developed an automated segmentation algorithm, called Blebbed Nuclei Detector (BleND), which relies on two-pass thresholding for initial nuclear contour detection, and an optimal path finding algorithm, based on dynamic programming, for refining these contours. Using a robust error metric, we show that our method matches manual segmentation in terms of precision and outperforms state-of-the-art nuclear segmentation methods. Its high performance allowed for building and integrating a robust classifier that recognizes dysmorphic nuclei with an accuracy above 95%. The combined segmentation-classification routine is bound to facilitate nucleus-based diagnostics and enable real-time recognition of dysmorphic nuclei in intelligent microscopy workflows.

Accurate Detection of Dysmorphic Nuclei Using Dynamic Programming and Supervised Classification

PubMed Central

Verschuuren, Marlies; De Vylder, Jonas; Catrysse, Hannes; Robijns, Joke; Philips, Wilfried

2017-01-01

A vast array of pathologies is typified by the presence of nuclei with an abnormal morphology. Dysmorphic nuclear phenotypes feature dramatic size changes or foldings, but also entail much subtler deviations such as nuclear protrusions called blebs. Due to their unpredictable size, shape and intensity, dysmorphic nuclei are often not accurately detected in standard image analysis routines. To enable accurate detection of dysmorphic nuclei in confocal and widefield fluorescence microscopy images, we have developed an automated segmentation algorithm, called Blebbed Nuclei Detector (BleND), which relies on two-pass thresholding for initial nuclear contour detection, and an optimal path finding algorithm, based on dynamic programming, for refining these contours. Using a robust error metric, we show that our method matches manual segmentation in terms of precision and outperforms state-of-the-art nuclear segmentation methods. Its high performance allowed for building and integrating a robust classifier that recognizes dysmorphic nuclei with an accuracy above 95%. The combined segmentation-classification routine is bound to facilitate nucleus-based diagnostics and enable real-time recognition of dysmorphic nuclei in intelligent microscopy workflows. PMID:28125723

Novel de novo pathogenic variant in the NR2F2 gene in a boy with congenital heart defect and dysmorphic features.

PubMed

Upadia, Jariya; Gonzales, Patrick R; Robin, Nathaniel H

2018-04-16

The NR2F2 gene plays an important role in angiogenesis and heart development. Moreover, this gene is involved in organogenesis in many other organs in mouse models. Variants in this gene have been reported in a number of patients with nonsyndromic atrioventricular septal defect, and in one patient with congenital heart defect and dysmorphic features. Here we report an 11-month-old Caucasian male with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect. He was later found to have a pathogenic mutation in the NR2F2 gene by whole exome sequencing. This is the second instance in which an NR2F2 mutation has been identified in a child with a congenital heart defect and other anomalies. This case suggests that some variants in NR2F2 may cause syndromic forms of congenital heart defect. © 2018 Wiley Periodicals, Inc.

Age of heart disease presentation and dysmorphic nuclei in patients with LMNA mutations

PubMed Central

Core, Jason Q.; Mehrabi, Mehrsa; Robinson, Zachery R.; Ochs, Alexander R.; McCarthy, Linda A.; Zaragoza, Michael V.

2017-01-01

Nuclear shape defects are a distinguishing characteristic in laminopathies, cancers, and other pathologies. Correlating these defects to the symptoms, mechanisms, and progression of disease requires unbiased, quantitative, and high-throughput means of quantifying nuclear morphology. To accomplish this, we developed a method of automatically segmenting fluorescently stained nuclei in 2D microscopy images and then classifying them as normal or dysmorphic based on three geometric features of the nucleus using a package of Matlab codes. As a test case, cultured skin-fibroblast nuclei of individuals possessing LMNA splice-site mutation (c.357-2A>G), LMNA nonsense mutation (c.736 C>T, pQ246X) in exon 4, LMNA missense mutation (c.1003C>T, pR335W) in exon 6, Hutchinson-Gilford Progeria Syndrome, and no LMNA mutations were analyzed. For each cell type, the percentage of dysmorphic nuclei, and other morphological features such as average nuclear area and average eccentricity were obtained. Compared to blind observers, our procedure implemented in Matlab codes possessed similar accuracy to manual counting of dysmorphic nuclei while being significantly more consistent. The automatic quantification of nuclear defects revealed a correlation between in vitro results and age of patients for initial symptom onset. Our results demonstrate the method’s utility in experimental studies of diseases affecting nuclear shape through automated, unbiased, and accurate identification of dysmorphic nuclei. PMID:29149195

Age of heart disease presentation and dysmorphic nuclei in patients with LMNA mutations.

PubMed

Core, Jason Q; Mehrabi, Mehrsa; Robinson, Zachery R; Ochs, Alexander R; McCarthy, Linda A; Zaragoza, Michael V; Grosberg, Anna

2017-01-01

Nuclear shape defects are a distinguishing characteristic in laminopathies, cancers, and other pathologies. Correlating these defects to the symptoms, mechanisms, and progression of disease requires unbiased, quantitative, and high-throughput means of quantifying nuclear morphology. To accomplish this, we developed a method of automatically segmenting fluorescently stained nuclei in 2D microscopy images and then classifying them as normal or dysmorphic based on three geometric features of the nucleus using a package of Matlab codes. As a test case, cultured skin-fibroblast nuclei of individuals possessing LMNA splice-site mutation (c.357-2A>G), LMNA nonsense mutation (c.736 C>T, pQ246X) in exon 4, LMNA missense mutation (c.1003C>T, pR335W) in exon 6, Hutchinson-Gilford Progeria Syndrome, and no LMNA mutations were analyzed. For each cell type, the percentage of dysmorphic nuclei, and other morphological features such as average nuclear area and average eccentricity were obtained. Compared to blind observers, our procedure implemented in Matlab codes possessed similar accuracy to manual counting of dysmorphic nuclei while being significantly more consistent. The automatic quantification of nuclear defects revealed a correlation between in vitro results and age of patients for initial symptom onset. Our results demonstrate the method's utility in experimental studies of diseases affecting nuclear shape through automated, unbiased, and accurate identification of dysmorphic nuclei.

Severe Craniofacial Involvement due to Amniotic Band Sequence.

PubMed

Becerra-Solano, Luis Eduardo; Castañeda-Cisneros, Gema; Corona-Rivera, Jorge Roman; Díaz-Rodríguez, Manuel; Figuera, Luis Eduardo; López-Muñoz, Eunice; Nastasi-Catanese, José Antonio; Toscano-Flores, José Jesús; Ramírez-Dueñas, María de Lourdes; García-Ortíz, José Elias

2018-02-01

Disruptive amniotic band sequence (DABS) is a sporadic, non-familial disorder with unclear etiology. Diagnosis is based on clinical features because there is currently no reliable laboratory diagnostic tests. We describe six cases of DABS with severe craniofacial deformations, three with and three without classical constrictive limb deformation. The craniofacial deformities were delimited by peripheral sharply demarcated scarring. When a sharply demarcated linear disruptive craniofacial lesion is observed, DABS should be considered despite the absence of constrictive limb scarring.

Demographic Characteristics, Phenomenology, Comorbidity, and Family History in 200 Individuals With Body Dysmorphic Disorder

PubMed Central

Phillips, Katharine A.; Menard, William; Fay, Christina; Weisberg, Risa

2005-01-01

The authors examined characteristics of body dysmorphic disorder in the largest sample for which a wide range of clinical features has been reported. The authors also compared psychiatrically treated and untreated subjects. Body dysmorphic disorder usually began during adolescence, involved numerous body areas and behaviors, and was characterized by poor insight, high comorbidity rates, and high rates of functional impairment, suicidal ideation, and suicide attempts. There were far more similarities than differences between the currently treated and untreated subjects, although the treated subjects displayed better insight and had more comorbidity. PMID:16000674

Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features.

PubMed

Steinfeld, Hallie; Cho, Megan T; Retterer, Kyle; Person, Rick; Schaefer, G Bradley; Danylchuk, Noelle; Malik, Saleem; Wechsler, Stephanie Burns; Wheeler, Patricia G; van Gassen, Koen L I; Terhal, P A; Verhoeven, Virginie J M; van Slegtenhorst, Marjon A; Monaghan, Kristin G; Henderson, Lindsay B; Chung, Wendy K

2016-07-01

Human immunodeficiency virus type I enhancer binding protein 2 (HIVEP2) has been previously associated with intellectual disability and developmental delay in three patients. Here, we describe six patients with developmental delay, intellectual disability, and dysmorphic features with de novo likely gene-damaging variants in HIVEP2 identified by whole-exome sequencing (WES). HIVEP2 encodes a large transcription factor that regulates various neurodevelopmental pathways. Our findings provide further evidence that pathogenic variants in HIVEP2 lead to intellectual disabilities and developmental delay.

Craniofacial and Dental Development in Costello Syndrome

PubMed Central

Goodwin, Alice F.; Oberoi, Snehlata; Landan, Maya; Charles, Cyril; Massie, Jessica C.; Fairley, Cecilia; Rauen, Katherine A.; Klein, Ophir D.

2014-01-01

Costello syndrome (CS) is a RASopathy characterized by a wide range of cardiac, musculoskeletal, dermatological, and developmental abnormalities. The RASopathies are defined as a group of syndromes caused by activated Ras/mitogen-activated protein kinase (MAPK) signaling. Specifically, CS is caused by activating mutations in HRAS. Although receptor tyrosine kinase (RTK) signaling, which is upstream of Ras/MAPK, is known to play a critical role in craniofacial and dental development, the craniofacial and dental features of CS have not been systematically defined in a large group of individuals. In order to address this gap in our understanding and fully characterize the CS phenotype, we evaluated the craniofacial and dental phenotype in a large cohort (n=41) of CS individuals. We confirmed that the craniofacial features common in CS include macrocephaly, bitemporal narrowing, convex facial profile, full cheeks, and large mouth. Additionally, CS patients have a characteristic dental phenotype that includes malocclusion with anterior open bite and posterior crossbite, enamel hypo-mineralization, delayed tooth development and eruption, gingival hyperplasia, thickening of the alveolar ridge, and high palate. Comparison of the craniofacial and dental phenotype in CS with other RASopathies, such as cardio-facio-cutaneous syndrome (CFC), provides insight into the complexities of Ras/MAPK signaling in human craniofacial and dental development. PMID:24668879

Craniofacial and dental development in Costello syndrome.

PubMed

Goodwin, Alice F; Oberoi, Snehlata; Landan, Maya; Charles, Cyril; Massie, Jessica C; Fairley, Cecilia; Rauen, Katherine A; Klein, Ophir D

2014-06-01

Costello syndrome (CS) is a RASopathy characterized by a wide range of cardiac, musculoskeletal, dermatological, and developmental abnormalities. The RASopathies are defined as a group of syndromes caused by activated Ras/mitogen-activated protein kinase (MAPK) signaling. Specifically, CS is caused by activating mutations in HRAS. Although receptor tyrosine kinase (RTK) signaling, which is upstream of Ras/MAPK, is known to play a critical role in craniofacial and dental development, the craniofacial and dental features of CS have not been systematically defined in a large group of individuals. In order to address this gap in our understanding and fully characterize the CS phenotype, we evaluated the craniofacial and dental phenotype in a large cohort (n = 41) of CS individuals. We confirmed that the craniofacial features common in CS include macrocephaly, bitemporal narrowing, convex facial profile, full cheeks, and large mouth. Additionally, CS patients have a characteristic dental phenotype that includes malocclusion with anterior open bite and posterior crossbite, enamel hypo-mineralization, delayed tooth development and eruption, gingival hyperplasia, thickening of the alveolar ridge, and high palate. Comparison of the craniofacial and dental phenotype in CS with other RASopathies, such as cardio-facio-cutaneous syndrome (CFC), provides insight into the complexities of Ras/MAPK signaling in human craniofacial and dental development. © 2014 Wiley Periodicals, Inc.

Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion

PubMed Central

Grassi, Marcília S.; Jacob, Cristina M. A.; Kulikowski, Leslie D.; Pastorino, Antonio C.; Dutra, Roberta L.; Miura, Nana; Jatene, Marcelo B.; Pegler, Stephanie P.; Kim, Chong A.; Carneiro-Sampaio, Magda

2014-01-01

Background To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD). Objective To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS. Methods The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed. Results CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients. Conclusion Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients. PMID:25317860

Comparison of facial features of DiGeorge syndrome (DGS) due to deletion 10p13-10pter with DGS due to 22q11 deletion

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

Goodship, J.; Lynch, S.; Brown, J.

1994-09-01

DiGeorge syndrome (DGS) is a congenital anomaly consisting of cardiac defects, aplasia or hypoplasia of the thymus and parathroid glands, and dysmorphic facial features. The majority of DGS cases have a submicroscopic deletion within chromosome 22q11. However there have been a number of reports of DGS in association with other chromosomal abnormalities including four cases with chromosome 10p deletions. We describe a further 10p deletion case and suggest that the facial features in children with DGS due to deletions of 10p are different from those associated with chromosome 22 deletions. The propositus was born at 39 weeks gestation to unrelatedmore » caucasian parents, birth weight 2580g (10th centile) and was noted to be dysmorphic and cyanosed shortly after birth. The main dysmorphic facial features were a broad nasal bridge with very short palpebral fissures. Echocardiography revealed a large subsortic VSD and overriding aorta. She had a low ionised calcium and low parathroid hormone level. T cell subsets and PHA response were normal. Abdominal ultrasound showed duplex kidneys and on further investigation she was found to have reflux and raised plasma creatinine. She had an anteriorly placed anus. Her karyotype was 46,XX,-10,+der(10)t(3;10)(p23;p13)mat. The dysmorphic facial features in this baby are strikingly similar to those noted by Bridgeman and Butler in child with DGS as the result of a 10p deletion and distinct from the face seen in children with DiGeorge syndrome resulting from interstitial chromosome 22 deletions.« less

Cosmetic Professionals' Awareness of Body Dysmorphic Disorder.

PubMed

Bouman, Theo K; Mulkens, Sandra; van der Lei, Berend

2017-02-01

Preoccupation with a perceived appearance flaw is the main feature of body dysmorphic disorder. The majority of these patients seek and often receive some sort of cosmetic procedure, although this condition is considered to be a contraindication. This study evaluates cosmetic professionals' recognition of body dysmorphic disorder and the way they act on this. Members of Dutch professional associations for aesthetic plastic surgery, dermatology, and cosmetic medicine received an online survey by means of their association's digital mailing lists; the survey was completed by 173 respondents. Most participants indicated being more or less familiar with the diagnostic criteria and clinical picture of body dysmorphic disorder. Approximately two-thirds of the participants reported that they had encountered between one and five of these patients in their practice over the past year, a percentage that is significantly lower than the estimated prevalence of body dysmorphic disorder. The majority of professionals sometimes or often address body image problems during consultation, most of them collaborate with psychologists or psychiatrists when encountering a patient with body dysmorphic disorder, and approximately 70 percent had refused to perform a procedure in such a patient. Our results converge with those of previous studies, showing that most cosmetic professionals have some degree of awareness of body dysmorphic disorder, although the number they report encountering in clinical practice departs from prevalence figures. When a patient is identified as having body dysmorphic disorder, the professionals use this knowledge to guide their decision to perform a cosmetic procedure.

Computed tomography assessment of peripubertal craniofacial morphology in a sheep model of binge alcohol drinking in the first trimester

PubMed Central

Birch, Sharla M.; Lenox, Mark W.; Kornegay, Joe N.; Shen, Li; Ai, Huisi; Ren, Xiaowei; Goodlett, Charles R.; Cudd, Tim A.; Washburn, Shannon E.

2015-01-01

Identification of facial dysmorphology is essential for the diagnosis of fetal alcohol syndrome (FAS); however, most children with fetal alcohol spectrum disorders (FASD) do not meet the dysmorphology criterion. Additional objective indicators are needed to help identify the broader spectrum of children affected by prenatal alcohol exposure. Computed tomography (CT) was used in a sheep model of prenatal binge alcohol exposure to test the hypothesis that quantitative measures of craniofacial bone volumes and linear distances could identify alcohol-exposed lambs. Pregnant sheep were randomly assigned to four groups: heavy binge alcohol, 2.5 g/kg/day (HBA); binge alcohol, 1.75 g/kg/day (BA); saline control (SC); and normal control (NC). Intravenous alcohol (BA; HBA) or saline (SC) infusions were given three consecutive days per week from gestation day 4–41, and a CT scan was performed on postnatal day 182. The volumes of eight skull bones, cranial circumference, and 19 linear measures of the face and skull were compared among treatment groups. Lambs from both alcohol groups showed significant reduction in seven of the eight skull bones and total skull bone volume, as well as cranial circumference. Alcohol exposure also decreased four of the 19 craniofacial measures. Discriminant analysis showed that alcohol-exposed and control lambs could be classified with high accuracy based on total skull bone volume, frontal, parietal, or mandibular bone volumes, cranial circumference, or interorbital distance. Total skull volume was significantly more sensitive than cranial circumference in identifying the alcohol-exposed lambs when alcohol-exposed lambs were classified using the typical FAS diagnostic cutoff of ≤10th percentile. This first demonstration of the usefulness of CT-derived craniofacial measures in a sheep model of FASD following binge-like alcohol exposure during the first trimester suggests that volumetric measurement of cranial bones may be a novel biomarker for binge alcohol exposure during the first trimester to help identify non-dysmorphic children with FASD. PMID:26496796

Classifying dysmorphic syndromes by using artificial neural network based hierarchical decision tree.

PubMed

Özdemir, Merve Erkınay; Telatar, Ziya; Eroğul, Osman; Tunca, Yusuf

2018-05-01

Dysmorphic syndromes have different facial malformations. These malformations are significant to an early diagnosis of dysmorphic syndromes and contain distinctive information for face recognition. In this study we define the certain features of each syndrome by considering facial malformations and classify Fragile X, Hurler, Prader Willi, Down, Wolf Hirschhorn syndromes and healthy groups automatically. The reference points are marked on the face images and ratios between the points' distances are taken into consideration as features. We suggest a neural network based hierarchical decision tree structure in order to classify the syndrome types. We also implement k-nearest neighbor (k-NN) and artificial neural network (ANN) classifiers to compare classification accuracy with our hierarchical decision tree. The classification accuracy is 50, 73 and 86.7% with k-NN, ANN and hierarchical decision tree methods, respectively. Then, the same images are shown to a clinical expert who achieve a recognition rate of 46.7%. We develop an efficient system to recognize different syndrome types automatically in a simple, non-invasive imaging data, which is independent from the patient's age, sex and race at high accuracy. The promising results indicate that our method can be used for pre-diagnosis of the dysmorphic syndromes by clinical experts.

Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing*

PubMed Central

Hong, Nan; Chen, Yan-hua; Xie, Chen; Xu, Bai-sheng; Huang, Hui; Li, Xin; Yang, Yue-qing; Huang, Ying-ping; Deng, Jian-lian; Qi, Ming; Gu, Yang-shun

2014-01-01

Objective: Nance-Horan syndrome (NHS) is a rare X-linked disorder characterized by congenital nuclear cataracts, dental anomalies, and craniofacial dysmorphisms. Mental retardation was present in about 30% of the reported cases. The purpose of this study was to investigate the genetic and clinical features of NHS in a Chinese family. Methods: Whole exome sequencing analysis was performed on DNA from an affected male to scan for candidate mutations on the X-chromosome. Sanger sequencing was used to verify these candidate mutations in the whole family. Clinical and ophthalmological examinations were performed on all members of the family. Results: A combination of exome sequencing and Sanger sequencing revealed a nonsense mutation c.322G>T (E108X) in exon 1 of NHS gene, co-segregating with the disease in the family. The nonsense mutation led to the conversion of glutamic acid to a stop codon (E108X), resulting in truncation of the NHS protein. Multiple sequence alignments showed that codon 108, where the mutation (c.322G>T) occurred, was located within a phylogenetically conserved region. The clinical features in all affected males and female carriers are described in detail. Conclusions: We report a nonsense mutation c.322G>T (E108X) in a Chinese family with NHS. Our findings broaden the spectrum of NHS mutations and provide molecular insight into future NHS clinical genetic diagnosis. PMID:25091991

Craniofacial reconstruction evaluation by geodesic network.

PubMed

Zhao, Junli; Liu, Cuiting; Wu, Zhongke; Duan, Fuqing; Wang, Kang; Jia, Taorui; Liu, Quansheng

2014-01-01

Craniofacial reconstruction is to estimate an individual's face model from its skull. It has a widespread application in forensic medicine, archeology, medical cosmetic surgery, and so forth. However, little attention is paid to the evaluation of craniofacial reconstruction. This paper proposes an objective method to evaluate globally and locally the reconstructed craniofacial faces based on the geodesic network. Firstly, the geodesic networks of the reconstructed craniofacial face and the original face are built, respectively, by geodesics and isogeodesics, whose intersections are network vertices. Then, the absolute value of the correlation coefficient of the features of all corresponding geodesic network vertices between two models is taken as the holistic similarity, where the weighted average of the shape index values in a neighborhood is defined as the feature of each network vertex. Moreover, the geodesic network vertices of each model are divided into six subareas, that is, forehead, eyes, nose, mouth, cheeks, and chin, and the local similarity is measured for each subarea. Experiments using 100 pairs of reconstructed craniofacial faces and their corresponding original faces show that the evaluation by our method is roughly consistent with the subjective evaluation derived from thirty-five persons in five groups.

De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features.

PubMed

Tanaka, Akemi J; Cho, Megan T; Retterer, Kyle; Jones, Julie R; Nowak, Catherine; Douglas, Jessica; Jiang, Yong-Hui; McConkie-Rosell, Allyn; Schaefer, G Bradley; Kaylor, Julie; Rahman, Omar A; Telegrafi, Aida; Friedman, Bethany; Douglas, Ganka; Monaghan, Kristin G; Chung, Wendy K

2016-01-01

We identified five unrelated individuals with significant global developmental delay and intellectual disability (ID), dysmorphic facial features and frequent microcephaly, and de novo predicted loss-of-function variants in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). Our findings are consistent with recently reported de novo mutations in CHAMP1 in five other individuals with similar features. CHAMP1 is a zinc finger protein involved in kinetochore-microtubule attachment and is required for regulating the proper alignment of chromosomes during metaphase in mitosis. Mutations in CHAMP1 may affect cell division and hence brain development and function, resulting in developmental delay and ID.

4p- syndrome and 9p tetrasomy mosaicism with cleft lip and palate.

PubMed

Kobayashi, J; Kimijima, Y; Yamada, S; Amagasa, T; Saito-Ohara, F

2000-06-01

Chromosome 4p- syndrome is a multiple malformation syndrome associated with partial deletion of the short arm of chromosome 4 (4p-). It is characterized by dysmorphic features and retarded development. Cleft lip and/or palate are the major clinical manifestations. Cases of tetrasomy 9p are extremely rare; the principal clinical manifestations of this condition are characteristic craniofacial abnormalities, generalized hypotonia and severe mental retardation. We present the first case of a female infant with 4p deletion and tetrasomy 9p mosaicism, exhibiting a left-sided cleft lip, alveolus and soft palate. Karyotype analysis of lymphocytes cultured from the patient revealed that she was mosaic: 86% of the cells were 46, XX, add (4) (p15.32) and 14% were 47, XX, add (4) (p15.32), +idic (9)(q12). The G-banding pattern appeared consistent with either translocation or partial proximal deletion of 4p. In order to make a definitive cytogenetic diagnosis of isodicentric chromosome 9, fluorescence in situ hybridization (FISH) was applied. At 8 months, when the patient weighed 4.3 kg, her cleft lip was repaired. Before and after surgery there were no seizures, and the postoperative course was uneventful. Copyright 2000 European Association for Cranio-Maxillofacial Surgery.

Mild Zellweger syndrome due to a novel PEX6 mutation: correlation between clinical phenotype and in silico prediction of variant pathogenicity.

PubMed

Rydzanicz, Małgorzata; Stradomska, Teresa Joanna; Jurkiewicz, Elżbieta; Jamroz, Ewa; Gasperowicz, Piotr; Kostrzewa, Grażyna; Płoski, Rafał; Tylki-Szymańska, Anna

2017-11-01

Zellweger syndrome (ZS) is a consequence of a peroxisome biogenesis disorder (PBD) caused by the presence of a pathogenic mutation in one of the 13 genes from the PEX family. ZS is a severe multisystem condition characterized by neonatal appearance of symptoms and a shorter life. Here, we report a case of ZS with a mild phenotype, due to a novel PEX6 gene mutation. The patient presented subtle craniofacial dysmorphic features and slightly slower psychomotor development. At the age of 2 years, he was diagnosed with adrenal insufficiency, hypoacusis, and general deterioration. Magnetic resonance imaging showed a symmetrical hyperintense signal in the frontal and parietal white matter. Biochemical tests showed elevated liver transaminases, elevated serum very long chain fatty acids, and phytanic acid. After the death of the child at the age of 6 years, molecular diagnostics were continued in order to provide genetic counseling for his parents. Next generation sequencing (NGS) analysis with the TruSight One™ Sequencing Panel revealed a novel homozygous PEX6 p.Ala94Pro mutation. In silico prediction of variant severity suggested its possible benign effect. To conclude, in the milder phenotypes, adrenal insufficiency, hypoacusis, and leukodystrophy together seem to be pathognomonic for ZS.

[An updated review of 1p36 deletion (monosomy) syndrome].

PubMed

Bello, Sabina; Rodríguez-Moreno, Antonio

The Monosomy 1p36 deletion syndrome is part of the group of diseases known as Rare Diseases. The objective of the present work is to review the characteristics of Monosomy 1p36 deletion syndrome. The monosomy 1p36 deletion syndrome phenotype includes: dysmorphic craniofacial features; large anterior fontanelle, unibrow, deep-set eyes, epicanthus, wide nasal root/bridge, mandible hypoplasia, abnormal location of the pinna, philtrum and pointed chin; neurological alterations: seizures and hydrocephalus (in some cases). Cerebral malformations: ventricular hypertrophy, increased subarachnoid space, morphological alterations of corpus callosum, cortical atrophy, delays in myelinisation, periventricular leukomalacia and periventricular heterotopia. These alterations produce intellectual disability and delays in motor growth, communication skills, language, social and adaptive behaviour. It is Hearing and vision impairments are also observed in subjects with this syndrome, as well as alterations of cardiac, endocrine and urinary systems and alterations at skin and skeletal level. Approximately 100 cases have been documented since 1981. This rare disease is the most common subtelomeric-micro-deletion syndrome. In situ hybridization with fluorescence (FISH) and array-comparative genomic hybridization (CGH-array) are at present the two best diagnostic techniques. There is currently no effective medical treatment for this disease. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Reliable classification of facial phenotypic variation in craniofacial microsomia: a comparison of physical exam and photographs.

PubMed

Birgfeld, Craig B; Heike, Carrie L; Saltzman, Babette S; Leroux, Brian G; Evans, Kelly N; Luquetti, Daniela V

2016-03-31

Craniofacial microsomia is a common congenital condition for which children receive longitudinal, multidisciplinary team care. However, little is known about the etiology of craniofacial microsomia and few outcome studies have been published. In order to facilitate large, multicenter studies in craniofacial microsomia, we assessed the reliability of phenotypic classification based on photographs by comparison with direct physical examination. Thirty-nine children with craniofacial microsomia underwent a physical examination and photographs according to a standardized protocol. Three clinicians completed ratings during the physical examination and, at least a month later, using respective photographs for each participant. We used descriptive statistics for participant characteristics and intraclass correlation coefficients (ICCs) to assess reliability. The agreement between ratings on photographs and physical exam was greater than 80 % for all 15 categories included in the analysis. The ICC estimates were higher than 0.6 for most features. Features with the highest ICC included: presence of epibulbar dermoids, ear abnormalities, and colobomas (ICC 0.85, 0.81, and 0.80, respectively). Orbital size, presence of pits, tongue abnormalities, and strabismus had the lowest ICC, values (0.17 or less). There was not a strong tendency for either type of rating, physical exam or photograph, to be more likely to designate a feature as abnormal. The agreement between photographs and physical exam regarding the presence of a prior surgery was greater than 90 % for most features. Our results suggest that categorization of facial phenotype in children with CFM based on photographs is reliable relative to physical examination for most facial features.

Constitutional trisomy 8 mosaicism syndrome: case report and review

PubMed Central

Udayakumar, Achandira M.; Al-Kindy, Adila

2013-01-01

Trisomy 8 mosaicism (Warkany syndrome) is a rare viable condition with variable phenotypes, ranging from mild dysmorphic features to severe malformations. Karyotyping and fluorescence in-situ hybridization potentially help detecting this low mosaic clone to confirm the diagnosis of patients with classical and unusual clinical presentations. This report reviews few previous cases to describe our case - a boy who had trisomy 8 mosaicism with severe dysmorphic features, born to a consanguineous Arabic couple. This study concludes that careful cytogenetic diagnoses of trisomy 8 mosaicism is essential for appropriate management and follow up of this rare disorder. PMID:27625859

Constitutional trisomy 8 mosaicism syndrome: case report and review.

PubMed

Udayakumar, Achandira M; Al-Kindy, Adila

2013-12-01

Trisomy 8 mosaicism (Warkany syndrome) is a rare viable condition with variable phenotypes, ranging from mild dysmorphic features to severe malformations. Karyotyping and fluorescence in-situ hybridization potentially help detecting this low mosaic clone to confirm the diagnosis of patients with classical and unusual clinical presentations. This report reviews few previous cases to describe our case - a boy who had trisomy 8 mosaicism with severe dysmorphic features, born to a consanguineous Arabic couple. This study concludes that careful cytogenetic diagnoses of trisomy 8 mosaicism is essential for appropriate management and follow up of this rare disorder.

Severe intellectual disability, West syndrome, Dandy-Walker malformation, and syndactyly in a patient with partial tetrasomy 17q25.3.

PubMed

Hackmann, Karl; Stadler, Anja; Schallner, Jens; Franke, Kathlen; Gerlach, Eva-Maria; Schrock, Evelin; Rump, Andreas; Fauth, Christine; Tinschert, Sigrid; Oexle, Konrad

2013-12-01

We report on a de novo 0.5 Mb triplication (partial tetrasomy) of chromosome 17q25.3 in a 10-year-old girl with severe intellectual disability, infantile seizures (West syndrome), moderate hearing loss, Dandy-Walker malformation, microcephaly, craniofacial dysmorphism, striking cutaneous syndactyly (hands 3-4, feet 2-3), joint laxity, and short stature. The triplication resulted from the unusual combination of a terminal duplication at 17qter and a cryptic translocation of an extra copy of the same segment onto chromosome 10qter. The breakpoint at 17q25.3 was located within the FOXK2 gene. SNP chip analysis suggested that the rearrangement occurred during paternal meiosis involving both paternal chromosomes 17. © 2013 Wiley Periodicals, Inc.

Novel FOXA2 mutation causes Hyperinsulinism, Hypopituitarism with Craniofacial and Endoderm-derived organ abnormalities.

PubMed

Giri, Dinesh; Vignola, Maria Lillina; Gualtieri, Angelica; Scagliotti, Valeria; McNamara, Paul; Peak, Matthew; Didi, Mohammed; Gaston-Massuet, Carles; Senniappan, Senthil

2017-11-15

Congenital hypopituitarism (CH) is characterized by the deficiency of one or more pituitary hormones and can present alone or in association with complex disorders. Congenital hyperinsulinism (CHI) is a disorder of unregulated insulin secretion despite hypoglycaemia that can occur in isolation or as part of a wider syndrome. Molecular diagnosis is unknown in many cases of CH and CHI. The underlying genetic etiology causing the complex phenotype of CH and CHI is unknown. In this study, we identified a de novo heterozygous mutation in the developmental transcription factor, forkhead box A2, FOXA2 (c.505T>C, p.S169P) in a child with CHI and CH with craniofacial dysmorphic features, choroidal coloboma and endoderm-derived organ malformations in liver, lung and gastrointestinal tract by whole exome sequencing. The mutation is at a highly conserved residue within the DNA binding domain. We demonstrated strong expression of Foxa2 mRNA in the developing hypothalamus, pituitary, pancreas, lungs and oesophagus of mouse embryos using in situ hybridization. Expression profiling on human embryos by immunohistochemistry showed strong expression of hFOXA2 in the neural tube, third ventricle, diencephalon and pancreas. Transient transfection of HEK293T cells with Wt (Wild type) hFOXA2 or mutant hFOXA2 showed an impairment in transcriptional reporter activity by the mutant hFOXA2. Further analyses using western blot assays showed that the FOXA2 p.(S169P) variant is pathogenic resulting in lower expression levels when compared with Wt hFOXA2. Our results show, for the first time, the causative role of FOXA2 in a complex congenital syndrome with hypopituitarism, hyperinsulinism and endoderm-derived organ abnormalities. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Phenotypic Analysis of Korean Patients with Abnormal Chromosomal Microarray in Patients with Unexplained Developmental Delay/Intellectual Disability.

PubMed

Kim, Hyo Jeong; Park, Chang Il; Lim, Jae Woo; Lee, Gyung Min; Cho, Eunhae; Kim, Hyon J

2018-05-01

The present study aimed to investigate chromosomal microarray (CMA) and clinical data in patients with unexplained developmental delay/intellectual disability (DD/ID) accompanying dysmorphism, congenital anomalies, or epilepsy. We also aimed to evaluate phenotypic clues in patients with pathogenic copy number variants (CNVs). We collected clinical and CMA data from patients at Konyang University Hospital between September 2013 and October 2014. We included patients who had taken the CMA test to evaluate the etiology of unexplained DD/ID. All of the 50 patients identified had DD/ID. Thirty-nine patients had dysmorphism, 19 patients suffered from epilepsy, and 12 patients had congenital anomalies. Twenty-nine of the 50 patients (58%) showed abnormal results. Eighteen (36%) were considered to have pathogenic CNVs. Dysmorphism (p=0.028) was significantly higher in patients with pathogenic CNVs than in those with normal CMA. Two or more clinical features were presented by 61.9% (13/21) of the patients with normal CMA and by 83.3% (15/18) of the patients with pathogenic CMA. Dysmorphism can be a phenotypic clue to pathogenic CNVs. Furthermore, pathogenic CNV might be more frequently found if patients have two or more clinical features in addition to DD/ID. © Copyright: Yonsei University College of Medicine 2018.

Twin infant with lymphatic dysplasia diagnosed with Noonan syndrome by molecular genetic testing.

PubMed

Mathur, Deepan; Somashekar, Santhosh; Navarrete, Cristina; Rodriguez, Maria M

2014-08-01

Noonan Syndrome is an autosomal dominant disorder characterized by short stature, congenital heart defects, developmental delay, dysmorphic facial features and occasional lymphatic dysplasias. The features of Noonan Syndrome change with age and have variable expression. The diagnosis has historically been based on clinical grounds. We describe a child that was born with congenital refractory chylothorax and subcutaneous edema suspected to be secondary to pulmonary lymphangiectasis. The infant died of respiratory failure and anasarca at 80 days. The autopsy confirmed lymphatic dysplasia in lungs and mesentery. The baby had no dysmorphic facial features and was diagnosed postmortem with Noonan syndrome by genomic DNA sequence analysis as he had a heterozygous mutation for G503R in the PTPN11 gene.

Occurrence and clinical features of epileptic and non-epileptic paroxysmal events in five children with Pallister–Killian syndrome

PubMed Central

Filloux, Francis M.; Carey, John C.; Krantz, Ian D.; Ekstrand, Jeffrey J.; Candee, Meghan S.

2013-01-01

Pallister–Killian syndrome (PKS) is a rare, sporadic genetic disorder caused by tetrasomy 12p mosaicism associated with a supernumerary isochromosome. Craniofacial dysmorphism, learning impairment and seizures are considered characteristic. However, little is known of the seizure and epilepsy patterns seen in PKS. To better define the occurrence and nature of epileptic and non-epileptic paroxysmal events in PKS, we describe our experience with 5 patients and compare their features with data from a larger cohort of PKS patients ascertained via a web-based parental questionnaire. Three of the 5 patients have had definite epileptic seizures, and one other has had paroxysmal events as yet not clarified. Four of the 5 have also had either non-epileptic paroxysmal events or episodes of uncertain nature. In those with epilepsy, all have had some period of relatively refractory seizures, all have required more than one antiepileptic drug, but none experienced status epilepticus. Only one of the patients with epilepsy (the oldest) has gone into remission. In two of the four with non-epileptic events, video-electroencephalographic monitoring has been valuable in clarifying the nature of the events. EEG characteristics include a slow dominant frequency as well as generalized and focal epileptiform features. Brain MRI findings can be normal but are variable. These specific findings correspond well to information reported by parents in a larger cohort of 51 individuals with PKS. Better understanding of the nature of epileptic and non-epileptic events in PKS will result from a more detailed analysis of objective data obtained from this larger cohort, and from deeper understanding of the molecular impact of 12p tetrasomy in selected cell lines. PMID:22349688

Population differences in dysmorphic features among children with fetal alcohol spectrum disorders.

PubMed

May, Philip A; Gossage, J Phillip; Smith, Matthew; Tabachnick, Barbara G; Robinson, Luther K; Manning, Melanie; Cecanti, Mauro; Jones, Kenneth Lyons; Khaole, Nathaniel; Buckley, David; Kalberg, Wendy O; Trujillo, Phyllis M; Hoyme, H Eugene

2010-05-01

To examine the variation in significant dysmorphic features in children from 3 different populations with the most dysmorphic forms of fetal alcohol spectrum disorders, fetal alcohol syndrome (FAS), and partial fetal alcohol syndrome (PFAS). Advanced multiple regression techniques are used to determine the discriminating physical features in the diagnosis of FAS and PFAS among children from Northern Plains Indian communities, South Africa, and Italy. Within the range of physical features used to identify children with fetal alcohol spectrum disorders, specifically FAS and PFAS, there is some significant variation in salient diagnostic features from one population to the next. Intraclass correlations in diagnostic features between these 3 populations is 0.20, indicating that about 20% of the variability in dysmorphology core features is associated with location and, therefore, specific racial/ethnic population. The highly significant diagnostic indicators present in each population are identified for the full samples of FAS, PFAS, and normals and also among children with FAS only. A multilevel model for these populations combined indicates that these variables predict dysmorphology unambiguously: small palpebral fissures, narrow vermillion, smooth philtrum, flat nasal bridge, and fifth finger clinodactyly. Long philtrum varies substantially as a predictor in the 3 populations. Predictors not significantly related to fetal alcohol spectrum disorders dysmorphology across the 3 populations are centile of height (except in Italy) strabismus, interpupilary distance, intercanthal distance, and heart murmurs. The dysmorphology associated with FAS and PFAS vary across populations, yet a particular array of common features occurs in each population, which permits a consistent diagnosis across populations.

A Newborn with Panhypopituitarism and Seizures.

PubMed

Kale, Trupti; Patil, Rachit; Pandit, Ramesh

2017-01-01

Interstitial deletions on the short arm of chromosome 20 are uncommon, and therefore the clinical phenotype is poorly defined. Very few cases have been reported in the literature so far. In this report, we describe a 4-month-old female with a heterozygous deletion at 20p11.21p12.1 with panhypopituitarism and cardiac, gastrointestinal, and genitourinary anomalies along with dysmorphic facial features. We compared and discussed similar cases with overlapping deletions in 20p11 region. We wish to report this rare occurrence as this may better define the phenotypes of the 20p interstitial deletion with certain dysmorphic features, multiorgan involvement, and related clinical characteristics in this patient population.

A de novo 11p12-p15.4 duplication in a patient with pharmacoresistant epilepsy, mental retardation, and dysmorphisms.

PubMed

Coppola, Antonietta; Striano, Pasquale; Gimelli, Stefania; Ciampa, Clotilde; Santulli, Lia; Caranci, Ferdinando; Zuffardi, Orsetta; Gimelli, Giorgio; Striano, Salvatore; Zara, Federico

2010-03-01

We report a 22-year-old male patient with pharmacoresistant epilepsy, mental retardation and dysmorphisms. Standard cytogenetic analysis revealed a de novo interstitial duplication of the short arm of chromosome 11 (11p). High density array-CGH analysis showed that the rearrangement spans about 35Mb on chromosome 11p12-p15.4. Duplications of 11p are rare and usually involve the distal part of the chromosome arm (11p15), being not associated with epilepsy, whereas our patient showed a unique epileptic phenotype associated with mental retardation and dysmorphic features. The role of some rearranged genes in epilepsy pathogenesis in this patient is also discussed.

Body image concern and selective attention to disgusting and non-self appearance-related stimuli.

PubMed

Onden-Lim, Melissa; Wu, Ray; Grisham, Jessica R

2012-09-01

Although selective attention to one's own appearance has been widely documented in studies of body dysmorphic disorder (BDD), little is known about attentional bias toward non-self appearance-related stimuli in BDD. Furthermore, despite reports of heightened experience of disgust in BDD, it is unknown whether these individuals differentially attend to disgusting stimuli and whether disgust is important in processing of unattractive stimuli. We used a dot probe procedure to investigate the relationship between dysmorphic concern, a defining feature of BDD, and selective attention to faces, attractive, unattractive and disgusting images in a female heterosexual student population (N=92). At the long stimulus presentation (1000 ms), dysmorphic concern was positively associated with attention to faces in general and attractive appearance-related images. In contrast, at the short stimulus presentation (200 ms), there was a positive association between dysmorphic concern and disgusting images. Implications for theoretical models of BDD are discussed. Copyright © 2012. Published by Elsevier Ltd.

Severe developmental delay and multiple strawberry naevi: a new syndrome?

PubMed Central

Upton, C J; Young, I D

1993-01-01

An 18 month old girl with dysmorphic features, severe developmental delay, multiple strawberry naevi, and capillary naevi is described. No previous report of a similar association of features has been identified. Images PMID:8230170

Mosaic variegated aneuploidy associated with a dysmorphic syndrome and mental handicap

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

Mehta, L.; Babu, A.; Willner, J.

1994-09-01

A 41-year-old woman was evaluated for dysmorphic features and mental handicap. Prior karyotyping had revealed 7% mosaicism for trisomy 18 in skin fibroblasts with normal blood chromosomes. Clinical features consisted of short stature, mild mental retardation, sensorineural deafness and the following dysmorphic features: short, broad neck, low posterior hairline, small palpebral fissures with iris coloboma on the right, epicanthic folds, small mouth, high palate and prominent mandible, short metacarpals and digits, particularly the fifth, with bilateral simian creases. Medical problems included non-insulin dependent diabetes mellitus, hypertension, oligomenorrhea and recent onset of diabetic neuropathy and retinal exudates. Head size and brainmore » MRI were within normal limits. Peripheral blood chromosomes revealed: 46,XX (45 cells), 46,XX,t(7;16)(q21;q21) in 1 cell, 45,X (1 cell), 48,XXXX (1 cell), 47,XX,+mar (1 cell), 48,XX,+mar,+mar (1 cell). Skin fibroblasts revealed the following karyotypes: 46,XX (25 cells), 45,X (14 cells), 47,XX,+2 (10 cells) and 47,X,+2,+7 (1 cell). Previously reported cases of mosaic variegated aneuploidy include microcephaly as a prominent feature. Chromosomes involved in the abnormality are variable. Clinical presentations in such patients are not consistent and do not appear to correlate with specific chromosome defects. This patient represents an interesting example of probable mitotic instability disrupting normal developmental processes.« less

OCT imaging of craniofacial anatomy in xenopus embryos (Conference Presentation)

NASA Astrophysics Data System (ADS)

Deniz, Engin; Jonas, Stephan M.; Griffin, John; Hooper, Michael C.; Choma, Michael A.; Khokha, Mustafa K.

2016-03-01

The etiology of craniofacial defects is incompletely understood. The ability to obtain large amounts of gene sequence data from families affected by craniofacial defects is opening up new ways to understand molecular genetic etiological factors. One important link between gene sequence data and clinical relevance is biological research into candidate genes and molecular pathways. We present our recent research using OCT as a nondestructive phenotyping modality of craniofacial morphology in Xenopus embryos, an important animal model for biological research in gene and pathway discovery. We define 2D and 3D scanning protocols for a standardized approach to craniofacial imaging in Xenopus embryos. We define standard views and planar reconstructions for visualizing normal anatomy and landmarks. We compare these views and reconstructions to traditional histopathology using alcian blue staining. In addition to being 3D, nondestructive, and having much faster throughout, OCT can identify craniofacial features that are lost during traditional histopathological preparation. We also identify quantitative morphometric parameters to define normative craniofacial anatomy. We also note that craniofacial and cardiac defects are not infrequently present in the same patient (e.g velocardiofacial syndrome). Given that OCT excels at certain aspects of cardiac imaging in Xenopus embryos, our work highlights the potential of using OCT and Xenopus to study molecular genetic factors that impact both cardiac and craniofacial development.

A Newborn with Panhypopituitarism and Seizures

PubMed Central

Patil, Rachit; Pandit, Ramesh

2017-01-01

Interstitial deletions on the short arm of chromosome 20 are uncommon, and therefore the clinical phenotype is poorly defined. Very few cases have been reported in the literature so far. In this report, we describe a 4-month-old female with a heterozygous deletion at 20p11.21p12.1 with panhypopituitarism and cardiac, gastrointestinal, and genitourinary anomalies along with dysmorphic facial features. We compared and discussed similar cases with overlapping deletions in 20p11 region. We wish to report this rare occurrence as this may better define the phenotypes of the 20p interstitial deletion with certain dysmorphic features, multiorgan involvement, and related clinical characteristics in this patient population. PMID:28255477

Newly recognized recessive syndrome characterized by dysmorphic features, hypogonadotropic hypogonadism, severe microcephaly, and sensorineural hearing loss maps to 3p21.3.

PubMed

Jenkinson, Emma M; Kingston, Helen; Urquhart, Jill; Khan, Naz; Melville, Athalie; Swinton, Martin; Crow, Yanick J; Davis, Julian R E; Trump, Dorothy; Newman, William G

2011-12-01

We present a newly recognized, likely autosomal recessive, pleiotropic disorder seen in four individuals (three siblings and their nephew) from a consanguineous family of Pakistani origin. The condition is characterized by hypogonadotropic hypogonadism, severe microcephaly, sensorineural deafness, moderate learning disability, and distinctive facial dysmorphic features. Autozygosity mapping using SNP array genotyping defined a single, large autozygous region of 13.1 Mb on chromosome 3p21 common to the affected individuals. The critical region contains 227 genes and initial sequence analysis of a functional candidate gene has not identified causative mutations. Copyright © 2011 Wiley Periodicals, Inc.

Computed tomography assessment of peripubertal craniofacial morphology in a sheep model of binge alcohol drinking in the first trimester.

PubMed

Birch, Sharla M; Lenox, Mark W; Kornegay, Joe N; Shen, Li; Ai, Huisi; Ren, Xiaowei; Goodlett, Charles R; Cudd, Tim A; Washburn, Shannon E

2015-11-01

Identification of facial dysmorphology is essential for the diagnosis of fetal alcohol syndrome (FAS); however, most children with fetal alcohol spectrum disorders (FASD) do not meet the dysmorphology criterion. Additional objective indicators are needed to help identify the broader spectrum of children affected by prenatal alcohol exposure. Computed tomography (CT) was used in a sheep model of prenatal binge alcohol exposure to test the hypothesis that quantitative measures of craniofacial bone volumes and linear distances could identify alcohol-exposed lambs. Pregnant sheep were randomly assigned to four groups: heavy binge alcohol, 2.5 g/kg/day (HBA); binge alcohol, 1.75 g/kg/day (BA); saline control (SC); and normal control (NC). Intravenous alcohol (BA; HBA) or saline (SC) infusions were given three consecutive days per week from gestation day 4-41, and a CT scan was performed on postnatal day 182. The volumes of eight skull bones, cranial circumference, and 19 linear measures of the face and skull were compared among treatment groups. Lambs from both alcohol groups showed significant reduction in seven of the eight skull bones and total skull bone volume, as well as cranial circumference. Alcohol exposure also decreased four of the 19 craniofacial measures. Discriminant analysis showed that alcohol-exposed and control lambs could be classified with high accuracy based on total skull bone volume, frontal, parietal, or mandibular bone volumes, cranial circumference, or interorbital distance. Total skull volume was significantly more sensitive than cranial circumference in identifying the alcohol-exposed lambs when alcohol-exposed lambs were classified using the typical FAS diagnostic cutoff of ≤10th percentile. This first demonstration of the usefulness of CT-derived craniofacial measures in a sheep model of FASD following binge-like alcohol exposure during the first trimester suggests that volumetric measurement of cranial bones may be a novel biomarker for binge alcohol exposure during the first trimester to help identify non-dysmorphic children with FASD. Copyright © 2015 Elsevier Inc. All rights reserved.

Craniosynostosis in 10q26 deletion patients: A consequence of brain underdevelopment or altered suture biology?

PubMed

Faria, Ágatha Cristhina; Rabbi-Bortolini, Eliete; Rebouças, Maria R G O; de S Thiago Pereira, Andréia L A; Frasson, Milena G Tonini; Atique, Rodrigo; Lourenço, Naila Cristina V; Rosenberg, Carla; Kobayashi, Gerson S; Passos-Bueno, Maria Rita; Errera, Flávia Imbroisi Valle

2016-02-01

Approximately a hundred patients with terminal 10q deletions have been described. They present with a wide range of clinical features always accompanied by delayed development, intellectual disability and craniofacial dysmorphisms. Here, we report a girl and a boy with craniosynostosis, developmental delay and other congenital anomalies. Karyotyping and molecular analysis including Multiplex Ligation dependent probe amplification (MLPA) and Array Comparative Genomic Hybridization (aCGH) were performed in both patients. We detected a 13.1 Mb pure deletion at 10q26.12-q26.3 in the girl and a 10.9 Mb pure deletion at 10q26.13-q26.3 in the boy, both encompassing about 100 genes. The clinical and molecular findings in these patients reinforce the importance of the DOCK1 smallest region of overlap I (SRO I), previously suggested to explain the clinical signs, and together with a review of the literature suggest a second 3.5 Mb region important for the phenotype (SRO II). Genotype-phenotype correlations and literature data suggest that the craniosynostosis is not directly related to dysregulated signaling in suture development, but may be secondary to alterations in brain development instead. Further, genes at 10q26 may be involved in the molecular crosstalk between brain and cranial vault. © 2015 Wiley Periodicals, Inc.

Constitutional chromoanasynthesis: description of a rare chromosomal event in a patient.

PubMed

Plaisancié, Julie; Kleinfinger, Pascale; Cances, Claude; Bazin, Anne; Julia, Sophie; Trost, Detlef; Lohmann, Laurence; Vigouroux, Adeline

2014-10-01

Structural alterations in chromosomes are a frequent cause of cancers and congenital diseases. Recently, the phenomenon of chromosome crisis, consisting of a set of tens to hundreds of clustered genomic rearrangements, localized in one or a few chromosomes, was described in cancer cells under the term chromothripsis. Better knowledge and recognition of this catastrophic chromosome event has brought to light two distinct entities, chromothripsis and chromoanasynthesis. The complexity of these rearrangements and the original descriptions in tumor cells initially led to the thought that it was an acquired anomaly. In fact, a few patients have been reported with constitutional chromothripsis or chromoanasynthesis. Using microarray we identified a very complex chromosomal rearrangement in a patient who had a cytogenetically visible rearrangement of chromosome 18. The rearrangement contained more than 15 breakpoints localized on a single chromosome. Our patient displayed intellectual disability, behavioral troubles and craniofacial dysmorphism. Interestingly, the succession of duplications and triplications identified in our patient was not clustered on a single chromosomal region but spread over the entire chromosome 18. In the light of this new spectrum of chromosomal rearrangements, this report outlines the main features of these catastrophic events and discusses the underlying mechanism of the complex chromosomal rearrangement identified in our patient, which is strongly evocative of a chromoanasynthesis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Prevalence of body dysmorphic disorder and associated features in German adolescents: A self-report survey.

PubMed

Möllmann, Anne; Dietel, Fanny A; Hunger, Antje; Buhlmann, Ulrike

2017-08-01

Prior research has not yet investigated the prevalence of body dysmorphic disorder (BDD) in adolescents and young adults based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). In the current study, the point prevalence of BDD, comorbid symptoms, and associated features, such as appearance-related suicidality, level of insight or history of plastic surgeries, were examined in a non-clinical sample of German adolescents and young adults (n=308), between 15 and 21 years old, using self-report measures. Eleven participants (3.6%; 95% CI=[1.9, 5.8]) met DSM-5 criteria for BDD. Self-reported BDD (vs. no-BDD) was related to respondents showing significantly more obsessive-compulsive (OC) symptoms and lower degrees of insight regarding appearance concerns. Significantly more adolescents and young adults with vs. without self-reported BDD (36.4% vs. 8.8%) reported appearance-related suicidal ideation. In conclusion, body dysmorphic symptoms are common in adolescents and young adults and are associated with high rates of comorbid symptoms and suicidal ideation. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Wiedemann-Steiner Syndrome With 2 Novel KMT2A Mutations.

PubMed

Min Ko, Jung; Cho, Jae So; Yoo, Yongjin; Seo, Jieun; Choi, Murim; Chae, Jong-Hee; Lee, Hye-Ran; Cho, Tae-Joon

2017-02-01

Wiedemann-Steiner syndrome is a rare genetic disorder characterized by short stature, hairy elbows, facial dysmorphism, and developmental delay. It can also be accompanied by musculoskeletal anomalies such as muscular hypotonia and small hands and feet. Mutations in the KMT2A gene have only recently been identified as the cause of Wiedemann-Steiner syndrome; therefore, only 16 patients from 15 families have been described, and new phenotypic features continue to be added. In this report, we describe 2 newly identified patients with Wiedemann-Steiner syndrome who presented with variable severity. One girl exhibited developmental dysplasia of the hip and fibromatosis colli accompanied by other clinical features, including facial dysmorphism, hypertrichosis, patent ductus arteriosus, growth retardation, and borderline intellectual disability. The other patient, a boy, showed severe developmental retardation with automatic self-mutilation, facial dysmorphism, and hypertrichosis at a later age. Exome sequencing analysis of these patients and their parents revealed a de novo nonsense mutation, p.Gln1978*, of KMT2A in the former, and a missense mutation, p.Gly1168Asp, in the latter, which molecularly confirmed the diagnosis of Wiedemann-Steiner syndrome.

Photoanthropometric study of dysmorphic features of the face in children with autism and asperger syndrome.

PubMed

Gorczyca, Piotr; Kapinos-Gorczyca, Agnieszka; Ziora, Katarzyna; Oświęcimska, Joanna

2012-01-01

Childhood autism is a neurodevelopmental disorder characterized by impairments in social interactions, verbal and non-verbal communication and by a pattern of stereotypical behaviors and interests. The aim of this study was to estimate the dysmorphic facial features of children with autism and children with Asperger syndrome. The examination was conducted on 60 children (30 with childhood autism and 30 with Asperger syndrome). The photo anthropometric method used in this study followed the protocol established by Stengel-Rutkowski et al. The performed statistical analysis showed that in patients with childhood autism, the anteriorly rotated ears and the long back of the nose appeared more often. In the group of children with autism, there was a connection between the amount of dysmorphies and the presence of some somatic diseases in the first-degree relatives. There was also a connection between the motor coordination and the age the child began to walk. In patients with childhood autism, there were certain dysmorphies (like the anterior rotated ears and the long back of the nose) which appeared more often. Although the connection was not statistically significant, it seemed to concur with data from the literature. Formulation of the other conclusions would require broader studies e.g. dealing with a familial analysis of dysmorphic features.

Hypoparathyroidism-retardation-Dysmorphism (HRD) syndrome--a review.

PubMed

Hershkovitz, Eli; Parvari, Ruti; Diaz, George A; Gorodischer, Rafael

2004-12-01

Hypoparathyroidism, retardation, and dysmorphism (HRD) is a newly recognized genetic syndrome, described in patients of Arab origin. The syndrome consists of permanent congenital hypoparathyroidism, severe prenatal and postnatal growth retardation, and profound global developmental delay. The patients are susceptible to severe infections including life-threatening pneumococcal infections especially during infancy. The main dysmorphic features are microcephaly, deep-set eyes or microphthalmia, ear abnormalities, depressed nasal bridge, thin upper lip, hooked small nose, micrognathia, and small hands and feet. A single 12-bp deletion (del52-55) in the second coding exon of the tubulin cofactor E (TCFE) gene, located on the long arm of chromosome 1, is the cause of HRD among Arab patients. Early recognition and therapy of hypocalcemia is important as is daily antibiotic prophylaxis against pneumococcal infections.

A case of Pitt-Hopkins syndrome with absence of hyperventilation.

PubMed

Inati, Adlette; Abbas, Hussein A; Korjian, Serge; Daaboul, Yazan; Harajeily, Mohamad; Saab, Raya

2013-12-01

Pitt-Hopkins syndrome is characterized by mental retardation, hyperventilation, and dysmorphic features due to TCF4 mutations. We report a case of Pitt-Hopkins syndrome in a 2½-year-old boy presenting with psychomotor retardation, recurrent respiratory tract infections, and dysmorphic features with absence of hyperventilation or other breathing abnormalities. Comparative genomic hybridization and quantitative real-time polymerase chain reaction were used to confirm TCF4 haploinsufficiency. Pitt-Hopkins syndrome is a rare debilitating disease that should be in the differential diagnosis of other neurodevelopmental disorders characterized by mental retardation and hypotonicity despite the absence of hyperapnea and seizures. Quantitative real-time polymerase chain reaction is another method to identify TCF4 and to confirm Pitt-Hopkins syndrome diagnosis.

Xp22.33p22.12 Duplication in a Patient with Intellectual Disability and Dysmorphic Facial Features

PubMed Central

Lintas, Carla; Picinelli, Chiara; Piras, Ignazio S.; Sacco, Roberto; Gabriele, Stefano; Verdecchia, Magda; Persico, Antonio M.

2016-01-01

A novel 19.98-Mb duplication in chromosome Xp22.33p22.12 was detected by array CGH in a 30-year-old man affected by intellectual disability, congenital hypotonia and dysmorphic features. The duplication encompasses more than 100 known genes. Many of these genes (such as neuroligin 4, cyclin-dependent kinase like 5, and others) have already correlated with X-linked intellectual disability and/or neurodevelopmental disorders. Due to the high number of potentially pathogenic genes involved in the reported duplication, we cannot correlate the clinical phenotype to a single gene. Indeed, we suggest that the resulting clinical phenotype may have arisen from the overexpression and consequent perturbation of fine gene dosage. PMID:26997944

Xp22.33p22.12 Duplication in a Patient with Intellectual Disability and Dysmorphic Facial Features.

PubMed

Lintas, Carla; Picinelli, Chiara; Piras, Ignazio S; Sacco, Roberto; Gabriele, Stefano; Verdecchia, Magda; Persico, Antonio M

2016-02-01

A novel 19.98-Mb duplication in chromosome Xp22.33p22.12 was detected by array CGH in a 30-year-old man affected by intellectual disability, congenital hypotonia and dysmorphic features. The duplication encompasses more than 100 known genes. Many of these genes (such as neuroligin 4, cyclin-dependent kinase like 5, and others) have already correlated with X-linked intellectual disability and/or neurodevelopmental disorders. Due to the high number of potentially pathogenic genes involved in the reported duplication, we cannot correlate the clinical phenotype to a single gene. Indeed, we suggest that the resulting clinical phenotype may have arisen from the overexpression and consequent perturbation of fine gene dosage.

Clinical features of body dysmorphic disorder in adolescents and adults

PubMed Central

Phillips, Katharine A.; Didie, Elizabeth R.; Menard, William; Pagano, Maria E.; Fay, Christina; Weisberg, Risa B.

2006-01-01

Body dysmorphic disorder (BDD) usually begins during adolescence, but its clinical features have received little investigation in this age group. Two hundred individuals with BDD (36 adolescents; 164 adults) completed interviewer-administered and self-report measures. Adolescents were preoccupied with numerous aspects of their appearance, most often their skin, hair, and stomach. Among the adolescents, 94.3% reported moderate, severe, or extreme distress due to BDD, 80.6% had a history of suicidal ideation, and 44.4% had attempted suicide. Adolescents experienced high rates and levels of impairment in school, work, and other aspects of psychosocial functioning. Adolescents and adults were comparable on most variables, although adolescents had significantly more delusional BDD beliefs and a higher lifetime rate of suicide attempts. Thus, adolescents with BDD have high levels of distress and rates of functional impairment, suicidal ideation, and suicide attempts. BDD’s clinical features in adolescents appear largely similar to those in adults. PMID:16499973

Growth hormone positive effects on craniofacial complex in Turner syndrome.

PubMed

Juloski, Jovana; Dumančić, Jelena; Šćepan, Ivana; Lauc, Tomislav; Milašin, Jelena; Kaić, Zvonimir; Dumić, Miroslav; Babić, Marko

2016-11-01

Turner syndrome occurs in phenotypic females with complete or partial absence of X chromosome. The leading symptom is short stature, while numerous but mild stigmata manifest in the craniofacial region. These patients are commonly treated with growth hormone to improve their final height. The aim of this study was to assess the influence of long-term growth hormone therapy on craniofacial morphology in Turner syndrome patients. In this cross-sectional study cephalometric analysis was performed on 13 lateral cephalograms of patients with 45,X karyotype and the average age of 17.3 years, who have received growth hormone for at least two years. The control group consisted of 13 Turner syndrome patients naive to growth hormone treatment, matched to study group by age and karyotype. Sixteen linear and angular measurements were obtained from standard lateral cephalograms. Standard deviation scores were calculated in order to evaluate influence of growth hormone therapy on craniofacial components. In Turner syndrome patients treated with growth hormone most of linear measurements were significantly larger compared to untreated patients. Growth hormone therapy mainly influenced posterior face height, mandibular ramus height, total mandibular length, anterior face height and maxillary length. While the increase in linear measurements was evident, angular measurements and facial height ratio did not show statistically significant difference. Acromegalic features were not found. Long-term growth hormone therapy has positive influence on craniofacial development in Turner syndrome patients, with the greatest impact on posterior facial height and mandibular ramus. However, it could not compensate X chromosome deficiency and normalize craniofacial features. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thalamic Massa Intermedia Duplication in a Dysmorphic 14 month-old Toddler.

PubMed

Whitehead, Matthew T

2015-06-01

The massa intermedia is an inconstant parenchymal band connecting the medial thalami. It may be thickened in various disease processes such as Chiari II malformation or absent in other disease states. However, the massa intermedia may also be absent in up to 30% of normal human brains. To the best of my knowledge, detailed imaging findings of massa intermedia duplication have only been described in a single case report. An additional case of thalamic massa intermedia duplication discovered on a routine brain MR performed for dysmorphic facial features is reported herein.

Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies.

PubMed

Cheng, Hanyin; Dharmadhikari, Avinash V; Varland, Sylvia; Ma, Ning; Domingo, Deepti; Kleyner, Robert; Rope, Alan F; Yoon, Margaret; Stray-Pedersen, Asbjørg; Posey, Jennifer E; Crews, Sarah R; Eldomery, Mohammad K; Akdemir, Zeynep Coban; Lewis, Andrea M; Sutton, Vernon R; Rosenfeld, Jill A; Conboy, Erin; Agre, Katherine; Xia, Fan; Walkiewicz, Magdalena; Longoni, Mauro; High, Frances A; van Slegtenhorst, Marjon A; Mancini, Grazia M S; Finnila, Candice R; van Haeringen, Arie; den Hollander, Nicolette; Ruivenkamp, Claudia; Naidu, Sakkubai; Mahida, Sonal; Palmer, Elizabeth E; Murray, Lucinda; Lim, Derek; Jayakar, Parul; Parker, Michael J; Giusto, Stefania; Stracuzzi, Emanuela; Romano, Corrado; Beighley, Jennifer S; Bernier, Raphael A; Küry, Sébastien; Nizon, Mathilde; Corbett, Mark A; Shaw, Marie; Gardner, Alison; Barnett, Christopher; Armstrong, Ruth; Kassahn, Karin S; Van Dijck, Anke; Vandeweyer, Geert; Kleefstra, Tjitske; Schieving, Jolanda; Jongmans, Marjolijn J; de Vries, Bert B A; Pfundt, Rolph; Kerr, Bronwyn; Rojas, Samantha K; Boycott, Kym M; Person, Richard; Willaert, Rebecca; Eichler, Evan E; Kooy, R Frank; Yang, Yaping; Wu, Joseph C; Lupski, James R; Arnesen, Thomas; Cooper, Gregory M; Chung, Wendy K; Gecz, Jozef; Stessman, Holly A F; Meng, Linyan; Lyon, Gholson J

2018-05-03

N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of the N-terminal acetyltransferase A (NatA) complex. The auxiliary subunit of the NatA complex, NAA15, is the dimeric binding partner for NAA10. Through a genotype-first approach with whole-exome or genome sequencing (WES/WGS) and targeted sequencing analysis, we identified and phenotypically characterized 38 individuals from 33 unrelated families with 25 different de novo or inherited, dominantly acting likely gene disrupting (LGD) variants in NAA15. Clinical features of affected individuals with LGD variants in NAA15 include variable levels of intellectual disability, delayed speech and motor milestones, and autism spectrum disorder. Additionally, mild craniofacial dysmorphology, congenital cardiac anomalies, and seizures are present in some subjects. RNA analysis in cell lines from two individuals showed degradation of the transcripts with LGD variants, probably as a result of nonsense-mediated decay. Functional assays in yeast confirmed a deleterious effect for two of the LGD variants in NAA15. Further supporting a mechanism of haploinsufficiency, individuals with copy-number variant (CNV) deletions involving NAA15 and surrounding genes can present with mild intellectual disability, mild dysmorphic features, motor delays, and decreased growth. We propose that defects in NatA-mediated N-terminal acetylation (NTA) lead to variable levels of neurodevelopmental disorders in humans, supporting the importance of the NatA complex in normal human development. Copyright © 2018 American Society of Human Genetics. All rights reserved.

Photoanthropometric Study of Dysmorphic Features of the Face in Children with Autism and Asperger Syndrome

PubMed Central

Kapinos- Gorczyca, Agnieszka; Ziora, Katarzyna; Oświęcimska, Joanna

2012-01-01

Objective Childhood autism is a neurodevelopmental disorder characterized by impairments in social interactions, verbal and non-verbal communication and by a pattern of stereotypical behaviors and interests. The aim of this study was to estimate the dysmorphic facial features of children with autism and children with Asperger syndrome. Methods The examination was conducted on 60 children (30 with childhood autism and 30 with Asperger syndrome). The photo anthropometric method used in this study followed the protocol established by Stengel-Rutkowski et al. Results The performed statistical analysis showed that in patients with childhood autism, the anteriorly rotated ears and the long back of the nose appeared more often. In the group of children with autism, there was a connection between the amount of dysmorphies and the presence of some somatic diseases in the first-degree relatives. There was also a connection between the motor coordination and the age the child began to walk. Discussion In patients with childhood autism, there were certain dysmorphies (like the anterior rotated ears and the long back of the nose) which appeared more often. Although the connection was not statistically significant, it seemed to concur with data from the literature. Conclusion Formulation of the other conclusions would require broader studies e.g. dealing with a familial analysis of dysmorphic features. PMID:23056117

Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.

PubMed

Mühlebner, Angelika; van Scheppingen, Jackelien; Hulshof, Hanna M; Scholl, Theresa; Iyer, Anand M; Anink, Jasper J; van den Ouweland, Ans M W; Nellist, Mark D; Jansen, Floor E; Spliet, Wim G M; Krsek, Pavel; Benova, Barbora; Zamecnik, Josef; Crino, Peter B; Prayer, Daniela; Czech, Thomas; Wöhrer, Adelheid; Rahimi, Jasmin; Höftberger, Romana; Hainfellner, Johannes A; Feucht, Martha; Aronica, Eleonora

2016-01-01

Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1) activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.

Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex

PubMed Central

Hulshof, Hanna M.; Scholl, Theresa; Iyer, Anand M.; Anink, Jasper J.; van den Ouweland, Ans M. W.; Nellist, Mark D.; Jansen, Floor E.; Spliet, Wim G. M.; Krsek, Pavel; Benova, Barbora; Zamecnik, Josef; Crino, Peter B.; Prayer, Daniela; Czech, Thomas; Wöhrer, Adelheid; Rahimi, Jasmin; Höftberger, Romana; Hainfellner, Johannes A.; Feucht, Martha; Aronica, Eleonora

2016-01-01

Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1) activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC. PMID:27295297

Radiological features of late-onset lymphoedema in Noonan's syndrome.

PubMed

Ho, Wan-Ling; Wang, Jou-Kou; Li, Yiu-Wah

2003-03-01

Noonan's syndrome is a multiple congenital anomaly syndrome with diverse manifestations. Lymphatic abnormalities occur in less than 20% of patients. We report a 14-year-old boy who presented with swollen lower limbs and dysmorphic features characteristic of Noonan's syndrome. The radiological features of this unusual case of late-onset lymphoedema in association with Noonan's syndrome are presented.

Activated Braf induces esophageal dilation and gastric epithelial hyperplasia in mice.

PubMed

Inoue, Shin-Ichi; Takahara, Shingo; Yoshikawa, Takeo; Niihori, Tetsuya; Yanai, Kazuhiko; Matsubara, Yoichi; Aoki, Yoko

2017-12-01

Germline mutations in BRAF are a major cause of cardio-facio-cutaneous (CFC) syndrome, which is characterized by heart defects, characteristic craniofacial dysmorphology and dermatologic abnormalities. Patients with CFC syndrome also commonly show gastrointestinal dysfunction, including feeding and swallowing difficulties and gastroesophageal reflux. We have previously found that knock-in mice expressing a Braf Q241R mutation exhibit CFC syndrome-related phenotypes, such as growth retardation, craniofacial dysmorphisms, congenital heart defects and learning deficits. However, it remains unclear whether BrafQ241R/+ mice exhibit gastrointestinal dysfunction. Here, we report that BrafQ241R/+ mice have neonatal feeding difficulties and esophageal dilation. The esophagus tissues from BrafQ241R/+ mice displayed incomplete replacement of smooth muscle with skeletal muscle and decreased contraction. Furthermore, the BrafQ241R/+ mice showed hyperkeratosis and a thickened muscle layer in the forestomach. Treatment with MEK inhibitors ameliorated the growth retardation, esophageal dilation, hyperkeratosis and thickened muscle layer in the forestomach in BrafQ241R/+ mice. The esophageal dilation with aberrant skeletal-smooth muscle boundary in BrafQ241R/+ mice were recovered after treatment with the histone H3K27 demethylase inhibitor GSK-J4. Our results provide clues to elucidate the pathogenesis and possible treatment of gastrointestinal dysfunction and failure to thrive in patients with CFC syndrome. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Further delineation of the SATB2 phenotype.

PubMed

Döcker, Dennis; Schubach, Max; Menzel, Moritz; Munz, Marita; Spaich, Christiane; Biskup, Saskia; Bartholdi, Deborah

2014-08-01

SATB2 is an evolutionarily highly conserved chromatin remodeling gene located on chromosome 2q33.1. Vertebrate animal models have shown that Satb2 has a crucial role in craniofacial patterning and osteoblast differentiation, as well as in determining the fates of neuronal projections in the developing neocortex. In humans, chromosomal translocations and deletions of 2q33.1 leading to SATB2 haploinsufficiency are associated with cleft palate (CP), facial dysmorphism and intellectual disability (ID). A single patient carrying a nonsense mutation in SATB2 has been described to date. In this study, we performed trio-exome sequencing in a 3-year-old girl with CP and severely delayed speech development, and her unaffected parents. Previously, the girl had undergone conventional and molecular karyotyping (microarray analysis), as well as targeted analysis for different diseases associated with developmental delay, including Angelman syndrome, Rett syndrome and Fragile X syndrome. No diagnosis could be established. Exome sequencing revealed a de novo nonsense mutation in the SATB2 gene (c.715C>T; p.R239*). The identification of a second patient carrying a de novo nonsense mutation in SATB2 confirms that this gene is essential for normal craniofacial patterning and cognitive development. Based on our data and the literature published so far, we propose a new clinically recognizable syndrome - the SATB2-associated syndrome (SAS). SAS is likely to be underdiagnosed and should be considered in children with ID, severe speech delay, cleft or high-arched palate and abnormal dentition with crowded and irregularly shaped teeth.

Confirmation of chromosomal microarray as a first-tier clinical diagnostic test for individuals with developmental delay, intellectual disability, autism spectrum disorders and dysmorphic features.

PubMed

Battaglia, Agatino; Doccini, Viola; Bernardini, Laura; Novelli, Antonio; Loddo, Sara; Capalbo, Anna; Filippi, Tiziana; Carey, John C

2013-11-01

Submicroscopic chromosomal rearrangements are the most common identifiable causes of intellectual disability and autism spectrum disorders associated with dysmorphic features. Chromosomal microarray (CMA) can detect copy number variants <1 Mb and identifies size and presence of known genes. The aim of this study was to demonstrate the usefulness of CMA, as a first-tier tool in detecting the etiology of unexplained intellectual disability/autism spectrum disorders (ID/ASDs) associated with dysmorphic features in a large cohort of pediatric patients. We studied 349 individuals; 223 males, 126 females, aged 5 months-19 years. Blood samples were analyzed with CMA at a resolution ranging from 1 Mb to 40 Kb. The imbalance was confirmed by FISH or qPCR. We considered copy number variants (CNVs) causative if the variant was responsible for a known syndrome, encompassed gene/s of known function, occurred de novo or, if inherited, the parent was variably affected, and/or the involved gene/s had been reported in association with ID/ASDs in dedicated databases. 91 CNVs were detected in 77 (22.06%) patients: 5 (6.49%) of those presenting with borderline cognitive impairment, 54 (70.13%) with a variable degree of DD/ID, and 18/77 (23.38%) with ID of variable degree and ASDs. 16/77 (20.8%) patients had two different rearrangements. Deletions exceeded duplications (58 versus 33); 45.05% (41/91) of the detected CNVs were de novo, 45.05% (41/91) inherited, and 9.9% (9/91) unknown. The CNVs caused the phenotype in 57/77 (74%) patients; 12/57 (21.05%) had ASDs/ID, and 45/57 (78.95%) had DD/ID. Our study provides further evidence of the high diagnostic yield of CMA for genetic testing in children with unexplained ID/ASDs who had dysmorphic features. We confirm the value of CMA as the first-tier tool in the assessment of those conditions in the pediatric setting. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Subtelomeric Deletion of Chromosome 10p15.3: Clinical Findings and Molecular Cytogenetic Characterization

PubMed Central

DeScipio, Cheryl; Conlin, Laura; Rosenfeld, Jill; Tepperberg, James; Pasion, Romela; Patel, Ankita; McDonald, Marie T; Aradhya, Swaroop; Ho, Darlene; Goldstein, Jennifer; McGuire, Marianne; Mulchandani, Surabhi; Medne, Livija; Rupps, Rosemarie; Serrano, Alvaro H.; Thorland, Erik C; Tsai, Anne C-H; Hilhorst-Hofstee, Yvonne; Ruivenkamp, Claudia AL; Van Esch, Hilde; Addor, Marie-Claude; Martinet, Danielle; Mason, Thornton B.A.; Clark, Dinah; Spinner, Nancy B; Krantz, Ian D

2012-01-01

We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11,), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM# 608668) and DIP2C (OMIM# 611380) (UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study. PMID:22847950

Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization.

PubMed

DeScipio, Cheryl; Conlin, Laura; Rosenfeld, Jill; Tepperberg, James; Pasion, Romela; Patel, Ankita; McDonald, Marie T; Aradhya, Swaroop; Ho, Darlene; Goldstein, Jennifer; McGuire, Marianne; Mulchandani, Surabhi; Medne, Livija; Rupps, Rosemarie; Serrano, Alvaro H; Thorland, Erik C; Tsai, Anne C-H; Hilhorst-Hofstee, Yvonne; Ruivenkamp, Claudia A L; Van Esch, Hilde; Addor, Marie-Claude; Martinet, Danielle; Mason, Thornton B A; Clark, Dinah; Spinner, Nancy B; Krantz, Ian D

2012-09-01

We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM 608668) and DIP2C (OMIM 611380; UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study. Copyright © 2012 Wiley Periodicals, Inc.

Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type

PubMed Central

Isrie, Mala; Breuss, Martin; Tian, Guoling; Hansen, Andi Harley; Cristofoli, Francesca; Morandell, Jasmin; Kupchinsky, Zachari A.; Sifrim, Alejandro; Rodriguez-Rodriguez, Celia Maria; Dapena, Elena Porta; Doonanco, Kurston; Leonard, Norma; Tinsa, Faten; Moortgat, Stéphanie; Ulucan, Hakan; Koparir, Erkan; Karaca, Ender; Katsanis, Nicholas; Marton, Valeria; Vermeesch, Joris Robert; Davis, Erica E.; Cowan, Nicholas J.; Keays, David Anthony; Van Esch, Hilde

2015-01-01

Circumferential skin creases Kunze type (CSC-KT) is a specific congenital entity with an unknown genetic cause. The disease phenotype comprises characteristic circumferential skin creases accompanied by intellectual disability, a cleft palate, short stature, and dysmorphic features. Here, we report that mutations in either MAPRE2 or TUBB underlie the genetic origin of this syndrome. MAPRE2 encodes a member of the microtubule end-binding family of proteins that bind to the guanosine triphosphate cap at growing microtubule plus ends, and TUBB encodes a β-tubulin isotype that is expressed abundantly in the developing brain. Functional analyses of the TUBB mutants show multiple defects in the chaperone-dependent tubulin heterodimer folding and assembly pathway that leads to a compromised yield of native heterodimers. The TUBB mutations also have an impact on microtubule dynamics. For MAPRE2, we show that the mutations result in enhanced MAPRE2 binding to microtubules, implying an increased dwell time at microtubule plus ends. Further, in vivo analysis of MAPRE2 mutations in a zebrafish model of craniofacial development shows that the variants most likely perturb the patterning of branchial arches, either through excessive activity (under a recessive paradigm) or through haploinsufficiency (dominant de novo paradigm). Taken together, our data add CSC-KT to the growing list of tubulinopathies and highlight how multiple inheritance paradigms can affect dosage-sensitive biological systems so as to result in the same clinical defect. PMID:26637975

Study on the performance of different craniofacial superimposition approaches (II): Best practices proposal.

PubMed

Damas, S; Wilkinson, C; Kahana, T; Veselovskaya, E; Abramov, A; Jankauskas, R; Jayaprakash, P T; Ruiz, E; Navarro, F; Huete, M I; Cunha, E; Cavalli, F; Clement, J; Lestón, P; Molinero, F; Briers, T; Viegas, F; Imaizumi, K; Humpire, D; Ibáñez, O

2015-12-01

Craniofacial superimposition, although existing for one century, is still a controversial technique within the scientific community. Objective and unbiased validation studies over a significant number of cases are required to establish a more solid picture on the reliability. However, there is lack of protocols and standards in the application of the technique leading to contradictory information concerning reliability. Instead of following a uniform methodology, every expert tends to apply his own approach to the problem, based on the available technology and deep knowledge on human craniofacial anatomy, soft tissues, and their relationships. The aim of this study was to assess the reliability of different craniofacial superimposition methodologies and the corresponding technical approaches to this type of identification. With all the data generated, some of the most representative experts in craniofacial identification joined in a discussion intended to identify and agree on the most important issues that have to be considered to properly employ the craniofacial superimposition technique. As a consequence, the consortium has produced the current manuscript, which can be considered the first standard in the field; including good and bad practices, sources of error and uncertainties, technological requirements and desirable features, and finally a common scale for the craniofacial matching evaluation. Such a document is intended to be part of a more complete framework for craniofacial superimposition, to be developed during the FP7-founded project MEPROCS, which will favour and standardize its proper application. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

An eye on the head: the development and evolution of craniofacial muscles.

PubMed

Sambasivan, Ramkumar; Kuratani, Shigeru; Tajbakhsh, Shahragim

2011-06-01

Skeletal muscles exert diverse functions, enabling both crushing with great force and movement with exquisite precision. A remarkably distinct repertoire of genes and ontological features characterise this tissue, and recent evidence has shown that skeletal muscles of the head, the craniofacial muscles, are evolutionarily, morphologically and molecularly distinct from those of the trunk. Here, we review the molecular basis of craniofacial muscle development and discuss how this process is different to trunk and limb muscle development. Through evolutionary comparisons of primitive chordates (such as amphioxus) and jawless vertebrates (such as lampreys) with jawed vertebrates, we also provide some clues as to how this dichotomy arose.

Craniofacial Duplication: A Case Report

PubMed Central

Suryawanshi, Pradeep; Deshpande, Mandar; Verma, Nitin; Mahendrakar, Vivek; Mahendrakar, Sandhya

2013-01-01

A craniofacial duplication or diprosopus is an unusual variant of conjoined twinning. The reported incidence is one in 180,000-15 million births and 35 cases have been reported till date. The phenotype is wide, with the partial duplication of a few facial structures to complete dicephalus. A complete duplication is associated with a high incidence of anomalies in the central nervous system, cardiovascular system, gastrointestinal system and the respiratory system, whereas no major anomalies are found in the infants with a partial duplication. A term baby with the features of a craniofacial duplication has been described, with the proposed theories on embryogenesis and a brief review of the literature. PMID:24179933

Craniofacial duplication: a case report.

PubMed

Suryawanshi, Pradeep; Deshpande, Mandar; Verma, Nitin; Mahendrakar, Vivek; Mahendrakar, Sandhya

2013-09-01

A craniofacial duplication or diprosopus is an unusual variant of conjoined twinning. The reported incidence is one in 180,000-15 million births and 35 cases have been reported till date. The phenotype is wide, with the partial duplication of a few facial structures to complete dicephalus. A complete duplication is associated with a high incidence of anomalies in the central nervous system, cardiovascular system, gastrointestinal system and the respiratory system, whereas no major anomalies are found in the infants with a partial duplication. A term baby with the features of a craniofacial duplication has been described, with the proposed theories on embryogenesis and a brief review of the literature.

The effects of growth hormone therapy on the somatic development of a group of Polish children with Silver-Russell syndrome.

PubMed

Sienko, Magdalena; Petriczko, Elżbieta; Zajaczek, Stanislaw; Zygmunt-Gorska, Agata; Starzyk, Jerzy; Korpysz, Alicja; Petriczko, Jan; Walczak, Alicja; Walczak, Mieczysław

2017-12-01

Silver-Russell Syndrome is both clinically and genetically a heterogeneous syndrome. Among the most important dysmorphic features of this condition are: a triangular shaped face with a small mandible, a prominent frontal eminence, a thin vermilion border with downward-pointing lip corners, clino- and brachydactyly of the 5th fingers as well as body asymmetry. The most well-known genetic mutations in this syndrome are: the 11p15 epimutation (20-60% patients) and the maternal uniparental chromosome 7 disomy present in 7% to 15% of patients. Children with SRS have severely impaired physical growth - intrauterine and after birth. This, together with the aforementioned dysmorphic features, forms the main diagnostic criteria. The study group consisted of 12 children treated with growth hormone, aged 2 to 17 (8.9±4.0 years), therein, all of whom met the phenotype diagnostic criteria by Wollmann and Price. The effects of growth hormone therapy on somatic development of these children are also presented. Height and weight improved as a result of growth hormone treatment, but the effects were significantly worse than in children with IUGR. Children from the study group presented also a smaller an improvement in growth velocity than children from the control group, but the difference was statistically insignificant. Growth hormone therapy accelerates the growth of children with SRS but to a smaller extent than the growth of children born with intrauterine growth retardation without dysmorphic features.

A unique combination of 17pter trisomy and 21qter monosomy in a boy with developmental delay, severe intellectual disability, growth retardation and dysmorphisms.

PubMed

Zheng, Zhaojing; Yao, Ru-En; Geng, Juan; Jin, Xingming; Shen, Yongnian; Ying, Daming; Fu, Qihua; Yu, Yongguo

2013-03-10

Microduplication at 17p13.3 and microdeletion at 21q22 are both rare chromosomal aberrations. The presence of both genomic imbalances in one patient has not been previously reported in literature. In this study, we performed a molecular diagnostic testing with a whole genome microarray on a 3-year-old boy with developmental delay, mental retardation and multiple malformations. A routine G-banding karyotype analysis was performed using peripheral lymphocytes. Chromosome microarray analysis (CMA) was done using Affymetrix CytoScan™ HD array. Genomic imbalances were further confirmed by multiple ligation-dependent probe amplification (MLPA). The result of karyotyping was normal but CMA detected a 9.8 Mb microduplication at 17p13.3-13.1 (chr17: 1-9,875,545) and a 2.8 Mb microdeletion involving 21q22.3-qter (chr21: 45,239,077-48,097,372). The imbalances were due to a balanced translocation present in patient's mother. The patient was characterized with short stature, profound developmental delay, non-verbal, intellectual disability as well as craniofacial dysmorphism, subtle brain structural anomaly and sparse scalp hair. This is the first patient reported with a combination of a microduplication at 17p13.3-13.1 and a microdeletion at 21q22.3-qter. Both genomic imbalances were undetected by conventional karyotyping but were delineated with CMA test. Synergistic effect from the two rare genomic imbalances is likely responsible for the severe clinical phenotypes observed in this patient. Copyright © 2012 Elsevier B.V. All rights reserved.

Double trisomy 48,XXX,+18 with multiple dysmorphic features.

PubMed

Jiang, Zi-Yan; Wu, Xiao-Hui; Zou, Chao-Chun

2015-02-01

Chromosomal abnormality is a common cause of congenital anomalies, psychiatric disorders, and mental retardation. However, the double trisomy 48,XXX,+18 is a rare chromosome abnormality. Case report and literature review. A 7-hour-old girl presented to our unit because of poor response after birth. She presented with multiple dysmorphic features, including small for gestational age infant, flat nasal bridge, widely-spaced eyes, the left thumb deformities, flat facial profile, raised sternum, ventricular septal defect, the third lateral brain ventricle enlargement, and small liver. This case expands the spectrum of malformations reported in association with the double trisomy 48,XXX,+18. The literature on 16 fetuses or infants with the 48,XXX,+18 were also reviewed. These data suggested that in patients with clinical features similar to trisomy 18, especially with anomalies of the ears and/or reproductive malformations, double trisomy (48,XXX,+18) should be considered and karyotyping should be performed although it is a rare disease.

Syndromic intellectual disability: a new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant.

PubMed

Graziano, Claudio; Wischmeijer, Anita; Pippucci, Tommaso; Fusco, Carlo; Diquigiovanni, Chiara; Nõukas, Margit; Sauk, Martin; Kurg, Ants; Rivieri, Francesca; Blau, Nenad; Hoffmann, Georg F; Chaubey, Alka; Schwartz, Charles E; Romeo, Giovanni; Bonora, Elena; Garavelli, Livia; Seri, Marco

2015-04-01

The causative variant in a consanguineous family in which the three patients (two siblings and a cousin) presented with intellectual disability, Marfanoid habitus, craniofacial dysmorphisms, chronic diarrhea and progressive kyphoscoliosis, has been identified through whole exome sequencing (WES) analysis. WES study identified a homozygous DDC variant in the patients, c.1123C>T, resulting in p.Arg375Cys missense substitution. Mutations in DDC cause a recessive metabolic disorder (aromatic amino acid decarboxylase, AADC, deficiency, OMIM #608643) characterized by hypotonia, oculogyric crises, excessive sweating, temperature instability, dystonia, severe neurologic dysfunction in infancy, and specific abnormalities of neurotransmitters and their metabolites in the cerebrospinal fluid (CSF). In our family, analysis of neurotransmitters and their metabolites in patient's CSF shows a pattern compatible with AADC deficiency, although the clinical signs are different from the classic form. Our work expands the phenotypic spectrum associated with DDC variants, which therefore can cause an additional novel syndrome without typical movement abnormalities. Copyright © 2015 Elsevier B.V. All rights reserved.

Morphometric study of the true S1 and S2 of the normal and dysmorphic sacralized sacra.

PubMed

Firat, Ayşegül; Alemdaroğlu, Kadir Bahadır; Özmeriç, Ahmet; Yücens, Mehmet; Göksülük, Dinçer

2017-06-12

This study aimed to generate data for the S1 and S2 alar pedicle and body and the alar orientations for both dysmorphic and normal sacra. The study comprised two groups: Group N consisted of 53 normal sacra and Group D included 10 dysmorphic sacra. Various features such as alar pedicle circumference; anterior, middle, and posterior axis of the sacral ala; sacral body height and width; and sagittal thickness were measured. In group N, the median anterior axis of the alae was observed to be 30° on the right and 25° on the left, the median midline axis was found to be 20° on the right and 15° on the left, and the median posterior alar axis was -15° on the right and -20° on the left. The true S1 and S2 alar pedicle circumferences were observed to be significantly smaller in group D, which demonstrated a shorter S1 alar pedicle mean circumference, significantly narrower S1 body mean width, and considerably tapered sagittal thickness. Our analysis indicated that dysmorphic sacra have a lower sagittal thickness and width of bodies and smaller alar pedicles, which explains the difficulties in their percutaneous fixation.

North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2

ClinicalTrials.gov

2018-06-06

Epilepsy; Seizure; Neuromuscular Diseases; Brain Malformation; Intellectual Disability; Autism Spectrum Disorder; Hypotonia; Inborn Errors of Metabolism; Movement Disorders; Genetic Disease; Development Delay; Chromosome Abnormality; Hearing Loss; Dysmorphic Features; Skeletal Dysplasia; Congenital Abnormality; Microcephaly; Macrocephaly

Partial monosomy Xq(Xq23 --> qter) and trisomy 4p(4p15.33 --> pter) in a woman with intractable focal epilepsy, borderline intellectual functioning, and dysmorphic features.

PubMed

Bartocci, Arnaldo; Striano, Pasquale; Mancardi, Maria Margherita; Fichera, Marco; Castiglia, Lucia; Galesi, Ornella; Michelucci, Roberto; Elia, Maurizio

2008-06-01

Studies of epilepsy associated with chromosomal abnormalities may provide information about clinical and EEG phenotypes and possibly to identify new epilepsy genes. We describe a female patient with intractable focal epilepsy, borderline intellectual functioning, and facial dysmorphisms, in whom genetic study (i.e., karyotype and array-CGH analysis) revealed a distal trisomy 4p and distal monosomy Xq. Although any genetic hypothesis remains speculative, several genes are located in the 4p chromosome segment involved in the rearrangement, some of which may be related to epilepsy.

Clinical features of muscle dysmorphia among males with body dysmorphic disorder.

PubMed

Pope, Courtney G; Pope, Harrison G; Menard, William; Fay, Christina; Olivardia, Roberto; Phillips, Katharine A

2005-12-01

Muscle dysmorphia - a pathological preoccupation with muscularity - appears to be a form of body dysmorphic disorder (BDD) with a focus on muscularity. However, little is known about muscle dysmorphia in men with BDD, and no study has compared men with BDD who do and do not report muscle dysmorphia. To explore this issue, we reviewed the histories of 63 men with BDD; we compared those rated as having a history of muscle dysmorphia with those who had BDD but not muscle dysmorphia in several domains. The 14 men with muscle dysmorphia resembled the 49 comparison men in demographic features, BDD severity, delusionality, and number of non-muscle-related body parts of concern. However, those with muscle dysmorphia were more likely to have attempted suicide, had poorer quality of life, and had a higher frequency of any substance use disorder and anabolic steroid abuse. Thus, muscle dysmorphia was associated with greater psychopathology.

Clinical features of muscle dysmorphia among males with body dysmorphic disorder

PubMed Central

Pope, Courtney G.; Pope, Harrison G.; Menard, William; Fay, Christina; Olivardia, Roberto; Phillips, Katharine A.

2006-01-01

Muscle dysmorphia – a pathological preoccupation with muscularity – appears to be a form of body dysmorphic disorder (BDD) with a focus on muscularity. However, little is known about muscle dysmorphia in men with BDD, and no study has compared men with BDD who do and do not report muscle dysmorphia. To explore this issue, we reviewed the histories of 63 men with BDD; we compared those rated as having a history of muscle dysmorphia with those who had BDD but not muscle dysmorphia in several domains. The 14 men with muscle dysmorphia resembled the 49 comparison men in demographic features, BDD severity, delusionality, and number of non-muscle-related body parts of concern. However, those with muscle dysmorphia were more likely to have attempted suicide, had poorer quality of life, and had a higher frequency of any substance use disorder and anabolic steroid abuse. Thus, muscle dysmorphia was associated with greater psychopathology. PMID:17075613

Body dysmorphic symptoms: phenomenology and ethnicity.

PubMed

Marques, Luana; LeBlanc, Nicole; Weingarden, Hilary; Greenberg, Jennifer L; Traeger, Lara N; Keshaviah, Aparna; Wilhelm, Sabine

2011-03-01

Differences in the presentation of clinical features of body dysmorphic disorder (BDD) across ethnic groups have received little investigation. The current study assessed BDD symptoms in an ethnically diverse sample of adults (n=401) using an online survey. Participants completed self-report measures assessing BDD symptoms, body parts of concern and BDD behaviors. Compared to Caucasian participants, no significant differences were found in body parts or behaviors reported by Latino or African American participants. Significant group differences did emerge between Asian and Caucasian participants. Specifically, Asians reported more concern with straight hair and dark skin and fewer body shape concerns than Caucasians. Asians also endorsed lower rates of grooming, touching body parts, and camouflaging and higher rates of exercise compared to Caucasians. Although most clinical features of BDD appear similar across ethnic groups, results showed some differences in body parts and behaviors between Caucasians and Asian Americans with BDD symptoms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Current research on pycnodysostosis.

PubMed

Turan, Serap

2014-08-01

Pycnodysostosis is a rare autosomal recessive disorder caused by an inactivating mutation in cathepsin K (CTSK) and characterized by dysmorphic facial features, a short stature, acroosteolysis, osteosclerosis with increased bone fragility, and delayed closure of cranial sutures. Patients usually present with short stature or dysmorphic features the Pediatric Endocrinology or Genetics clinics, with atypical fractures to the orthopedics clinics or hematological abnormalities to the hematology clinics. However, under-diagnosis or misdiagnosis of this condition is a major issue. Pycnodysostosis is not a life threatening condition, but craniosynostosis, frequent fractures, respiratory-sleep problems, and dental problems may cause significant morbidity. Although no specific treatment for this disorder has been described, patients should be followed for complications and treated accordingly. A specific treatment for the disorder must be established in the future to prevent complications and improve quality of life for patients in the current era of advanced molecular research.

Obstructive Sleep Apnea in Women: Study of Speech and Craniofacial Characteristics

PubMed Central

Tyan, Marina; Fernández Pozo, Rubén; Toledano, Doroteo; Lopez Gonzalo, Eduardo; Alcazar Ramirez, Jose Daniel; Hernandez Gomez, Luis Alfonso

2017-01-01

Background Obstructive sleep apnea (OSA) is a common sleep disorder characterized by frequent cessation of breathing lasting 10 seconds or longer. The diagnosis of OSA is performed through an expensive procedure, which requires an overnight stay at the hospital. This has led to several proposals based on the analysis of patients’ facial images and speech recordings as an attempt to develop simpler and cheaper methods to diagnose OSA. Objective The objective of this study was to analyze possible relationships between OSA and speech and facial features on a female population and whether these possible connections may be affected by the specific clinical characteristics in OSA population and, more specifically, to explore how the connection between OSA and speech and facial features can be affected by gender. Methods All the subjects are Spanish subjects suspected to suffer from OSA and referred to a sleep disorders unit. Voice recordings and photographs were collected in a supervised but not highly controlled way, trying to test a scenario close to a realistic clinical practice scenario where OSA is assessed using an app running on a mobile device. Furthermore, clinical variables such as weight, height, age, and cervical perimeter, which are usually reported as predictors of OSA, were also gathered. Acoustic analysis is centered in sustained vowels. Facial analysis consists of a set of local craniofacial features related to OSA, which were extracted from images after detecting facial landmarks by using the active appearance models. To study the probable OSA connection with speech and craniofacial features, correlations among apnea-hypopnea index (AHI), clinical variables, and acoustic and facial measurements were analyzed. Results The results obtained for female population indicate mainly weak correlations (r values between .20 and .39). Correlations between AHI, clinical variables, and speech features show the prevalence of formant frequencies over bandwidths, with F2/i/ being the most appropriate formant frequency for OSA prediction in women. Results obtained for male population indicate mainly very weak correlations (r values between .01 and .19). In this case, bandwidths prevail over formant frequencies. Correlations between AHI, clinical variables, and craniofacial measurements are very weak. Conclusions In accordance with previous studies, some clinical variables are found to be good predictors of OSA. Besides, strong correlations are found between AHI and some clinical variables with speech and facial features. Regarding speech feature, the results show the prevalence of formant frequency F2/i/ over the rest of features for the female population as OSA predictive feature. Although the correlation reported is weak, this study aims to find some traces that could explain the possible connection between OSA and speech in women. In the case of craniofacial measurements, results evidence that some features that can be used for predicting OSA in male patients are not suitable for testing female population. PMID:29109068

[Determination of somatotype of man in cranio-facial personality identification].

PubMed

2004-01-01

On the basis of their independent research and through the analysis of published data the authors suggested quantitative criteria for the diagnosis of a somatotype of man by the dimensional features of the face and skull. M. A. Negasheva method, based on the discriminative analysis of 7 measurement features, was used in the individual diagnosis of a somatotype by V. V. Bunaka scheme (somatotypes-pectoral, muscular, abdominal and indefinite). The authors suggest 2 diagnostic models based on the linear and discriminative analysis of 11 and 7 measurement features for the skull. The diagnostic accuracy in case of main male som-atotypes makes 87 and 64.4%, respectively, with the canonic correlations of 0.574 and 0.292. The designed methods can be used in forensic medicine for the cranio-facial and portrait expertise.

Craniofacial morphology and dental maturity in children with reduced somatic growth of different aetiology and the effect of growth hormone treatment.

PubMed

Davidopoulou, Sotiria; Chatzigianni, Athina

2017-12-01

Children with reduced somatic growth may present various endocrinal diseases, especially growth hormone deficiency (GHD), idiopathic short stature (ISS), chromosomal aberrations, or genetic disorders. In an attempt to normalize the short stature, growth hormone (GH) is administered to these children. The aim of this literature review was to collect information about the craniofacial morphology and dental maturity in these children and to present the existing knowledge on the effect of GH treatment on the above structures.This review demonstrated that regardless of the origin of the somatic growth retardation, these children show similar craniofacial features, such as short length of the cranial base and the mandible, increased lower facial height, retropositioned mandible, and obtuse gonion angle. On the other hand, dental maturation does not demonstrate a specific pattern. Except for the above findings, muscle alterations seem to be present in individuals with short stature, who present low body muscle mass and strength, while studies on their craniofacial muscles seem to be lacking. After GH administration, the exact amount and pattern of craniofacial growth is unpredictable; however, the facial convexity decreases, mandibular length increases, and posterior facial height increases, while tooth eruption remains unaffected. Thus, it is of great importance to gain more insight into the craniofacial growth of treated and untreated children with reduced somatic growth so that the influence of GH therapy on the various craniofacial structures could be ascertained and proper orthodontic treatment could be selected.

Further delineation of the SATB2 phenotype

PubMed Central

Döcker, Dennis; Schubach, Max; Menzel, Moritz; Munz, Marita; Spaich, Christiane; Biskup, Saskia; Bartholdi, Deborah

2014-01-01

SATB2 is an evolutionarily highly conserved chromatin remodeling gene located on chromosome 2q33.1. Vertebrate animal models have shown that Satb2 has a crucial role in craniofacial patterning and osteoblast differentiation, as well as in determining the fates of neuronal projections in the developing neocortex. In humans, chromosomal translocations and deletions of 2q33.1 leading to SATB2 haploinsufficiency are associated with cleft palate (CP), facial dysmorphism and intellectual disability (ID). A single patient carrying a nonsense mutation in SATB2 has been described to date. In this study, we performed trio-exome sequencing in a 3-year-old girl with CP and severely delayed speech development, and her unaffected parents. Previously, the girl had undergone conventional and molecular karyotyping (microarray analysis), as well as targeted analysis for different diseases associated with developmental delay, including Angelman syndrome, Rett syndrome and Fragile X syndrome. No diagnosis could be established. Exome sequencing revealed a de novo nonsense mutation in the SATB2 gene (c.715C>T; p.R239*). The identification of a second patient carrying a de novo nonsense mutation in SATB2 confirms that this gene is essential for normal craniofacial patterning and cognitive development. Based on our data and the literature published so far, we propose a new clinically recognizable syndrome – the SATB2-associated syndrome (SAS). SAS is likely to be underdiagnosed and should be considered in children with ID, severe speech delay, cleft or high-arched palate and abnormal dentition with crowded and irregularly shaped teeth. PMID:24301056

A regional method for craniofacial reconstruction based on coordinate adjustments and a new fusion strategy.

PubMed

Deng, Qingqiong; Zhou, Mingquan; Wu, Zhongke; Shui, Wuyang; Ji, Yuan; Wang, Xingce; Liu, Ching Yiu Jessica; Huang, Youliang; Jiang, Haiyan

2016-02-01

Craniofacial reconstruction recreates a facial outlook from the cranium based on the relationship between the face and the skull to assist identification. But craniofacial structures are very complex, and this relationship is not the same in different craniofacial regions. Several regional methods have recently been proposed, these methods segmented the face and skull into regions, and the relationship of each region is then learned independently, after that, facial regions for a given skull are estimated and finally glued together to generate a face. Most of these regional methods use vertex coordinates to represent the regions, and they define a uniform coordinate system for all of the regions. Consequently, the inconsistence in the positions of regions between different individuals is not eliminated before learning the relationships between the face and skull regions, and this reduces the accuracy of the craniofacial reconstruction. In order to solve this problem, an improved regional method is proposed in this paper involving two types of coordinate adjustments. One is the global coordinate adjustment performed on the skulls and faces with the purpose to eliminate the inconsistence of position and pose of the heads; the other is the local coordinate adjustment performed on the skull and face regions with the purpose to eliminate the inconsistence of position of these regions. After these two coordinate adjustments, partial least squares regression (PLSR) is used to estimate the relationship between the face region and the skull region. In order to obtain a more accurate reconstruction, a new fusion strategy is also proposed in the paper to maintain the reconstructed feature regions when gluing the facial regions together. This is based on the observation that the feature regions usually have less reconstruction errors compared to rest of the face. The results demonstrate that the coordinate adjustments and the new fusion strategy can significantly improve the craniofacial reconstructions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies.

PubMed

Maini, I; Ivanovski, I; Djuric, O; Caraffi, S G; Errichiello, E; Marinelli, M; Franchi, F; Bizzarri, V; Rosato, S; Pollazzon, M; Gelmini, C; Malacarne, M; Fusco, C; Gargano, G; Bernasconi, S; Zuffardi, O; Garavelli, L

2018-03-09

Since 2010, array-CGH (aCGH) has been the first-tier test in the diagnostic approach of children with neurodevelopmental disorders (NDD) or multiple congenital anomalies (MCA) of unknown origin. Its broad application led to the detection of numerous variants of uncertain clinical significance (VOUS). How to appropriately interpret aCGH results represents a challenge for the clinician. We present a retrospective study on 293 patients with age range 1 month - 29 years (median 7 years) with NDD and/or MCA and/or dysmorphisms, investigated through aCGH between 2005 and 2016. The aim of the study was to analyze clinical and molecular cytogenetic data in order to identify what elements could be useful to interpret unknown or poorly described aberrations. Comparison of phenotype and cytogenetic characteristics through univariate analysis and multivariate logistic regression was performed. Copy number variations (CNVs) with a frequency < 1% were detected in 225 patients of the total sample, while 68 patients presented only variants with higher frequency (heterozygous deletions or amplification) and were considered to have negative aCGH. Proved pathogenic CNVs were detected in 70 patients (20.6%). Delayed psychomotor development, intellectual disability, intrauterine growth retardation (IUGR), prematurity, congenital heart disease, cerebral malformations and dysmorphisms correlated to reported pathogenic CNVs. Prematurity, ventricular septal defect and dysmorphisms remained significant predictors of pathogenic CNVs in the multivariate logistic model whereas abnormal EEG and limb dysmorphisms were mainly detected in the group with likely pathogenic VOUS. A flow-chart regarding the care for patients with NDD and/or MCA and/or dysmorphisms and the interpretation of aCGH has been made on the basis of the data inferred from this study and literature. Our work contributes to make the investigative process of CNVs more informative and suggests possible directions in aCGH interpretation and phenotype correlation.

Prevalence and clinical characteristics of body dysmorphic disorder in an adult inpatient setting†

PubMed Central

Conroy, Michelle; Menard, William; Fleming-Ives, Kathryn; Modha, Poonam; Cerullo, Hilary; Phillips, Katharine A.

2008-01-01

Objective Body dysmorphic disorder (BDD), a distressing or impairing preoccupation with an imagined or slight defect in appearance, is an often-severe, understudied disorder. We determined BDD’s prevalence and clinical features on a general adult psychiatric inpatient unit. To our knowledge, only one previous prevalence study has been done in this setting. Method One hundred patients completed 3 self-report measures: the Body Dysmorphic Disorder Questionnaire (BDD-Q), Beck Anxiety Inventory (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D). Those who screened positive for BDD were interviewed to confirm DSM-IV BDD and its clinical features. Charts were reviewed for demographic and clinical information. Results BDD was diagnosed in 16.0% (95% CI=8.7–23.3%) (n=16) of patients. A high proportion of those with BDD reported that BDD symptoms contributed to suicidality. Patients revealed BDD symptoms to a mean of only 15.1%±33.7% lifetime mental health clinicians; only one (6.3%) reported symptoms to his current inpatient psychiatrist. Most did not disclose their symptoms due to embarrassment. Those with BDD were younger (P=.008) and had higher CES-D scores (P=.008). The two groups did not significantly differ on BAI score, demographic characteristics or discharge diagnoses. Conclusions BDD is relatively common but underdiagnosed in psychiatric inpatients and is associated with more severe depressive symptoms. PMID:18164943

Spectrum of mucocutaneous, ocular and facial features and delineation of novel presentations in 62 classical Ehlers-Danlos syndrome patients.

PubMed

Colombi, M; Dordoni, C; Venturini, M; Ciaccio, C; Morlino, S; Chiarelli, N; Zanca, A; Calzavara-Pinton, P; Zoppi, N; Castori, M; Ritelli, M

2017-12-01

Classical Ehlers-Danlos syndrome (cEDS) is characterized by marked cutaneous involvement, according to the Villefranche nosology and its 2017 revision. However, the diagnostic flow-chart that prompts molecular testing is still based on experts' opinion rather than systematic published data. Here we report on 62 molecularly characterized cEDS patients with focus on skin, mucosal, facial, and articular manifestations. The major and minor Villefranche criteria, additional 11 mucocutaneous signs and 15 facial dysmorphic traits were ascertained and feature rates compared by sex and age. In our cohort, we did not observe any mandatory clinical sign. Skin hyperextensibility plus atrophic scars was the most frequent combination, whereas generalized joint hypermobility according to the Beighton score decreased with age. Skin was more commonly hyperextensible on elbows, neck, and knees. The sites more frequently affected by abnormal atrophic scarring were knees, face (especially forehead), pretibial area, and elbows. Facial dysmorphism commonly affected midface/orbital areas with epicanthal folds and infraorbital creases more commonly observed in young patients. Our findings suggest that the combination of ≥1 eye dysmorphism and facial/forehead scars may support the diagnosis in children. Minor acquired traits, such as molluscoid pseudotumors, subcutaneous spheroids, and signs of premature skin aging are equally useful in adults. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The incidence of chromosome abnormalities in neonates with structural heart disease.

PubMed

Dykes, John C; Al-mousily, Mohammad F; Abuchaibe, Eda-Cristina; Silva, Jennifer N; Zadinsky, Jennifer; Duarte, Daniel; Welch, Elizabeth

2016-04-01

This study was conducted to determine the prevalence of chromosomal anomalies in newborns with structural heart disease admitted to the cardiac intensive care unit (CICU) at Nicklaus Children's Hospital (NCH). A retrospective review identified newborns age 30 days or less admitted to NCH CICU between 2004 and 2010. Patients with structural heart disease who required admission to our CICU and received karyotype or karyotype and fluorescent in situ hybridization (FISH) testing were included in the study. All patients were examined for the presence of dysmorphic features. Four hundred and eighty-two patients met the criteria for the study; 405 (84%) received both karyotype and FISH. Chromosome abnormalities were present in 86 (17.8%) patients. Syndromes accounted for 20 (5.1%) of those with normal chromosomes. Dysmorphic features were seen in 79.1% of patients with abnormal chromosomes and 25.5% of those with normal chromosomes. All patients with syndromes were dysmorphic. Race and gender did not significantly affect the incidence of genetic abnormalities. Chromosome abnormalities, including syndromes, are prevalent in newborns with congenital heart disease. Further research is needed to evaluate the utility of cytogenetic screening in all children with congenital heart disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Imaging findings in craniofacial childhood rhabdomyosarcoma

PubMed Central

Merks, Johannes H. M.; Saeed, Peerooz; Balm, Alfons J. M.; Bras, Johannes; Pieters, Bradley R.; Adam, Judit A.; van Rijn, Rick R.

2010-01-01

Rhabdomyosarcoma (RMS) is the commonest paediatric soft-tissue sarcoma constituting 3–5% of all malignancies in childhood. RMS has a predilection for the head and neck area and tumours in this location account for 40% of all childhood RMS cases. In this review we address the clinical and imaging presentations of craniofacial RMS, discuss the most appropriate imaging techniques, present characteristic imaging features and offer an overview of differential diagnostic considerations. Post-treatment changes will be briefly addressed. PMID:20725831

Characterizing facial features in individuals with craniofacial microsomia: A systematic approach for clinical research.

PubMed

Heike, Carrie L; Wallace, Erin; Speltz, Matthew L; Siebold, Babette; Werler, Martha M; Hing, Anne V; Birgfeld, Craig B; Collett, Brent R; Leroux, Brian G; Luquetti, Daniela V

2016-11-01

Craniofacial microsomia (CFM) is a congenital condition with wide phenotypic variability, including hypoplasia of the mandible and external ear. We assembled a cohort of children with facial features within the CFM spectrum and children without known craniofacial anomalies. We sought to develop a standardized approach to assess and describe the facial characteristics of the study cohort, using multiple sources of information gathered over the course of this longitudinal study and to create case subgroups with shared phenotypic features. Participants were enrolled between 1996 and 2002. We classified the facial phenotype from photographs, ratings using a modified version of the Orbital, Ear, Mandible, Nerve, Soft tissue (OMENS) pictorial system, data from medical record abstraction, and health history questionnaires. The participant sample included 142 cases and 290 controls. The average age was 13.5 years (standard deviation, 1.3 years; range, 11.1-17.1 years). Sixty-one percent of cases were male, 74% were white non-Hispanic. Among cases, the most common features were microtia (66%) and mandibular hypoplasia (50%). Case subgroups with meaningful group definitions included: (1) microtia without other CFM-related features (n = 24), (2) microtia with mandibular hypoplasia (n = 46), (3) other combinations of CFM- related facial features (n = 51), and (4) atypical features (n = 21). We developed a standardized approach for integrating multiple data sources to phenotype individuals with CFM, and created subgroups based on clinically-meaningful, shared characteristics. We hope that this system can be used to explore associations between phenotype and clinical outcomes of children with CFM and to identify the etiology of CFM. Birth Defects Research (Part A) 106:915-926, 2016.© 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Identification of new TRIP12 variants and detailed clinical evaluation of individuals with non-syndromic intellectual disability with or without autism

PubMed Central

Lüdecke, H.-J.; Pettersson, M.; Albrecht, B.; Bernier, R. A.; Cremer, K.; Eichler, E. E.; Falkenstein, D.; Gerdts, J.; Jansen, S.; Kuechler, A.; Kvarnung, M.; Lindstrand, A.; Nilsson, D.; Nordgren, A.; Pfundt, R.; Spruijt, L.; Surowy, H. M.; de Vries, B. B. A.; Wieland, T.; Engels, H.; Strom, T. M.; Kleefstra, T.; Wieczorek, D.

2018-01-01

The ubiquitin pathway is an enzymatic cascade including activating E1, conjugating E2, and ligating E3 enzymes, which governs protein degradation and sorting. It is crucial for many physiological processes. Compromised function of members of the ubiquitin pathway leads to a wide range of human diseases, such as cancer, neurodegenerative diseases, and neurodevelopmental disorders. Mutations in the thyroid hormone receptor interactor 12 (TRIP12) gene (OMIM 604506), which encodes an E3 ligase in the ubiquitin pathway, have been associated with autism spectrum disorder (ASD). In addition to autistic features, TRIP12 mutation carriers showed intellectual disability (ID). More recently, TRIP12 was postulated as a novel candidate gene for intellectual disability in a meta-analysis of published ID cohorts. However, detailed clinical information characterizing the phenotype of these individuals was not provided. In this study, we present seven novel individuals with private TRIP12 mutations including two splice site mutations, one nonsense mutation, three missense mutations, and one translocation case with a breakpoint in intron 1 of the TRIP12 gene and clinically review four previously published cases. The TRIP12 mutation-positive individuals presented with mild to moderate ID (10/11) or learning disability [intelligence quotient (IQ) 76 in one individual], ASD (8/11) and some of them with unspecific craniofacial dysmorphism and other anomalies. In this study, we provide detailed clinical information of 11 TRIP12 mutation-positive individuals and thereby expand the clinical spectrum of the TRIP12 gene in non-syndromic intellectual disability with or without ASD. PMID:27848077

Further delineation of the KBG syndrome phenotype caused by ANKRD11 aberrations

PubMed Central

Ockeloen, Charlotte W; Willemsen, Marjolein H; de Munnik, Sonja; van Bon, Bregje WM; de Leeuw, Nicole; Verrips, Aad; Kant, Sarina G; Jones, Elizabeth A; Brunner, Han G; van Loon, Rosa LE; Smeets, Eric EJ; van Haelst, Mieke M; van Haaften, Gijs; Nordgren, Ann; Malmgren, Helena; Grigelioniene, Giedre; Vermeer, Sascha; Louro, Pedro; Ramos, Lina; Maal, Thomas JJ; van Heumen, Celeste C; Yntema, Helger G; Carels, Carine EL; Kleefstra, Tjitske

2015-01-01

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases. PMID:25424714

Identification of new TRIP12 variants and detailed clinical evaluation of individuals with non-syndromic intellectual disability with or without autism.

PubMed

Bramswig, Nuria C; Lüdecke, H-J; Pettersson, M; Albrecht, B; Bernier, R A; Cremer, K; Eichler, E E; Falkenstein, D; Gerdts, J; Jansen, S; Kuechler, A; Kvarnung, M; Lindstrand, A; Nilsson, D; Nordgren, A; Pfundt, R; Spruijt, L; Surowy, H M; de Vries, B B A; Wieland, T; Engels, H; Strom, T M; Kleefstra, T; Wieczorek, D

2017-02-01

The ubiquitin pathway is an enzymatic cascade including activating E1, conjugating E2, and ligating E3 enzymes, which governs protein degradation and sorting. It is crucial for many physiological processes. Compromised function of members of the ubiquitin pathway leads to a wide range of human diseases, such as cancer, neurodegenerative diseases, and neurodevelopmental disorders. Mutations in the thyroid hormone receptor interactor 12 (TRIP12) gene (OMIM 604506), which encodes an E3 ligase in the ubiquitin pathway, have been associated with autism spectrum disorder (ASD). In addition to autistic features, TRIP12 mutation carriers showed intellectual disability (ID). More recently, TRIP12 was postulated as a novel candidate gene for intellectual disability in a meta-analysis of published ID cohorts. However, detailed clinical information characterizing the phenotype of these individuals was not provided. In this study, we present seven novel individuals with private TRIP12 mutations including two splice site mutations, one nonsense mutation, three missense mutations, and one translocation case with a breakpoint in intron 1 of the TRIP12 gene and clinically review four previously published cases. The TRIP12 mutation-positive individuals presented with mild to moderate ID (10/11) or learning disability [intelligence quotient (IQ) 76 in one individual], ASD (8/11) and some of them with unspecific craniofacial dysmorphism and other anomalies. In this study, we provide detailed clinical information of 11 TRIP12 mutation-positive individuals and thereby expand the clinical spectrum of the TRIP12 gene in non-syndromic intellectual disability with or without ASD.

Disruption of RAB40AL function leads to Martin--Probst syndrome, a rare X-linked multisystem neurodevelopmental human disorder.

PubMed

Bedoyan, Jirair Krikor; Schaibley, Valerie M; Peng, Weiping; Bai, Yongsheng; Mondal, Kajari; Shetty, Amol C; Durham, Mark; Micucci, Joseph A; Dhiraaj, Arti; Skidmore, Jennifer M; Kaplan, Julie B; Skinner, Cindy; Schwartz, Charles E; Antonellis, Anthony; Zwick, Michael E; Cavalcoli, James D; Li, Jun Z; Martin, Donna M

2012-05-01

Martin--Probst syndrome (MPS) is a rare X-linked disorder characterised by deafness, cognitive impairment, short stature and distinct craniofacial dysmorphisms, among other features. The authors sought to identify the causative mutation for MPS. Massively parallel sequencing in two affected, related male subjects with MPS identified a RAB40AL (also called RLGP) missense mutation (chrX:102,079,078-102,079,079AC→GA p.D59G; hg18). RAB40AL encodes a small Ras-like GTPase protein with one suppressor of cytokine signalling box. The p.D59G variant is located in a highly conserved region of the GTPase domain between β-2 and β-3 strands. Using RT-PCR, the authors show that RAB40AL is expressed in human fetal and adult brain and kidney, and adult lung, heart, liver and skeletal muscle. RAB40AL appears to be a primate innovation, with no orthologues found in mouse, Xenopus or zebrafish. Western analysis and fluorescence microscopy of GFP-tagged RAB40AL constructs from transiently transfected COS7 cells show that the D59G missense change renders RAB40AL unstable and disrupts its cytoplasmic localisation. This is the first study to show that mutation of RAB40AL is associated with a human disorder. Identification of RAB40AL as the gene mutated in MPS allows for further investigations into the molecular mechanism(s) of RAB40AL and its roles in diverse processes such as cognition, hearing and skeletal development.

Disruption of RAB40AL function leads to Martin–Probst syndrome, a rare X-linked multisystem neurodevelopmental human disorder

PubMed Central

Bedoyan, Jirair Krikor; Schaibley, Valerie M; Peng, Weiping; Bai, Yongsheng; Mondal, Kajari; Shetty, Amol C; Durham, Mark; Micucci, Joseph A; Dhiraaj, Arti; Skidmore, Jennifer M; Kaplan, Julie B; Skinner, Cindy; Schwartz, Charles E; Antonellis, Anthony; Zwick, Michael E; Cavalcoli, James D; Li, Jun Z

2012-01-01

Background and aim Martin–Probst syndrome (MPS) is a rare X-linked disorder characterised by deafness, cognitive impairment, short stature and distinct craniofacial dysmorphisms, among other features. The authors sought to identify the causative mutation for MPS. Methods and results Massively parallel sequencing in two affected, related male subjects with MPS identified a RAB40AL (also called RLGP) missense mutation (chrX:102,079,078-102,079,079AC→GA p.D59G; hg18). RAB40AL encodes a small Ras-like GTPase protein with one suppressor of cytokine signalling box. The p.D59G variant is located in a highly conserved region of the GTPase domain between β-2 and β-3 strands. Using RT-PCR, the authors show that RAB40AL is expressed in human fetal and adult brain and kidney, and adult lung, heart, liver and skeletal muscle. RAB40AL appears to be a primate innovation, with no orthologues found in mouse, Xenopus or zebrafish. Western analysis and fluorescence microscopy of GFP-tagged RAB40AL constructs from transiently transfected COS7 cells show that the D59G missense change renders RAB40AL unstable and disrupts its cytoplasmic localisation. Conclusions This is the first study to show that mutation of RAB40AL is associated with a human disorder. Identification of RAB40AL as the gene mutated in MPS allows for further investigations into the molecular mechanism(s) of RAB40AL and its roles in diverse processes such as cognition, hearing and skeletal development. PMID:22581972

Further delineation of the KBG syndrome phenotype caused by ANKRD11 aberrations.

PubMed

Ockeloen, Charlotte W; Willemsen, Marjolein H; de Munnik, Sonja; van Bon, Bregje W M; de Leeuw, Nicole; Verrips, Aad; Kant, Sarina G; Jones, Elizabeth A; Brunner, Han G; van Loon, Rosa L E; Smeets, Eric E J; van Haelst, Mieke M; van Haaften, Gijs; Nordgren, Ann; Malmgren, Helena; Grigelioniene, Giedre; Vermeer, Sascha; Louro, Pedro; Ramos, Lina; Maal, Thomas J J; van Heumen, Celeste C; Yntema, Helger G; Carels, Carine E L; Kleefstra, Tjitske

2015-09-01

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.

Evolution of middle-late Pleistocene human cranio-facial form: a 3-D approach.

PubMed

Harvati, Katerina; Hublin, Jean-Jacques; Gunz, Philipp

2010-11-01

The classification and phylogenetic relationships of the middle Pleistocene human fossil record remains one of the most intractable problems in paleoanthropology. Several authors have noted broad resemblances between European and African fossils from this period, suggesting a single taxon ancestral to both modern humans and Neanderthals. Others point out 'incipient' Neanderthal features in the morphology of the European sample and have argued for their inclusion in the Neanderthal lineage exclusively, following a model of accretionary evolution of Neanderthals. We approach these questions using geometric morphometric methods which allow the intuitive visualization and quantification of features previously described qualitatively. We apply these techniques to evaluate proposed cranio-facial 'incipient' facial, vault, and basicranial traits in a middle-late Pleistocene European hominin sample when compared to a sample of the same time depth from Africa. Some of the features examined followed the predictions of the accretion model and relate the middle Pleistocene European material to the later Neanderthals. However, although our analysis showed a clear separation between Neanderthals and early/recent modern humans and morphological proximity between European specimens from OIS 7 to 3, it also shows that the European hominins from the first half of the middle Pleistocene still shared most of their cranio-facial architecture with their African contemporaries. Copyright © 2010 Elsevier Ltd. All rights reserved.

Body Image and Quality of Life in Adolescents With Craniofacial Conditions

PubMed Central

Crerand, Canice E.; Sarwer, David B.; Kazak, Anne E.; Clarke, Alexandra; DPsych; Rumsey, Nichola

2017-01-01

Objective To evaluate body image in adolescents with and without craniofacial conditions; and to examine relationships between body image and quality of life. Design Case-control design. Setting A pediatric hospital’s craniofacial center and primary care practices. Participants 70 adolescents with visible craniofacial conditions and a demographically-matched sample of 42 adolescents without craniofacial conditions. Main Outcome Measure Adolescents completed measures of quality of life and body image including satisfaction with weight, facial and overall appearance; investment in appearance (importance of appearance to self-worth); and body image disturbance (appearance-related distress and impairment in functioning). Results Adolescents with craniofacial conditions reported lower appearance investment (p < 0.001) and were more likely to report concerns about facial features (p < 0.02) compared to non-affected youth. Females in both groups reported greater investment in appearance, greater body image disturbance, and lower weight satisfaction compared to males (p < 0.01). Within both groups, greater body image disturbance was associated with lower quality of life (p <0.01). The two groups did not differ significantly on measures of quality of life, body image disturbance, or satisfaction with appearance. Conclusions Body image and quality of life in adolescents with craniofacial conditions are similar to non-affected youth. Relationships between body image and quality of life emphasize that appearance perceptions are important to adolescents’ well-being regardless of whether they have a facial disfigurement. Investment in one’s appearance may explain variations in body image satisfaction and serve as an intervention target particularly for females. PMID:26751907

Obstructive Sleep Apnea in Women: Study of Speech and Craniofacial Characteristics.

PubMed

Tyan, Marina; Espinoza-Cuadros, Fernando; Fernández Pozo, Rubén; Toledano, Doroteo; Lopez Gonzalo, Eduardo; Alcazar Ramirez, Jose Daniel; Hernandez Gomez, Luis Alfonso

2017-11-06

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by frequent cessation of breathing lasting 10 seconds or longer. The diagnosis of OSA is performed through an expensive procedure, which requires an overnight stay at the hospital. This has led to several proposals based on the analysis of patients' facial images and speech recordings as an attempt to develop simpler and cheaper methods to diagnose OSA. The objective of this study was to analyze possible relationships between OSA and speech and facial features on a female population and whether these possible connections may be affected by the specific clinical characteristics in OSA population and, more specifically, to explore how the connection between OSA and speech and facial features can be affected by gender. All the subjects are Spanish subjects suspected to suffer from OSA and referred to a sleep disorders unit. Voice recordings and photographs were collected in a supervised but not highly controlled way, trying to test a scenario close to a realistic clinical practice scenario where OSA is assessed using an app running on a mobile device. Furthermore, clinical variables such as weight, height, age, and cervical perimeter, which are usually reported as predictors of OSA, were also gathered. Acoustic analysis is centered in sustained vowels. Facial analysis consists of a set of local craniofacial features related to OSA, which were extracted from images after detecting facial landmarks by using the active appearance models. To study the probable OSA connection with speech and craniofacial features, correlations among apnea-hypopnea index (AHI), clinical variables, and acoustic and facial measurements were analyzed. The results obtained for female population indicate mainly weak correlations (r values between .20 and .39). Correlations between AHI, clinical variables, and speech features show the prevalence of formant frequencies over bandwidths, with F2/i/ being the most appropriate formant frequency for OSA prediction in women. Results obtained for male population indicate mainly very weak correlations (r values between .01 and .19). In this case, bandwidths prevail over formant frequencies. Correlations between AHI, clinical variables, and craniofacial measurements are very weak. In accordance with previous studies, some clinical variables are found to be good predictors of OSA. Besides, strong correlations are found between AHI and some clinical variables with speech and facial features. Regarding speech feature, the results show the prevalence of formant frequency F2/i/ over the rest of features for the female population as OSA predictive feature. Although the correlation reported is weak, this study aims to find some traces that could explain the possible connection between OSA and speech in women. In the case of craniofacial measurements, results evidence that some features that can be used for predicting OSA in male patients are not suitable for testing female population. ©Marina Tyan, Fernando Espinoza-Cuadros, Rubén Fernández Pozo, Doroteo Toledano, Eduardo Lopez Gonzalo, Jose Daniel Alcazar Ramirez, Luis Alfonso Hernandez Gomez. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 06.11.2017.

Melorheostosis and central giant cell granuloma of the mandible in a 15-year-old girl.

PubMed

Anderson, K M; Shintaku, W H; Rosebush, M S; Rawal, Y B; Woodard, E S

2013-11-01

Melorheostosis is a nonhereditary bone dysplasia primarily affecting the appendicular skeleton. Because clinical and histologic features are often nonspecific, the diagnosis is often based on the radiographic presentation. Involvement of the craniofacial skeleton is rare. We describe a case of a 15-year-old girl with appendicular and craniofacial melorheostosis with adjacent central giant cell granuloma. We discuss the possible significance of this previously unreported finding. Copyright © 2013 Elsevier Inc. All rights reserved.

19q13.32 microdeletion syndrome: three new cases.

PubMed

Castillo, Angela; Kramer, Nancy; Schwartz, Charles E; Miles, Judith H; DuPont, Barbara R; Rosenfeld, Jill A; Graham, John M

2014-01-01

A previous report described a unique phenotype associated with an apparently de novo 732 kb 19q13.32 microdeletion, consisting of intellectual disability, facial asymmetry, ptosis, oculomotor abnormalities, orofacial clefts, cardiac defects, scoliosis and chronic constipation. We report three unrelated patients with developmental delay and dysmorphic features, who were all found to have interstitial 19q13.32 microdeletions of varying sizes. Both the previously reported patient and our Patient 1 with a larger, 1.3-Mb deletion have distinctive dysmorphic features and medical problems, allowing us to define a recognizable 19q13.32 microdeletion syndrome. Patient 1 was hypotonic and dysmorphic at birth, with aplasia of the posterior corpus callosum, bilateral ptosis, oculomotor paralysis, down-slanting palpebral fissures, facial asymmetry, submucosal cleft palate, micrognathia, wide-spaced nipples, right-sided aortic arch, hypospadias, bilateral inguinal hernias, double toenail of the left second toe, partial 2-3 toe syndactyly, kyphoscoliosis and colonic atony. Therefore, the common features of the 19q13.32 microdeletion syndrome include facial asymmetry, ptosis, oculomotor paralysis, orofacial clefting, micrognathia, kyphoscoliosis, aortic defects and colonic atony. These findings are probably related to a deletion of some combination of the 20-23 genes in common between these two patients, especially NPAS1, NAPA, ARHGAP35, SLC8A2, DHX34, MEIS3, and ZNF541. These candidate genes are expressed in the brain parenchyma, glia, heart, gastrointestinal tract and musculoskeletal system and likely play a fundamental role in the expression of this phenotype. This report delineates the phenotypic spectrum associated with the haploinsufficiency of genes found in 19q13.32. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Body Dysmorphic Symptoms, Functional Impairment, and Depression: The Role of Appearance-Based Teasing.

PubMed

Weingarden, Hilary; Renshaw, Keith D

2016-01-01

Body dysmorphic disorder is associated with elevated social and occupational impairment and comorbid depression, but research on risk factors for body dysmorphic symptoms and associated outcomes is limited. Appearance-based teasing may be a potential risk factor. To examine the specificity of this factor, the authors assessed self-reported appearance-based teasing, body dysmorphic, and obsessive-compulsive symptom severity, functional impairment (i.e., social, occupational, family impairment), and depression in a nonclinical sample of undergraduates. As hypothesized, appearance-based teasing was positively correlated with body dysmorphic symptoms. The correlation between teasing and body dysmorphic symptoms was stronger than that between teasing and obsessive-compulsive symptom severity. Last, body dysmorphic symptom severity and appearance-based teasing interacted in predicting functional impairment and depression. Specifically, appearance-based teasing was positively associated with depression and functional impairment only in those with elevated body dysmorphic symptoms. When a similar moderation was tested with obsessive-compulsive, in place of body dysmorphic, symptom severity, the interaction was nonsignificant. Findings support theory that appearance-based teasing is a specific risk factor for body dysmorphic symptoms and associated functional impairment.

Sanjad-Sakati syndrome with macrocytic anemia and failure to thrive: a case from South Jordan.

PubMed

Ajarmeh, Salma A; Al Tamimi, Eyad M

2018-04-25

Backgorund: Sanjad-Sakati syndrome (SSS) is a rare autosomal recessive disease caused by a deletion mutation (155-166del) in exon 3 of the TBCE gene on chromosome 1q42-43. The syndrome is characterized by primary hypoparathyroidism, typical dysmorphic features and severe growth retardation. We encountered a 2-year-old boy with hypocalcemia, failure to thrive and macrocytic anemia. The patient had the characteristic features of SSS and genetic testing confirmed that he was homozygous for the TBCE mutation. Although malabsorption was initially considered the cause of his symptoms, the results did not confirm that diagnosis. Our patient had cow milk protein allergy and folic acid deficiency, which has not been described in previous SSS cases. It was difficult to treat the patient's hyperphosphatemia and we ultimately selected sevelamer treatment, which was tolerated well and improved his hypocalcemia. SSS should be considered in the differential diagnosis of any infant with hypocalcemia, dysmorphism and failure to thrive.

Cognitive-Behavioral Therapy for Youth with Body Dysmorphic Disorder: Current Status and Future Directions

PubMed Central

Phillips, Katharine A.; Rogers, Jamison

2011-01-01

SYNOPSIS Body dysmorphic disorder (BDD), a distressing or impairing preoccupation with nonexistent or slight defect(s) in appearance, usually begins during early adolescence and appears to be common in youth. BDD is characterized by substantial impairment in psychosocial functioning and markedly high rates of suicidality. Cognitive-behavioral therapy (CBT) tailored to BDD’s unique features is the best tested and most promising psychosocial treatment for adults with BDD. CBT has been used for youth with BDD, but it has not been systematically developed for or tested in this age group, and there is a pressing need for this work to be done. This article focuses on CBT for BDD in adults and youth, possible adaptations for youth, and the need for treatment research in youth. We also discuss BDD’s prevalence, clinical features, how to diagnose BDD in youth, recommended pharmacotherapy for BDD (serotonin-reuptake inhibitors), and treatments that are not recommended (surgery and other cosmetic treatments). PMID:21440856

Allometry and Interspecific Differences in the Facial Cranium of Two Closely Related Macaque Species

PubMed Central

Ito, Tsuyoshi; Nishimura, Takeshi; Takai, Masanaru

2011-01-01

Interpreting evolutionary history of macaque monkeys from fossil evidence is difficult, because their evolutionary fluctuations in body size might have removed or formed important morphological features differently in each lineage. We employed geometric morphometrics to explore allometric trajectories of craniofacial shape in two closely related species, Macaca fascicularis and M. fuscata. These two species exhibit a single shared allometric trajectory in superoinferior deflection of the anterior face, indicating that the differences in this feature can be explained by size variation. In contrast, two parallel trajectories are demonstrated in craniofacial protrusion, indicating that even if they are comparable in size, M. fuscata has a higher and shorter face than M. fascicularis. The degree of facial protrusion is most likely a critical feature for phyletic evaluation in the fascicularis group. Such analyses in various macaques would help to resolve controversies regarding phyletic interpretations of fossil macaques. PMID:22567301

Minor physical anomalies and craniofacial measures in patients with treatment-resistant schizophrenia.

PubMed

Lin, A-S; Chang, S-S; Lin, S-H; Peng, Y-C; Hwu, H-G; Chen, W J

2015-07-01

Schizophrenia patients have higher rates of minor physical anomalies (MPAs) than controls, particularly in the craniofacial region; this difference lends support to the neurodevelopmental model of schizophrenia. Whether MPAs are associated with treatment response in schizophrenia remains unknown. The aim of this case-control study was to investigate whether more MPAs and specific quantitative craniofacial features in patients with schizophrenia are associated with operationally defined treatment resistance. A comprehensive scale, consisting of both qualitatively measured MPAs and quantitative measurements of the head and face, was applied in 108 patients with treatment-resistant schizophrenia (TRS) and in 104 non-TRS patients. Treatment resistance was determined according to the criteria proposed by Conley & Kelly (2001; Biological Psychiatry 50, 898-911). Our results revealed that patients with TRS had higher MPA scores in the mouth region than non-TRS patients, and the two groups also differed in four quantitative measurements (facial width, lower facial height, facial height, and length of the philtrum), after controlling for multiple comparisons using the false discovery rate. Among these dysmorphological measurements, three MPA item types (mouth MPA score, facial width, and lower facial height) and earlier disease onset were further demonstrated to have good discriminant validity in distinguishing TRS from non-TRS patients in a multivariable logistic regression analysis, with an area under the curve of 0.84 and a generalized R 2 of 0.32. These findings suggest that certain MPAs and craniofacial features may serve as useful markers for identifying TRS at early stages of the illness.

Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes

PubMed Central

de Peralta, Mauro S Porcel; Mouguelar, Valeria S; Sdrigotti, María Antonella; Ishiy, Felipe A A; Fanganiello, Roberto D; Passos-Bueno, Maria R; Coux, Gabriela; Calcaterra, Nora B

2016-01-01

Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1+/− mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region. An increase of ROS along with the overexpression of redox-responsive genes was detected; furthermore, treatment with antioxidants ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae. On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp, a protein required for proper craniofacial development. Tcof1 knockdown in transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial cartilage development, reinforcing the notion that Cnbp has a role in the pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose-dependent manner by a ROS-cytoprotective action that prevented the redox-responsive genes' upregulation but did not normalize the synthesis of rRNAs. Finally, a positive correlation between the expression of CNBP and TCOF1 in mesenchymal cells from both control and TCS subjects was found. Based on this, we suggest CNBP as an additional target for new alternative therapeutic treatments to reduce craniofacial defects not only in TCS but also in other neurocristopathies. PMID:27711076

Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes.

PubMed

de Peralta, Mauro S Porcel; Mouguelar, Valeria S; Sdrigotti, María Antonella; Ishiy, Felipe A A; Fanganiello, Roberto D; Passos-Bueno, Maria R; Coux, Gabriela; Calcaterra, Nora B

2016-10-06

Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1 +/- mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region. An increase of ROS along with the overexpression of redox-responsive genes was detected; furthermore, treatment with antioxidants ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae. On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp, a protein required for proper craniofacial development. Tcof1 knockdown in transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial cartilage development, reinforcing the notion that Cnbp has a role in the pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose-dependent manner by a ROS-cytoprotective action that prevented the redox-responsive genes' upregulation but did not normalize the synthesis of rRNAs. Finally, a positive correlation between the expression of CNBP and TCOF1 in mesenchymal cells from both control and TCS subjects was found. Based on this, we suggest CNBP as an additional target for new alternative therapeutic treatments to reduce craniofacial defects not only in TCS but also in other neurocristopathies.

Using Zebrafish to Test the Genetic Basis of Human Craniofacial Diseases.

PubMed

Machado, R Grecco; Eames, B Frank

2017-10-01

Genome-wide association studies (GWASs) opened an innovative and productive avenue to investigate the molecular basis of human craniofacial disease. However, GWASs identify candidate genes only; they do not prove that any particular one is the functional villain underlying disease or just an unlucky genomic bystander. Genetic manipulation of animal models is the best approach to reveal which genetic loci identified from human GWASs are functionally related to specific diseases. The purpose of this review is to discuss the potential of zebrafish to resolve which candidate genetic loci are mechanistic drivers of craniofacial diseases. Many anatomic, embryonic, and genetic features of craniofacial development are conserved among zebrafish and mammals, making zebrafish a good model of craniofacial diseases. Also, the ability to manipulate gene function in zebrafish was greatly expanded over the past 20 y, enabling systems such as Gateway Tol2 and CRISPR-Cas9 to test gain- and loss-of-function alleles identified from human GWASs in coding and noncoding regions of DNA. With the optimization of genetic editing methods, large numbers of candidate genes can be efficiently interrogated. Finding the functional villains that underlie diseases will permit new treatments and prevention strategies and will increase understanding of how gene pathways operate during normal development.

Thin-plate spline analysis of craniofacial growth in Class I and Class II subjects.

PubMed

Franchi, Lorenzo; Baccetti, Tiziano; Stahl, Franka; McNamara, James A

2007-07-01

To compare the craniofacial growth characteristics of untreated subjects with Class II division 1 malocclusion with those of subjects with normal (Class I) occlusion from the prepubertal through the postpubertal stages of development. The Class II division 1 sample consisted of 17 subjects (11 boys and six girls). The Class I sample also consisted of 17 subjects (13 boys and four girls). Three craniofacial regions (cranial base, maxilla, and mandible) were analyzed on the lateral cephalograms of the subjects in both groups by means of thin-plate spline analysis at T1 (prepubertal) and T2 (postpubertal). Both cross-sectional and longitudinal comparisons were performed on both size and shape differences between the two groups. The results showed an increased cranial base angulation as a morphological feature of Class II malocclusion at the prepubertal developmental phase. Maxillary changes in either shape or size were not significant. Subjects with Class II malocclusion exhibited a significant deficiency in the size of the mandible at the completion of active craniofacial growth as compared with Class I subjects. A significant deficiency in the size of the mandible became apparent in Class II subjects during the circumpubertal period and it was still present at the completion of active craniofacial growth.

Tissue-nonspecific Alkaline Phosphatase Deficiency Causes Abnormal Craniofacial Bone Development in the Alpl−/− Mouse Model of Infantile Hypophosphatasia

PubMed Central

Liu, Jin; Nam, Hwa Kyung; Campbell, Cassie; Gasque, Kellen Cristina da Silva; Millán, José Luis; Hatch, Nan E.

2014-01-01

Tissue-nonspecific alkaline phosphatase (TNAP) is an enzyme present on the surface of mineralizing cells and their derived matrix vesicles that promotes hydroxyapatite crystal growth. Hypophosphatasia (HPP) is an inborn-error-of-metabolism that, dependent upon age of onset, features rickets or osteomalacia due to loss-of function mutations in the gene (Alpl) encoding TNAP. Craniosynostosis is prevalent in infants with HPP and other forms of rachitic disease but how craniosynostosis develops in these disorders is unknown. Objectives: Because craniosynostosis carries high morbidity, we are investigating craniofacial skeletal abnormalities in Alpl−/− mice to establish these mice as a model of HPP-associated craniosynostosis and determine mechanisms by which TNAP influences craniofacial skeletal development. Methods: Cranial bone, cranial suture and cranial base abnormalities were analyzed by micro-CT and histology. Craniofacial shape abnormalities were quantified using digital calipers. TNAP expression was suppressed in MC3T3E1(C4) calvarial cells by TNAP-specific shRNA. Cells were analyzed for changes in mineralization, gene expression, proliferation, apoptosis, matrix deposition and cell adhesion. Results: Alpl−/− mice feature craniofacial shape abnormalities suggestive of limited anterior-posterior growth. Craniosynostosis in the form of bony coronal suture fusion is present by three weeks after birth. Alpl−/− mice also exhibit marked histologic abnormalities of calvarial bones and the cranial base involving growth plates, cortical and trabecular bone within two weeks of birth. Analysis of calvarial cells in which TNAP expression was suppressed by shRNA indicates that TNAP deficiency promotes aberrant osteoblastic gene expression, diminished matrix deposition, diminished proliferation, increased apoptosis and increased cell adhesion. Conclusions: These findings demonstrate that Alpl−/− mice exhibit a craniofacial skeletal phenotype similar to that seen in infants with HPP, including true bony craniosynostosis in the context of severely diminished bone mineralization. Future studies will be required to determine if TNAP deficiency and other forms of rickets promote craniosynostosis directly through abnormal calvarial cell behavior, or indirectly due to deficient growth of the cranial base. PMID:25014884

A Review of Body Dysmorphic Disorder and Its Presentation in Different Clinical Settings

PubMed Central

Mufaddel, Amir; Osman, Ossama T.; Almugaddam, Fadwa

2013-01-01

Objective: Body dysmorphic disorder (BDD) is a relatively common psychiatric disorder characterized by preoccupations with perceived defects in physical appearance. This review aimed to explore epidemiology, clinical features, comorbidities, and treatment options for BDD in different clinical settings. Data Source and Study Selection: A search of the literature from 1970 to 2011 was performed using the MEDLINE search engine. English-language articles, with no restriction regarding the type of articles, were identified using the search terms body dysmorphic disorder, body dysmorphic disorder clinical settings, body dysmorphic disorder treatment, and body dysmorphic disorder & psychodermatology. Results: BDD occurs in 0.7% to 2.4% of community samples and 13% of psychiatric inpatients. Etiology is multifactorial, with recent findings indicating deficits in visual information processing. There is considerable overlap between BDD and obsessive-compulsive disorder (OCD) in symptom etiology and response to treatment, which has led to suggestions that BDD can be classified with anxiety disorders and OCD. A recent finding indicated genetic overlap between BDD and OCD. Over 60% of patients with BDD had a lifetime anxiety disorder, and 38% had social phobia, which tends to predate the onset of BDD. Studies reported a high level of comorbidity with depression and social phobia occurring in > 70% of patients with BDD. Individuals with BDD present frequently to dermatologists (about 9%–14% of dermatologic patients have BDD). BDD co-occurs with pathological skin picking in 26%–45% of cases. BDD currently has 2 variants: delusional and nondelusional, and both variants respond similarly to serotonin reuptake inhibitors (SRIs), which may have effect on obsessive thoughts and rituals. Cognitive-behavioral therapy has the best established treatment results. Conclusions: A considerable overlap exists between BDD and other psychiatric disorders such as OCD, anxiety, and delusional disorder, and this comorbidity should be considered in evaluation, management, and long-term follow-up of the disorder. Individuals with BDD usually consult dermatologists and cosmetic surgeons rather than psychiatrists. Collaboration between different specialties (such as primary care, dermatology, cosmetic surgery, and psychiatry) is required for better treatment outcome. PMID:24392251

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

Thin-plate spline analysis of craniofacial morphology in subjects with adenoid or tonsillar hypertrophy.

PubMed

Baroni, Michela; Ballanti, Fabiana; Polimeni, Antonella; Franchi, Lorenzo; Cozza, Paola

2011-04-01

To compare the skeletal features of subjects with adenoid hypertrophy with those of children with tonsillar hypertrophy using thin-plate spline (TPS) analysis. A group of 20 subjects (9 girls and 11 boys; mean age 8.4 ± 0.9 years) with adenoid hypertrophy (AG) was compared with a group of 20 subjects (10 girls and 10 boys; mean age 8.2 ± 1.1 years) with tonsillar hypertrophy (TG). Craniofacial morphology was analyzed on the lateral cephalograms of the subjects in both groups by means of TPS analysis. A cross-sectional comparison was performed on both size and shape differences between the two groups. AG exhibited statistically significant shape and size differences in craniofacial configuration with respect to TG. Subjects with adenoid hypertrophy showed an upward dislocation of the anterior region of the maxilla, a more downward/backward position of the anterior region of the mandibular body and an upward/backward displacement of the condylar region. Conversely, subjects with tonsillar hypertrophy showed a downward dislocation of the anterior region of the maxilla, a more upward/forward position of the anterior region of the mandibular body and a downward/forward displacement of the condylar region. Subjects with adenoid hypertrophy exhibited features suggesting a more retrognathic mandible while subjects with tonsillar hypertrophy showed features suggesting a more prognathic mandible. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Nanomaterials for Craniofacial and Dental Tissue Engineering.

PubMed

Li, G; Zhou, T; Lin, S; Shi, S; Lin, Y

2017-07-01

Tissue engineering shows great potential as a future treatment for the craniofacial and dental defects caused by trauma, tumor, and other diseases. Due to the biomimetic features and excellent physiochemical properties, nanomaterials are of vital importance in promoting cell growth and stimulating tissue regeneration in tissue engineering. For craniofacial and dental tissue engineering, the frequently used nanomaterials include nanoparticles, nanofibers, nanotubes, and nanosheets. Nanofibers are attractive for cell invasion and proliferation because of their resemblance to extracellular matrix and the presence of large pores, and they have been used as scaffolds in bone, cartilage, and tooth regeneration. Nanotubes and nanoparticles improve the mechanical and chemical properties of scaffold, increase cell attachment and migration, and facilitate tissue regeneration. In addition, nanofibers and nanoparticles are also used as a delivery system to carry the bioactive agent in bone and tooth regeneration, have better control of the release speed of agent upon degradation of the matrix, and promote tissue regeneration. Although applications of nanomaterials in tissue engineering remain in their infancy with numerous challenges to face, the current results indicate that nanomaterials have massive potential in craniofacial and dental tissue engineering.

Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets

PubMed Central

Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C.; Marrs, James A.

2013-01-01

Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection. PMID:24961433

Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets.

PubMed

Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C; Marrs, James A

2013-06-19

Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.

Expanding the clinical spectrum of chromosome 15q26 terminal deletions associated with IGF-1 resistance.

PubMed

O'Riordan, Aisling M; McGrath, Niamh; Sharif, Farhana; Murphy, Nuala P; Franklin, Orla; Lynch, Sally Ann; O'Grady, Michael J

2017-01-01

Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene on chromosome 15q26.3 is associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. Terminal deletions of chromosome 15q26 arising more proximally may also be associated with congenital heart disease, epilepsy, diaphragmatic hernia and renal anomalies. We report three additional cases of 15q26 terminal deletions with novel features which may further expand the spectrum of this rarely reported contiguous gene syndrome. Phenotypic features including neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been reported previously. Similarly, laboratory features of insulin-like growth factor 1 (IGF-1) resistance are described, including markedly elevated IGF-1 of up to +4.7 SDS. In one patient, the elevated IGF-1 declined over time and this coincided with a period of spontaneous growth acceleration. Deletions of 15q26 are a potential risk factor for aortic root dilatation, neonatal lymphedema and aplasia cutis in addition to causing growth restriction. What is Known: • Terminal deletions of chromosome 15q26 are associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. What is New: • Neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been previously described in 15q26 terminal deletions and may represent novel features. • IGF-1 levels may be increased up to 4.7 SDS.

[Noonan syndrome can be diagnosed clinically and through molecular genetic analyses].

PubMed

Henningsen, Marie Krab; Jelsig, Anne Marie; Andersen, Helle; Brusgaard, Klaus; Ousager, Lilian Bomme; Hertz, Jens Michael

2015-08-03

Noonan syndrome is part of the group of RASopathies caused by germ line mutations in genes involved in the RAS/MAPK pathway. There is substantial phenotypic overlap among the RASopathies. Diagnosis of Noonan syndrome is often based on clinical features including dysmorphic facial features, short stature and congenital heart disease. Rapid advances in sequencing technology have made molecular genetic analyses a helpful tool in diagnosing and distinguishing Noonan syndrome from other RASopathies.

The relationship between perceived social support and severity of body dysmorphic disorder symptoms: the role of gender.

PubMed

Marques, Luana; Weingarden, Hilary M; LeBlanc, Nicole J; Siev, Jedidiah; Wilhelm, Sabine

2011-09-01

Whether social support is associated with severity of body dysmorphic symptoms is unknown. To address this gap in the literature, the present study aims to examine the association between three domains of perceived social support (i.e., family, friends, and significant others) and severity of body dysmorphic disorder symptoms. Participants (N = 400) with symptoms consistent with diagnosis of body dysmorphic disorder completed measures of symptomatology and social support via the internet. More perceived social support from friends and significant others was associated with less severe body dysmorphic disorder symptoms for males, and more perceived social support from family and friends was associated with less severe body dysmorphic disorder symptoms among females. Additionally, gender moderated the association between perceived social support from significant others and symptom severity, such that perceived social support from a significant other was significantly negatively associated with body dysmorphic symptom severity in males, but not females. The present study implicates social support as an important area of future body dysmorphic disorder research.

Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis

PubMed Central

Bagheri, Hani; Badduke, Chansonette; Qiao, Ying; Colnaghi, Rita; Abramowicz, Iga; Alcantara, Diana; Dunham, Christopher; Wen, Jiadi; Wildin, Robert S.; Nowaczyk, Malgorzata J.M.; Eichmeyer, Jennifer; Lehman, Anna; Maranda, Bruno; Martell, Sally; Shan, Xianghong; Lewis, Suzanne M.E.; O’Driscoll, Mark; Gregory-Evans, Cheryl Y.

2016-01-01

The 2p15p16.1 microdeletion syndrome has a core phenotype consisting of intellectual disability, microcephaly, hypotonia, delayed growth, common craniofacial features, and digital anomalies. So far, more than 20 cases of 2p15p16.1 microdeletion syndrome have been reported in the literature; however, the size of the deletions and their breakpoints vary, making it difficult to identify the candidate genes. Recent reports pointed to 4 genes (XPO1, USP34, BCL11A, and REL) that were included, alone or in combination, in the smallest deletions causing the syndrome. Here, we describe 8 new patients with the 2p15p16.1 deletion and review all published cases to date. We demonstrate functional deficits for the above 4 candidate genes using patients’ lymphoblast cell lines (LCLs) and knockdown of their orthologs in zebrafish. All genes were dosage sensitive on the basis of reduced protein expression in LCLs. In addition, deletion of XPO1, a nuclear exporter, cosegregated with nuclear accumulation of one of its cargo molecules (rpS5) in patients’ LCLs. Other pathways associated with these genes (e.g., NF-κB and Wnt signaling as well as the DNA damage response) were not impaired in patients’ LCLs. Knockdown of xpo1a, rel, bcl11aa, and bcl11ab resulted in abnormal zebrafish embryonic development including microcephaly, dysmorphic body, hindered growth, and small fins as well as structural brain abnormalities. Our multifaceted analysis strongly implicates XPO1, REL, and BCL11A as candidate genes for 2p15p16.1 microdeletion syndrome. PMID:27699255

Psychological treatment of social anxiety disorder improves body dysmorphic concerns.

PubMed

Fang, Angela; Sawyer, Alice T; Aderka, Idan M; Hofmann, Stefan G

2013-10-01

Social anxiety disorder and body dysmorphic disorder are considered nosologically distinct disorders. In contrast, some cognitive models suggest that social anxiety disorder and body dysmorphic disorder share similar cognitive maintenance factors. The aim of this study was to examine the effects of psychological treatments for social anxiety disorder on body dysmorphic disorder concerns. In Study 1, we found that 12 weekly group sessions of cognitive-behavioral therapy led to significant decreases in body dysmorphic symptom severity. In Study 2, we found that an attention retraining intervention for social anxiety disorder was associated with a reduction in body dysmorphic concerns, compared to a placebo control condition. These findings support the notion that psychological treatments for individuals with primary social anxiety disorder improve co-occurring body dysmorphic disorder symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Monozygotic twin discordant for Down syndrome: mos 47,XX,+21/46,XX and 46,XX.

PubMed

Choi, Sun Ah; Ko, Jung Min; Shin, Choong Ho; Yang, Sei Won; Choi, Jin Sun; Oh, Sun Kyung

2013-08-01

Monozygotic twins, developed from a single zygote, are almost identical in clinical phenotype and concordant karyotypes. Monozygotic twins with discordant karyotypes are thought to be quite rare. Here, we report monochorionic-diamniotic twins discordant for Down syndrome. On findings of prenatal ultrasonography, nuchal translucency thickness was different between twins, and suggested that one of the twins was at high risk for having chromosomal abnormalities including Down syndrome. The twins were monochorionic-diamniotic; therefore, chorionic villi sampling of the common placenta was performed. The karyotype of the chorionic villi cells was 46,XX, and pregnancy was maintained. After delivery, dysmorphic clinical features suggesting Down syndrome were found in one of the twins, while the other twin showed a morphologically normal appearance. Karyotypes of peripheral blood leukocytes were repeatedly normal in the dysmorphic twin; however, the karyotype of skin fibroblasts from the dysmorphic twin indicated Down syndrome mosaicism; 47,XX,+21[99]/46,XX[2]. The karyotype of skin fibroblasts from the morphologically normal twin was 46,XX. Monozygosity of the twins was confirmed by a short tandem repeat analysis using 16 polymorphic markers. A mitotic nondisjunction followed by the twinning would explain the discordant karyotypes between monozygotic twins.

Hypertelorism in Charcot-Marie-Tooth disease 1A from the common PMP22 duplication: A Case Report

PubMed Central

Finsterer, Josef

2012-01-01

The 1.4Mb tandem-duplication in the PMP22 gene at 17p11.2 usually manifests as hereditary sensorimotor polyneuropathy with foot deformity, sensorineural hearing-loss, moderate developmental delay, and gait disturbance. Hypertelorism and marked phenotypic variability within a single family has not been reported. In a single family, the PMP22 tandem-duplication manifested as short stature, sensorimotor polyneuropathy, tremor, ataxia, sensorineural hearing-loss, and hypothyroidism in the 27 years-old index case, as mild facial dysmorphism, muscle cramps, tinnitus, intention tremor, bradydiadochokinesia, and sensorimotor polyneuropathy in the 31 year-old half-brother of the index-patient, and as sensorimotor polyneuropathy and foot-deformity in the father of the two. The half-brother additionally presented with hypertelorism, not previously reported in PMP22 tandem-duplication carriers. The presented cases show that the tandem-duplication 17p11.2 may present with marked intra-familial phenotype variability and that mild facial dysmorphism with stuck-out ears and hypertelorism may be a rare phenotypic feature of this mutation. The causal relation between facial dysmorphism and the PMP22 tandem-duplication, however, remains speculative. PMID:22496945

Body Dysmorphic Disorder: Neurobiological Features and an Updated Model

PubMed Central

Li, Wei; Arienzo, Donatello; Feusner, Jamie D.

2013-01-01

Body Dysmorphic Disorder (BDD) affects approximately 2% of the population and involves misperceived defects of appearance along with obsessive preoccupation and compulsive behaviors. There is evidence of neurobiological abnormalities associated with symptoms in BDD, although research to date is still limited. This review covers the latest neuropsychological, genetic, neurochemical, psychophysical, and neuroimaging studies and synthesizes these findings into an updated (yet still preliminary) neurobiological model of the pathophysiology of BDD. We propose a model in which visual perceptual abnormalities, along with frontostriatal and limbic system dysfunction, may combine to contribute to the symptoms of impaired insight and obsessive thoughts and compulsive behaviors expressed in BDD. Further research is necessary to gain a greater understanding of the etiological formation of BDD symptoms and their evolution over time. PMID:25419211

Seizures and EEG features in 74 patients with genetic-dysmorphic syndromes.

PubMed

Alfei, Enrico; Raviglione, Federico; Franceschetti, Silvana; D'Arrigo, Stefano; Milani, Donatella; Selicorni, Angelo; Riva, Daria; Zuffardi, Orsetta; Pantaleoni, Chiara; Binelli, Simona

2014-12-01

Epilepsy is one of the most common findings in chromosome aberrations. Types of seizures and severity may significantly vary both between different conditions and within the same aberration. Hitherto specific seizures and EEG patterns are identified for only few syndromes. We studied 74 patients with defined genetic-dysmorphic syndromes with and without epilepsy in order to assess clinical and electroencephalographic features, to compare our observation with already described electro-clinical phenotypes, and to identify putative electroencephalographic and/or seizure characteristics useful to address the diagnosis. In our population, 10 patients had chromosomal disorders, 19 microdeletion or microduplication syndromes, and 32 monogenic syndromes. In the remaining 13, syndrome diagnosis was assessed on clinical grounds. Our study confirmed the high incidence of epilepsy in genetic-dysmorphic syndromes. Moreover, febrile seizures and neonatal seizures had a higher incidence compared to general population. In addition, more than one third of epileptic patients had drug-resistant epilepsy. EEG study revealed poor background organization in 42 patients, an excess of diffuse rhythmic activities in beta, alpha or theta frequency bands in 34, and epileptiform patterns in 36. EEG was completely normal only in 20 patients. No specific electro-clinical pattern was identified, except for inv-dup15, Angelman, and Rett syndromes. Nevertheless some specific conditions are described in detail, because of notable differences from what previously reported. Regarding the diagnostic role of EEG, we found that--even without any epileptiform pattern--the generation of excessive rhythmic activities in different frequency bandwidths might support the diagnosis of a genetic syndrome. © 2014 Wiley Periodicals, Inc.

Phenotype-genotype correlation in potential female carriers of X-linked developmental cataract (Nance-Horan syndrome).

PubMed

Khan, Arif O; Aldahmesh, Mohammed A; Mohamed, Jawahir Y; Alkuraya, Fowzan S

2012-06-01

To correlate clinical examination with underlying genotype in asymptomatic females who are potential carriers of X-linked developmental cataract (Nance-Horan syndrome). An ophthalmologist blind to the pedigree performed comprehensive ophthalmic examination for 16 available family members (two affected and six asymptomatic females, five affected and three asymptomatic males). Facial features were also noted. Venous blood was collected for sequencing of the gene NHS. All seven affected family members had congenital or infantile cataract and facial dysmorphism (long face, bulbous nose, abnormal dentition). The six asymptomatic females ranged in age from 4-35 years old. Four had posterior Y-suture centered lens opacities; these four also exhibited the facial dysmorphism of the seven affected family members. The fifth asymptomatic girl had scattered fine punctate lens opacities (not centered on the Y-suture) while the sixth had clear lenses, and neither exhibited the facial dysmorphism. A novel NHS mutation (p.Lys744AsnfsX15 [c.2232delG]) was found in the seven patients with congenital or infantile cataract. This mutation was also present in the four asymptomatic girls with Y-centered lens opacities but not in the other two asymptomatic girls or in the three asymptomatic males (who had clear lenses). Lens opacities centered around the posterior Y-suture in the context of certain facial features were sensitive and specific clinical signs of carrier status for NHS mutation in asymptomatic females. Lens opacities that did not have this characteristic morphology in a suspected female carrier were not a carrier sign, even in the context of her affected family members.

Mosaic Trisomy 9p in a Patient with Mild Dysmorphic Features and Normal Intelligence.

PubMed

Brar, Randeep; Basel, Donald G; Bick, David P; Weik, LuAnn; vanTuinen, Peter; Peterson, Jess F

2017-01-01

To the Editor: Partial and whole duplications of the short arm of chromosome 9 have been commonly reported in the literature with characteristic phenotypic features and intellectual disabilities. The clinical features of 9p duplications are broad and can include growth retardation, developmental delay, intellectual disability, microbrachycephaly, deep set eyes, hypertelorism, downslanting palpebral fissures, prominent nasal root, bulbous nasal tip, low-set ears, short fingers and toes with hypoplastic nails, and delayed bone age (Bonaglia et al., 2002; Zou et al., 2009; Guilherme et al., 2014).

Generation algorithm of craniofacial structure contour in cephalometric images

NASA Astrophysics Data System (ADS)

Mondal, Tanmoy; Jain, Ashish; Sardana, H. K.

2010-02-01

Anatomical structure tracing on cephalograms is a significant way to obtain cephalometric analysis. Computerized cephalometric analysis involves both manual and automatic approaches. The manual approach is limited in accuracy and repeatability. In this paper we have attempted to develop and test a novel method for automatic localization of craniofacial structure based on the detected edges on the region of interest. According to the grey scale feature at the different region of the cephalometric images, an algorithm for obtaining tissue contour is put forward. Using edge detection with specific threshold an improved bidirectional contour tracing approach is proposed by an interactive selection of the starting edge pixels, the tracking process searches repetitively for an edge pixel at the neighborhood of previously searched edge pixel to segment images, and then craniofacial structures are obtained. The effectiveness of the algorithm is demonstrated by the preliminary experimental results obtained with the proposed method.

The slant of the forehead as a craniofacial feature of impulsiveness.

PubMed

Guerrero-Apolo, J David; Navarro-Pastor, J Blas; Bulbena-Vilarrasa, Antonio; Gabarre-Mir, Julián

2018-03-12

Impulsiveness has been the subject of much research, but little is known about the possible relationship between craniofacial anatomy and impulsiveness. The present study was designed to investigate the relationship between one aspect of craniofacial structure (the angle of inclination of the forehead) and impulsiveness. Photographs in profile were obtained from 131 volunteers who had been fined for driving at high speed and were undergoing a court-mandated driving license point-recovery course. They completed the Barratt Impulsiveness Scale (BIS-11), the Impulsive Behavior Scale (UPPS-P), and Zuckerman's Sensation Seeking Scale (V). The angle of the slant of the forehead was measured with a photographic support and a protractor. High positive concordance was found between forehead inclination and 14 out of the 15 impulsiveness factors studied. The angle of inclination of the forehead was significantly associated with self-reported impulsiveness in this sample of traffic violators.

Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

PubMed Central

Foster, B.L.; Ao, M.; Willoughby, C.; Soenjaya, Y.; Holm, E.; Lukashova, L.; Tran, A. B.; Wimer, H.F.; Zerfas, P.M.; Nociti, F.H.; Kantovitz, K.R.; Quan, B.D.; Sone, E.D.; Goldberg, H.A.; Somerman, M.J.

2015-01-01

Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp−/− mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp−/− mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp−/− mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp−/− mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified in endochondral ossification in the cranial base, and craniofacial morphology was unaffected in Bsp−/− mice. These analyses confirm a critical role for BSP in processes of cementogenesis and intramembranous ossification of craniofacial bone, whereas endochondral ossification in the cranial base was minimally affected and dentinogenesis was normal in Bsp−/− molar teeth. Dissimilar effects of loss of BSP on mineralization of dental and craniofacial tissues suggest local differences in the role of BSP and/or yet to be defined interactions with site-specific factors. PMID:25963390

A Case of Treatment- resistant Depression and Body Dysmorphic Disorder: The Role of Electroconvulsive Therapy Revisited.

PubMed

Mahato, Ram S; San Gabriel, Maria Chona P; Longshore, Carrol T; Schnur, David B

2016-01-01

Body dysmorphic disorder is a common, often disabling condition, and is frequently comorbid with major depressive disorder. Selective serotonin reuptake inhibitors constitute first line set of somatic interventions but the management of refractory patients remains challenging. Electroconvulsive therapy, an often highly beneficial treatment for medication resistant-depression, is not considered an effective therapeutic alternative for treatment refractory body dysmorphic disorder. Here we present a 50-year-old woman with body dysmorphic disorder and comorbid major depressive disorder who remained incapacitated and suicidal despite several trials with selective serotonin reuptake inhibitors and antipsychotic medication. Depressive and dysmorphic symptoms appeared to resolve with electroconvulsive therapy, and remission was sustained for two months. Electroconvulsive therapy has an important place in the management of treatment- resistant depression associated with body dysmorphic disorder, and, in select cases, may be effective for dysmorphic symptoms as well.

Sensory Motor and Functional Skills of Dizygotic Twins: One with Smith-Magenis Syndrome and a Twin Control

ERIC Educational Resources Information Center

Smith, Michaele R.; Hildenbrand, Hanna; Smith, Ann C. M.

2009-01-01

Smith-Magenis syndrome (SMS), the result of an interstitial deletion within chromosome 17p11.2, is a disorder that may include minor dysmorphic features, brachydactyly, short stature, hypotonia, speech delays, cognitive deficits, signs of peripheral neuropathy, scoliosis, and neurobehavioral problems including sleep disturbances and maladaptive…

Cognitive Profile in a Large French Cohort of Adults with Prader-Willi Syndrome: Differences between Genotypes

ERIC Educational Resources Information Center

Copet, P.; Jauregi, J.; Laurier, V.; Ehlinger, V.; Arnaud, C.; Cobo, A. -M.; Molinas, C.; Tauber, M.; Thuilleaux, D.

2010-01-01

Background: Prader-Willi syndrome (PWS) is a rare genetic disorder characterised by developmental abnormalities leading to somatic and psychological symptoms. These include dysmorphic features, impaired growth and sexual maturation, hyperphagia, intellectual delay, learning disabilities and maladaptive behaviours. PWS is caused by a lack of…

Body Dysmorphic Disorder in Patients Seeking Abdominoplasty, Rhinoplasty, and Rhytidectomy.

PubMed

de Brito, Maria José Azevedo; Nahas, Fábio Xerfan; Cordás, Táki Athanássios; Tavares, Hermano; Ferreira, Lydia Masako

2016-02-01

Body dysmorphic disorder may negatively affect self-perception of body shape and lead patients to seek cosmetic surgery. This study estimates the level of body dissatisfaction and prevalence of body dysmorphic disorder symptoms in candidates for three plastic surgical procedures. Three hundred patients of both sexes divided into three groups (abdominoplasty, n = 90; rhinoplasty, n =151; and rhytidectomy, n =59) were classified as having (n =51, n =79, and n =25, respectively) or not having (n =39, n =72, and n =34, respectively) body dysmorphic disorder symptoms, based on the Body Dysmorphic Disorder Examination, which was administered preoperatively. Prevalence rates of body dysmorphic disorder symptoms in the abdominoplasty, rhinoplasty, and rhytidectomy groups were 57, 52, and 42 percent, respectively. Significant between-group differences were observed regarding age (p < 0.001), body mass index (p = 0.001), and onset of body dysmorphic disorder symptoms (p < 0.001). Within-group differences in body dysmorphic disorder severity were observed in the abdominoplasty (p < 0.001), rhinoplasty (p < 0.001), and rhytidectomy (p = 0.005) groups. Body dysmorphic disorder severity was significantly associated with degree of body dissatisfaction (mean Body Dysmorphic Disorder Examination total scores; p < 0.001), avoidance behaviors (p< 0.001), sexual abuse (p = 0.026), suicidal ideation (p < 0.001), and suicide attempt (p = 0.012). Abdominoplasty candidates showed the highest prevalence; rhytidectomy candidates exhibited the highest percentage of severe cases, and rhinoplasty candidates had the lowest percentage of severe cases.

EVALUATION AND DIAGNOSIS OF THE DYSMORPHIC INFANT

PubMed Central

Jones, Kelly L.; Adam, Margaret P.

2015-01-01

SYNOPSIS Neonatologists often have the unique opportunity to be the first to identify abnormalities in the neonate. In this review, multiple anomalies and physical features are discussed along with the potential associated genetic syndromes. The anomalies and physical features that are discussed include birth parameters, aplasia cutis congenita, holoprosencephaly, asymmetric crying facies, preauricular ear tags and pits, cleft lip with or without cleft palate, esophageal atresia/tracheoesophageal fistula, congenital heart defects, ventral wall defects, and polydactyly. PMID:26042903

Similar PDK1-AKT-mTOR pathway activation in balloon cells and dysmorphic neurons of type II focal cortical dysplasia with refractory epilepsy.

PubMed

Lin, Yuan-xiang; Lin, Kun; Kang, De-zhi; Liu, Xin-xiu; Wang, Xing-fu; Zheng, Shu-fa; Yu, Liang-hong; Lin, Zhang-ya

2015-05-01

Dysmorphic neurons and balloon cells constitute the neuropathological hallmarks of type II focal cortical dysplasias (FCDs) with refractory epilepsy. The genesis of these cells may be critical to the histological findings in type II FCD. Recent work has shown enhanced activation of the mTOR cascade in both balloon cells and dysmorphic neurons, suggesting a common pathogenesis for these two neuropathological hallmarks. A direct comparative analysis of balloon cells and dysmorphic neurons might identify a molecular link between balloon cells and dysmorphic neurons. Here, we addressed whether PDK1-AKT-mTOR activation differentiates balloon cells from dysmorphic neurons. We used immunohistochemistry with antibodies against phosphorylated (p)-PDK1 (Ser241), p-AKT (Thr308), p-AKT (Ser473), p-mTOR (Ser2448), p-P70S6K (Thr229), and p-p70S6 kinase (Thr389) in balloon cells compared with dysmorphic neurons. Strong or moderate staining for components of the PDK1-AKT-mTOR signaling pathway was observed in both balloon cells and dysmorphic neurons. However, only a few pyramidal neurons displayed weak staining in control group (perilesional neocortex and histologically normal neocortex). Additionally, p-PDK1 (Ser241) and p-AKT (Thr308) staining in balloon cells were stronger than in dysmorphic neurons, whereas p-P70S6K (Thr229) and p-p70S6 kinase (Thr389) staining in balloon cells was weaker than in dysmorphic neurons. In balloon cells, p-AKT (Ser473) and p-mTOR (Ser2448) staining was comparable with the staining in dysmorphic neurons. Our data support the previously suggested pathogenic relationship between balloon cells and dysmorphic neurons concerning activation of the PDK1-AKT-mTOR, which may play important roles in the pathogenesis of type II FCD. Differential expression of some components of the PDK1-AKT-mTOR pathway between balloon cells and dysmorphic neurons may result from cell-specific gene expression. Copyright © 2015 Elsevier B.V. All rights reserved.

A three-dimensional comparison of a morphometric and conventional cephalometric midsagittal planes for craniofacial asymmetry.

PubMed

Damstra, Janalt; Fourie, Zacharias; De Wit, Marnix; Ren, Yijin

2012-02-01

Morphometric methods are used in biology to study object symmetry in living organisms and to determine the true plane of symmetry. The aim of this study was to determine if there are clinical differences between three-dimensional (3D) cephalometric midsagittal planes used to describe craniofacial asymmetry and a true symmetry plane derived from a morphometric method based on visible facial features. The sample consisted of 14 dry skulls (9 symmetric and 5 asymmetric) with metallic markers which were imaged with cone-beam computed tomography. An error study and statistical analysis were performed to validate the morphometric method. The morphometric and conventional cephalometric planes were constructed and compared. The 3D cephalometric planes constructed as perpendiculars to the Frankfort horizontal plane resembled the morphometric plane the most in both the symmetric and asymmetric groups with mean differences of less than 1.00 mm for most variables. However, the standard deviations were often large and clinically significant for these variables. There were clinically relevant differences (>1.00 mm) between the different 3D cephalometric midsagittal planes and the true plane of symmetry determined by the visible facial features. The difference between 3D cephalometric midsagittal planes and the true plane of symmetry determined by the visible facial features were clinically relevant. Care has to be taken using cephalometric midsagittal planes for diagnosis and treatment planning of craniofacial asymmetry as they might differ from the true plane of symmetry as determined by morphometrics.

Microdeletion del(22)(q12.2) encompassing the facial development-associated gene, MN1 (meningioma 1) in a child with Pierre-Robin sequence (including cleft palate) and neurofibromatosis 2 (NF2): a case report and review of the literature.

PubMed

Davidson, Tom B; Sanchez-Lara, Pedro A; Randolph, Linda M; Krieger, Mark D; Wu, Shi-Qi; Panigrahy, Ashok; Shimada, Hiroyuki; Erdreich-Epstein, Anat

2012-03-22

Pierre-Robin sequence (PRS) is defined by micro- and/or retrognathia, glossoptosis and cleft soft palate, either caused by deformational defect or part of a malformation syndrome. Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by mutations in the NF2 gene on chromosome 22q12.2. NF2 is characterized by bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas and ependymomas, and juvenile cataracts. To date, NF2 and PRS have not been described together in the same patient. We report a female with PRS (micrognathia, cleft palate), microcephaly, ocular hypertelorism, mental retardation and bilateral hearing loss, who at age 15 was also diagnosed with severe NF2 (bilateral cerebellopontine schwannomas and multiple extramedullary/intradural spine tumors). This is the first published report of an individual with both diagnosed PRS and NF2. High resolution karyotype revealed 46, XX, del(22)(q12.1q12.3), FISH confirmed a deletion encompassing NF2, and chromosomal microarray identified a 3,693 kb deletion encompassing multiple genes including NF2 and MN1 (meningioma 1).Five additional patients with craniofacial dysmorphism and deletion in chromosome 22-adjacent-to or containing NF2 were identified in PubMed and the DECIPHER clinical chromosomal database. Their shared chromosomal deletion encompassed MN1, PITPNB and TTC28. MN1, initially cloned from a patient with meningioma, is an oncogene in murine hematopoiesis and participates as a fusion gene (TEL/MN1) in human myeloid leukemias. Interestingly, Mn1-haploinsufficient mice have abnormal skull development and secondary cleft palate. Additionally, Mn1 regulates maturation and function of calvarial osteoblasts and is an upstream regulator of Tbx22, a gene associated with murine and human cleft palate. This suggests that deletion of MN1 in the six patients we describe may be causally linked to their cleft palates and/or craniofacial abnormalities. Thus, our report describes a NF2-adjacent chromosome 22q12.2 deletion syndrome and is the first to report association of MN1 deletion with abnormal craniofacial development and/or cleft palate in humans.

Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism.

PubMed

Mattioli, Francesca; Piton, Amelie; Gérard, Bénédicte; Superti-Furga, Andrea; Mandel, Jean-Louis; Unger, Sheila

2016-06-01

The cardinal features of Primrose syndrome (MIM 259050) are dysmorphic facial features, macrocephaly, and intellectual disability, as well as large body size, height and weight, and calcified pinnae. A variety of neurological signs and symptoms have been reported including hearing loss, autism, behavioral abormalities, hypotonia, cerebral calcifications, and hypoplasia of the corpus callosum. Recently, heterozygous de novo missense mutations in ZBTB20, coding for a zing finger protein, have been identified in Primrose syndrome patients. We report a boy with intellectual disability carrying two de novo missense mutations in the last exon of ZBTB20 (Ser616Phe and Gly741Arg; both previously unreported). One of them, Ser616Phe, affects an amino acid located in one of the C2H2 zing-fingers involved in DNA-binding and close to other missense mutations already described. Reverse phenotyping showed that this patient presents with classic features of Primrose syndrome (dysmorphic facies, macrocephaly, hearing loss, hypotonia, hypoplasia of the corpus callosum) and, in addition, congenital hypothyroidism. Review of the literature reveals another Primrose syndrome patient with hypothyroidism and thus, this may represent an under recognized component that should be investigated in other patients. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A comparison study of body dysmorphic disorder versus social phobia

PubMed Central

Kelly, Megan M.; Dalrymple, Kristy; Zimmerman, Mark; Phillips, Katharine A.

2012-01-01

Body dysmorphic disorder (BDD) shares many characteristics with social phobia (SP), including high levels of social anxiety and avoidance, but to our knowledge no studies have directly compared these disorders’ demographic and clinical features. Demographic and clinical features were compared in individuals with BDD (n=172), SP (n=644), and comorbid BDD/SP (n=125). SP participants had a significantly earlier age of onset and lower educational attainment than BDD participants. BDD participants were significantly less likely to ever be married than SP participants, had a greater likelihood of ever being psychiatrically hospitalized, and had significantly lower mean GAF scores than SP participants. The two groups had different comorbidity patterns, which included a greater likelihood for BDD participants to have comorbid obsessive-compulsive disorder (OCD) or an eating disorder, versus a greater likelihood for SP participants to have a comorbid non-OCD anxiety disorder. The comorbid BDD/SP group had significantly greater morbidity across several domains than the SP only group, but not the BDD only group. In summary, although BDD and SP were similar across many demographic and clinical features, they had important differences. Future studies are needed to confirm these findings and address similarities and differences between these disorders across a broader range of variables. PMID:22999105

New perspectives in the treatment of body dysmorphic disorder

PubMed Central

Hong, Kevin; Nezgovorova, Vera; Hollander, Eric

2018-01-01

Body dysmorphic disorder (BDD) is a disabling illness with a high worldwide prevalence. Patients demonstrate a debilitating preoccupation with one or more perceived defects, often marked by poor insight or delusional convictions. Multiple studies have suggested that selective serotonin reuptake inhibitors and various cognitive behavioral therapy modalities are effective first-line treatments in decreasing BDD severity, relieving depressive symptoms, restoring insight, and increasing quality of life. Selective serotonin reuptake inhibitors have also recently been shown to be effective for relapse prevention. This review provides a comprehensive summary of the current understanding of BDD, including its clinical features, epidemiology, genetics, and current treatment modalities. Additional research is needed to fully elucidate the relationship between BDD and comorbid illnesses such as obsessive–compulsive-related disorders and depression and to develop therapies for refractory patients and those who have contraindications for pharmacological intervention. PMID:29636904

How do people with body dysmorphic disorder view themselves? A thematic analysis.

PubMed

Silver, Joanna; Reavey, Paula; Anne Fineberg, Naomi

2010-09-01

Abstract Objectives. To examine the accounts of people with body dysmorphic disorder (BDD) and qualitatively explore self perceptions. Methods. Eleven people with BDD were interviewed using a semi-structured schedule. Participants brought photographs of themselves and drew a self-portrait. Transcribed interviews were analysed using a thematic analysis. Results. The most common theme was increased threat perception resulting in disordered interpersonal relationships. Other themes included the wish for regularity and symmetry in appearance, an idealised childhood self, the duty to look good, and a focus on specific "defective" features rather than general ugliness. Conclusions. Using thematic analysis and visual methods, we identified core themes that appear to characterise the way individuals with BDD perceive themselves and their interpersonal relationships. Thematic analysis offers promise as a tool to explore the overlap between BDD and other putatively related mental health problems.

22q11.2 microduplication syndrome with congenital aural atresia: a family report.

PubMed

Boudewyns, An; van den Ende, Jenneke; Boiy, Tine; Van de Heyning, Paul; Declau, Frank

2012-06-01

22q11.2 microduplication syndrome is characterized by a large phenotypic variability including facial dysmorphism, developmental delay, and hearing loss. We describe a family in whom 5 of 11 children were affected by a unilateral or bilateral congenital aural atresia. Four of these 5 carried a 22q11.2 microduplication and had typical dysmorphic features. Computed tomography with 3-D reconstructions allowed for a detailed examination of the middle ear structures and classification of the atresia type. Audiometry revealed a moderately severe conductive hearing loss in accordance with the clinical and computed tomography findings. Detailed examination of the ear is warranted in patients with a 22q11.2 microduplication. When outer ear abnormalities are encountered, an additional workup including audiometry and computed tomography with 3-D reconstructions is required.

The accuracy of a designed software for automated localization of craniofacial landmarks on CBCT images.

PubMed

Shahidi, Shoaleh; Bahrampour, Ehsan; Soltanimehr, Elham; Zamani, Ali; Oshagh, Morteza; Moattari, Marzieh; Mehdizadeh, Alireza

2014-09-16

Two-dimensional projection radiographs have been traditionally considered the modality of choice for cephalometric analysis. To overcome the shortcomings of two-dimensional images, three-dimensional computed tomography (CT) has been used to evaluate craniofacial structures. However, manual landmark detection depends on medical expertise, and the process is time-consuming. The present study was designed to produce software capable of automated localization of craniofacial landmarks on cone beam (CB) CT images based on image registration and to evaluate its accuracy. The software was designed using MATLAB programming language. The technique was a combination of feature-based (principal axes registration) and voxel similarity-based methods for image registration. A total of 8 CBCT images were selected as our reference images for creating a head atlas. Then, 20 CBCT images were randomly selected as the test images for evaluating the method. Three experts twice located 14 landmarks in all 28 CBCT images during two examinations set 6 weeks apart. The differences in the distances of coordinates of each landmark on each image between manual and automated detection methods were calculated and reported as mean errors. The combined intraclass correlation coefficient for intraobserver reliability was 0.89 and for interobserver reliability 0.87 (95% confidence interval, 0.82 to 0.93). The mean errors of all 14 landmarks were <4 mm. Additionally, 63.57% of landmarks had a mean error of <3 mm compared with manual detection (gold standard method). The accuracy of our approach for automated localization of craniofacial landmarks, which was based on combining feature-based and voxel similarity-based methods for image registration, was acceptable. Nevertheless we recommend repetition of this study using other techniques, such as intensity-based methods.

Three-dimensional Procrustes analysis of modern human craniofacial form.

PubMed

Badawi-Fayad, Jackie; Cabanis, Emmanuel-Alain

2007-03-01

The objective of this study was to analyze modern human craniofacial form using 3D Procrustes superimposition in order to establish a reference model and validate it on computed tomography (CT). The sample consists of 136 specimens from five modern human regional groups. Thirty-three craniofacial landmark coordinates have been recorded using a Microscribe and calculated on CT scans for five crania from the sample. Procrustes superimposition has been performed to calculate the mean shape, and a discriminant analysis has also been carried out to estimate the variability of shape. The results show that the repeatability of measurements made on CT and on Microscribe is excellent (R = 0.99). There is no major distinctiveness in the craniofacial shape; however, discriminant function 1 separates out the European crania from the others, especially African and American. It includes the width and the length of the face, the flatness of the upper face, the prognathism of the maxilla, as well as the length and the inclination of the palate. The width of the maxilla and the palate do not show a great variability. This may be the common invariant feature responsible for the alignment of the teeth in all specimens. It may correspond to functional patterns related to masticatory constraints manifested by the important interproximal and occlusal dental wear in all specimens. This study confirms the high accuracy of measurements made on CT scan and the importance of geometric morphometrics, which provides an accurate characterization of the overall craniofacial shape and its variation within the entire population.

Dwarfism with gloomy face: a new syndrome with features of 3-M syndrome.

PubMed Central

Le Merrer, M; Brauner, R; Maroteaux, P

1991-01-01

Nine children with primordial dwarfism are described and a new syndrome is delineated. The significant features of this syndrome include facial dysmorphism with gloomy face and very short stature, but no radiological abnormality or hormone deficiency. Mental development is normal. The mode of inheritance seems to be autosomal recessive because of consanguinity in three of the four sibships. Some overlap with the 3-M syndrome is discussed but the autonomy of the gloomy face syndrome seems to be real. Images PMID:2051454

Ductal paucity and Warkany syndrome in a patient with congenital extrahepatic portocaval shunt

PubMed Central

Sood, Vikrant; Khanna, Rajeev; Alam, Seema; Rawat, Dinesh; Bhatnagar, Shorav; Rastogi, Archana

2014-01-01

An eleven-year-old clinically dysmorphic and developmentally retarded male child presenting with complaints of 5 episodes of recurrent cholestatic jaundice since 3 years of age was evaluated. Imaging revealed features consistent with congenital extrahepatic portocaval shunt (Abernethy type 1b), multiple regenerative liver nodules and intrahepatic biliary radical dilatation. The presence of ductal paucity and trisomy 8 were confirmed on liver biopsy and karyotyping. The explanation for unusual and previously unreported features in the present case has been proposed. PMID:24868329

A novel heterozygous RIT1 mutation in a patient with Noonan syndrome, leukopenia, and transient myeloproliferation-a review of the literature.

PubMed

Nemcikova, Michaela; Vejvalkova, Sarka; Fencl, Filip; Sukova, Martina; Krepelova, Anna

2016-04-01

Noonan syndrome (NS) is a genetic condition presenting with typical facies, cardiac defects, short stature, variable developmental deficit, cryptorchidism, skeletal, and other abnormalities. Germline mutations in genes involved in the RAS/MAPK signaling have been discovered to underlie NS. Recently, missense mutations in RIT1 have been reported as causative for individuals with clinical signs of NS. We report on a 2.5-year-old boy with NS phenotype with a novel heterozygous change in the RIT1 gene. The patient was born prematurely from pregnancy monitored for polyhydramnios. At 7 months of age, non-immune neutropenia and splenomegaly have been observed. During the severe pneumonia at 10 months, significant progression of hepatosplenomegaly, leukopenia with monocytosis (15-29 %), and thrombocytopenia occurred. Bone marrow evaluation showed myeloid hyperplasia and monocytosis, suggestive of myeloproliferative syndrome. Clinical phenotype (facial dysmorphism, soft hair, short neck, broad chest, widely spaced nipples, mild pectus carinatum, deep palmar creases, unilateral cryptorchidism), and moderate pulmonary valve stenosis with mild psychomotor delay were indicative of NS. DNA analysis identified a de novo heterozygous variant c.69A >T, p.(Lys23Asn) in exon 2 of the RIT1 gene, presumed to be causative. We present a patient with a clinical suspicion of NS carrying a novel substitution in RIT1 and hematologic findings not being observed in RIT1 positive patients to date. Thus, the case broadens variability of hematologic symptoms in RIT1 positive NS individuals. • Noonan syndrome is a common genetically heterogeneous disorder of autosomal dominant inheritance characterized by craniofacial dysmorphism, short stature, congenital heart defects, variable cognitive deficit, and other anomalies. What is new: • We report on a 2.5-year-old male patient with clinical signs of NS and hematologic abnormalities, in whom a novel heterozygous substitution in RIT1 with probable pathogenicity was detected.

Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency

PubMed Central

2013-01-01

Background 22q13 deletion syndrome, also known as Phelan-McDermid syndrome, is a neurodevelopmental disorder characterized by intellectual disability, hypotonia, delayed or absent speech, and autistic features. SHANK3 has been identified as the critical gene in the neurological and behavioral aspects of this syndrome. The phenotype of SHANK3 deficiency has been described primarily from case studies, with limited evaluation of behavioral and cognitive deficits. The present study used a prospective design and inter-disciplinary clinical evaluations to assess patients with SHANK3 deficiency, with the goal of providing a comprehensive picture of the medical and behavioral profile of the syndrome. Methods A serially ascertained sample of patients with SHANK3 deficiency (n = 32) was evaluated by a team of child psychiatrists, neurologists, clinical geneticists, molecular geneticists and psychologists. Patients were evaluated for autism spectrum disorder using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-G. Results Thirty participants with 22q13.3 deletions ranging in size from 101 kb to 8.45 Mb and two participants with de novo SHANK3 mutations were included. The sample was characterized by high rates of autism spectrum disorder: 27 (84%) met criteria for autism spectrum disorder and 24 (75%) for autistic disorder. Most patients (77%) exhibited severe to profound intellectual disability and only five (19%) used some words spontaneously to communicate. Dysmorphic features, hypotonia, gait disturbance, recurring upper respiratory tract infections, gastroesophageal reflux and seizures were also common. Analysis of genotype-phenotype correlations indicated that larger deletions were associated with increased levels of dysmorphic features, medical comorbidities and social communication impairments related to autism. Analyses of individuals with small deletions or point mutations identified features related to SHANK3 haploinsufficiency, including ASD, seizures and abnormal EEG, hypotonia, sleep disturbances, abnormal brain MRI, gastroesophageal reflux, and certain dysmorphic features. Conclusions This study supports findings from previous research on the severity of intellectual, motor, and speech impairments seen in SHANK3 deficiency, and highlights the prominence of autism spectrum disorder in the syndrome. Limitations of existing evaluation tools are discussed, along with the need for natural history studies to inform clinical monitoring and treatment development in SHANK3 deficiency. PMID:23758760

Gender similarities and differences in 200 individuals with body dysmorphic disorder⋆

PubMed Central

Phillips, Katharine A.; Menard, William; Fay, Christina

2006-01-01

Background Gender is a critically important moderator of psychopathology. However, gender similarities and differences in body dysmorphic disorder (BDD) have received scant investigation. In this study, we examined gender similarities and differences in the broadest sample in which this topic has been examined. Methods Two hundred subjects with BDD recruited from diverse sources were assessed with a variety of standard measures. Results There were more similarities than differences between men and women, but many gender differences were found. The men were significantly older and more likely to be single and living alone. Men were more likely to obsess about their genitals, body build, and thinning hair/balding; excessively lift weights; and have a substance use disorder. In contrast, women were more likely to obsess about their skin, stomach, weight, breasts/chest, buttocks, thighs, legs, hips, toes, and excessive body/facial hair, and they were excessively concerned with more body areas. Women also performed more repetitive and safety behaviors, and were more likely to camouflage and use certain camouflaging techniques, check mirrors, change their clothes, pick their skin, and have an eating disorder. Women also had earlier onset of subclinical BDD symptoms and more severe BDD as assessed by the Body Dysmorphic Disorder Examination. However, men had more severe BDD as assessed by the Psychiatric Status Rating Scale for Body Dysmorphic Disorder, and they had poorer Global Assessment of Functioning Scale scores, were less likely to be working because of psychopathology, and were more likely to be receiving disability, including disability for BDD. Conclusions The clinical features of BDD in men and women have many similarities but also some interesting and important differences. These findings have implications for the detection and treatment of BDD. PMID:16490564

Correlates of dysmorphic concern in people seeking cosmetic enhancement

PubMed Central

Castle, David J.; Molton, Michael; Hoffman, Keturah; Preston, Neil J.; Phillips, Katharine A.

2006-01-01

Objective To determine the clinical correlates of dysmorphic concern in persons seeking cosmetic enhancement from cosmetic physicians. Method A questionnaire survey of 137 patients attending the practices of two cosmetic physicians. Results Four subjects (2.9%; 95% CI = 0.8%–7.3%) had a diagnosis of body dysmorphic disorder (BDD), but many more expressed overconcern with physical appearance (‘dysmorphic concern’). Dysmorphic concern accounted for a substantial amount of the variance for mood, social anxiety, and impairment in work and social functioning, while concerns related to how self or others perceive the putative flaw in appearance, impacted significantly on work and leisure activities, but did not apparently influence mood and social anxiety to any significant degree. Conclusions Dysmorphic concern is a broad dimensional construct that is related to both inter- and intrapsychic distress and disablement associated with people seeking cosmetic enhancement PMID:15209836

De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype.

PubMed

Shashi, Vandana; Pena, Loren D M; Kim, Katherine; Burton, Barbara; Hempel, Maja; Schoch, Kelly; Walkiewicz, Magdalena; McLaughlin, Heather M; Cho, Megan; Stong, Nicholas; Hickey, Scott E; Shuss, Christine M; Freemark, Michael S; Bellet, Jane S; Keels, Martha Ann; Bonner, Melanie J; El-Dairi, Maysantoine; Butler, Megan; Kranz, Peter G; Stumpel, Constance T R M; Klinkenberg, Sylvia; Oberndorff, Karin; Alawi, Malik; Santer, Rene; Petrovski, Slavé; Kuismin, Outi; Korpi-Heikkilä, Satu; Pietilainen, Olli; Aarno, Palotie; Kurki, Mitja I; Hoischen, Alexander; Need, Anna C; Goldstein, David B; Kortüm, Fanny

2016-10-06

The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during embryogenesis and encode proteins involved in epigenetic regulation and assembly of transcription factors to specific genomic loci. Germline de novo truncating variants in ASXL1 and ASXL3 have been respectively implicated in causing Bohring-Opitz and Bainbridge-Ropers syndromes, which result in overlapping features of severe intellectual disability and dysmorphic features. ASXL2 has not yet been associated with a human Mendelian disorder. In this study, we performed whole-exome sequencing in six unrelated probands with developmental delay, macrocephaly, and dysmorphic features. All six had de novo truncating variants in ASXL2. A careful review enabled the recognition of a specific phenotype consisting of macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, hypotonia, and developmental disabilities. Although overlapping features with Bohring-Opitz and Bainbridge-Ropers syndromes exist, features that distinguish the ASXL2-associated condition from ASXL1- and ASXL3-related disorders are macrocephaly, absence of growth retardation, and more variability in the degree of intellectual disabilities. We were also able to demonstrate with mRNA studies that these variants are likely to exert a dominant-negative effect, given that both alleles are expressed in blood and the mutated ASXL2 transcripts escape nonsense-mediated decay. In conclusion, de novo truncating variants in ASXL2 underlie a neurodevelopmental syndrome with a clinically recognizable phenotype. This report expands the germline disorders that are linked to the ASXL genes. Copyright © 2016. Published by Elsevier Inc.

Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis.

PubMed

Harel, Itamar; Maezawa, Yoshiro; Avraham, Roi; Rinon, Ariel; Ma, Hsiao-Yen; Cross, Joe W; Leviatan, Noam; Hegesh, Julius; Roy, Achira; Jacob-Hirsch, Jasmine; Rechavi, Gideon; Carvajal, Jaime; Tole, Shubha; Kioussi, Chrissa; Quaggin, Susan; Tzahor, Eldad

2012-11-13

The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.

Craniofacial anthropometry in newborns of Sikkimese origin.

PubMed

Sinha, P; Tamang, B K; Chakraborty, S

2014-06-01

Head and face dimensions vary according to race and geographical zone. Hereditary factors also greatly affect the size and shape of the head. There are important medical applications of craniofacial data specific to different racial and ethnic groups. Various cranial and facial anthropometric parameters were assessed in singleton, healthy, full-term newborns of Sikkimese origin in a tertiary care hospital in Sikkim, India. The data were then analysed to determine statistically significant differences between sexes. Forty-five newborns were included in the study. Both male and female newborns were observed to be hyperbrachycephalic and hyperleptoprosopic. The only significant difference between the sexes was in commissural length, which was observed to be greater in male newborns. Craniofacial parameters in Sikkimese newborns vary in comparison with those of other newborns from around the world. Larger studies are needed in order to reveal sex-related variations. Similar studies on various racial groups in North-East India are needed to establish standards for populations with East Asian features.

Reliability of Craniofacial Superimposition Using Three-Dimension Skull Model.

PubMed

Gaudio, Daniel; Olivieri, Lara; De Angelis, Danilo; Poppa, Pasquale; Galassi, Andrea; Cattaneo, Cristina

2016-01-01

Craniofacial superimposition is a technique potentially useful for the identification of unidentified human remains if a photo of the missing person is available. We have tested the reliability of the 2D-3D computer-aided nonautomatic superimposition techniques. Three-dimension laser scans of five skulls and ten photographs were overlaid with an imaging software. The resulting superimpositions were evaluated using three methods: craniofacial landmarks, morphological features, and a combination of the two. A 3D model of each skull without its mandible was tested for superimposition; we also evaluated whether separating skulls by sex would increase correct identifications. Results show that the landmark method employing the entire skull is the more reliable one (5/5 correct identifications, 40% false positives [FP]), regardless of sex. However, the persistence of a high percentage of FP in all the methods evaluated indicates that these methods are unreliable for positive identification although the landmark-only method could be useful for exclusion. © 2015 American Academy of Forensic Sciences.

Craniofacial variation and dietary adaptations of African colobines.

PubMed

Koyabu, Daisuke B; Endo, Hideki

2009-06-01

African colobine monkeys show considerable craniofacial variation among species, although the evolutionary causes of this diversity are unclear. In light of growing evidence that diet varies considerably among colobine species, we investigated whether colobine craniofacial morphology varies as a function of their diet. We compared craniofacial morphology among five African species: Colobus angolensis, C. guereza, C. polykomos, Piliocolobus badius, and P. verus. Matrix correlation analysis indicated a significant correlation between species-specific morphological distance and dietary distance matrices. The mechanical advantage of the masseter muscle was higher in seed-eaters (C. angolensis and C. polykomos) and lower in those that eat mainly young leaves (C. guereza, P. badius, and P. verus). Canonical correspondence analysis revealed that the durophagous colobines possess relatively wider bigonial breadths, anteroposteriorly shorter faces, shorter postcanine tooth rows, more medially positioned dental batteries, wider bizygomatic arches, and anteroposteriorly longer zygomatic arches. Under the constrained lever model, these morphological features suggest that durophagous colobines have the capacity to generate relatively greater maximum bite forces. However, no consistent relationship was observed between diet and variation in the mandibular corpus and symphysis, implying that robust mandibles are not necessarily adaptations for stress resistance. Factors that may influence mandibular robusticity include allometry of symphyseal curvature and canine tooth support. Finally, linear measures of mandibular robusticity may suffer from error.

Body Dysmorphic Symptoms Scale for patients seeking esthetic surgery: cross-cultural validation study.

PubMed

Ramos, Tatiana Dalpasquale; Brito, Maria José Azevedo de; Piccolo, Mônica Sarto; Rosella, Maria Fernanda Normanha da Silva Martins; Sabino, Miguel; Ferreira, Lydia Masako

2016-07-21

Rhinoplasty is one of the most sought-after esthetic operations among individuals with body dysmorphic disorder. The aim of this study was to cross-culturally adapt and validate the Body Dysmorphic Symptoms Scale. Cross-cultural validation study conducted in a plastic surgery outpatient clinic of a public university hospital. Between February 2014 and March 2015, 80 consecutive patients of both sexes seeking rhinoplasty were selected. Thirty of them participated in the phase of cultural adaptation of the instrument. Reproducibility was tested on 20 patients and construct validity was assessed on 50 patients, with correlation against the Yale-Brown Obsessive Compulsive Scale for Body Dysmorphic Disorder. The Brazilian version of the instrument showed Cronbach's alpha of 0.805 and excellent inter-rater reproducibility (intraclass correlation coefficient, ICC = 0.873; P < 0.001) and intra-rater reproducibility (ICC = 0.939; P < 0.001). Significant differences in total scores were found between patients with and without symptoms (P < 0.001). A strong correlation (r = 0.841; P < 0.001) was observed between the Yale-Brown Obsessive Compulsive Scale for Body Dysmorphic Disorder and the Body Dysmorphic Symptoms Scale. The area under the receiver operating characteristic curve was 0.981, thus showing good accuracy for discriminating between presence and absence of symptoms of body dysmorphic disorder. Forty-six percent of the patients had body dysmorphic symptoms and 54% had moderate to severe appearance-related obsessive-compulsive symptoms. The Brazilian version of the Body Dysmorphic Symptoms Scale is a reproducible instrument that presents face, content and construct validity.

Body Dysmorphic Symptoms Scale for patients seeking esthetic surgery: cross-cultural validation study.

PubMed

Ramos, Tatiana Dalpasquale; Brito, Maria José Azevedo de; Piccolo, Mônica Sarto; Rosella, Maria Fernanda Normanha da Silva Martins; Sabino, Miguel; Ferreira, Lydia Masako

2016-01-01

Rhinoplasty is one of the most sought-after esthetic operations among individuals with body dysmorphic disorder. The aim of this study was to cross-culturally adapt and validate the Body Dysmorphic Symptoms Scale. Cross-cultural validation study conducted in a plastic surgery outpatient clinic of a public university hospital. Between February 2014 and March 2015, 80 consecutive patients of both sexes seeking rhinoplasty were selected. Thirty of them participated in the phase of cultural adaptation of the instrument. Reproducibility was tested on 20 patients and construct validity was assessed on 50 patients, with correlation against the Yale-Brown Obsessive Compulsive Scale for Body Dysmorphic Disorder. The Brazilian version of the instrument showed Cronbach's alpha of 0.805 and excellent inter-rater reproducibility (intraclass correlation coefficient, ICC = 0.873; P < 0.001) and intra-rater reproducibility (ICC = 0.939; P < 0.001). Significant differences in total scores were found between patients with and without symptoms (P < 0.001). A strong correlation (r = 0.841; P < 0.001) was observed between the Yale-Brown Obsessive Compulsive Scale for Body Dysmorphic Disorder and the Body Dysmorphic Symptoms Scale. The area under the receiver operating characteristic curve was 0.981, thus showing good accuracy for discriminating between presence and absence of symptoms of body dysmorphic disorder. Forty-six percent of the patients had body dysmorphic symptoms and 54% had moderate to severe appearance-related obsessive-compulsive symptoms. The Brazilian version of the Body Dysmorphic Symptoms Scale is a reproducible instrument that presents face, content and construct validity.

Social-evaluative versus self-evaluative appearance concerns in Body Dysmorphic Disorder.

PubMed

Anson, Martin; Veale, David; de Silva, Padmal

2012-12-01

Body Dysmorphic Disorder (BDD) is characterised by significant preoccupation and distress relating to an imagined or slight defect in appearance. Individuals with BDD frequently report marked concerns relating to perceived negative evaluation of their appearance by others, but research specifically investigating such concerns remains limited. This study investigated the extent and nature of appearance-related social-evaluative and self-evaluative concerns in individuals with BDD and healthy controls. BDD participants, in comparison to controls, reported high levels of importance and anxiety associated with perceptions of others' views of their appearance, in addition to their own view. No differences were observed in the level of importance and anxiety associated with their self-view in comparison to others' views. These findings support existing evidence indicating that appearance-related social-evaluative concerns are a central feature of BDD. Cognitive-behavioural treatment implications are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Drivers of Academic Success in Cleft and Craniofacial Centers: A 10-Year Analysis of over 2000 Publications.

PubMed

Plana, Natalie M; Massie, Jonathan P; Stern, Marleigh J; Alperovich, Michael; Runyan, Christopher M; Staffenberg, David A; Koniaris, Leonidas G; Grayson, Barry H; Diaz-Siso, J Rodrigo; Flores, Roberto L

2017-02-01

Cleft and craniofacial centers require significant investment by medical institutions, yet variables contributing to their academic productivity remain unknown. This study characterizes the elements associated with high academic productivity in these centers. The authors analyzed cleft and craniofacial centers accredited by the American Cleft Palate-Craniofacial Association. Variables such as university affiliation; resident training; number of plastic surgery, oral-maxillofacial, and dental faculty; and investment in a craniofacial surgery, craniofacial orthodontics fellowship program, or both, were obtained. Craniofacial and cleft-related research published between July of 2005 and June of 2015 was identified. A stepwise multivariable linear regression analysis was performed to measure outcomes of total publications, summative impact factor, basic science publications, total journals, and National Institutes of Health funding. One hundred sixty centers were identified, comprising 920 active faculty, 34 craniofacial surgery fellowships, and eight craniofacial orthodontic fellowships; 2356 articles were published in 191 journals. Variables most positively associated with a high number of publications were craniofacial surgery and craniofacial orthodontics fellowships (β = 0.608), craniofacial surgery fellowships (β = 0.231), number of plastic surgery faculty (β = 0.213), and university affiliation (β = 0.165). Variables most positively associated with high a number of journals were craniofacial surgery and craniofacial orthodontics fellowships (β = 0.550), university affiliation (β = 0.251), number of plastic surgery faculty (β = 0.230), and craniofacial surgery fellowship (β = 0.218). Variables most positively associated with a high summative impact factor were craniofacial surgery and craniofacial orthodontics fellowships (β = 0.648), craniofacial surgery fellowship (β = 0.208), number of plastic surgery faculty (β = 0.207), and university affiliation (β = 0.116). Variables most positively associated with basic science publications were craniofacial surgery and craniofacial orthodontics fellowships (β = 0.676) and craniofacial surgery fellowship (β = 0.208). The only variable associated with National Institutes of Health funding was craniofacial surgery and craniofacial orthodontics fellowship (β = 0.332). Participation in both craniofacial surgery and orthodontics fellowships demonstrates the strongest association with academic success; craniofacial surgery fellowship, university affiliation, and number of surgeons are also predictive.

Mild Intellectual Disability Associated with a Progeny of Father-Daughter Incest: Genetic and Environmental Considerations

ERIC Educational Resources Information Center

Ansermet, Francois; Lespinasse, James; Gimelli, Stefania; Bena, Frederique; Paoloni-Giacobino, Ariane

2010-01-01

We report the case of a 34-year-old female resulting from a father-daughter sexual abuse and presenting a phenotype of mild intellectual disability with minor dysmorphic features. Karyotyping showed a normal 46, XX constitution. Array-based comparative genomic hybridization (array-CGH) revealed a heterozygote 320kb 6p22.3 microdeletion in the…

A Case of Partial Trisomy of Chromosome 8p Associated with Autism

ERIC Educational Resources Information Center

Papanikolaou, Katerina; Paliokosta, Elena; Gyftodimou, Jolanda; Kolaitis, Gerassimos; Vgenopoulou, Sofia; Sarri, Catherine; Tsiantis, John

2006-01-01

We report on a case of a 6-year-old female with partial trisomy 8p(21-23) associated with autism, mild dysmorphic features, and moderate learning disability. Although mental retardation is a common finding in patients with mosaic trisomy 8 or partial trisomy of various regions of chromosome 8, only two cases associated with autism have been…

Severe short stature due to 3-M syndrome with a novel OBSL1 gene mutation.

PubMed

Demir, Korcan; Altıncık, Ayça; Böber, Ece

2013-01-01

3-M syndrome is an underdiagnosed autosomal recessive disorder characterized by severe pre- and postnatal growth retardation with minimal dysmorphic features and distinguishing radiological findings. We report a patient who was first admitted at 7.5 years of age. He was born to consanguineous parents with a birth weight of 2250 g. Physical examination revealed a severe short stature (height, 95 cm; SD score -5.64) and minimal dysmorphic features. Biochemistry, endocrine work-up, and karyotype were normal. Reevaluation at 16.5 years of age revealed a height of 128.5 cm (SD score -5.27), prominent forehead, anteverted nasal openings, fleshy nasal tip, full lips, malar hypoplasia, hyperlordosis, prominent heels, testicular volumes 8-10 mL, and pubic hair consistent with Tanner stage II. Growth hormone trial for a year resulted in inadequate height gain (3 cm). The diagnosis of 3-M syndrome was made upon typical findings (thin long bones with diaphyseal narrowing and tall lumbar vertebrae) in a recent skeletal survey. Genetic analysis disclosed a homozygote frame shift mutation in exon 2: c.457_458delinsT resulting in p.Gly153fs.

Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features.

PubMed

Lamb, Allen N; Rosenfeld, Jill A; Neill, Nicholas J; Talkowski, Michael E; Blumenthal, Ian; Girirajan, Santhosh; Keelean-Fuller, Debra; Fan, Zheng; Pouncey, Jill; Stevens, Cathy; Mackay-Loder, Loren; Terespolsky, Deborah; Bader, Patricia I; Rosenbaum, Kenneth; Vallee, Stephanie E; Moeschler, John B; Ladda, Roger; Sell, Susan; Martin, Judith; Ryan, Shawnia; Jones, Marilyn C; Moran, Rocio; Shealy, Amy; Madan-Khetarpal, Suneeta; McConnell, Juliann; Surti, Urvashi; Delahaye, Andrée; Heron-Longe, Bénédicte; Pipiras, Eva; Benzacken, Brigitte; Passemard, Sandrine; Verloes, Alain; Isidor, Bertrand; Le Caignec, Cedric; Glew, Gwen M; Opheim, Kent E; Descartes, Maria; Eichler, Evan E; Morton, Cynthia C; Gusella, James F; Schultz, Roger A; Ballif, Blake C; Shaffer, Lisa G

2012-04-01

SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system. Despite its important developmental roles, SOX5 disruption has yet to be associated with human disease. We report one individual with a reciprocal translocation breakpoint within SOX5, eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent), and seven individuals with larger 12p12 deletions encompassing SOX5. Common features in these subjects include prominent speech delay, intellectual disability, behavior abnormalities, and dysmorphic features. The phenotypic impact of the deletions may depend on the location of the deletion and, consequently, which of the three major SOX5 protein isoforms are affected. One intragenic deletion, involving only untranslated exons, was present in a more mildly affected subject, was inherited from a healthy parent and grandparent, and is similar to a deletion found in a control cohort. Therefore, some intragenic SOX5 deletions may have minimal phenotypic effect. Based on the location of the deletions in the subjects compared to the controls, the de novo nature of most of these deletions, and the phenotypic similarities among cases, SOX5 appears to be a dosage-sensitive, developmentally important gene. © 2012 Wiley Periodicals, Inc.

Rejection Sensitivity Mediates the Relationship between Social Anxiety and Body Dysmorphic Concerns

PubMed Central

Fang, Angela; Asnaani, Anu; Gutner, Cassidy; Cook, Courtney; Wilhelm, Sabine; Hofmann, Stefan G.

2011-01-01

The goal of this study was to examine the role of rejection sensitivity in the relationship between social anxiety and body dysmorphic concerns. To test our hypothesis that rejection sensitivity mediates the link between social anxiety and body dysmorphic concerns, we administered self-report questionnaires to 209 student volunteers. Consistent with our prediction, rejection sensitivity partially mediated the relationship between social anxiety symptoms and body dysmorphic concerns. The implications of the overlap between these constructs are discussed. PMID:21741203

Antenatal diagnosis of complete facial duplication--a case report of a rare craniofacial defect.

PubMed

Rai, V S; Gaffney, G; Manning, N; Pirrone, P G; Chamberlain, P F

1998-06-01

We report a case of the prenatal sonographic detection of facial duplication, the diprosopus abnormality, in a twin pregnancy. The characteristic sonographic features of the condition include duplication of eyes, mouth, nose and both mid- and anterior intracranial structures. A heart-shaped abnormality of the cranial vault should prompt more detailed examination for other supportive features of this rare condition.

High prevalence of body dysmorphic disorder symptoms in patients seeking rhinoplasty.

PubMed

Picavet, Valerie A; Prokopakis, Emmanuel P; Gabriëls, Lutgardis; Jorissen, Mark; Hellings, Peter W

2011-08-01

Nasal aesthetic deformities may be associated with significant body image dissatisfaction. The only diagnostic category in the current list of psychiatric disorders that directly addresses these concerns is body dysmorphic disorder. This large-scale study determined the prevalence of body dysmorphic disorder and its symptoms in patients seeking rhinoplasty and evaluated the clinical profile of these patients. Two hundred twenty-six patients were given questionnaires including demographic characteristics, visual analogue scales for nasal shape, the Yale-Brown Obsessive Compulsive Scale modified for body dysmorphic disorder to assess severity of symptoms, a generic quality-of-life questionnaire, and the Derriford Appearance Scale 59, to assess appearance-related disruption of everyday living. Independent observers scored the nasal shape. Thirty-three percent of patients showed at least moderate symptoms of body dysmorphic disorder. Aesthetic goals (p < 0.001), revision rhinoplasty (p = 0.003), and psychiatric history (p = 0.031) were associated with more severe symptoms. There was no correlation between the objective and subjective scoring of the nasal shape. Yale-Brown scale modified for body dysmorphic disorder scores correlated inversely with the subjective nasal scoring (n = 210, p < 0.001), without relation to the objective deformity of the nose. Body dysmorphic disorder symptoms significantly reduced the generic quality of life (n = 160, p < 0.001) and led to significant appearance-related disruption of everyday living (n = 161, p < 0.001). The prevalence of moderate to severe body dysmorphic disorder symptoms in an aesthetic rhinoplasty population is high. Patients undergoing revision rhinoplasty and with psychiatric history are particularly at risk. Body dysmorphic disorder symptoms significantly reduce the quality of life and cause significant appearance-related disruption of everyday living. Risk, III.

Leopard spot retinal pigmentation in infancy indicating a peroxisomal disorder.

PubMed

Lyons, C J; Castano, G; McCormick, A Q; Applegarth, D

2004-02-01

Neonatal adrenoleucodystrophy (NALD) is a rare disorder resulting from abnormal peroxisomal biogenesis. Affected patients present in infancy with developmental delay, hypotonia, and seizures. Blindness and nystagmus are prominent features. The authors suggest a characteristic leopard spot pigmentary pattern in the peripheral retina to be diagnostic. Three patients are reported with this presentation; the characteristic retinal appearance resulted in early diagnosis for one of these. Leopard spot retinopathy in an infant with hypotonia, seizures, developmental delay, with or without dysmorphic features and hearing impairment, is a clue to the diagnosis of NALD.

Validation of Spanish Language Evaluation Instruments for Body Dysmorphic Disorder and the Dysmorphic Concern Construct

PubMed Central

Senín-Calderón, Cristina; Valdés-Díaz, María; Benítez-Hernández, Ma M.; Núñez-Gaitán, Ma C.; Perona-Garcelán, Salvador; Martínez-Cervantes, Rafael; Rodríguez-Testal, Juan F.

2017-01-01

Dysmorphic concern (DC) refers to excessive preoccupation with a slight or imagined defect in physical appearance with social avoidance and behavior directed at controlling the defect in appearance. This study attempted to adapt the factor structure of two instruments that cover the DC construct, the Dysmorphic Concern Questionnaire (DCQ) and the Body Dysmorphic Disorder Examination Self-Report (BDDE-SR), to Spanish and establish their psychometric properties. A total of 920 subjects (62.7% women, Mage = 32.44 years) participated. Exploratory and Confirmatory Factor Analysis of both scales found adequate goodness of fit indices. A one-dimensional structure was found for the DCQ and two first-order factors (dissatisfaction/preoccupation with body image (BI) and BI avoidance behavior) were identified for the BDDE-SR. The psychometric test–retest reliability and validity properties (content, convergent, and discriminant) were satisfactory. It is suggested that the DC construct includes both cognitive and behavioral aspects and may represent a continuum of severity with Body Dysmorphic Disorder at the end. PMID:28713311

Validation of Spanish Language Evaluation Instruments for Body Dysmorphic Disorder and the Dysmorphic Concern Construct.

PubMed

Senín-Calderón, Cristina; Valdés-Díaz, María; Benítez-Hernández, Ma M; Núñez-Gaitán, Ma C; Perona-Garcelán, Salvador; Martínez-Cervantes, Rafael; Rodríguez-Testal, Juan F

2017-01-01

Dysmorphic concern (DC) refers to excessive preoccupation with a slight or imagined defect in physical appearance with social avoidance and behavior directed at controlling the defect in appearance. This study attempted to adapt the factor structure of two instruments that cover the DC construct, the Dysmorphic Concern Questionnaire (DCQ) and the Body Dysmorphic Disorder Examination Self-Report (BDDE-SR), to Spanish and establish their psychometric properties. A total of 920 subjects (62.7% women, M age = 32.44 years) participated. Exploratory and Confirmatory Factor Analysis of both scales found adequate goodness of fit indices. A one-dimensional structure was found for the DCQ and two first-order factors (dissatisfaction/preoccupation with body image (BI) and BI avoidance behavior) were identified for the BDDE-SR. The psychometric test-retest reliability and validity properties (content, convergent, and discriminant) were satisfactory. It is suggested that the DC construct includes both cognitive and behavioral aspects and may represent a continuum of severity with Body Dysmorphic Disorder at the end.

Dysmorphic concern is related to delusional proneness and negative affect in a community sample.

PubMed

Keating, Charlotte; Thomas, Neil; Stephens, Jessie; Castle, David J; Rossell, Susan L

2016-06-30

Body image concerns are common in the general population and in some mental illnesses reach pathological levels. We investigated whether dysmorphic concern with appearance (a preoccupation with minor or imagined defects in appearance) is explained by psychotic processes in a community sample. In a cross-sectional design, two hundred and twenty six participants completed an online survey battery including: The Dysmorphic Concern Questionnaire; the Peters Delusional inventory; the Aberrant Salience Inventory; and the Depression, Anxiety, Stress Scale. Participants were native English speakers residing in Australia. Dysmorphic concern was positively correlated with delusional proneness, aberrant salience and negative emotion. Regression established that negative emotion and delusional proneness predicted dysmorphic concern, whereas, aberrant salience did not. Although delusional proneness was related to body dysmorphia, there was no evidence that it was related to aberrant salience. Understanding the contribution of other psychosis processes, and other health related variables to the severity of dysmorphic concern will be a focus of future research. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Body Dysmorphic Disorder: Contraindication or Ethical Justification for Female Genital Cosmetic Surgery in Adolescents.

PubMed

Spriggs, Merle; Gillam, Lynn

2016-11-01

Is Female Genital Cosmetic Surgery for an adolescent with Body Dysmorphic Disorder ever ethically justified? Cosmetic genital surgery (specifically labioplasty) for adolescent girls is one of the most ethically controversial forms of cosmetic surgery and Body Dysmorphic Disorder is typically seen as a contraindication for cosmetic surgery. Two key ethical concerns are (1) that Body Dysmorphic Disorder undermines whatever capacity for autonomy the adolescent has; and (2) even if there is valid parental consent, the presence of Body Dysmorphic Disorder means that cosmetic surgery will fail in its aims. In this article, we challenge, in an evidence-based way, the standard view that Body Dysmorphic Disorder is a contraindication for genital cosmetic surgery in adolescents. Our argument gathers together and unifies a substantial amount of disparate research in the context of an ethical argument. We focus on empirical questions about benefit and harm, because these are ethically significant. Answers to these questions affect the answer to the ethical question. We question the claim that there would be no benefit from surgery in this situation, and we consider possible harms that might be done if treatment is refused. For an adolescent with Body Dysmorphic Disorder, the most important thing may be to avoid harm. We find ourselves arguing for the ethical justifiability of cosmetic labioplasty for an adolescent with Body Dysmorphic Disorder, even though we recognize that it is a counter intuitive position. We explain how we reached our conclusion. © 2016 John Wiley & Sons Ltd.

PUF60 variants cause a syndrome of ID, short stature, microcephaly, coloboma, craniofacial, cardiac, renal and spinal features

PubMed Central

Low, Karen J; Ansari, Morad; Abou Jamra, Rami; Clarke, Angus; El Chehadeh, Salima; FitzPatrick, David R; Greenslade, Mark; Henderson, Alex; Hurst, Jane; Keller, Kory; Kuentz, Paul; Prescott, Trine; Roessler, Franziska; Selmer, Kaja K; Schneider, Michael C; Stewart, Fiona; Tatton-Brown, Katrina; Thevenon, Julien; Vigeland, Magnus D; Vogt, Julie; Willems, Marjolaine; Zonana, Jonathan; Study, D D D; Smithson, Sarah F

2017-01-01

PUF60 encodes a nucleic acid-binding protein, a component of multimeric complexes regulating RNA splicing and transcription. In 2013, patients with microdeletions of chromosome 8q24.3 including PUF60 were found to have developmental delay, microcephaly, craniofacial, renal and cardiac defects. Very similar phenotypes have been described in six patients with variants in PUF60, suggesting that it underlies the syndrome. We report 12 additional patients with PUF60 variants who were ascertained using exome sequencing: six through the Deciphering Developmental Disorders Study and six through similar projects. Detailed phenotypic analysis of all patients was undertaken. All 12 patients had de novo heterozygous PUF60 variants on exome analysis, each confirmed by Sanger sequencing: four frameshift variants resulting in premature stop codons, three missense variants that clustered within the RNA recognition motif of PUF60 and five essential splice-site (ESS) variant. Analysis of cDNA from a fibroblast cell line derived from one of the patients with an ESS variants revealed aberrant splicing. The consistent feature was developmental delay and most patients had short stature. The phenotypic variability was striking; however, we observed similarities including spinal segmentation anomalies, congenital heart disease, ocular colobomata, hand anomalies and (in two patients) unilateral renal agenesis/horseshoe kidney. Characteristic facial features included micrognathia, a thin upper lip and long philtrum, narrow almond-shaped palpebral fissures, synophrys, flared eyebrows and facial hypertrichosis. Heterozygote loss-of-function variants in PUF60 cause a phenotype comprising growth/developmental delay and craniofacial, cardiac, renal, ocular and spinal anomalies, adding to disorders of human development resulting from aberrant RNA processing/spliceosomal function. PMID:28327570

An emerging, recognizable facial phenotype in association with mutations in GLI-similar 3 (GLIS3).

PubMed

Dimitri, Paul; De Franco, Elisa; Habeb, Abdelhadi M; Gurbuz, Fatih; Moussa, Khairya; Taha, Doris; Wales, Jerry K H; Hogue, Jacob; Slavotinek, Anne; Shetty, Ambika; Balasubramanian, Meena

2016-07-01

Neonatal diabetes and hypothyroidism (NDH) syndrome was first described in 2003 in a consanguineous Saudi Arabian family where two out of four siblings were reported to have presented with proportionate IUGR, neonatal non-autoimmune diabetes mellitus, severe congenital hypothyroidism, cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by enlarged kidneys and multiple small cysts with deficient cortico-medullary junction differentiation and normal kidney function. There was minor facial dysmorphism (depressed nasal bridge, large anterior fontanelle, long philtrum) reported but no facial photographs were published. Mutations in the transcription factor GLI-similar 3 (GLIS3) gene in the original family and two other families were subsequently reported in 2006. All affected individuals had neonatal diabetes, congenital hypothyroidism but glaucoma and liver and kidney involvement were less consistent features. Detailed descriptions of the facial dysmorphism have not been reported previously. In this report, we describe the common facial dysmorphism consisting of bilateral low-set ears, depressed nasal bridge with overhanging columella, elongated, upslanted palpebral fissures, persistent long philtrum with a thin vermilion border of the upper lip in a cohort of seven patients with GLIS3 mutations and report the emergence of a distinct, probably recognizable facial gestalt in this group which evolves with age. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Selective cognitive impairment and tall stature due to chromosome 19 supernumerary ring.

PubMed

Melis, Daniela; Genesio, Rita; Del Giudice, Ennio; Taurisano, Roberta; Mormile, Angela; D'Elia, Federica; Conti, Anna; Imperati, Floriana; Andria, Generoso; Nitsch, Lucio

2012-01-01

Small supernumerary marker chromosomes (sSMC) occur with a frequency of approximately 0.4 per 1000 newborns and are more frequent in the population with mental retardation and/or with dysmorphic signs. Small supernumerary chromosome rings (sSCR) usually occur as apart of a mosaic karyotype (Liehr et al., 2004). Chromosome 19 supernumerary rings are very rare. Almost all cases of sSMC19 have been reported on Thomas Liehr's website (http://www.med.uni-jena.de/fish/sSMC/19.htm#Start19). Of these cases, 14 were with phenotypic abnormalities and a clear characterization of the sSMC; two cases were suitable for comparison with our case with regard to their genetic content, but not with regard to the structure ofthe sSMC (Manvelyan et al., 2008). The phenotype, associated with partial trisomy 19q, includes facial dysmorphism, growth and mental retardation, macrocephaly, heart malformation and anomalies of the genitourinary and gastrointestinal tracts. The phenotype associated with partial trisomy 19p is characterized by dysmorphic features, severe mental retardation, abnormalities of brain morphology and anomalies of the fingers (Tercanli et al., 2000; Qorri et al., 2002; Novelli et al., 2005; Vraneković et al., 2008). Herein, we report the phenotype and molecular cytogenetic analysis in a patient with the smallest de-novo constitutional ring extended from the p12 to q12 region of chromosome 19.

Facial dysmorphism in Leigh syndrome with SURF-1 mutation and COX deficiency.

PubMed

Yüksel, Adnan; Seven, Mehmet; Cetincelik, Umran; Yeşil, Gözde; Köksal, Vedat

2006-06-01

Leigh syndrome is an inherited, progressive neurodegenerative disorder of infancy and childhood. Mutations in the nuclear SURF-1 gene are specifically associated with cytochrome C oxidase-deficient Leigh syndrome. This report describes two patients with similar facial features. One of them was a 2(1/2)-year-old male, and the other was a 3-year-old male with a mutation in SURF-1 gene and facial dysmorphism including frontal bossing, brachycephaly, hypertrichosis, lateral displacement of inner canthi, esotropia, maxillary hypoplasia, hypertrophic gums, irregularly placed teeth, upturned nostril, low-set big ears, and retrognathi. The first patient's magnetic resonance imaging at 15 months of age indicated mild symmetric T2 prolongation involving the subthalamic nuclei. His second magnetic resonance imaging at 2 years old revealed a symmetric T2 prolongation involving the subthalamic nuclei, substantia nigra, and medulla lesions. In the second child, at the age of 2 the first magnetic resonance imaging documented heavy brainstem and subthalamic nuclei involvement. A second magnetic resonance imaging, performed when he was 3 years old, revealed diffuse involvement of the substantia nigra and hyperintense lesions of the central tegmental tract in addition to previous lesions. Facial dysmorphism and magnetic resonance imaging findings, observed in these cases, can be specific findings in Leigh syndrome patients with cytochrome C oxidase deficiency. SURF-1 gene mutations must be particularly reviewed in such patients.

Infantile spasms with periventricular nodular heterotopia, unbalanced chromosomal translocation 3p26.2 -10p15.1 and 6q22.31 duplication.

PubMed

Jones, Kevin; Weiss, Shelly K; Minassian, Berge

2016-07-01

Patients presenting with infantile spasms, dysmorphic features, and periventricular nodular heterotopia may benefit from genetic copy number variation microarray, or whole-exome sequencing to identify candidate genes. This will allow personalized diagnosis and prognostication and the eventual understanding of single and combined gene functions in brain health and disease.

Growth retardation, intellectual disability, facial anomalies, cataract, thoracic hypoplasia and skeletal abnormalities: a novel phenotype

PubMed Central

Shah, Hitesh; Bens, Susanne; Caliebe, Almuth; Graham, John M.; Girisha, Katta Mohan

2012-01-01

We report a fourteen year old adolescent girl with growth deficiency, microcephaly, intellectual disability, distinctive dysmorphic features (bulbous nose with wide nasal base, hypotelorism, deeply set eyes, protruding cupped ears and thick lips), cataract, pigmentary retinopathy, hypoplastic thorax, kyphoscoliosis and unusual skeletal changes but without chromosomal imbalances detected by array-CGH who probably represents a novel phenotype. PMID:22987502

Analysis of Practice Settings for Craniofacial Surgery Fellowship Graduates in North America.

PubMed

Silvestre, Jason; Runyan, Christopher; Taylor, Jesse A

In North America, the number of craniofacial surgery fellowship graduates is increasing, yet an analysis of practice settings upon graduation is lacking. We characterize the practice types of recent graduates of craniofacial fellowship programs in the United States and Canada. A 6-year cohort of craniofacial fellows in the United States and Canada (2010-2016) were obtained from craniofacial programs recognized by the American Society of Craniofacial Surgery. Practice setting was determined at 1 and 3 years of postgraduation, and predictors of practice setting were determined. A total of 175 craniofacial surgeons were trained at 35 fellowship programs. At 1 year of postgraduation, 33.6% had an academic craniofacial position and 27.1% were in private practice (p = 0.361). A minority of graduates pursued additional fellowships (16.4%), nonacademic craniofacial positions (10.0%), academic noncraniofacial positions (5.7%), and international practices (7.1%). At 3 years of postgraduation, the percentage of graduates in academic craniofacial positions was unchanged (34.5% vs 33.6%, p = 0.790). The strongest predictors of future academic craniofacial practice were completing plastic surgery residency at a program with a craniofacial fellowship program (odds ratio = 6.78, p < 0.001) and completing an academic craniofacial fellowship program (odds ratio = 4.48, p = 0.020). A minority of craniofacial fellowship graduates practice academic craniofacial surgery. A strong academic craniofacial surgery background during residency and fellowship is associated with a future career in academic craniofacial surgery. These data may assist trainees choose training programs that align with career goals and educators select future academic surgeons. Copyright © 2017. Published by Elsevier Inc.

Genetic background has a major effect on the penetrance and severity of craniofacial defects in mice heterozygous for the gene encoding the nucleolar protein Treacle.

PubMed

Dixon, Jill; Dixon, Michael James

2004-04-01

Treacher Collins syndrome (TCS) is a craniofacial disorder that results from mutations in TCOF1, which encodes the nucleolar protein Treacle. The severity of the clinical features exhibits wide variation and includes hypoplasia of the mandible and maxilla, abnormalities of the external ears and middle ear ossicles, and cleft palate. To determine the in vivo function of Treacle, we previously generated Tcof1 heterozygous mice on a mixed C57BL/6 and 129 background. These mice exhibited a lethal phenotype, which included abnormal development of the maxilla, absence of the eyes and nasal passages, and neural tube defects. Here, we show that placing the mutation onto different genetic backgrounds has a major effect on the penetrance and severity of the craniofacial and other defects. The offspring exhibit markedly variable strain-dependent phenotypes that range from extremely severe and lethal in a mixed CBA/Ca and 129 background, to apparently normal and viable in a mixed BALB/c and 129 background. In the former case, in addition to a profoundly severe craniofacial phenotype, CBA-derived heterozygous mice also exhibited delayed ossification of the long bones, rib fusions, and digit anomalies. The results of our studies indicate that factors in the different genetic backgrounds contribute extensively to the Tcof1 phenotype. Copyright 2004 Wiley-Liss, Inc.

Visual selective attention in body dysmorphic disorder, bulimia nervosa and healthy controls.

PubMed

Kollei, Ines; Horndasch, Stefanie; Erim, Yesim; Martin, Alexandra

2017-01-01

Cognitive behavioral models postulate that selective attention plays an important role in the maintenance of body dysmorphic disorder (BDD). It is suggested that individuals with BDD overfocus on perceived defects in their appearance, which may contribute to the excessive preoccupation with their appearance. The present study used eye tracking to examine visual selective attention in individuals with BDD (n=19), as compared to individuals with bulimia nervosa (BN) (n=21) and healthy controls (HCs) (n=21). Participants completed interviews, questionnaires, rating scales and an eye tracking task: Eye movements were recorded while participants viewed photographs of their own face and attractive as well as unattractive other faces. Eye tracking data showed that BDD and BN participants focused less on their self-rated most attractive facial part than HCs. Scanning patterns in own and other faces showed that BDD and BN participants paid as much attention to attractive as to unattractive features in their own face, whereas they focused more on attractive features in attractive other faces. HCs paid more attention to attractive features in their own face and did the same in attractive other faces. Results indicate an attentional bias in BDD and BN participants manifesting itself in a neglect of positive features compared to HCs. Perceptual retraining may be an important aspect to focus on in therapy in order to overcome the neglect of positive facial aspects. Future research should aim to disentangle attentional processes in BDD by examining the time course of attentional processing. Copyright © 2016 Elsevier Inc. All rights reserved.

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.

PubMed

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-03-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

PubMed Central

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-01-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant. PMID:22872100

Clinical and cytogenetic features of a Potocki-Lupski syndrome with the shortest 0.25Mb microduplication in 17p11.2 including RAI1.

PubMed

Lee, Cha Gon; Park, Sang-Jin; Yim, Shin-Young; Sohn, Young Bae

2013-08-01

Potocki-Lupski syndrome (PTLS [MIM 610883]) is a recently recognized microduplication syndrome associated with 17p11.2. It is characterized by mild facial dysmorphic features, hypermetropia, infantile hypotonia, failure to thrive, mental retardation, autistic spectrum disorders, behavioral abnormalities, sleep apnea, and cardiovascular anomalies. In several studies, the critical PTLS region was deduced to be 1.3Mb in length, and included RAI1 and 17 other genes. We report a 3-year-old Korean boy with the smallest duplication in 17p11.2 and a milder phenotype. He had no family history of neurologic disease or developmental delay and no history of seizure, autistic features, or behavior problems. He showed subtle facial dysmorphic features (dolichocephaly and a mildly asymmetric smile) and flat feet. All laboratory tests were normal and he had no evidence of internal organ anomalies. He was found to have mild intellectual disabilities (full scale IQ 65 on K-WPPSI) and language developmental delay (age of 2.2year-old on PRESS). Array comparative genomic hybridization (CGH) showed about a 0.25Mb microduplication on chromosome 17p11.2 containing four Refseq (NCBI reference sequence) genes, including RAI1 [arr 17p11.2(17,575,978-17,824,623)×3]. When compared with previously reported cases, the milder phenotype of our patient may be associated with the smallest duplication in 17p11.2, 0.25Mb in length. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Does skull shape mediate the relationship between objective features and subjective impressions about the face?

PubMed

Marečková, Klára; Chakravarty, M Mallar; Huang, Mei; Lawrence, Claire; Leonard, Gabriel; Perron, Michel; Pike, Bruce G; Richer, Louis; Veillette, Suzanne; Pausova, Zdenka; Paus, Tomáš

2013-10-01

In our previous work, we described facial features associated with a successful recognition of the sex of the face (Marečková et al., 2011). These features were based on landmarks placed on the surface of faces reconstructed from magnetic resonance (MR) images; their position was therefore influenced by both soft tissue (fat and muscle) and bone structure of the skull. Here, we ask whether bone structure has dissociable influences on observers' identification of the sex of the face. To answer this question, we used a novel method of studying skull morphology using MR images and explored the relationship between skull features, facial features, and sex recognition in a large sample of adolescents (n=876; including 475 adolescents from our original report). To determine whether skull features mediate the relationship between facial features and identification accuracy, we performed mediation analysis using bootstrapping. In males, skull features mediated fully the relationship between facial features and sex judgments. In females, the skull mediated this relationship only after adjusting facial features for the amount of body fat (estimated with bioimpedance). While body fat had a very slight positive influence on correct sex judgments about male faces, there was a robust negative influence of body fat on the correct sex judgments about female faces. Overall, these results suggest that craniofacial bone structure is essential for correct sex judgments about a male face. In females, body fat influences negatively the accuracy of sex judgments, and craniofacial bone structure alone cannot explain the relationship between facial features and identification of a face as female. Copyright © 2013 Elsevier Inc. All rights reserved.

Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates.

PubMed

Sessle, B J

2000-01-01

This paper reviews the recent advances in knowledge of brainstem mechanisms related to craniofacial pain. It also draws attention to their clinical implications, and concludes with a brief overview and suggestions for future research directions. It first describes the general organizational features of the trigeminal brainstem sensory nuclear complex (VBSNC), including its input and output properties and intrinsic characteristics that are commensurate with its strategic role as the major brainstem relay of many types of somatosensory information derived from the face and mouth. The VBSNC plays a crucial role in craniofacial nociceptive transmission, as evidenced by clinical, behavioral, morphological, and electrophysiological data that have been especially derived from studies of the relay of cutaneous nociceptive afferent inputs through the subnucleus caudalis of the VBSNC. The recent literature, however, indicates that some fundamental differences exist in the processing of cutaneous vs. other craniofacial nociceptive inputs to the VBSNC, and that rostral components of the VBSNC may also play important roles in some of these processes. Modulatory mechanisms are also highlighted, including the neurochemical substrate by which nociceptive transmission in the VBSNC can be modulated. In addition, the long-term consequences of peripheral injury and inflammation and, in particular, the neuroplastic changes that can be induced in the VBSNC are emphasized in view of the likely role that central sensitization, as well as peripheral sensitization, can play in acute and chronic pain. The recent findings also provide new insights into craniofacial pain behavior and are particularly relevant to many approaches currently in use for the management of pain and to the development of new diagnostic and therapeutic procedures aimed at manipulating peripheral inputs and central processes underlying nociceptive transmission and its control within the VBSNC.

Update on 13 Syndromes Affecting Craniofacial and Dental Structures

PubMed Central

Bartzela, Theodosia N.; Carels, Carine; Maltha, Jaap C.

2017-01-01

Care of individuals with syndromes affecting craniofacial and dental structures are mostly treated by an interdisciplinary team from early childhood on. In addition to medical and dental specialists that have a vivid interest in these syndromes and for whom these syndromes are of evident interest, experts of scientific background—like molecular and developmental geneticists, but also computational biologists and bioinformaticians—, become more frequently involved in the refined diagnostic and etiological processes of these patients. Early diagnosis is often crucial for the effective treatment of functional and developmental aspects. However, not all syndromes can be clinically identified early, especially in cases of absence of known family history. Moreover, the treatment of these patients is often complicated because of insufficient medical knowledge, and because of the dental and craniofacial developmental variations. The role of the team is crucial for the prevention, proper function, and craniofacial development which is often combined with orthognathic surgery. Although the existing literature does not provide considerable insight into this topic, this descriptive review aims to provide tools for the interdisciplinary team by giving an update on the genetics and general features, and the oral and craniofacial manifestations for early diagnosis. Clinical phenotyping together with genetic data and pathway information will ultimately pave the way for preventive strategies and therapeutic options in the future. This will improve the prognosis for better functional and aesthetic outcome for these patients and lead to a better quality of life, not only for the patients themselves but also for their families. The aim of this review is to promote interdisciplinary interaction and mutual understanding among all specialists involved in the diagnosis and therapeutic guidance of patients with these syndromal conditions in order to provide optimal personalized care in an integrated approach. PMID:29311971

Facial recognition techniques applied to the automated registration of patients in the emergency treatment of head injuries.

PubMed

Gooroochurn, M; Kerr, D; Bouazza-Marouf, K; Ovinis, M

2011-02-01

This paper describes the development of a registration framework for image-guided solutions to the automation of certain routine neurosurgical procedures. The registration process aligns the pose of the patient in the preoperative space to that of the intraoperative space. Computerized tomography images are used in the preoperative (planning) stage, whilst white light (TV camera) images are used to capture the intraoperative pose. Craniofacial landmarks, rather than artificial markers, are used as the registration basis for the alignment. To create further synergy between the user and the image-guided system, automated methods for extraction of these landmarks have been developed. The results obtained from the application of a polynomial neural network classifier based on Gabor features for the detection and localization of the selected craniofacial landmarks, namely the ear tragus and eye corners in the white light modality are presented. The robustness of the classifier to variations in intensity and noise is analysed. The results show that such a classifier gives good performance for the extraction of craniofacial landmarks.

Body dysmorphic concerns, social adaptation, and motivation for psychotherapeutic support in dermatological outpatients.

PubMed

Ritter, Viktoria; Fluhr, Joachim W; Schliemann-Willers, Sibylle; Elsner, Peter; Strauß, Bernhard; Stangier, Ulrich

2016-09-01

Dermatologists are increasingly confronted with patients affected by body dysmorphic disorder (BDD). BDD is characterized by excessive preoccupation with one or more perceived defect(s) or flaw(s) in physical appearance which are not observable or appear slight to others. So far, there have been only few studies examining the prevalence of BDD in dermatological outpatients. In addition, the need for psychotherapeutic support in dermatological outpatients with body dysmorphic concerns has not yet been systematically examined. The objective of the present study was therefore to investigate the frequency of body dysmorphic concerns as well as social adaptation and the need for psychotherapeutic support in the aforementioned patient group. A total of 252 dermatological outpatients seen at a German university hospital were consecutively enrolled, and examined using the Dysmorphic Concerns Questionnaire, the Social Adaptation Self-Evaluation Scale, and the German version of the University of Rhode Island Change Assessment Scale. 7.9 % of all outpatients (unselected sample) showed positive test results, suggesting clinically relevant body dysmorphic concerns. Patients with clinically relevant body dysmorphic concerns exhibited poor social adaptation. Contrary to expectations, these patients revealed a high motivation for change, indicating the necessity for psychotherapeutic support. Our findings confirm previous prevalence rates of BDD in dermatological outpatients, and highlight the need for providing psychotherapeutic support to dermatological patients. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Safe Zone Quantification of the Third Sacral Segment in Normal and Dysmorphic Sacra.

PubMed

Hwang, John S; Reilly, Mark C; Shaath, Mohammad K; Changoor, Stuart; Eastman, Jonathan; Routt, Milton Lee Chip; Sirkin, Michael S; Adams, Mark R

2018-04-01

To quantify the osseous anatomy of the dysmorphic third sacral segment and assess its ability to accommodate internal fixation. Retrospective chart review of a trauma database. University Level 1 Trauma Center. Fifty-nine patients over the age of 18 with computed tomography scans of the pelvis separated into 2 groups: a group with normal pelvic anatomy and a group with sacral dysmorphism. The sacral osseous area was measured on computed tomography scans in the axial, coronal, and sagittal planes in normal and dysmorphic pelves. These measurements were used to determine the possibility of accommodating a transiliac transsacral screw in the third sacral segment. In the normal group, the S3 coronal transverse width averaged 7.71 mm and the S3 axial transverse width averaged 7.12 mm. The mean S3 cross-sectional area of the normal group was 55.8 mm. The dysmorphic group was found to have a mean S3 coronal transverse width of 9.49 mm, an average S3 axial transverse width of 9.14 mm, and an S3 cross-sectional area of 77.9 mm. The third sacral segment of dysmorphic sacra has a larger osseous pathway available to safely accommodate a transiliac transsacral screw when compared with normal sacra. The S3 segment of dysmorphic sacra can serve as an additional site for screw placement when treating unstable posterior pelvic ring fractures.

A twin study of body dysmorphic concerns.

PubMed

Monzani, B; Rijsdijk, F; Anson, M; Iervolino, A C; Cherkas, L; Spector, T; Mataix-Cols, D

2012-09-01

Dysmorphic concern refers to an excessive preoccupation with a perceived or slight defect in physical appearance. It lies on a continuum of severity from no or minimal concerns to severe concerns over one's appearance. The present study examined the heritability of dysmorphic concerns in a large sample of twins. Twins from the St Thomas UK twin registry completed a valid and reliable self-report measure of dysmorphic concerns, which also includes questions about perceived body odour and malfunction. Twin modelling methods (female twins only, n=3544) were employed to decompose the variance in the liability to dysmorphic concerns into additive genetic, shared and non-shared environmental factors. Model-fitting analyses showed that genetic factors accounted for approximately 44% [95% confidence intervals (CI) 36-50%] of the variance in dysmorphic concerns, with non-shared environmental factors and measurement error accounting for the remaining variance (56%; 95% CI 50-63%). Shared environmental factors were negligible. The results remained unchanged when excluding individuals reporting an objective medical condition/injury accounting for their concern in physical appearance. Over-concern with a perceived or slight defect in physical appearance is a heritable trait, with non-shared environmental factors also playing an important role in its causation. The results are relevant for various psychiatric disorders characterized by excessive concerns in body appearance, odour or function, including but not limited to body dysmorphic disorder.

Atelosteogenesis type 2.

PubMed Central

Newbury-Ecob, R

1998-01-01

Atelosteogenesis type 2 (AO2) (MIM 256050) is a neonatally lethal chondrodysplasia characterised by severe limb shortening and deficient ossification of parts of the skeleton. Other features include facial dysmorphism, cleft palate, talipes, and abducted thumbs and toes. Phenotypic overlap with non-lethal diastrophic dysplasia (DTD) suggested a common aetiology and it has recently been confirmed that both syndromes result from mutations in the DTDST (diastrophic dysplasia sulphate transporter) gene. Images PMID:9475095

Primary perivascular epithelioid cell tumors of the liver: CT/MRI findings and clinical outcomes.

PubMed

O'Malley, Martin E; Chawla, Tanya P; Lavelle, Lisa P; Cleary, Sean; Fischer, Sandra

2017-06-01

The purpose of our study was to describe the CT and MRI features of primary PEComas of the liver and to document the associated clinical outcomes. Retrospective study included 20 patients with primary hepatic perivascular epithelioid cell tumors (PEComa) with pathology and clinical outcomes for correlation. Study group included 20 patients: 16 women, 4 men; mean age 53 (range 35-77) years. Initial pathology diagnoses were classic angiomyolipoma (AML) (n = 11), epithelioid AML (n = 7), and PEComa not otherwise specified (n = 2). Mean tumor size was 5.1 (range 1.3-15.0) cm. CT/MRI features included well-defined margins 20/20 (100%), arterial enhancement 18/19 (95%), subcapsular location 17/20 (85%), heterogeneous 16/20 (80%), dysmorphic vessels 14/20 (70%), fat 13/20 (65%), hemorrhage 4/20 (20%), cystic components 4/20 (20%), and calcification 1/20 (5%). At the time of discovery, 18 patients were asymptomatic and their tumors were incidentally detected on imaging, and 2 patients were symptomatic. Ultimately, 18 tumors were benign and 2 developed metastases. On CT/MRI, most primary hepatic PEComas were well-defined, arterial enhancing, subcapsular, heterogeneous masses that often had dysmorphic vessels and contained fat. Most tumors were benign but complications included local symptoms, bleeding, and malignant change.

Neuroligin 2 nonsense variant associated with anxiety, autism, intellectual disability, hyperphagia, and obesity.

PubMed

Parente, Daniel J; Garriga, Caryn; Baskin, Berivan; Douglas, Ganka; Cho, Megan T; Araujo, Gabriel C; Shinawi, Marwan

2017-01-01

Neuroligins are post-synaptic, cellular adhesion molecules implicated in synaptic formation and function. NLGN2 is strongly linked to inhibitory, GABAergic signaling and is crucial for maintaining the excitation-inhibition balance in the brain. Disruption of the excitation-inhibition balance is associated with neuropsychiatric disease. In animal models, altered NLGN2 expression causes anxiety, developmental delay, motor discoordination, social impairment, aggression, and sensory processing defects. In humans, mutations in NLGN3 and NLGN4 are linked to autism and schizophrenia; NLGN2 missense variants are implicated in schizophrenia. Copy number variants encompassing NLGN2 on 17p13.1 are associated with autism, intellectual disability, metabolic syndrome, diabetes, and dysmorphic features, but an isolated NLGN2 nonsense variant has not yet been described in humans. Here, we describe a 15-year-old male with severe anxiety, obsessive-compulsive behaviors, developmental delay, autism, obesity, macrocephaly, and some dysmorphic features. Exome sequencing identified a heterozygous, de novo, c.441C>A p.(Tyr147Ter) variant in NLGN2 that is predicted to cause loss of normal protein function. This is the first report of an NLGN2 nonsense variant in humans, adding to the accumulating evidence that links synaptic proteins with a spectrum of neurodevelopmental phenotypes. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities.

PubMed

van der Crabben, Saskia N; Harakalova, Magdalena; Brilstra, Eva H; van Berkestijn, Frédérique M C; Hofstede, Floris C; van Vught, Adrianus J; Cuppen, Edwin; Kloosterman, Wigard; Ploos van Amstel, Hans Kristian; van Haaften, Gijs; van Haelst, Mieke M

2014-01-01

Phosphatidyl inositol glycan (PIG) enzyme subclasses are involved in distinct steps of glycosyl phosphatidyl inositol anchor protein biosynthesis. Glycolsyl phosphatidyl inositol-anchored proteins have heterogeneous functions; they can function as enzymes, adhesion molecules, complement regulators and co-receptors in signal transduction pathways. Germline mutations in genes encoding different members of the PIG family result in diverse conditions with (severe) developmental delay, (neonatal) seizures, hypotonia, CNS abnormalities, growth abnormalities, and congenital abnormalities as hallmark features. The variability of clinical features resembles the typical diversity of other glycosylation pathway deficiencies such as the congenital disorders of glycosylation. Here, we report the first germline missense mutation in the PIGA gene associated with accelerated linear growth, obesity, central hypotonia, severe refractory epilepsy, cardiac anomalies, mild facial dysmorphic features, mildly elevated alkaline phosphatase levels, and CNS anomalies consisting of progressive cerebral atrophy, insufficient myelinization, and cortical MRI signal abnormalities. X-exome sequencing in the proband identified a c.278C>T (p.Pro93Leu) mutation in the PIGA gene. The mother and maternal grandmother were unaffected carriers and the mother showed 100% skewing of the X-chromosome harboring the mutation. These results together with the clinical similarity of the patient reported here and the previously reported patients with a germline nonsense mutation in PIGA support the determination that this mutation caused the phenotype in this family. © 2013 Wiley Periodicals, Inc.

Familial testicular germ cell tumor: no associated syndromic pattern identified

PubMed Central

2014-01-01

Background Testicular germ cell tumor (TGCT) is the most common malignancy in young men. Familial clustering, epidemiologic evidence of increased risk with family or personal history, and the association of TGCT with genitourinary (GU) tract anomalies have suggested an underlying genetic predisposition. Linkage data have not identified a rare, highly-penetrant, single gene in familial TGCT (FTGCT) cases. Based on its association with congenital GU tract anomalies and suggestions that there is an intrauterine origin to TGCT, we hypothesized the existence of unrecognized dysmorphic features in FTGCT. Methods We evaluated 38 FTGCT individuals and 41 first-degree relatives from 22 multiple-case families with detailed dysmorphology examinations, physician-based medical history and physical examination, laboratory testing, and genitourinary imaging studies. Results The prevalence of major abnormalities and minor variants did not significantly differ between either FTGCT individuals or their first-degree relatives when compared with normal population controls, except for tall stature, macrocephaly, flat midface, and retro-/micrognathia. However, these four traits were not manifest as a constellation of features in any one individual or family. We did detect an excess prevalence of the genitourinary anomalies cryptorchidism and congenital inguinal hernia in our population, as previously described in sporadic TGCT, but no congenital renal, retroperitoneal or mediastinal anomalies were detected. Conclusions Overall, our study did not identify a constellation of dysmorphic features in FTGCT individuals, which is consistent with results of genetic studies suggesting that multiple low-penetrance genes are likely responsible for FTGCT susceptibility. PMID:24559313

Placento-Cranial Adhesions in Amniotic Band Syndrome and the Role of Surgery in Their Management: An Unusual Case Presentation and Systematic Literature Review.

PubMed

Menekse, Guner; Mert, Mustafa Kurthan; Olmaz, Burak; Celik, Tamer; Celik, Umit Sizmaz; Okten, Ali Ihsan

2015-01-01

Amniotic band syndrome is a group of sporadic congenital anomalies that involve the limbs, craniofacial regions and trunk, ranging from simple digital band constriction to complex craniofacial and central nervous system abnormalities. Placento-cranial adhesions in amniotic band syndrome are extremely rare, and severe conditions are associated with high morbidity and mortality rates. In this study, we pooled placento-cranial adhesion case reports that were published in the medical literature and added an unpublished case from our institution. The purpose of this article was to review and discuss the clinical features and outcomes of placento-cranial adhesions in amniotic band syndrome. © 2015 S. Karger AG, Basel.

Pharmacotherapy Relapse Prevention in Body Dysmorphic Disorder: A Double-Blind, Placebo-Controlled Trial.

PubMed

Phillips, Katharine A; Keshaviah, Aparna; Dougherty, Darin D; Stout, Robert L; Menard, William; Wilhelm, Sabine

2016-09-01

Body dysmorphic disorder is common, distressing, and often severely impairing. Serotonin reuptake inhibitors appear efficacious, but the few existing pharmacotherapy studies were short term (≤4 months), and no relapse prevention studies or continuation phase studies have been conducted to the authors' knowledge. The authors report results from the first relapse prevention study in body dysmorphic disorder. Adults (N=100) with DSM-IV body dysmorphic disorder received open-label escitalopram for 14 weeks (phase 1); 58 responders were then randomized to double-blind continuation treatment with escitalopram versus switch to placebo for 6 months (phase 2). Reliable and valid outcome measures were utilized. In phase 1, 67.0% of treated subjects and 81.1% of subjects who completed phase 1 responded to escitalopram. Body dysmorphic disorder severity (in both the intent-to-treat and the completer groups) and insight, depressive symptoms, psychosocial functioning, and quality of life significantly improved from baseline to end of phase 1. In phase 2, time to relapse was significantly longer with escitalopram than with placebo treatment (hazard ratio=2.72, 95% CI=1.01-8.57). Phase 2 relapse proportions were 18% for escitalopram and 40% for placebo. Among escitalopram-treated subjects, body dysmorphic disorder severity significantly decreased over time during the continuation phase, with 35.7% of subjects showing further improvement. There were no significant group differences in body dysmorphic disorder severity or insight, depressive symptoms, psychosocial functioning, or quality of life. Continuation-phase escitalopram delayed time to relapse, and fewer escitalopram-treated subjects relapsed than did placebo-treated subjects. Body dysmorphic disorder severity significantly improved during 6 additional months of escitalopram treatment following acute response; more than one-third of escitalopram-treated subjects experienced further improvement.

The 3-M syndrome. A heritable low birthweight dwarfism.

PubMed

Van Goethem, H; Malvaux, P

1987-10-01

Two male siblings and one girl with the 3-M syndrome are reported. The main clinical features include low birthweight, proportionate dwarfism, hatched-shaped cranio-facial configuration, abnormalities of mouth and teeth, short broad neck with prominent trapezius, pectus deformity, transverse grooves of anterior chest, and winged scapulae.

Smith-Magenis Syndrome: Genetic Basis and Clinical Implications

ERIC Educational Resources Information Center

Finucane, Brenda; Haas-Givler, Barbara

2009-01-01

Smith-Magenis syndrome (SMS) is a neurobehavioral disorder associated with deletions and mutations of the "RAI1" gene on chromosome 17p11.2. Clinical features of the syndrome include intellectual disability, sleep disturbance, craniofacial differences, and a distinctive profile of stereotypic and self-injurious behaviors. Although the functional…

Brain connectome modularity in weight-restored anorexia nervosa and body dysmorphic disorder

PubMed Central

Zhang, A; Leow, A; Zhan, L; GadElkarim, J; Moody, T; Khalsa, S; Strober, M; Feusner, JD

2017-01-01

Background Anorexia nervosa (AN) and body dysmorphic disorder (BDD) frequently co-occur, and have several overlapping phenomenological features. Little is known about their shared neurobiology. Aims To compare modular organization of brain structural connectivity. Methods We acquired diffusion-weighted magnetic resonance imaging data on unmedicated individuals with BDD (n=29), weight-restored AN (n=24), and healthy controls (HC) (n=31). We constructed connectivity matrices using whole-brain white matter tractography, and compared modular structures across groups. Results AN showed abnormal modularity involving frontal, basal ganglia, and posterior cingulate nodes. There was a trend in BDD for similar abnormalities, but no significant differences compared with AN. In AN, poor insight correlated with longer path length in right caudal anterior cingulate and right posterior cingulate. Conclusions Abnormal network organization patterns in AN, partially shared with BDD, may have implications for understanding integration between reward and habit/ritual formation, as well as conflict monitoring/error detection. PMID:27429183

Retinal detachment and cataract, facial dysmorphism, generalized osteoporosis, immobile spine and platyspondyly in a consanguinous kindred--a possible new syndrome.

PubMed

Schmidt, H; Rudolph, G; Hergersberg, M; Schneider, K; Moradi, S; Meitinger, T

2001-02-01

We report on a consanguineous family with 6 children (out of 7) affected by a spondylo-ocular syndrome. Clinical features include cataract, loss of vision due to retinal detachment, facial dysmorphism, facial hypotonia, normal height with disproportional short trunk, immobile spine with thorakal kyphosis and reduced lumbal lordosis. On ophthalmological examination of the index patient, a dense cataract and complete retinal detachment could be detected on the right eye. On the left eye, an absent lens nucleus was found, but no retinal detachment. On radiological examination, there was generalized moderate osteoporosis; the spine showed marked platyspondyly and the bone age was advanced. On laboratory investigations, a normal excretion of amino acids, mucopolysaccharides and oligosaccharides could be found. The phenotypical spectrum observed in the 6 affected individuals was rather uniform. The karyotype was normal in all affected children. This hitherto undescribed combination of oculo-skeletal symptoms shows most resemblance with connective tissue disorders, suggesting a range of candidate genes for mutation analysis.

Potential link between body dysmorphic disorder symptoms and alexithymia in an eating-disordered treatment-seeking sample.

PubMed

Fenwick, Andrea Siân; Sullivan, Karen Anne

2011-09-30

This study aimed to explore the manifestation of body dysmorphic disorder symptoms in a sample of people with eating disorders and to investigate possible associations between body dysmorphia and alexithymia. Forty patients currently seeking treatment for an eating disorder completed a battery of six measures assessing alexithymia, mood, eating behaviours, weight-related body image, body dysmorphia and non-weight related body image. Significant moderate positive correlations (Pearson's r) between selected variables were found, suggesting that participants with high levels of dysmorphic concern (imagined ugliness) have more difficulty with the affective elements of alexithymia, that is, identifying and describing feelings. When depression, eating attitudes, and weight-related body image concerns were controlled for, significant moderate positive correlations between this alexithymia factor and dysmorphic concerns remained present. An independent-samples t-test between eating-disordered participants with and without symptoms of body dysmorphic disorder (BDD) revealed significant group differences in difficulties identifying feelings. This pattern of results was replicated when the groups were identified on the basis of dysmorphic concerns, as opposed to BDD symptoms. This study highlights the associations between alexithymia and body dysmorphia that have not previously been demonstrated. Copyright © 2011 Elsevier Ltd. All rights reserved.

Haploinsufficiency of a Spliceosomal GTPase Encoded by EFTUD2 Causes Mandibulofacial Dysostosis with Microcephaly

PubMed Central

Lines, Matthew A.; Huang, Lijia; Schwartzentruber, Jeremy; Douglas, Stuart L.; Lynch, Danielle C.; Beaulieu, Chandree; Guion-Almeida, Maria Leine; Zechi-Ceide, Roseli Maria; Gener, Blanca; Gillessen-Kaesbach, Gabriele; Nava, Caroline; Baujat, Geneviève; Horn, Denise; Kini, Usha; Caliebe, Almuth; Alanay, Yasemin; Utine, Gulen Eda; Lev, Dorit; Kohlhase, Jürgen; Grix, Arthur W.; Lohmann, Dietmar R.; Hehr, Ute; Böhm, Detlef; Majewski, Jacek; Bulman, Dennis E.; Wieczorek, Dagmar; Boycott, Kym M.

2012-01-01

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome. PMID:22305528

Clinical, cytogenetic and molecular investigation in a fetus with Wolf-Hirschhorn syndrome with paternally derived 4p deletion. Case report and review of the literature.

PubMed

Dietze, Ilona; Fritz, Barbara; Huhle, Dagmar; Simoens, Wouter; Piecha, Ernestine; Rehder, Helga

2004-01-01

Wolf-Hirschhorn (4p-) syndrome (WHS), caused by partial deletion of the short arm of chromosome 4, has been extensively described in children and young adults. Knowledge on fetuses with WHS is still limited due to the small number of published cases. We report on a fetus with prenatally diagnosed severe intrauterine growth retardation, reduced thoracal diameter, clubfeet deformity and midface hypoplasia including slight microretrognathia indicative for fetal karyotyping. Chromosome analysis after amniocentesis revealed a de novo terminal deletion of chromosome 4p [karyotype: 46,XX,del(4) (p16)] which was confirmed by FISH. Analyses of a set of polymorphic markers mapping in 4pter->4p15.3 showed absence of paternal haplotypes. These observations corroborate the preferential paternal origin of the de novo 4p deletion in WHS patients. Furthermore, the distal breakpoint could be narrowed to band 4p16.1. At autopsy, the fetus showed typical craniofacial dysmorphic signs of WHS, severe IUGR and delayed bone age. This report suggests the possibility of recognising the particular phenotype of WHS in utero by prenatal ultrasound and emphasises the importance of karyotyping fetuses with severe IUGR, especially when the amount of amniotic fluid is normal. Copyright 2004 S. Karger AG, Basel

Low-dose dasatinib rescues cardiac function in Noonan syndrome

PubMed Central

Yi, Jae-Sung; Huang, Yan; Kwaczala, Andrea T.; Kuo, Ivana Y.; Ehrlich, Barbara E.; Campbell, Stuart G.; Giordano, Frank J.; Bennett, Anton M.

2016-01-01

Noonan syndrome (NS) is a common autosomal dominant disorder that presents with short stature, craniofacial dysmorphism, and cardiac abnormalities. Activating mutations in the PTPN11 gene encoding for the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2 (SHP2) causes approximately 50% of NS cases. In contrast, NS with multiple lentigines (NSML) is caused by mutations that inactivate SHP2, but it exhibits some overlapping abnormalities with NS. Protein zero-related (PZR) is a SHP2-binding protein that is hyper-tyrosyl phosphorylated in the hearts of mice from NS and NSML, suggesting that PZR and the tyrosine kinase that catalyzes its phosphorylation represent common targets for these diseases. We show that the tyrosine kinase inhibitor, dasatinib, at doses orders of magnitude lower than that used for its anticancer activities inhibited PZR tyrosyl phosphorylation in the hearts of NS mice. Low-dose dasatinib treatment of NS mice markedly improved cardiomyocyte contractility and functionality. Remarkably, a low dose of dasatinib reversed the expression levels of molecular markers of cardiomyopathy and reduced cardiac fibrosis in NS and NSML mice. These results suggest that PZR/SHP2 signaling is a common target of both NS and NSML and that low-dose dasatinib may represent a unifying therapy for the treatment of PTPN11-related cardiomyopathies. PMID:27942593

De novo FBXO11 mutations are associated with intellectual disability and behavioural anomalies.

PubMed

Fritzen, Daniel; Kuechler, Alma; Grimmel, Mona; Becker, Jessica; Peters, Sophia; Sturm, Marc; Hundertmark, Hela; Schmidt, Axel; Kreiß, Martina; Strom, Tim M; Wieczorek, Dagmar; Haack, Tobias B; Beck-Wödl, Stefanie; Cremer, Kirsten; Engels, Hartmut

2018-05-01

Intellectual disability (ID) has an estimated prevalence of 1.5-2%. In most affected individuals, its genetic basis remains unclear. Whole exome sequencing (WES) studies have identified a multitude of novel causative gene defects and have shown that a large proportion of sporadic ID cases results from de novo mutations. Here, we present two unrelated individuals with similar clinical features and deleterious de novo variants in FBXO11 detected by WES. Individual 1, a 14-year-old boy, has mild ID as well as mild microcephaly, corrected cleft lip and alveolus, hyperkinetic disorder, mild brain atrophy and minor facial dysmorphism. WES detected a heterozygous de novo 1 bp insertion in the splice donor site of exon 3. Individual 2, a 3-year-old boy, showed ID and pre- and postnatal growth retardation, postnatal mild microcephaly, hyperkinetic and restless behaviour, as well as mild dysmorphism. WES detected a heterozygous de novo frameshift mutation. While ten individuals with ID and de novo variants in FBXO11 have been reported as part of larger studies, only one of the reports has some additional clinical data. Interestingly, the latter individual carries the identical mutation as our individual 2 and also displays ID, intrauterine growth retardation, microcephaly, behavioural anomalies, and dysmorphisms. Thus, we confirm deleterious de novo mutations in FBXO11 as a cause of ID and start the delineation of the associated clinical picture which may also comprise postnatal microcephaly or borderline small head size and behavioural anomalies.

Hennekam lymphangiectasia syndrome

PubMed Central

Lakshminarayana, G.; Mathew, A.; Rajesh, R.; Kurien, G.; Unni, V. N.

2011-01-01

Hennekam lymphangiectasia syndrome is a rare disorder comprising of intestinal and renal lymphangiectasia, dysmorphic facial appearance and mental retardation. The facial features include hypertelorism with a wide, flat nasal bridge, epicanthic folds, small mouth and small ears. We describe a case of a multigravida with bad obstetric history and characteristic facial and dental anomalies and bilateral renal lymphangiectasia. To our knowledge this is the first case of Hennekam lymphangiectasia syndrome with anodontia to be reported from India. PMID:22022089

Use of the S3 Corridor for Iliosacral Fixation in a Dysmorphic Sacrum: A Case Report.

PubMed

El Dafrawy, Mostafa H; Strike, Sophia A; Osgood, Greg M

2017-01-01

The S1 and S2 corridors are the typical osseous pathways for iliosacral screw fixation of posterior pelvic ring fractures. In dysmorphic sacra, the S1 screw trajectory is often different from that in normal sacra. We present a case of iliosacral screw placement in the third sacral segment for fixation of a complex lateral compression type-3 pelvic fracture in a patient with a dysmorphic sacrum. In patients with dysmorphic sacra and unstable posterior pelvic ring fractures or dislocations, the S3 corridor may be a feasible osseous fixation pathway that can be used in a manner equivalent to the S2 corridor in a normal sacrum.

Victimization, social anxiety, and body dysmorphic concerns: appearance-based rejection sensitivity as a mediator.

PubMed

Lavell, Cassie H; Zimmer-Gembeck, Melanie J; Farrell, Lara J; Webb, Haley

2014-09-01

Body dysmorphic disorder (BDD) is characterized by extreme preoccupation with perceived deficits in physical appearance, and sufferers experience severe impairment in functioning. Previous research has indicated that individuals with BDD are high in social anxiety, and often report being the victims of appearance-based teasing. However, there is little research into the possible mechanisms that might explain these relationships. The current study examined appearance-based rejection sensitivity as a mediator between perceived appearance-based victimization, social anxiety, and body dysmorphic symptoms in a sample of 237 Australian undergraduate psychology students. Appearance-based rejection sensitivity fully mediated the relationship between appearance-based victimization and body dysmorphic symptoms, and partially mediated the relationship between social anxiety and body dysmorphic symptoms. Findings suggest that individuals high in social anxiety or those who have a history of more appearance-based victimization may have a bias towards interpreting further appearance-based rejection, which may contribute to extreme appearance concerns such as BDD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pharmacological Treatment Of Body Dysmorphic Disorder.

PubMed

Hong, Kevin; Nezgovorova, Vera; Uzunova, Genoveva; Schlussel, Danya; Hollander, Eric

2018-04-26

Body dysmorphic disorder is a challenging disorder that manifests as erroneously perceived flaws in one's physical appearance and repetitive behaviors in response to appearance concerns. This disorder is also frequently comorbid with other psychiatric disorders, including major depressive disorder and autism spectrum disorder. It is currently understood to arise from a combination of biological, psychological, and environmental factors. Treatment of body dysmorphic disorder typically consists of a combination of pharmacotherapy and cognitive behavioral therapy. However, not all patients respond to treatment, and BDD symptoms remain even in those who do respond. This review outlines current pharmacological and neuromodulation treatments for body dysmorphic disorder, and suggests directions for future studies of novel treatments such as augmentation with atypical antipsychotics and the use of intranasal oxytocin in cases of body dysmorphic disorder that show residual symptomatology even with tailored monotherapy. There is emerging evidence suggesting that non-invasive neurostimulatory techniques, such as repetitive transcranial magnetic stimulation, may be of value in treatment-resistant cases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cognitive-behavioral therapy for body dysmorphic disorder: a review of its efficacy

PubMed Central

Prazeres, Angélica M; Nascimento, Antônio L; Fontenelle, Leonardo F

2013-01-01

The aim of this study was to review the efficacy of different methods of cognitive and/or behavioral therapies used to treat body dysmorphic disorder. We evaluated all case series, open studies, controlled trials, and meta-analyses of cognitive and/or behavioral treatment approaches to body dysmorphic disorder published up to July 2012, identified through a search in the PubMed/Medline, PsycINFO, ISI Web of Knowledge, and Scopus databases. Our findings indicate that individual and group cognitive behavioral therapies are superior to waiting list for the treatment of body dysmorphic disorder. While the efficacy of cognitive therapy is supported by one controlled trial, utility of behavioral therapy is suggested by one open study and one controlled relapse prevention follow-up study. There is a pressing need to conduct head-to-head studies, with appropriate, active, control treatment groups, in order to examine further the efficacy of cognitive and/or behavioral therapies for body dysmorphic disorder. PMID:23467711

Placebo-Controlled Study of Pimozide Augmentation of Fluoxetine in Body Dysmorphic Disorder

PubMed Central

Phillips, Katharine A.

2006-01-01

Objective Although body dysmorphic disorder often responds to serotonin reuptake inhibitors (SRIs), most patients do not respond or respond only partially. However, placebo-controlled studies of augmentation of SRIs have not been done. Furthermore, although 40%–50% of patients are delusional, studies of antipsychotic medications have not been done. Method Twenty-eight patients with body dysmorphic disorder or its delusional variant participated in an 8-week, placebo-controlled, double-blind, parallel-group study of pimozide augmentation of fluoxetine. Results Pimozide was not more effective than placebo: two (18.2%) of 11 subjects responded to pimozide and three (17.6%) of 17 subjects responded to placebo. There was no significant effect of baseline delusionality on endpoint severity of body dysmorphic disorder. Delusionality did not decrease significantly more with pimozide than placebo. Conclusions Pimozide augmentation of fluoxetine treatment for body dysmorphic disorder was not more effective than placebo, even in more delusional patients. Further studies of augmentation for SRIs are needed. PMID:15677604

Personality traits as vulnerability factors in body dysmorphic disorder.

PubMed

Schieber, Katharina; Kollei, Ines; de Zwaan, Martina; Müller, Astrid; Martin, Alexandra

2013-11-30

Cognitive behavioural models consider certain personality traits to be risk factors for the development of Body Dysmorphic Disorder (BDD). Research on personality traits in BDD is scarce, therefore this study examined perfectionism, aesthetic sensitivity and the behavioural inhibition system (BIS) in BDD. Furthermore, the association between these personality traits and the extent of dysmorphic concerns was investigated. Individuals with BDD (n=58) and a population based control sample (n=2071), selected from a representative German population survey, completed self-report questionnaires assessing DSM-5 criteria of BDD, dysmorphic concerns, perfectionism, aesthetic sensitivity and BIS-reactivity. Individuals with BDD reported significantly higher degrees of perfectionism as well as of BIS-reactivity compared to the population based control sample, whereas the groups did not differ significantly regarding aesthetic sensitivity. However, for the total sample, each of the personality traits was related dimensionally to dysmorphic concerns. Current BDD models consider perfectionism and aesthetic sensitivity to be vulnerability factors. In addition to these concepts, the present study suggests that BIS-reactivity is related to BDD. Self-reported aesthetic sensitivity was not found to be specifically pronounced in BDD, but along with perfectionism and BIS-reactivity aesthetic sensitivity was generally associated with dysmorphic concerns. © 2013 Elsevier Ireland Ltd. All rights reserved.

Osteoglophonic dwarfism in two generations.

PubMed Central

Kelley, R I; Borns, P F; Nichols, D; Zackai, E H

1983-01-01

A father and son, both affected by a skeletal dysplasia with severe craniofacial deformities, are reported and compared to three previously described isolated cases of the same dwarfism. The principal features are craniosynostosis, multiple lucent metaphyseal defects, flattening and anterior beaking of the vertebral bodies, and abnormal dentition. Autosomal dominant inheritance is suggested. Images PMID:6606709

A New Syndrome with Hypotonia, Obesity, Mental Deficiency, and Facial, Oral, Ocular, and Limb Anomalies

ERIC Educational Resources Information Center

Cohen, M. Michael, Jr.; And Others

1973-01-01

Presented were three case reports of patients, 8 to 18 years of age, who shared common features, such as obesity beginning in midchildhood, hypotonia, mental deficiency characteristic craniofacial appearance (antimongoloid slant, open mouth, or prominent central incisors), oral and ocular anomalies, and tapering extremities with narrow hands and…

Morphological Integration of Soft-Tissue Facial Morphology in Down Syndrome and Siblings

PubMed Central

Starbuck, John; Reeves, Roger H.; Richtsmeier, Joan

2011-01-01

Down syndrome (DS), resulting from trisomy of chromosome 21, is the most common live-born human aneuploidy. The phenotypic expression of trisomy 21 produces variable, though characteristic, facial morphology. Although certain facial features have been documented quantitatively and qualitatively as characteristic of DS (e.g., epicanthic folds, macroglossia, and hypertelorism), all of these traits occur in other craniofacial conditions with an underlying genetic cause. We hypothesize that the typical DS face is integrated differently than the face of non-DS siblings, and that the pattern of morphological integration unique to individuals with DS will yield information about underlying developmental associations between facial regions. We statistically compared morphological integration patterns of immature DS faces (N = 53) with those of non-DS siblings (N = 54), aged 6–12 years using 31 distances estimated from 3D coordinate data representing 17 anthropometric landmarks recorded on 3D digital photographic images. Facial features are affected differentially in DS, as evidenced by statistically significant differences in integration both within and between facial regions. Our results suggest a differential affect of trisomy on facial prominences during craniofacial development. PMID:21996933

Morphological integration of soft-tissue facial morphology in Down Syndrome and siblings.

PubMed

Starbuck, John; Reeves, Roger H; Richtsmeier, Joan

2011-12-01

Down syndrome (DS), resulting from trisomy of chromosome 21, is the most common live-born human aneuploidy. The phenotypic expression of trisomy 21 produces variable, though characteristic, facial morphology. Although certain facial features have been documented quantitatively and qualitatively as characteristic of DS (e.g., epicanthic folds, macroglossia, and hypertelorism), all of these traits occur in other craniofacial conditions with an underlying genetic cause. We hypothesize that the typical DS face is integrated differently than the face of non-DS siblings, and that the pattern of morphological integration unique to individuals with DS will yield information about underlying developmental associations between facial regions. We statistically compared morphological integration patterns of immature DS faces (N = 53) with those of non-DS siblings (N = 54), aged 6-12 years using 31 distances estimated from 3D coordinate data representing 17 anthropometric landmarks recorded on 3D digital photographic images. Facial features are affected differentially in DS, as evidenced by statistically significant differences in integration both within and between facial regions. Our results suggest a differential affect of trisomy on facial prominences during craniofacial development. 2011 Wiley Periodicals, Inc.

Evidence for a genetic overlap between body dysmorphic concerns and obsessive-compulsive symptoms in an adult female community twin sample.

PubMed

Monzani, Benedetta; Rijsdijk, Fruhling; Iervolino, Alessandra C; Anson, Martin; Cherkas, Lynn; Mataix-Cols, David

2012-06-01

Body dysmorphic disorder (BDD) is thought to be etiologically related to obsessive-compulsive disorder (OCD) but the available evidence is incomplete. The current study examined the genetic and environmental sources of covariance between body dysmorphic and obsessive-compulsive symptoms in a community sample of adult twins. A total of 2,148 female twins (1,074 pairs) completed valid and reliable measures of body dysmorphic concerns and obsessive-compulsive symptoms. The data were analyzed using bivariate twin modeling methods and the statistical programme Mx. In the best-fitting model, the covariation between body dysmorphic and obsessive-compulsive traits was largely accounted for by genetic influences common to both phenotypes (64%; 95% CI: 0.50-0.80). This genetic overlap was even higher when specific obsessive-compulsive symptom dimensions were considered, with up to 82% of the phenotypic correlation between the obsessing and symmetry/ordering symptom dimensions and dysmorphic concerns being attributable to common genetic factors. Unique environmental factors, although influencing these traits individually, did not substantially contribute to their covariation. The results remained unchanged when excluding individuals reporting an objective medical condition/injury accounting for their concern in physical appearance. The association between body dysmorphic concerns and obsessive-compulsive symptoms is largely explained by shared genetic factors. Environmental risk factors were largely unique to each phenotype. These results support current recommendations to group BDD together with OCD in the same DSM-5 chapter, although comparison with other phenotypes such as somatoform disorders and social phobia is needed. Copyright © 2012 Wiley Periodicals, Inc.

[Three-dimensional computed tomography analysis and clinical application of sacroiliac screw placement].

PubMed

Yin, Y C; Zhang, R P; Li, S L; Hou, Z Y; Chen, W; Zhang, Y Z

2018-03-01

Objective: To evaluate the possibility of transverse sacroiliac screw placement in different segments of the sacrum. Methods: Data of 80 pelvic CT scans (slice thickness ≤1.0 mm) archived in CT department of the Third Hospital of Hebei Medical University from September 2016 to October 2017 were retrospectively collected. Mimics software was used to rebuild the pelvis three-dimensional model. According to whether the sacral 1(S(1)) segment could place the transverse sacroiliac screws or not, all the sacrums were divided into normal group ( n =55) and dysmorphic group ( n =25). Simulation the S(1), sacral 2(S(2)) transverse sacroiliac screw placement in 3-Matic software. Analysis whether there was any difference in maximum diameter and length of S(2) transverse sacroiliac screw between the normal group and the dysmorphic group. The pelvic CT data of the dysmorphic group were measured, and the optimal tilt angle and length of the oblique S(1) screw were obtained. The feasibility of transverse sacroiliac screw insertion in sacral 3(S(3)) segment was evaluated. t -test, rank sum test, and χ(2) test was used to analyze data, respectively. Results: In the dysmorphic group, the largest diameter of the S(1) transverse screw was (4.9±1.6)mm, and the normal group was (13.6±3.6)mm ( t =-15.07, P =0.00). In the dysmorphic group, the largest diameter of S(2) transverse screw was (13.8±3.0)mm, and was (12.4±2.2)mm in the normal group( t =2.11, P =0.04). There was no significant difference in the length of S(2) transverse sacroiliac screw between the two groups ( t =0.47, P =0.64). In the dysmorphic group, the anterior vertebral height of S(1) was (23.1±4.0)mm, which was significantly higher than that of the normal group ((14.1±4.2)mm)( t =9.01, P =0.00). The angle of S(1)S(2) in the dysmorphic group was 10.9°(3.8°, 17.6°), which was significantly larger than that of the normal group (2.0°(1.0°, 2.0°) ( Z =-4.03, P =0.00). In the dysmorphic group, the incline angle of the oblique S(1) sacroiliac screw was (35.6±6.2)°, the anteversion angle was (37.2±4.4)°, and the mean screw length was (90.2±4.7)mm. In the dysmorphic group, the placement rate of S(3) transverse sacroiliac screw was 48.0%, and that of the normal sacral group was 9.1%. Conclusions: There is often dysmorphic in the sacrum in patients with large S(1) anterior vertebral height and S(1)S(2) angle. Sacral dysmorphic patients with posterior pelvic ring injury may be treated with S(1) pedicle oblique sacroiliac screws. S(3) transverse sacroiliac screws should be carefully placed, especially for the absence of sacral dysmorphic in patients.

TBX1 protein interactions and microRNA-96-5p regulation controls cell proliferation during craniofacial and dental development: implications for 22q11.2 deletion syndrome

PubMed Central

Gao, Shan; Moreno, Myriam; Eliason, Steven; Cao, Huojun; Li, Xiao; Yu, Wenjie; Bidlack, Felicitas B.; Margolis, Henry C.; Baldini, Antonio; Amendt, Brad A.

2015-01-01

T-box transcription factor TBX1 is the major candidate gene for 22q11.2 deletion syndrome (22q11.2DS, DiGeorge syndrome/Velo-cardio-facial syndrome), whose phenotypes include craniofacial malformations such as dental defects and cleft palate. In this study, Tbx1 was conditionally deleted or over-expressed in the oral and dental epithelium to establish its role in odontogenesis and craniofacial developmental. Tbx1 lineage tracing experiments demonstrated a specific region of Tbx1-positive cells in the labial cervical loop (LaCL, stem cell niche). We found that Tbx1 conditional knockout (Tbx1cKO) mice featured microdontia, which coincides with decreased stem cell proliferation in the LaCL of Tbx1cKO mice. In contrast, Tbx1 over-expression increased dental epithelial progenitor cells in the LaCL. Furthermore, microRNA-96 (miR-96) repressed Tbx1 expression and Tbx1 repressed miR-96 expression, suggesting that miR-96 and Tbx1 work in a regulatory loop to maintain the correct levels of Tbx1. Cleft palate was observed in both conditional knockout and over-expression mice, consistent with the craniofacial/tooth defects associated with TBX1 deletion and the gene duplication that leads to 22q11.2DS. The biochemical analyses of TBX1 human mutations demonstrate functional differences in their transcriptional regulation of miR-96 and co-regulation of PITX2 activity. TBX1 interacts with PITX2 to negatively regulate PITX2 transcriptional activity and the TBX1 N-terminus is required for its repressive activity. Overall, our results indicate that Tbx1 regulates the proliferation of dental progenitor cells and craniofacial development through miR-96-5p and PITX2. Together, these data suggest a new molecular mechanism controlling pathogenesis of dental anomalies in human 22q11.2DS. PMID:25556186

[Bone dysplasia with dwarfism and diffuse skeletal alterations].

PubMed

Piussan, C; Maroteaux, P; Castroviejo, I; Risbourg, B

1975-01-01

Six cases of a new hereditary chondrodyplasia are reported. The features are severe dwarfism, generalized hypotonia, frequent and considerable desaxations of fingers and toes. Slight facial dysmorphism with evolutive scoliosis is often associated. Osteopetrosis is diffuse and is associated with important metaphyseal widening as well as epiphyseal irregularities and often carpal and tarsal supernumerary bones. No metabolic or chromosomal abnormality was found. The relations of the disease with related types described in Larsen's syndrome are considered.

Severe dystrophy in DiGeorge syndrome

PubMed Central

Rózsai, Barnabás; Kiss, Ákos; Csábi, Györgyi; Czakó, Márta; Decsi, Tamás

2009-01-01

We present the case history of a 3-year-old girl who was examined because of severe dystrophy. In the background, cow’s milk allergy was found, but her body weight was unchanged after eliminating milk from her diet. Other types of malabsorption were excluded. Based on nasal regurgitation and facial dysmorphisms, the possibility of DiGeorge syndrome was suspected and was confirmed by fluorescence in situ hybridization. The authors suggest a new feature associated with DiGeorge syndrome. PMID:19294771

Obsessive-compulsive disorder versus body dysmorphic disorder: a comparison study of two possibly related disorders.

PubMed

Phillips, Katharine A; Pinto, Anthony; Menard, William; Eisen, Jane L; Mancebo, Maria; Rasmussen, Steven A

2007-01-01

The relationship between obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD) is unclear. BDD has been proposed to be an OCD-spectrum disorder or even a type of OCD. However, few studies have directly compared these disorders' clinical features. We compared characteristics of subjects with OCD (n=210), BDD (n=45), and comorbid BDD/OCD (n=40). OCD and BDD did not significantly differ in terms of demographic features, age of OCD or BDD onset, illness duration, and many other variables. However, subjects with BDD had significantly poorer insight than those with OCD and were more likely to be delusional. Subjects with BDD were also significantly more likely than those with OCD to have lifetime suicidal ideation, as well as lifetime major depressive disorder and a lifetime substance use disorder. The comorbid BDD/OCD group evidenced greater morbidity than subjects with OCD or BDD in a number of domains, but differences between the comorbid BDD/OCD group and the BDD group were no longer significant after controlling for BDD severity. However, differences between the comorbid BDD/OCD group and the OCD group remained significant after controlling for OCD severity. In summary, OCD and BDD did not significantly differ on many variables but did have some clinically important differences. These findings have implications for clinicians and for the classification of these disorders. (c) 2006 Wiley-Liss, Inc.

Preoperative symptoms of body dysmorphic disorder determine postoperative satisfaction and quality of life in aesthetic rhinoplasty.

PubMed

Picavet, Valerie A; Gabriëls, Loes; Grietens, Jente; Jorissen, Mark; Prokopakis, Emmanuel P; Hellings, Peter W

2013-04-01

In patients seeking aesthetic rhinoplasty, a high prevalence of body dysmorphic disorder symptoms has recently been reported. However, the impact of these symptoms on the outcomes after rhinoplasty remains elusive. This large-scale study determines the influence of preoperative body dysmorphic disorder symptoms on patients' postoperative satisfaction and quality of life, using validated questionnaires. A 1-year prospective study of 166 adult patients undergoing cosmetic rhinoplasty in a tertiary referral center was performed. Severity of body dysmorphic disorder symptoms was assessed by the modified Yale-Brown Obsessive Compulsive Scale. Postoperative satisfaction was evaluated using a visual analog scale for patients' appraisal of nasal shape and the Rhinoplasty Outcome Evaluation. Generic quality of life was quantified by the Sheehan Disability Scale, whereas the appearance-related disruption of everyday life was measured by the Derriford Appearance Scale-59. Preoperative body dysmorphic disorder symptom scores inversely correlated with postoperative satisfaction at 3 months (visual analog scale nasal shape: rho = -0.43, p < 0.001; Rhinoplasty Outcome Evaluation: rho = -0.48, p < 0.001) and 12 months (rho = -0.40, p < 0.001; and rho = -0.41, p < 0.001, respectively) after surgery. In addition, body dysmorphic disorder symptom scores positively correlated with Sheehan Disability Scale scores and Derriford Appearance Scale-59 scores at 3 months (rho = 0.43, p < 0.001 and rho = 0.48, p < 0.001, respectively) and 12 months (rho = 0.32, p < 0.001, and rho = 0.48, p < 0.001, respectively) postoperatively. This study provides the first evidence of the negative impact of preoperative body dysmorphic disorder symptoms on subjective outcomes after rhinoplasty, hence unveiling a crucial factor in patient dissatisfaction after aesthetic rhinoplasty.

Three-dimensional navigation is more accurate than two-dimensional navigation or conventional fluoroscopy for percutaneous sacroiliac screw fixation in the dysmorphic sacrum: a randomized multicenter study.

PubMed

Matityahu, Amir; Kahler, David; Krettek, Christian; Stöckle, Ulrich; Grutzner, Paul Alfred; Messmer, Peter; Ljungqvist, Jan; Gebhard, Florian

2014-12-01

To evaluate the accuracy of computer-assisted sacral screw fixation compared with conventional techniques in the dysmorphic versus normal sacrum. Review of a previous study database. Database of a multinational study with 9 participating trauma centers. The reviewed group included 130 patients, 72 from the navigated group and 58 from the conventional group. Of these, 109 were in the nondysmorphic group and 21 in the dysmorphic group. Placement of sacroiliac (SI) screws was performed using standard fluoroscopy for the conventional group and BrainLAB navigation software with either 2-dimensional or 3-dimensional (3D) navigation for the navigated group. Accuracy of SI screw placement by 2-dimensional and 3D navigation versus conventional fluoroscopy in dysmorphic and nondysmorphic patients, as evaluated by 6 observers using postoperative computerized tomography imaging at least 1 year after initial surgery. Intraobserver agreement was also evaluated. There were 11.9% (13/109) of patients with misplaced screws in the nondysmorphic group and 28.6% (6/21) of patients with misplaced screws in the dysmorphic group, none of which were in the 3D navigation group. Raw agreement between the 6 observers regarding misplaced screws was 32%. However, the percent overall agreement was 69.0% (kappa = 0.38, P < 0.05). The use of 3D navigation to improve intraoperative imaging for accurate insertion of SI screws is magnified in the dysmorphic proximal sacral segment. We recommend the use of 3D navigation, where available, for insertion of SI screws in patients with normal and dysmorphic proximal sacral segments. Therapeutic level I.

Shadows of Beauty - Prevalence of Body Dysmorphic Concerns in Germany is Increasing: Data from Two Representative Samples from 2002 and 2013.

PubMed

Gieler, Tanja; Schmutzer, Gabriele; Braehler, Elmar; Schut, Christina; Peters, Eva; Kupfer, Jörg

2016-08-23

Body dysmorphic disorder (BDD) is a psychosomatic disease associated with reduced quality of life and suicidal ideations. Increasing attention to beauty and the development of beauty industries lead to the hypothesis that BDD is increasing. The aim of this study was to test this hypothesis in two representative samples of Germans, assessed in 2002 and 2013. In 2002, n = 2,066 and in 2013, n = 2,508 Germans were asked to fill in the Dysmorphic Concern Questionnaire (DCQ), which assesses dysmorphic concerns. Subclinical and clinical dysmorphic concerns increased from 2002 to 2013 (subclinical from 0.5% to 2.6%, OR = 5.16 (CI95% = 2.64; 10.06); clinical from 0.5% to 1.0%, OR = 2.20 (CI95% = 1.03; 4.73). Women reported more dysmorphic concerns than men, with rates of 0.7% subclinical and 0.8 clinical BDD in women and 0.3% subclinical and 0.1% clinical BDD in men in 2002. In 2013, 2.8% subclinical and 1.2% clinical BDD were found in women and 2.4% subclinical and 0.8% clinical BDD in men. Further studies should assess predictors for developing a BDD and evaluate factors determining the efficacy of disease-specific psychotherapeutic and psychotropic drug treatments.

An Intercenter Comparison of Dental Arch Relationships and Craniofacial Form Including a Center Using Nasoalveolar Molding.

PubMed

Peanchitlertkajorn, Supakit; Mercado, Ana; Daskalogiannakis, John; Hathaway, Ronald; Russell, Kathleen; Semb, Gunvor; Shaw, William; Lamichane, Manish; Fessler, Jennifer; Long, Ross E

2018-01-01

Objective To compare dental arch relationship and craniofacial morphology of patients with CUCLP in pre-adolescence from five cleft centers including a center using NAM. Design Retrospective cohort study. Setting Five cleft centers in North America. Patients One hundred eighty-two subjects with repaired CUCLP from the five cleft centers participated in the craniofacial form study. One hundred forty-eight subjects from four of the five centers participated in the dental arch relationship study. Methods Digital dental models were assessed using the GOSLON Yardstick. Eighteen cephalometric measurements were performed. Measurement means, by center, were compared. Analysis of variance and Tukey-Kramer analysis were used to compare GOSLON scores and cephalometric measurements. Results The center that performed neither PSOT (including NAM) nor primary bone grafting exhibited the most favorable mean GOSLON score. The same center also showed the highest mean SNA, ANB, and ANS-N-Pg angles. However, the mean ANB and ANS-N-Pg angles were not significantly different from those of the center using NAM. No statistically significant differences were seen for mandibular prominence, vertical dimensions, or dental inclinations. The center with NAM also showed a significantly smaller nasoform angle than two of the four other centers. Conclusion The centers that used NAM and other forms of PSOT did not have better dental arch relationships or craniofacial morphology compared with the centers that performed only primary lip repair. However, this study was not designed to investigate the cause-and-effect relationship between specific outcomes and particular features of those protocols.

Two Japanese patients with Leigh syndrome caused by novel SURF1 mutations.

PubMed

Tanigawa, Junpei; Kaneko, Kaori; Honda, Masakazu; Harashima, Hiroko; Murayama, Kei; Wada, Takahito; Takano, Kyoko; Iai, Mizue; Yamashita, Sumimasa; Shimbo, Hiroko; Aida, Noriko; Ohtake, Akira; Osaka, Hitoshi

2012-11-01

We report two patients with Leigh syndrome that showed a combination of facial dysmorphism and MRI imaging indicating an SURF1 deficiency, which was confirmed by sequence analysis. Case 1 is a 3-year-old girl with failure to thrive and developmental delay. She presented with tachypnea at rest and displayed facial dysmorphism including frontal bossing, lateral displacement of inner canthi, esotropia, maxillary hypoplasia, slightly upturned nostril, and hypertrichosis dominant on the forehead and extremities. Case 2 is an 8-year-old boy with respiratory failure. He had been diagnosed as selective complex IV deficiency. Case 2 displayed facial dysmorphism and hypertrichosis. Since both patients displayed characteristic facial dysmorphism and MRI findings, we sequenced the SURF1 gene and identified two heterozygous mutations; c.49+1 G>T and c.752_753del in Case 1, and homozygous c.743 C>A in Case 2. For patients with Leigh syndrome showing these facial dysmorphism and hypertrichosis, sequence analysis of the SURF1 gene may be useful. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development.

PubMed

Tan, Yu; Fu, Runqing; Liu, Jiaqiang; Wu, Yong; Wang, Bo; Jiang, Ning; Nie, Ping; Cao, Haifeng; Yang, Zhi; Fang, Bing

2016-07-08

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. Copyright © 2016 Elsevier Inc. All rights reserved.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

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

Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of themore » craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.« less

Modeling human craniofacial disorders in Xenopus

PubMed Central

Dubey, Aditi; Saint-Jeannet, Jean-Pierre

2017-01-01

Purpose of Review Craniofacial disorders are among the most common human birth defects and present an enormous health care and social burden. The development of animal models has been instrumental to investigate fundamental questions in craniofacial biology and this knowledge is critical to understand the etiology and pathogenesis of these disorders. Recent findings The vast majority of craniofacial disorders arise from abnormal development of the neural crest, a multipotent and migratory cell population. Therefore, defining the pathogenesis of these conditions starts with a deep understanding of the mechanisms that preside over neural crest formation and its role in craniofacial development. Summary This review discusses several studies using Xenopus embryos to model human craniofacial conditions, and emphasizes the strength of this system to inform important biological processes as they relate to human craniofacial development and disease. PMID:28255527

Risk and Resilience Factors for Combat-Related Posttraumatic Psychopathology and Post Combat Adjustment

DTIC Science & Technology

2010-06-01

Dysmorphic  Disorder   Substance-­‐Induced  Mood  Disorder   EaMng  Disorder   Anxiety  Disorder  NOS   Dysthymic  Disorder...0   10   20   30   40   50   60   PsychoMc  Symptoms   Hypochondriasis   Body   Dysmorphic  Disorder   Substance-­‐Induced...disorder  NOS,  ea4ng  disorder,  substance-­‐ induced  mood  disorder,  body   dysmorphic  disorder,

Body dysmorphic disorder and eating disorders in elite professional female ballet dancers.

PubMed

Nascimento, Antonio Leandro; Luna, Juliano Victor; Fontenelle, Leonardo F

2012-08-01

Our objective is to report the prevalence and the clinical features associated with body dysmorphic disorder (BDD) and eating disorders (ED) in a group of elite Brazilian professional female ballet dancers. Thirty-five elite Brazilian professional female ballet dancers were invited to participate in the study and 19 agreed to be assessed. Individuals were evaluated with a series of instruments, including the Mini International Neuropsychiatric Interview supplemented by the somatoform and eating disorders modules of the Structured Clinical Interview for DSM-IV disorders, the Bulimic Investigatory Test, and the Beck Depression Inventory. Three dancers (15.78%) had a lifetime diagnosis of anorexia nervosa (restrictive subtype) and 2 others (10.52%) presented a current diagnosis of BDD. No individuals had current or lifetime bulimia nervosa. Results could not be ascribed to comorbid major depression or increased severity of depression. The lifetime prevalence of BDD and ED among elite professional female ballet dancers was higher than the general population. High standards of beauty, public body exposure, and repeated exposure to mirrors in the rehearsal rooms may contribute to the development of body image disorders in this sample.

Craniofacial Tissue Engineering by Stem Cells

PubMed Central

Mao, J.J.; Giannobile, W.V.; Helms, J.A.; Hollister, S.J.; Krebsbach, P.H.; Longaker, M.T.; Shi, S.

2008-01-01

Craniofacial tissue engineering promises the regeneration or de novo formation of dental, oral, and craniofacial structures lost to congenital anomalies, trauma, and diseases. Virtually all craniofacial structures are derivatives of mesenchymal cells. Mesenchymal stem cells are the offspring of mesenchymal cells following asymmetrical division, and reside in various craniofacial structures in the adult. Cells with characteristics of adult stem cells have been isolated from the dental pulp, the deciduous tooth, and the periodontium. Several craniofacial structures—such as the mandibular condyle, calvarial bone, cranial suture, and subcutaneous adipose tissue—have been engineered from mesenchymal stem cells, growth factor, and/or gene therapy approaches. As a departure from the reliance of current clinical practice on durable materials such as amalgam, composites, and metallic alloys, biological therapies utilize mesenchymal stem cells, delivered or internally recruited, to generate craniofacial structures in temporary scaffolding biomaterials. Craniofacial tissue engineering is likely to be realized in the foreseeable future, and represents an opportunity that dentistry cannot afford to miss. PMID:17062735

Craniofacial imaging informatics and technology development.

PubMed

Vannier, M W

2003-01-01

'Craniofacial imaging informatics' refers to image and related scientific data from the dentomaxillofacial complex, and application of 'informatics techniques' (derived from disciplines such as applied mathematics, computer science and statistics) to understand and organize the information associated with the data. Major trends in information technology determine the progress made in craniofacial imaging and informatics. These trends include industry consolidation, disruptive technologies, Moore's law, electronic atlases and on-line databases. Each of these trends is explained and documented, relative to their influence on craniofacial imaging. Craniofacial imaging is influenced by major trends that affect all medical imaging and related informatics applications. The introduction of cone beam craniofacial computed tomography scanners is an example of a disruptive technology entering the field. An important opportunity lies in the integration of biologic knowledge repositories with craniofacial images. The progress of craniofacial imaging will continue subject to limitations imposed by the underlying technologies, especially imaging informatics. Disruptive technologies will play a major role in the evolution of this field.

Age- and sex-related growth patterns of the craniofacial complex in European children aged 3-6 years.

PubMed

Tutkuviene, Janina; Cattaneo, Cristina; Obertová, Zuzana; Ratnayake, Melanie; Poppa, Pasquale; Barkus, Arunas; Khalaj-Hedayati, Kerstin; Schroeder, Inge; Ritz-Timme, Stefanie

2016-11-01

Craniofacial growth changes in young children are not yet completely understood. Up-to-date references for craniofacial measurements are crucial for clinical assessment of orthodontic anomalies, craniofacial abnormalities and subsequent planning of interventions. To provide normal reference data and to identify growth patterns for craniofacial dimensions of European boys and girls aged 3-6 years. Using standard anthropometric methodology, body weight, body height and 23 craniofacial measurements were acquired for a cross-sectional sample of 681 healthy children (362 boys and 319 girls) aged 3-6 years from Germany, Italy and Lithuania. Descriptive statistics, correlation coefficients, percentage annual changes and percentage growth rates were used to analyse the dataset. Between the ages of 3-6 years, craniofacial measurements showed age- and sex-related patterns independent from patterns observed for body weight and body height. Sex-related differences were observed in the majority of craniofacial measurements. In both sexes, face heights and face depths showed the strongest correlation with age. Growth patterns differed by craniofacial measurement and can be summarised into eight distinct age- and sex-related patterns. This study provided reference data and identified sex- and age-related growth patterns of the craniofacial complex of young European children, which may be used for detailed assessment of normal growth in paediatrics, maxillofacial reconstructive surgery and possibly for forensic age assessment.

3D craniofacial registration using thin-plate spline transform and cylindrical surface projection

PubMed Central

Chen, Yucong; Deng, Qingqiong; Duan, Fuqing

2017-01-01

Craniofacial registration is used to establish the point-to-point correspondence in a unified coordinate system among human craniofacial models. It is the foundation of craniofacial reconstruction and other craniofacial statistical analysis research. In this paper, a non-rigid 3D craniofacial registration method using thin-plate spline transform and cylindrical surface projection is proposed. First, the gradient descent optimization is utilized to improve a cylindrical surface fitting (CSF) for the reference craniofacial model. Second, the thin-plate spline transform (TPST) is applied to deform a target craniofacial model to the reference model. Finally, the cylindrical surface projection (CSP) is used to derive the point correspondence between the reference and deformed target models. To accelerate the procedure, the iterative closest point ICP algorithm is used to obtain a rough correspondence, which can provide a possible intersection area of the CSP. Finally, the inverse TPST is used to map the obtained corresponding points from the deformed target craniofacial model to the original model, and it can be realized directly by the correspondence between the original target model and the deformed target model. Three types of registration, namely, reflexive, involutive and transitive registration, are carried out to verify the effectiveness of the proposed craniofacial registration algorithm. Comparison with the methods in the literature shows that the proposed method is more accurate. PMID:28982117

3D craniofacial registration using thin-plate spline transform and cylindrical surface projection.

PubMed

Chen, Yucong; Zhao, Junli; Deng, Qingqiong; Duan, Fuqing

2017-01-01

Craniofacial registration is used to establish the point-to-point correspondence in a unified coordinate system among human craniofacial models. It is the foundation of craniofacial reconstruction and other craniofacial statistical analysis research. In this paper, a non-rigid 3D craniofacial registration method using thin-plate spline transform and cylindrical surface projection is proposed. First, the gradient descent optimization is utilized to improve a cylindrical surface fitting (CSF) for the reference craniofacial model. Second, the thin-plate spline transform (TPST) is applied to deform a target craniofacial model to the reference model. Finally, the cylindrical surface projection (CSP) is used to derive the point correspondence between the reference and deformed target models. To accelerate the procedure, the iterative closest point ICP algorithm is used to obtain a rough correspondence, which can provide a possible intersection area of the CSP. Finally, the inverse TPST is used to map the obtained corresponding points from the deformed target craniofacial model to the original model, and it can be realized directly by the correspondence between the original target model and the deformed target model. Three types of registration, namely, reflexive, involutive and transitive registration, are carried out to verify the effectiveness of the proposed craniofacial registration algorithm. Comparison with the methods in the literature shows that the proposed method is more accurate.

An oral clinical approach to Gorlin-Goltz syndrome.

PubMed

Abreu, Lucas Guimaraes; Paiva, Saul Martins; Pretti, Henrique; Bastos Lages, Elizabeth Maria; Castro, Wagner Henriques

2015-01-01

Gorlin-Goltz syndrome is a rare hereditary disease that can have negative effects on one's quality of life. The main clinical features are multiple nevoid basal cell carcinomas, odontogenic keratocysts, congenital skeletal abnormalities, calcification of the falx cerebri, facial dysmorphism, and skin depressions (pits) on the palms and soles. Diagnosis is based on major and minor clinical and radiological criteria and can be confirmed by DNA analysis. This article describes the case of a child with Gorlin-Goltz syndrome and outlines the clinical manifestations of the disease.

Dominant inheritance of cerebral gigantism.

PubMed

Zonana, J; Sotos, J F; Romshe, C A; Fisher, D A; Elders, M J; Rimoin, D L

1977-08-01

Cerebral gigantism is a syndrome consisting of characteristic dysmorphic features, accelerated growth in early childhood, and variable degrees of mental retardation. Its etiology and pathogenesis have not been defined. Three families are presented with multiple affected members. The vertical transmission of the trait and equal expression in both sexes in these families indicates a genetic etiology with a dominant pattern of inheritance, probably autosomal. As in previously reported cases, extensive endocrine evaluation failed to define the pathogenesis of the accelerated growth present in this disorder.

A novel UBE2A mutation causes X-linked intellectual disability type Nascimento.

PubMed

Tsurusaki, Yoshinori; Ohashi, Ikuko; Enomoto, Yumi; Naruto, Takuya; Mitsui, Jun; Aida, Noriko; Kurosawa, Kenji

2017-01-01

X-linked intellectual disability (ID) type Nascimento (MIM #300860), also known as ubiquitin-conjugating enzyme E2 A (UBE2A) deficiency syndrome, is a congenital malformation syndrome characterized by moderate to severe ID, speech impairment, dysmorphic facial features, genital anomalies and skin abnormalities. Here, we report a Japanese patient with severe ID and congenital cataract. We identified a novel hemizygous mutation (c.76G>A, p.Gly26Arg) in UBE2A by whole-exome sequencing.

A novel UBE2A mutation causes X-linked intellectual disability type Nascimento

PubMed Central

Tsurusaki, Yoshinori; Ohashi, Ikuko; Enomoto, Yumi; Naruto, Takuya; Mitsui, Jun; Aida, Noriko; Kurosawa, Kenji

2017-01-01

X-linked intellectual disability (ID) type Nascimento (MIM #300860), also known as ubiquitin-conjugating enzyme E2 A (UBE2A) deficiency syndrome, is a congenital malformation syndrome characterized by moderate to severe ID, speech impairment, dysmorphic facial features, genital anomalies and skin abnormalities. Here, we report a Japanese patient with severe ID and congenital cataract. We identified a novel hemizygous mutation (c.76G>A, p.Gly26Arg) in UBE2A by whole-exome sequencing. PMID:28611923

A case of deletion 14(q22.1-->q22.3) associated with anophthalmia and pituitary abnormalities.

PubMed Central

Elliott, J; Maltby, E L; Reynolds, B

1993-01-01

An interstitial deletion of the region q22.1-->q22.3 of chromosome 14 is described in a child with bilateral anophthalmia, dysmorphic features including micrognathia, small tongue, and high arched palate, developmental and growth retardation, undescended testes with a micropenis, and hypothyroidism. Interstitial deletions of the long arm of chromosome 14 are extremely rare, but this case seems to confirm that the region q22 is specifically concerned with pituitary and eye development. Images PMID:7682620

Osteocraniostenosis.

PubMed Central

Verloes, A; Narcy, F; Grattagliano, B; Delezoide, A L; Guibaud, P; Schaaps, J P; Le Merrer, M; Maroteaux, P

1994-01-01

We report a multiple congenital anomalies (MCA) syndrome in three unrelated fetuses consisting of extremely thin, dense, fishbone-like diaphyses, flared metaphyses, mild micromelic dwarfism, brachydactyly, facial dysmorphism, ocular malformations (microphthalmia, aniridia), cloverleaf skull deformity, and splenic hypoplasia. Histopathological investigations showed abnormalities of the metaphyseal cartilage and adjacent diaphyseal ossification, excessive modelling of the metaphyses, and, in one case, dysplasia of the epiphyseal cartilage. We review three previously reported cases. We suggest the name osteocraniostenosis to describe this radiological and clinical disorder, pinpointing its major clinical and radiological features. Images PMID:7837254

16p11.2–p12.2 duplication syndrome; a genomic condition differentiated from euchromatic variation of 16p11.2

PubMed Central

Barber, John C K; Hall, Victoria; Maloney, Viv K; Huang, Shuwen; Roberts, Angharad M; Brady, Angela F; Foulds, Nicki; Bewes, Beverley; Volleth, Marianne; Liehr, Thomas; Mehnert, Karl; Bateman, Mark; White, Helen

2013-01-01

Chromosome 16 contains multiple copy number variations (CNVs) that predispose to genomic disorders. Here, we differentiate pathogenic duplications of 16p11.2–p12.2 from microscopically similar euchromatic variants of 16p11.2. Patient 1 was a girl of 18 with autism, moderate intellectual disability, behavioural difficulties, dysmorphic features and a 7.71-Mb (megabase pair) duplication (16:21 521 005–29 233 146). Patient 2 had a 7.81-Mb duplication (16:21 382 561–29 191 527), speech delay and obsessional behaviour as a boy and, as an adult, short stature, macrocephaly and mild dysmorphism. The duplications contain 65 coding genes of which Polo-like kinase 1 (PLK1) has the highest likelihood of being haploinsufficient and, by implication, a triplosensitive gene. An additional 1.11-Mb CNV of 10q11.21 in Patient 1 was a possible modifier containing the G-protein-regulated inducer of neurite growth 2 (GPRIN2) gene. In contrast, the euchromatic variants in Patients 3 and 4 were amplifications from a 945-kb region containing non-functional immunoglobulin heavy chain (IGHV), hect domain pseudogene (HERC2P4) and TP53-inducible target gene 3 (TP53TG3) loci in proximal 16p11.2 (16:31 953 353–32 898 635). Paralogous pyrosequencing gave a total copy number of 3–8 in controls and 8 to >10 in Patients 3 and 4. The 16p11.2–p12.2 duplication syndrome is a recurrent genomic disorder with a variable phenotype including developmental delay, dysmorphic features, mild to severe intellectual disability, autism, obsessive or stereotyped behaviour, short stature and anomalies of the hands and fingers. It is important to differentiate pathogenic 16p11.2–p12.2 duplications from harmless, microscopically similar euchromatic variants of proximal 16p11.2, especially at prenatal diagnosis. PMID:22828807

Body dysmorphic disorder: history and curiosities.

PubMed

França, Katlein; Roccia, Maria Grazia; Castillo, David; ALHarbi, Mana; Tchernev, Georgi; Chokoeva, Anastasia; Lotti, Torello; Fioranelli, Massimo

2017-10-01

Body dysmorphic disorder is a chronic psychiatric disorder characterized by excessive preoccupation with an absent or minimal physical deformity. It causes severe distress and impairs normal functioning. In the last centuries, this disorder has been mentioned in the medical literature by important mental health practitioners by different names, such as "dysmorphophobia" or "dermatologic hypochondriasis". However, not until the last century was it included among the obsessive-compulsive disorders, although its classification has changed over time.Patients with body dysmorphic disorder constantly seek cosmetic treatments in order to improve their physical appearance, which more often deteriorates their mental condition. The high prevalence of psychiatric disorders in cosmetic medical practice has led in this field of study to the new science "cosmetic psychodermatology". This paper presents a summary of important facts about body dysmorphic disorder and its description throughout the history of medicine.

[Body dysmorphic disorder : Anxiety about deformity].

PubMed

Gieler, T; Brähler, E

2016-05-01

Between 0.8 and 1.8 % of the German population suffers from a body dysmorphic disorder. In specific settings like dermatological offices up to 11.9 % of patients suffer from this disease. The highest prevalence could be found in the field of cosmetic dermatology with a prevalence of 13.1 %. Until now, the diagnosis has been made too rarely. The body dysmorphic disorder is a chronic psychic disease, in which the patients feel disfigured and experience shame and disgust at the same time. Comorbidities like social phobia, depression, suicidality, and eating disorders are frequent. The diagnosis is made using questionnaires (e.g., dysmorphic concern questionnaire) or by use of the DSM-5 manual. An early diagnosis seems to be important to avoid chronification and suicidal ideas. Therapeutic approaches should include cognitive behavioral therapies as well as the use of SSRIs.

Recognizing Body Dysmorphic Disorder (Dysmorphophobia)

PubMed Central

Varma, Anukriti; Rastogi, Rajesh

2015-01-01

Dysmorphophobia is a psychiatric condition which frequently presents in the clinics of dermatologists and plastic surgeons. This disorder (also called body dysmorphic disorder) is troublesome to the patient whilst being confusing for the doctor. This commonly undiagnosed condition can be detected by a few simple steps. Timely referral to a psychiatrist benefits most patients suffering from it. This article describes with a case vignette, how to recognize body dysmorphic disorder presenting in the dermatological or aesthetic surgery set up. Diagnostic criteria, eitiology, approach to patient, management strategy and when to refer are important learning points. The importance of recognizing this disorder timely and referring the patient to the psychiatrist for appropriate treatment is crucial. This article covers all aspects of body dysmorphic disorder relevant to dermatologists and plastic surgeons and hopes to be useful in a better understanding of this disorder. PMID:26644741

Loss of FTO antagonises Wnt signaling and leads to developmental defects associated with ciliopathies.

PubMed

Osborn, Daniel P S; Roccasecca, Rosa Maria; McMurray, Fiona; Hernandez-Hernandez, Victor; Mukherjee, Sriparna; Barroso, Inês; Stemple, Derek; Cox, Roger; Beales, Philip L; Christou-Savina, Sonia

2014-01-01

Common intronic variants in the Human fat mass and obesity-associated gene (FTO) are found to be associated with an increased risk of obesity. Overexpression of FTO correlates with increased food intake and obesity, whilst loss-of-function results in lethality and severe developmental defects. Despite intense scientific discussions around the role of FTO in energy metabolism, the function of FTO during development remains undefined. Here, we show that loss of Fto leads to developmental defects such as growth retardation, craniofacial dysmorphism and aberrant neural crest cells migration in Zebrafish. We find that the important developmental pathway, Wnt, is compromised in the absence of FTO, both in vivo (zebrafish) and in vitro (Fto(-/-) MEFs and HEK293T). Canonical Wnt signalling is down regulated by abrogated β-Catenin translocation to the nucleus whilst non-canonical Wnt/Ca(2+) pathway is activated via its key signal mediators CaMKII and PKCδ. Moreover, we demonstrate that loss of Fto results in short, absent or disorganised cilia leading to situs inversus, renal cystogenesis, neural crest cell defects and microcephaly in Zebrafish. Congruently, Fto knockout mice display aberrant tissue specific cilia. These data identify FTO as a protein-regulator of the balanced activation between canonical and non-canonical branches of the Wnt pathway. Furthermore, we present the first evidence that FTO plays a role in development and cilia formation/function.

Haploinsufficiency of a spliceosomal GTPase encoded by EFTUD2 causes mandibulofacial dysostosis with microcephaly.

PubMed

Lines, Matthew A; Huang, Lijia; Schwartzentruber, Jeremy; Douglas, Stuart L; Lynch, Danielle C; Beaulieu, Chandree; Guion-Almeida, Maria Leine; Zechi-Ceide, Roseli Maria; Gener, Blanca; Gillessen-Kaesbach, Gabriele; Nava, Caroline; Baujat, Geneviève; Horn, Denise; Kini, Usha; Caliebe, Almuth; Alanay, Yasemin; Utine, Gulen Eda; Lev, Dorit; Kohlhase, Jürgen; Grix, Arthur W; Lohmann, Dietmar R; Hehr, Ute; Böhm, Detlef; Majewski, Jacek; Bulman, Dennis E; Wieczorek, Dagmar; Boycott, Kym M

2012-02-10

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Geometric morphometrics in primatology: craniofacial variation in Homo sapiens and Pan troglodytes.

PubMed

Lynch, J M; Wood, C G; Luboga, S A

1996-01-01

Traditionally, morphometric studies have relied on statistical analysis of distances, angles or ratios to investigate morphometric variation among taxa. Recently, geometric techniques have been developed for the direct analysis of landmark data. In this paper, we offer a summary (with examples) of three of these newer techniques, namely shape coordinate, thin-plate spline and relative warp analyses. Shape coordinate analysis detected significant craniofacial variation between 4 modern human populations, with African and Australian Aboriginal specimens being relatively prognathous compared with their Eurasian counterparts. In addition, the Australian specimens exhibited greater basicranial flexion than all other samples. The observed relationships between size and craniofacial shape were weak. The decomposition of shape variation into affine and non-affine components is illustrated via a thin-plate spline analysis of Homo and Pan cranial landmarks. We note differences between Homo and Pan in the degree of prognathism and basicranial flexion and the position and orientation of the foramen magnum. We compare these results with previous studies of these features in higher primates and discuss the utility of geometric morphometrics as a tool in primatology and physical anthropology. We conclude that many studies of morphological variation, both within and between taxa, would benefit from the graphical nature of these techniques.

Williams-Beuren syndrome associated with single kidney and nephrocalcinosis: a case report.

PubMed

Abidi, Kamel; Jellouli, Manel; Ben Rabeh, Rania; Hammi, Yousra; Gargah, Tahar

2015-01-01

Williams-Beuren syndrome is a rare neurodevelopmental disorder, characterized by congenital heart defects, abnormal facial features, mental retardation with specific cognitive and behavioral profile, growth hormone deficiency, renal and skeletal anomalies, inguinal hernia, infantile hypercalcaemia. We report a case with Williams-Beuren syndrome associated with a single kidney and nephrocalcinosis complicated by hypercalcaemia. A male infant, aged 20 months presented growth retardation associated with a psychomotor impairment, dysmorphic features and nephrocalcinosis. He had also hypercalciuria and hypercalcemia. Echocardiography was normal. DMSA renal scintigraphy showed a single functioning kidney. The FISH generated one ELN signal in 20 metaphases read and found the presence of ELN deletion, with compatible Williams-Beuren syndrome.

Report of a trisomy 8p infant with carrier father.

PubMed

Funderburk, S J; Barrett, C T; Klisak, I

1978-12-01

This report describes an infant with fatal congenital heart disease, cleft palate, brain malformations, and trisomy 8p resultant from the paternal balanced reciprocal translocation, rcp(8;15) (p11;p11). Review of six previously reported trisomy 8p patients (resultant from parental balanced translocation in each instance) revealed severe mental retardation in five, short stature in all, and a variety of brain, skeletal, and cardiac defects. The features of the seven trisomy 8p patients reviewed here are not sufficiently similar to suggest a distinct dysmorphic syndrome. In addition the features differ from those in the trisomy 8 mosaicism syndrome, in which the mental retardation and malformations are generally less severe.

A patient with polymerase E1 deficiency (POLE1): clinical features and overlap with DNA breakage/instability syndromes.

PubMed

Thiffault, Isabelle; Saunders, Carol; Jenkins, Janda; Raje, Nikita; Canty, Kristi; Sharma, Mukta; Grote, Lauren; Welsh, Holly I; Farrow, Emily; Twist, Greyson; Miller, Neil; Zwick, David; Zellmer, Lee; Kingsmore, Stephen F; Safina, Nicole P

2015-05-07

Chromosome instability syndromes are a group of inherited conditions associated with chromosomal instability and breakage, often leading to immunodeficiency, growth retardation and increased risk of malignancy. We performed exome sequencing on a girl with a suspected chromosome instability syndrome that manifested as growth retardation, microcephaly, developmental delay, dysmorphic features, poikiloderma, immune deficiency with pancytopenia, and myelodysplasia. She was homozygous for a previously reported splice variant, c.4444 + 3A > G in the POLE1 gene, which encodes the catalytic subunit of DNA polymerase E. This is the second family with POLE1-deficency, with the affected individual demonstrating a more severe phenotype than previously described.

The 50 Most Cited Papers in Craniofacial Anomalies and Craniofacial Surgery.

PubMed

Mahon, Nicola A; Joyce, Cormac W; Thomas, Sangeetha; Concannon, Elizabeth; Murray, Dylan

2015-09-01

Citation analysis is a recognized scientometric method of classifying cited articles according to the frequency of which they have been referenced. The total number of citations an article receives is considered to reflect it's significance among it's peers. Until now, a bibliometric analysis has never been performed in the specialty of craniofacial anomalies and craniofacial surgery. This citation analysis generates an extensive list of the 50 most influential papers in this developing field. Journals specializing in craniofacial surgery, maxillofacial surgery, plastic surgery, neurosurgery, genetics and pediatrics were searched to demonstrate which articles have cultivated the specialty within the past 55 years. The results show an intriguing compilation of papers which outline the fundamental knowledge of craniofacial anomalies and the developments of surgical techniques to manage these patients. This citation analysis provides a summation of the current most popular trends in craniofacial literature. These esteemed papers aid to direct our decision making today within this specialty.

[Fitting of the reconstructed craniofacial hard and soft tissues based on 2-D digital radiographs].

PubMed

Feng, Yao-Pu; Qiao, Min; Zhou, Hong; Zhang, Yan-Ning; Si, Xin-Qin

2017-02-01

In this study, we reconstructed the craniofacial hard and soft tissues based on the data from digital cephalometric radiographs and laser scanning. The effective fitting of the craniofacial hard and soft tissues was performed in order to increase the level of orthognathic diagnosis and treatment, and promote the communication between doctors and patients. A small lead point was put on the face of a volunteer and frontal and lateral digital cephalometric radiographs were taken. 3-D reconstruction system of the craniofacial hard tissue based on 2-D digital radiograph was used to get the craniofacial hard tissue model by means of hard tissue deformation modeling. 3-D model of facial soft tissue was obtained by using laser scanning data. By matching the lead point coordinate, the hard tissue and soft tissue were fitted. The 3-D model of the craniofacial hard and soft tissues was rebuilt reflecting the real craniofacial tissue structure, and effective fitting of the craniofacial hard and soft tissues was realized. The effective reconstruction and fitting of the 3-D craniofacial structures have been realized, which lays a foundation for further orthognathic simulation and facial appearance prediction. The fitting result is reliable, and could be used in clinical practice.

The presence, predictive utility, and clinical significance of body dysmorphic symptoms in women with eating disorders

PubMed Central

2013-01-01

Background Both eating disorders (EDs) and body dysmorphic disorder (BDD) are disorders of body image. This study aimed to assess the presence, predictive utility, and impact of clinical features commonly associated with BDD in women with EDs. Methods Participants recruited from two non-clinical cohorts of women, symptomatic and asymptomatic of EDs, completed a survey on ED (EDE-Q) and BDD (BDDE-SR) psychopathology, psychological distress (K-10), and quality of life (SF-12). Results A strong correlation was observed between the total BDDE-SR and the global EDE-Q scores (r = 0.79, p < 0.001). Multivariate analyses demonstrated that participants with probable EDs (n = 61) and BDD (n = 23) scored higher on 28 of the 30 BDDE-SR items compared to healthy controls (n = 173; all p < 0.05), indicating greater severity of BDD symptoms. BDD participants also scored higher than ED participants on 15 of the 30 BDDE-SR items (all p < 0.05). The remaining 15 items that ED and BDD participants scored similarly on (all p > 0.05) measured appearance checking, reassurance-seeking, camouflaging, comparison-making, and social avoidance. In addition to these behaviors, inspection of sensitivity (Se) and specificity (Sp) revealed that BDDE-SR items measuring preoccupation and dissatisfaction with appearance were most predictive of ED cases (Se and Sp > 0.60). Higher total BDDE-SR scores were associated with greater distress on the K-10 and poorer quality of life on the SF-12 (all p < 0.01). Conclusions Clinical features central to the model of BDD are common in, predictive of, and associated with impairment in women with EDs. Practice implications are that these features be included in the assessment and treatment of EDs. PMID:24999401

Sf3b4-depleted Xenopus embryos: a model to study the pathogenesis of craniofacial defects in Nager syndrome

PubMed Central

Devotta, Arun; Juraver-Geslin, Hugo; Gonzalez, Jose Antonio; Hong, Chang-Soo; Saint-Jeannet, Jean-Pierre

2016-01-01

Mandibulofacial dysostosis (MFD) is a human developmental disorder characterized by defects of the facial bones. It is the second most frequent craniofacial malformation after cleft lip and palate. Nager syndrome combines many features of MFD with a variety of limb defects. Mutations in SF3B4 (splicing factor 3b, subunit 4) gene, which encodes a component of the pre-mRNA spliceosomal complex, were recently identified as a cause for Nager syndrome, accounting for 60% of affected individuals. Nothing is known about the cellular pathogenesis underlying Nager type MFD. Here we describe the first animal model for Nager syndrome, generated by knocking down Sf3b4 function in Xenopus laevis embryos, using morpholino antisense oligonucleotides. Our results indicate that Sf3b4-depleted embryos show reduced expression of the neural crest genes sox10, snail2 and twist at the neural plate border, associated with a broadening of the neural plate. This phenotype can be rescued by injection of wild-type human SF3B4 mRNA but not by mRNAs carrying mutations that cause Nager syndrome. At the tailbud stage, morphant embryos had decreased sox10 and tfap2a expression in the pharyngeal arches, indicative of a reduced number of neural crest cells. Later in development, Sf3b4-depleted tadpoles exhibited hypoplasia of neural crest-derived craniofacial cartilages, phenocopying aspects of the craniofacial skeletal defects seen in Nager syndrome patients. With this animal model we are now poised to gain important insights into the etiology and pathogenesis of Nager type MFD, and to identify the molecular targets of Sf3b4. PMID:26874011

Total anomalous pulmonary venous connection and a constellation of craniofacial, skeletal, and urogenital anomalies in a newborn and similar features in his 36-year-old father.

PubMed

Pierson, D M; Taboada, E M; Lofland, G K; Begleiter, M L; Smith, G S; Hall, F; Butler, M G

2001-04-01

We report on a newborn male born to non-consanguineous parents with total anomalous pulmonary venous connection (TAPVC) and additional findings of malformed ears, hypertelorism, brachyphalangy in the hands, pterygium of the elbows, knees, and wrists, complex lower limb pre-axial polydactyly, tibial shortening, clubfeet, horseshoe kidney and a micropenis. He had a 46,XY karyotype. His 36-year-old father had similar craniofacial and limb anomalies suggesting an autosomal dominant syndrome with variable expression. Our patients may represent the 3rd and 4th examples of a newly-described syndrome by Baraitser et al. [(1997) Clin Dysmorphol 6:111-121] which is distinguished by malformed ears, complex pre-axial polydactyly and tibial aplasia in the lower limbs, severe brachyphalangy in the hands, and a micropenis.

Bartsocas-papas syndrome: unusual findings in the first reported egyptian family.

PubMed

Abdalla, E M; Morsy, H

2011-01-01

Bartsocas-Papas syndrome (BPS) is an autosomal recessive syndrome with severe craniofacial, limb, and genital abnormalities. As of 2011, 24 published cases and families were registered in the Orphanet Report Series. Compared to other disorders characterized by pterygia, the condition is usually more severe and often lethal: most affected patients die in utero or shortly after birth. We report the first Egyptian family with Bartsocas-Papas syndrome comprising three cases; our proband who was a female infant with severe craniofacial and limb anomalies typical of Bartsocas-Papas syndrome, a similarly affected female fetus which died in utero at the 7th gestational month, and a 16-year-old mentally retarded uncle who presented with some of the typical features of Bartsocas-Papas syndrome, including syndactyly, thumb hypoplasia, and microphthalmia. This male patient actually did not present with pterygia, however, we find his clinical description noteworthy.

Implant-retained craniofacial prostheses for facial defects

PubMed Central

Federspil, Philipp A.

2012-01-01

Craniofacial prostheses, also known as epistheses, are artificial substitutes for facial defects. The breakthrough for rehabilitation of facial defects with implant-retained prostheses came with the development of the modern silicones and bone anchorage. Following the discovery of the osseointegration of titanium in the 1950s, dental implants have been made of titanium in the 1960s. In 1977, the first extraoral titanium implant was inserted in a patient. Later, various solitary extraoral implant systems were developed. Grouped implant systems have also been developed which may be placed more reliably in areas with low bone presentation, as in the nasal and orbital region, or the ideally pneumatised mastoid process. Today, even large facial prostheses may be securely retained. The classical atraumatic surgical technique has remained an unchanged prerequisite for successful implantation of any system. This review outlines the basic principles of osseointegration as well as the main features of extraoral implantology. PMID:22073096

Functional coupling constrains craniofacial diversification in Lake Tanganyika cichlids

PubMed Central

Tsuboi, Masahito; Gonzalez-Voyer, Alejandro; Kolm, Niclas

2015-01-01

Functional coupling, where a single morphological trait performs multiple functions, is a universal feature of organismal design. Theory suggests that functional coupling may constrain the rate of phenotypic evolution, yet empirical tests of this hypothesis are rare. In fish, the evolutionary transition from guarding the eggs on a sandy/rocky substrate (i.e. substrate guarding) to mouthbrooding introduces a novel function to the craniofacial system and offers an ideal opportunity to test the functional coupling hypothesis. Using a combination of geometric morphometrics and a recently developed phylogenetic comparative method, we found that head morphology evolution was 43% faster in substrate guarding species than in mouthbrooding species. Furthermore, for species in which females were solely responsible for mouthbrooding the males had a higher rate of head morphology evolution than in those with bi-parental mouthbrooding. Our results support the hypothesis that adaptations resulting in functional coupling constrain phenotypic evolution. PMID:25948565

Functional coupling constrains craniofacial diversification in Lake Tanganyika cichlids.

PubMed

Tsuboi, Masahito; Gonzalez-Voyer, Alejandro; Kolm, Niclas

2015-05-01

Functional coupling, where a single morphological trait performs multiple functions, is a universal feature of organismal design. Theory suggests that functional coupling may constrain the rate of phenotypic evolution, yet empirical tests of this hypothesis are rare. In fish, the evolutionary transition from guarding the eggs on a sandy/rocky substrate (i.e. substrate guarding) to mouthbrooding introduces a novel function to the craniofacial system and offers an ideal opportunity to test the functional coupling hypothesis. Using a combination of geometric morphometrics and a recently developed phylogenetic comparative method, we found that head morphology evolution was 43% faster in substrate guarding species than in mouthbrooding species. Furthermore, for species in which females were solely responsible for mouthbrooding the males had a higher rate of head morphology evolution than in those with bi-parental mouthbrooding. Our results support the hypothesis that adaptations resulting in functional coupling constrain phenotypic evolution.

Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome

PubMed Central

Willemsen, Marjolein H; Fernandez, Bridget A; Bacino, Carlos A; Gerkes, Erica; de Brouwer, Arjan PM; Pfundt, Rolph; Sikkema-Raddatz, Birgit; Scherer, Stephen W; Marshall, Christian R; Potocki, Lorraine; van Bokhoven, Hans; Kleefstra, Tjitske

2010-01-01

The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes. PMID:19920853

Pericentric inversion of chromosome 11 (p14.3q21) associated with developmental delays, hypopigmented skin lesions and abnormal brain MRI findings - a new case report

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

Zachor, D.A.; Lofton, M.

1994-09-01

We report 3 year old male, referred for evaluation of developmental delays. Pregnancy was complicated by oligohydramnios, proteinuria and prematurity. Medical history revealed: bilateral inguinal hernia, small scrotal sac, undescended testes, developmental delays and behavioral problems. The child had: microcephaly, facial dysmorphic features, single palmar creases, hypopigmented skin lesions of variable size, intermittent exotropia and small retracted testes. Neurological examination was normal. Cognitive level was at the average range with mild delay in his adaptive behavior. Expressive language delays and severe articulation disorder were noted, as well as clumsiness, poor control and precision of gross and fine motor skills. Chromosomalmore » analysis of peripheral leukocytes indicated that one of the number 11 chromosomes had undergone a pericentric inversion with breakpoints on the short (p) arm at band p14.3 and the long (q) arm at band q21. An MRI of the brain showed mild delay in myelinization pattern of white matter. Chromosome 11 inversion in other sites was associated with Beckwith-Wiedemann syndrome and several malignancies. To our knowledge this is the first description of inv(11)(p14.3q21) that is associated with microcephaly, dysmorphic features, hypopigmented skin lesions and speech delay. This inversion may disrupt the expression of the involved genes. However, additional cases with the same cytogenetic anomaly are needed to explore the phenotypic significance of this disorder.« less

Abnormalities of Object Visual Processing in Body Dysmorphic Disorder

PubMed Central

Feusner, Jamie D.; Hembacher, Emily; Moller, Hayley; Moody, Teena D.

2013-01-01

Background Individuals with body dysmorphic disorder may have perceptual distortions for their appearance. Previous studies suggest imbalances in detailed relative to configural/holistic visual processing when viewing faces. No study has investigated the neural correlates of processing non-symptom-related stimuli. The objective of this study was to determine whether individuals with body dysmorphic disorder have abnormal patterns of brain activation when viewing non-face/non-body object stimuli. Methods Fourteen medication-free participants with DSM-IV body dysmorphic disorder and 14 healthy controls participated. We performed functional magnetic resonance imaging while participants matched photographs of houses that were unaltered, contained only high spatial frequency (high detail) information, or only low spatial frequency (low detail) information. The primary outcome was group differences in blood oxygen level-dependent signal changes. Results The body dysmorphic disorder group showed lesser activity in the parahippocampal gyrus, lingual gyrus, and precuneus for low spatial frequency images. There were greater activations in medial prefrontal regions for high spatial frequency images, although no significant differences when compared to a low-level baseline. Greater symptom severity was associated with lesser activity in dorsal occipital cortex and ventrolateral prefrontal cortex for normal and high spatial frequency images. Conclusions Individuals with body dysmorphic disorder have abnormal brain activation patterns when viewing objects. Hypoactivity in visual association areas for configural and holistic (low detail) elements and abnormal allocation of prefrontal systems for details is consistent with a model of imbalances in global vs. local processing. This may occur not only for appearance but also for general stimuli unrelated to their symptoms. PMID:21557897

Face off against ROS: Tcof1/Treacle safeguards neuroepithelial cells and progenitor neural crest cells from oxidative stress during craniofacial development.

PubMed

Sakai, Daisuke; Trainor, Paul A

2016-09-01

One-third of all congenital birth defects affect the head and face, and most craniofacial anomalies are considered to arise through defects in the development of cranial neural crest cells. Cranial neural crest cells give rise to the majority of craniofacial bones, cartilages and connective tissues. Therefore, understanding the events that control normal cranial neural crest and subsequent craniofacial development is important for elucidating the pathogenetic mechanisms of craniofacial anomalies and for the exploring potential therapeutic avenues for their prevention. Treacher Collins syndrome (TCS) is a congenital disorder characterized by severe craniofacial anomalies. An animal model of TCS, generated through mutation of Tcof1, the mouse (Mus musculus) homologue of the gene primarily mutated in association with TCS in humans, has recently revealed significant insights into the pathogenesis of TCS. Apoptotic elimination of neuroepithelial cells including neural crest cells is the primary cause of craniofacial defects in Tcof1 mutant embryos. However, our understanding of the mechanisms that induce tissue-specific apoptosis remains incomplete. In this review, we describe recent advances in our understanding of the pathogenesis TCS. Furthermore, we discuss the role of Tcof1 in normal embryonic development, the correlation between genetic and environmental factors on the severity of craniofacial abnormalities, and the prospect for prenatal prevention of craniofacial anomalies. © 2016 Japanese Society of Developmental Biologists.

Face off against ROS: Tcof1/Treacle safeguards neuroepithelial cells and progenitor neural crest cells from oxidative stress during craniofacial development

PubMed Central

Sakai, Daisuke; Trainor, Paul A.

2016-01-01

One-third of all congenital birth defects affect the head and face, and most craniofacial anomalies are considered to arise through defects in the development of cranial neural crest cells. Cranial neural crest cells give rise to the majority of craniofacial bones, cartilages and connective tissues. Therefore understanding the events that control normal cranial neural crest and subsequent craniofacial development is important for elucidating the pathogenetic mechanisms of craniofacial anomalies and for the exploring potential therapeutic avenues for their prevention. Treacher Collins syndrome (TCS) is a congenital disorder characterized by severe craniofacial anomalies. An animal model of TCS, generated through mutation of Tcof1, the mouse (Mus musculus) homologue of the gene primarily mutated in association with TCS in humans, has recently revealed significant insights into the pathogenesis of TCS. Apoptotic elimination of neuroepithelial cells including neural crest cells is the primary cause of craniofacial defects in Tcof1 mutant embryos. However our understanding of the mechanisms that induce tissue-specific apoptosis remains incomplete. In this review, we describe recent advances in our understanding of the pathogenesis TCS. Furthermore, we discuss the role of Tcof1 in normal embryonic development, the correlation between genetic and environmental factors on the severity of craniofacial abnormalities, and the prospect for prenatal prevention of craniofacial anomalies. PMID:27481486

What difference can a minute make? Social skills and first impressions of youth with craniofacial differences.

PubMed

Edwards, Todd C; Topolski, Tari D; Kapp-Simon, Kathleen A; Aspinall, Cassandra L; Patrick, Donald L

2011-01-01

To determine whether raters' first impressions of youth with craniofacial differences are modifiable. Observational study of the association between first impressions and social skills as related to youth aged 11 to 18 years with craniofacial differences. University research offices and clinics. Youth aged 11 to 18 years with (n  =  29) and without (n  =  31) craniofacial differences; adults (n  =  40), dental/medical students (n  =  46), and education students (n  =  29), all without craniofacial differences. Participants were recruited from medical clinics and through community advertising at all three study sites. The First Impressions Rating Scale. After viewing 1-minute portrayals of positive social skills by actors with craniofacial differences, raters' perceptions moved significantly in the positive direction for all 26 attributes on the First Impressions Rating Scale; whereas, after viewing negative social skills, ratings moved significantly in the negative direction for 25 of 26 First Impressions Rating Scale attributes. It appears that first impressions others have of youth with craniofacial differences are significantly affected by how these youth present themselves in social situations, suggesting that positive social skills may help reduce the amount of stigma that youth with craniofacial differences encounter.

The 50 Most Cited Papers in Craniofacial Anomalies and Craniofacial Surgery

PubMed Central

Joyce, Cormac W; Thomas, Sangeetha; Concannon, Elizabeth; Murray, Dylan

2015-01-01

Background Citation analysis is a recognized scientometric method of classifying cited articles according to the frequency of which they have been referenced. The total number of citations an article receives is considered to reflect it's significance among it's peers. Methods Until now, a bibliometric analysis has never been performed in the specialty of craniofacial anomalies and craniofacial surgery. This citation analysis generates an extensive list of the 50 most influential papers in this developing field. Journals specializing in craniofacial surgery, maxillofacial surgery, plastic surgery, neurosurgery, genetics and pediatrics were searched to demonstrate which articles have cultivated the specialty within the past 55 years. Results The results show an intriguing compilation of papers which outline the fundamental knowledge of craniofacial anomalies and the developments of surgical techniques to manage these patients. Conclusions This citation analysis provides a summation of the current most popular trends in craniofacial literature. These esteemed papers aid to direct our decision making today within this specialty. PMID:26430626

The suture provides a niche for mesenchymal stem cells of craniofacial bones

PubMed Central

Zhao, Hu; Feng, Jifan; Ho, Thach-Vu; Grimes, Weston; Urata, Mark; Chai, Yang

2015-01-01

Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the major MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating these cells are an indispensible stem cell population. Twist1+/− mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair. PMID:25799059

A Turkish family with Nance-Horan Syndrome due to a novel mutation.

PubMed

Tug, Esra; Dilek, Nihal F; Javadiyan, Shahrbanou; Burdon, Kathryn P; Percin, Ferda E

2013-08-01

Nance-Horan Syndrome (NHS) is a rare X-linked syndrome characterized by congenital cataract which leads to profound vision loss, characteristic dysmorphic features and specific dental anomalies. Microcornea, microphthalmia and mild or moderate mental retardation may accompany these features. Heterozygous females often manifest similarly but with less severe features than affected males. We describe two brothers who have the NHS phenotype and their carrier mother who had microcornea but not cataract. We identified a previously unreported frameshift mutation (c.558insA) in exon 1 of the NHS gene in these patients and their mother which is predicted to result in the incorporation of 11 aberrant amino acids prior to a stop codon (p.E186Efs11X). We also discussed genotype-phenotype correlation according to relevant literature. Copyright © 2013 Elsevier B.V. All rights reserved.

Cerebro-facio-thoracic dysplasia (Pascual-Castroviejo syndrome): Identification of a novel mutation, use of facial recognition analysis, and review of the literature.

PubMed

Tender, Jennifer A F; Ferreira, Carlos R

2018-04-13

Cerebro-facio-thoracic dysplasia (CFTD) is a rare, autosomal recessive disorder characterized by facial dysmorphism, cognitive impairment and distinct skeletal anomalies and has been linked to the TMCO1 defect syndrome. To describe two siblings with features consistent with CFTD with a novel homozygous p.Arg114* pathogenic variant in the TMCO1 gene. We conducted a literature review and summarized the clinical features and laboratory results of two siblings with a novel pathogenic variant in the TMCO1 gene. Facial recognition analysis was utilized to assess the specificity of facial traits. The novel homozygous p.Arg114* pathogenic variant in the TMCO1 gene is responsible for the clinical features of CFTD in two siblings. Facial recognition analysis allows unambiguous distinction of this syndrome against controls.

Enhancing the Detection of Dysmorphic Red Blood Cells and Renal Tubular Epithelial Cells with a Modified Urinalysis Protocol.

PubMed

Chu-Su, Yu; Shukuya, Kenichi; Yokoyama, Takashi; Lin, Wei-Chou; Chiang, Chih-Kang; Lin, Chii-Wann

2017-01-11

Urinary sediment is used to evaluate patients with possible urinary tract diseases. Currently, numerous protocols are applied to detect dysmorphic red blood cells (RBCs) and renal tubular epithelial cells (RTECs) in urinary sediment. However, distinct protocols are used by nephrologists and medical technologists for specimen concentration and observation, which leads to major discrepancies in the differential counts of formed elements such as dysmorphic RBCs and RTECs and might interfere with an accurate clinical diagnosis. To resolve these problems, we first tested a modified urinalysis protocol with an increased relative centrifuge force and concentration factor in 20 biopsy-confirmed glomerulonephritis patients with haematuria. We successfully improved the recovery ratio of dysmorphic RBCs in clinical specimens from 34.7% to 42.0% (P < 0.001). Furthermore, we confirmed the correlation between counts by the modified urinary protocol and Sysmex UF-1000i urinary flow cytometer (r ≥ 0.898, P < 0.001). A total of 28 types of isomorphic and dysmorphic RBCs were detected using a bright field microscope, with results comparable to those using a standard phase contrast microscope. Finally, we applied Sternheimer stain to enhance the contrast of RTECs in the urinary sediments. We concluded that this modified urinalysis protocol significantly enhanced the quality of urinalysis.

Enhancing the Detection of Dysmorphic Red Blood Cells and Renal Tubular Epithelial Cells with a Modified Urinalysis Protocol

PubMed Central

Chu-Su, Yu; Shukuya, Kenichi; Yokoyama, Takashi; Lin, Wei-Chou; Chiang, Chih-Kang; Lin, Chii-Wann

2017-01-01

Urinary sediment is used to evaluate patients with possible urinary tract diseases. Currently, numerous protocols are applied to detect dysmorphic red blood cells (RBCs) and renal tubular epithelial cells (RTECs) in urinary sediment. However, distinct protocols are used by nephrologists and medical technologists for specimen concentration and observation, which leads to major discrepancies in the differential counts of formed elements such as dysmorphic RBCs and RTECs and might interfere with an accurate clinical diagnosis. To resolve these problems, we first tested a modified urinalysis protocol with an increased relative centrifuge force and concentration factor in 20 biopsy-confirmed glomerulonephritis patients with haematuria. We successfully improved the recovery ratio of dysmorphic RBCs in clinical specimens from 34.7% to 42.0% (P < 0.001). Furthermore, we confirmed the correlation between counts by the modified urinary protocol and Sysmex UF-1000i urinary flow cytometer (r ≥ 0.898, P < 0.001). A total of 28 types of isomorphic and dysmorphic RBCs were detected using a bright field microscope, with results comparable to those using a standard phase contrast microscope. Finally, we applied Sternheimer stain to enhance the contrast of RTECs in the urinary sediments. We concluded that this modified urinalysis protocol significantly enhanced the quality of urinalysis. PMID:28074941

Prevalence of Body Dysmorphic Disorder in Plastic Surgery and Dermatology Patients: A Systematic Review with Meta-Analysis.

PubMed

Ribeiro, Rafael Vilela Eiras

2017-08-01

The aim of the present study was to evaluate the prevalence of body dysmorphic disorder in plastic surgery and dermatology patients, by performing a systematic review of the literature and meta-analysis. The most relevant studies published originally in any language were analyzed. The literature search was performed using the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Scielo databases. The final sample comprised 33 publications that were submitted to meta-analysis. The study verified that 15.04% of plastic surgery patients had body dysmorphic disorder (range 2.21-56.67%); patient mean age was 34.54 ± 12.41 years, and most were women (74.38%). Among dermatology patients, 12.65% (range 4.52-35.16%) had body dysmorphic disorder; patient mean age was 27.79 ± 9.03 years, and most were women (76.09%). Both plastic surgeons and dermatologists must adequately assess their patients to identify those with a higher likelihood of body dysmorphic disorder and should arrange multidisciplinary care for such individuals. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Simpson-Golabi-Behmel syndrome types I and II.

PubMed

Tenorio, Jair; Arias, Pedro; Martínez-Glez, Víctor; Santos, Fernando; García-Miñaur, Sixto; Nevado, Julián; Lapunzina, Pablo

2014-09-20

Simpson-Golabi-Behmel syndrome (SGBS) is a rare overgrowth syndrome clinically characterized by multiple congenital abnormalities, pre/postnatal overgrowth, distinctive craniofacial features, macrocephaly, and organomegaly. Abnormalities of the skeletal system, heart, central nervous system, kidney, and gastrointestinal tract may also be observed. Intellectual disability, early motor milestones and speech delay are sometimes present; however, there are a considerable number of individuals with normal intelligence.

National Institute of Dental and Craniofacial Research

MedlinePlus

... In Skip to Main Content National Institute of Dental and Craniofacial Research (NIDCR) Improving the Nation's Oral ... Researchers NIDCR Strategic Plan The National Institute of Dental and Craniofacial Research remains committed to improving the ...

Etiologies of pediatric craniofacial injuries: a comparison of injuries involving all-terrain vehicles and golf carts.

PubMed

White, Lauren C; McKinnon, Brian J; Hughes, C Anthony

2013-03-01

To determine incidence and etiologies of craniofacial injuries in the pediatric population through comparison of injuries caused by all-terrain vehicles and golf cart trauma. Case series with chart review. Level 1 trauma center. Retrospective review of pediatric traumas at a tertiary academic medical center from 2003 to 2012 identified 196 patients whose injuries resulted from accidents involving either all-terrain vehicles or golf carts. Data was collected and variables such as age, gender, driver vs. passenger, location of accident, Glasgow coma scale, Injury severity scale, Abbreviated injury scale, and presence or absence of helmet use were examined. 196 pediatric patients were identified: 68 patients had injuries resulting from golf cart accidents, and 128 patients from ATV accidents. 66.4% of ATV-related traumas were male, compared to 52.9% of golf cart-related traumas. Ages of injured patients were similar between the two modalities with average age of ATV traumas 10.8 (±4.0) years and golf cart traumas 10.0 (±4.6) years. Caucasians were most commonly involved in both ATV (79.7%) and golf cart traumas (85.3%). 58.6% of all ATV related trauma and 69.1% of all golf cart trauma resulted in craniofacial injuries. The most common craniofacial injury was a closed head injury with brief loss of consciousness, occurring in 46.1% of the ATV traumas and 54.4% of the golf cart traumas. Temporal bone fractures were the second most common type of craniofacial injury, occurring in 5.5% of ATV accidents and 7.4% of the golf cart traumas. Length of hospital stay and, cases requiring surgery and severity scores were similar between both populations. Intensive care admissions and injury severity scores approached but not reach statistical significance (0.096 and 0.083, respectively). The only statistically significant differences between the two modalities were helmet use (P=0.00018%) and days requiring ventilator assistance (P=0.025). ATVs and golf carts are often exempt from the safety features and regulations required of motor vehicles, and ATV and golf cart accidents represent a significant portion of pediatric traumas. This study found that ATV and golf cart accidents contribute significantly to craniofacial trauma requiring hospitalization, with resultant morbidity and mortality. Further investigation of these injuries and their prevention in the pediatric population is needed before efforts to promote effective safety regulations for such vehicles in the future can be addressed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Virtual Surgical Planning in Craniofacial Surgery

PubMed Central

Chim, Harvey; Wetjen, Nicholas; Mardini, Samir

2014-01-01

The complex three-dimensional anatomy of the craniofacial skeleton creates a formidable challenge for surgical reconstruction. Advances in computer-aided design and computer-aided manufacturing technology have created increasing applications for virtual surgical planning in craniofacial surgery, such as preoperative planning, fabrication of cutting guides, and stereolithographic models and fabrication of custom implants. In this review, the authors describe current and evolving uses of virtual surgical planning in craniofacial surgery. PMID:25210509

Evaluation of Relationship Between Body Dysmorphic Disorder and Self-Esteem in Rhinoplasty Candidates.

PubMed

Baykal, Bahadir; Erdim, Ibrahim; Ozbay, Isa; Oghan, Fatih; Oncu, Fatih; Erdogdu, Zeynep; Kayhan, Fatma Tulin

2015-11-01

To investigate the relationship between body dysmorphic syndrome and self-esteem in rhinoplasty candidates. A negative statistical correlation was evident between Rosenberg Self-Esteem Scale (RSES) and Body Dysmorphic Disorder Examination-Self Report (BDDE-SR) scores. In terms of responses to the first Body Dysmorphic Disorder Questionnaire (BDDQ) question, which focuses on general attitude toward body dysmorphic syndrome, the average RSES "YES" score was significantly less than the "NO" score. No significant differences appeared between RSES scores and scores for the 4th subgroup of BDDQ questions (subgroups A, B, and C; these questions explore how much time is spent daily on maintenance of bodily appearance). However, significant differences appeared between scores for the 4th subgroup of BDDQ questions and BDDE-SR scores. The average BDD-SR score of subgroup A (less than 1 hour spent on bodily maintenance) was significantly lower than those of group B (1-3 hours) and group C (more than 3 hours). However, no significant differences appeared in average BDD-SR scores between subgroups B and C. In this prospective study, 56 patients (31 females and 25 males) were evaluated preoperatively using the BDDQ, the BDDE-SR, and the RSES. Patients younger than 15 years and those with deformities caused by trauma were excluded. Rhinoplasty candidates had higher levels of body dysmorphic disorder (BDD). Although patients with low RSES scores were more likely to have BDD, rhinoplasty candidates were not notably deficient in self-esteem. However, in rhinoplasty candidates with low RSES scores, the frequency of BDD was elevated. Therefore, the authors suggest that rhinoplasty candidates with low RSES scores should be investigated carefully in terms of BDD.

Body dysmorphic disorder: prevalence and outcomes in an oculofacial plastic surgery practice.

PubMed

Woolley, Austin J; Perry, Julian D

2015-06-01

To determine the prevalence, associated factors, and surgical outcomes of patients with body dysmorphic disorder in an oculofacial surgery practice. Retrospective cross-sectional analysis of a consecutive case series. Participants consisted of a consecutive series of 728 patients who completed the Dysmorphic Concern Questionnaire in an oculofacial surgery practice at The Cole Eye Institute between November 2013 and June 2014. A questionnaire score ≥9 was used as a positive screen for body dysmorphic disorder. Three control patients scoring ≤8 in the same month were randomly selected for each positive-screening patient. Main outcome measures included number of reoperations, surgical complications, and follow-up visits; preoperative and postoperative pain scores; and the technician word count. Categorical variables were analyzed with Pearson χ(2) tests or Fisher exact tests, while continuous variables were analyzed with Wilcoxon rank sum tests or t tests. A total of 728 patients completed the questionnaire and 50 (6.9%) scored 9 or more. Using a confidence interval of 95%, patients in the positive questionnaire screen group were younger (P = .004), had more eyelid surgeries (P = .007), experienced higher rates of complications after surgery (P = .002), reported higher postoperative pain scores (P = .034), required more reoperations (P = .050), and had a higher technician word count compared to the control group (P = .003). The prevalence of body dysmorphic disorder in an oculofacial surgical setting matches reports from other surgical specialties, and is significantly higher than in the general population. Patients screening positively for body dysmorphic disorder tend to have higher postoperative pain scores and more postoperative complications. Copyright © 2015 Elsevier Inc. All rights reserved.

Craniofacial Surgery Fellowship Websites.

PubMed

Silvestre, Jason; Agarwal, Divyansh; Taylor, Jesse A

2016-06-01

Applicants for craniofacial surgery fellowships utilize Internet-based resources like the San Francisco (SF) Match to manage applications. The purpose of this study was to evaluate the accessibility and content of craniofacial surgery fellowship websites (CSFWs). A list of available craniofacial surgery fellowships was compiled from directories of the American Society of Craniofacial Surgery (ACSFS) and SF Match. Accessibility of CSFWs was assessed via links from these directories and a Google search. Craniofacial surgery fellowship websites were evaluated on education and recruitment content and compared via program characteristics. Twenty-four of the 28 US-based craniofacial surgery fellowship programs had a CSFW (86%). The ACSFS and SF Match databases had limited CSFW accessibility, but a Google search revealed most CSFWs had the top search result (76%). In total, CSFWs provided an average of 39% of education and recruitment variables. While most programs provided fellowship program descriptions (96%), application links (96%), and faculty listings (83%), relatively few provided rotation schedules (13%), fellow selection process information (13%), or interview dates (8%). CSFW content did not vary by program location, faculty size, accreditation status, or institutional affiliations (P > 0.05). Craniofacial surgery fellowships often lack readily accessible websites from national program lists and have limited information for interested applicants. The consistent lack of online information across programs suggests future opportunities exist to improve these educational resources.

Identification of a 3.0-kb Major Recombination Hotspot in Patients with Sotos Syndrome Who Carry a Common 1.9-Mb Microdeletion

PubMed Central

Visser, Remco; Shimokawa, Osamu; Harada, Naoki; Kinoshita, Akira; Ohta, Tohru; Niikawa, Norio; Matsumoto, Naomichi

2005-01-01

Sotos syndrome (SoS) is a congenital dysmorphic disorder characterized by overgrowth in childhood, distinctive craniofacial features, and mental retardation. Haploinsufficiency of the NSD1 gene owing to either intragenic mutations or microdeletions is known to be the major cause of SoS. The common ∼2.2-Mb microdeletion encompasses the whole NSD1 gene and neighboring genes and is flanked by low-copy repeats (LCRs). Here, we report the identification of a 3.0-kb major recombination hotspot within these LCRs, in which we mapped deletion breakpoints in 78.7% (37/47) of patients with SoS who carry the common microdeletion. The deletion size was subsequently refined to 1.9 Mb. Sequencing of breakpoint fragments from all 37 patients revealed junctions between a segment of the proximal LCR (PLCR-B) and the corresponding region of the distal LCR (DLCR-2B). PLCR-B and DLCR-2B are the only directly oriented regions, whereas the remaining regions of the PLCR and DLCR are in inverted orientation. The PLCR, with a size of 394.0 kb, and the DLCR, with a size of of 429.8 kb, showed high overall homology (∼98.5%), with an increased sequence similarity (∼99.4%) within the 3.0-kb breakpoint cluster. Several recombination-associated motifs were identified in the hotspot and/or its vicinity. Interestingly, a 10-fold average increase of a translin motif, as compared with the normal distribution within the LCRs, was recognized. Furthermore, a heterozygous inversion of the interval between the LCRs was detected in all fathers of the children carrying a deletion in the paternally derived chromosome. The functional significance of these findings remains to be elucidated. Segmental duplications of the primate genome play a major role in chromosomal evolution. Evolutionary study showed that the duplication of the SoS LCRs occurred 23.3–47.6 million years ago, before the divergence of Old World monkeys. PMID:15580547

Pygmoid Australomelanesian Homo sapiens skeletal remains from Liang Bua, Flores: population affinities and pathological abnormalities.

PubMed

Jacob, T; Indriati, E; Soejono, R P; Hsü, K; Frayer, D W; Eckhardt, R B; Kuperavage, A J; Thorne, A; Henneberg, M

2006-09-05

Liang Bua 1 (LB1) exhibits marked craniofacial and postcranial asymmetries and other indicators of abnormal growth and development. Anomalies aside, 140 cranial features place LB1 within modern human ranges of variation, resembling Australomelanesian populations. Mandibular and dental features of LB1 and LB6/1 either show no substantial deviation from modern Homo sapiens or share features (receding chins and rotated premolars) with Rampasasa pygmies now living near Liang Bua Cave. We propose that LB1 is drawn from an earlier pygmy H. sapiens population but individually shows signs of a developmental abnormality, including microcephaly. Additional mandibular and postcranial remains from the site share small body size but not microcephaly.

Cutis laxa and excessive bone growth due to de novo mutations in PTDSS1.

PubMed

Piard, Juliette; Lespinasse, James; Vlckova, Marketa; Mensah, Martin A; Iurian, Sorin; Simandlova, Martina; Malikova, Marcela; Bartsch, Oliver; Rossi, Massimiliano; Lenoir, Marion; Nugues, Frédérique; Mundlos, Stefan; Kornak, Uwe; Stanier, Philip; Sousa, Sérgio B; Van Maldergem, Lionel

2018-03-01

The cutis laxa syndromes are multisystem disorders that share loose redundant inelastic and wrinkled skin as a common hallmark clinical feature. The underlying molecular defects are heterogeneous and 13 different genes have been involved until now, all of them being implicated in elastic fiber assembly. We provide here molecular and clinical characterization of three unrelated patients with a very rare phenotype associating cutis laxa, facial dysmorphism, severe growth retardation, hyperostotic skeletal dysplasia, and intellectual disability. This disorder called Lenz-Majewski syndrome (LMS) is associated with gain of function mutations in PTDSS1, encoding an enzyme involved in phospholipid biosynthesis. This report illustrates that LMS is an unequivocal cutis laxa syndrome and expands the clinical and molecular spectrum of this group of disorders. In the neonatal period, brachydactyly and facial dysmorphism are two early distinctive signs, later followed by intellectual disability and hyperostotic skeletal dysplasia with severe dwarfism allowing differentiation of this condition from other cutis laxa phenotypes. Further studies are needed to understand the link between PTDSS1 and extra cellular matrix assembly. © 2018 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Moyamoya disease associated with asymptomatic mosaic Turner syndrome: a rare cause of hemorrhagic stroke.

PubMed

Manjila, Sunil; Miller, Benjamin R; Rao-Frisch, Anitha; Otvos, Balint; Mitchell, Anna; Bambakidis, Nicholas C; De Georgia, Michael A

2014-01-01

Moyamoya disease is a rare cerebrovascular anomaly involving the intracranial carotid arteries that can present clinically with either ischemic or hemorrhagic disease. Moyamoya syndrome, indistinguishable from moyamoya disease at presentation, is associated with multiple clinical conditions including neurofibromatosis type 1, autoimmune disease, prior radiation therapy, Down syndrome, and Turner syndrome. We present the first reported case of an adult patient with previously unrecognized mosaic Turner syndrome with acute subarachnoid and intracerebral hemorrhage as the initial manifestation of moyamoya syndrome. A 52-year-old woman was admitted with a subarachnoid hemorrhage with associated flame-shaped intracerebral hemorrhage in the left frontal lobe. Physical examination revealed short stature, pectus excavatum, small fingers, micrognathia, and mild facial dysmorphism. Cerebral angiography showed features consistent with bilateral moyamoya disease, aberrant intrathoracic vessels, and an unruptured 4-mm right superior hypophyseal aneurysm. Genetic analysis confirmed a diagnosis of mosaic Turner syndrome. Our case report is the first documented presentation of adult moyamoya syndrome with subarachnoid and intracerebral hemorrhage as the initial presentation of mosaic Turner syndrome. It illustrates the utility of genetic evaluation in patients with cerebrovascular disease and dysmorphism. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Understanding Cleft and Craniofacial Team Care

MedlinePlus

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Craniofacial Characteristics of Thalassemia Major Patients

PubMed Central

Karakas, Sacide; Tellioglu, Ayfer Metin; Bilgin, Mehmet; Omurlu, Imran Kurt; Caliskan, Sercin; Coskun, Salih

2016-01-01

Objective: Thalassemias major are the most common autosomal recessive disorders; they are characterized by anomalies in the synthesis of the beta chains of hemoglobin and are often associated with varying degrees of craniofacial anomalies. The purpose of this study was to evaluate the craniofacial dimensions of β-thalassemia patients and to identify differences by comparing them to those of a control group. Materials and Methods: The study comprised 43 thalassemia major patients and 26 age- and sex- matched healthy control subjects. Anthropometric measurements were performed in six different craniofacial regions (head, face, nose, mouth, eyes, and ears); a total of 23 craniofacial variables were measured. Results: Craniofacial measurements in the regions of the face, nose, lips and mouth, and ears in the thalassemia major patient group yielded statistically significant differences compared to those in the control group (p<0.05). However, no statistically significant differences were observed in the measurements of the head and eye regions. Conclusion: The study increased our understanding of the craniofacial anatomy of thalassemia major patients and enabled us to obtain quantitative results. PMID:28149147

Whole-Exome Sequencing of Congenital Glaucoma Patients Reveals Hypermorphic Variants in GPATCH3, a New Gene Involved in Ocular and Craniofacial Development

PubMed Central

Ferre-Fernández, Jesús-José; Aroca-Aguilar, José-Daniel; Medina-Trillo, Cristina; Bonet-Fernández, Juan-Manuel; Méndez-Hernández, Carmen-Dora; Morales-Fernández, Laura; Corton, Marta; Cabañero-Valera, María-José; Gut, Marta; Tonda, Raul; Ayuso, Carmen; Coca-Prados, Miguel; García-Feijoo, Julián; Escribano, Julio

2017-01-01

Congenital glaucoma (CG) is a heterogeneous, inherited and severe optical neuropathy that originates from maldevelopment of the anterior segment of the eye. To identify new disease genes, we performed whole-exome sequencing of 26 unrelated CG patients. In one patient we identified two rare, recessive and hypermorphic coding variants in GPATCH3, a gene of unidentified function, and 5% of a second group of 170 unrelated CG patients carried rare variants in this gene. The recombinant GPATCH3 protein activated in vitro the proximal promoter of CXCR4, a gene involved in embryo neural crest cell migration. The GPATCH3 protein was detected in human tissues relevant to glaucoma (e.g., ciliary body). This gene was expressed in the dermis, skeletal muscles, periocular mesenchymal-like cells and corneal endothelium of early zebrafish embryos. Morpholino-mediated knockdown and transient overexpression of gpatch3 led to varying degrees of goniodysgenesis and ocular and craniofacial abnormalities, recapitulating some of the features of zebrafish embryos deficient in the glaucoma-related genes pitx2 and foxc1. In conclusion, our data suggest the existence of high genetic heterogeneity in CG and provide evidence for the role of GPATCH3 in this disease. We also show that GPATCH3 is a new gene involved in ocular and craniofacial development. PMID:28397860

Whole-genome sequencing in a pair of monozygotic twins with discordant cleft lip and palate subtypes.

PubMed

Takahashi, Masahiro; Hosomichi, Kazuyoshi; Yamaguchi, Tetsutaro; Nagahama, Ryo; Yoshida, Hiroshi; Maki, Koutaro; Marazita, Mary L; Weinberg, Seth M; Tajima, Atsushi

2018-06-06

Orofacial clefts (OFCs) are common and aetiologically complex birth defects. This study explored potential genetic differences in a pair of Japanese monozygotic (MZ) twins with different forms of OFC using whole-genome sequencing. One co-twin (MZ-1) presented with non-syndromic bilateral cleft lip and palate; the other co-twin (MZ-2) had non-syndromic bilateral cleft lip and unilateral left-sided cleft alveolus. Neither parent had an OFC. Craniofacial morphologic features and potential genetic differences were compared using standard cephalometry and whole-genome sequencing, respectively. Morphologically, MZ-1 had a smaller vertical mandibular height, compared to MZ-2. However, no discordant genetic differences were detected. Moreover, both twins and their parents harboured rare candidate gene variants (GRHL3; TPM1) considered to be associated with OFCs. The observed differences between MZ-1 and MZ-2 in craniofacial morphology assessed by cephalograms might be directly attributable to the effects of the OFC on growth and/or differences in surgical history, given the lack of any differences in genetic background. However, comparisons of discordant MZ twins should continue to identify novel candidates that might control OFC or that might partly explain the missing heritability for this common birth defect, in addition to understanding craniofacial growth and development. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Craniofacial orthodontics and postgraduate orthodontic training in Nigeria.

PubMed

Isiekwe, G I; Oguchi, C O; daCosta, O O; Utomi, I L

2016-01-01

Craniofacial orthodontics has been shown to be a critical component of the care of patients with craniofacial anomalies such as cleft lip and palate. Thus, the purpose of this study was to assess the perceptions and clinical experience in cleft and craniofacial care, of orthodontic residents in Nigeria. Questionnaires were sent out to orthodontic residents in the six Postgraduate Orthodontic Training Centers in the country at that time. The questionnaires were self-administered and covered areas in beliefs in cleft care and the clinical experience and challenges faced by the residents in the provision of craniofacial orthodontic care at their various institutions. Thirty-three respondents returned completed questionnaires, with a response rate of 97%. All the respondents believed that residents should be involved in cleft and craniofacial care. Postnatal counseling was the clinical procedure in which the residents reported the highest level of clinical experience (47.4%). The least clinical experience was recorded in pre-bone graft orthodontics (7.4%) and orthodontic preparation for orthognathic surgery (5.5%). Some of the challenges highlighted by the residents were low patients turn out for orthodontic care and the absence of multidisciplinary treatment for craniofacial patients in their centers. Orthodontic residents in Nigeria believe that they should be involved in the management of patients with craniofacial anomalies and cleft lip and palate. However, majority of the residents have limited clinical experience in the management of these patients. A lot more needs to be done, to expose orthodontic residents in training, to all aspects of the orthodontic and multidisciplinary team care required for the cleft/craniofacial patient.

Quantifying Normal Craniofacial Form and Baseline Craniofacial Asymmetry in the Pediatric Population.

PubMed

Cho, Min-Jeong; Hallac, Rami R; Ramesh, Jananie; Seaward, James R; Hermann, Nuno V; Darvann, Tron A; Lipira, Angelo; Kane, Alex A

2018-03-01

Restoring craniofacial symmetry is an important objective in the treatment of many craniofacial conditions. Normal form has been measured using anthropometry, cephalometry, and photography, yet all of these modalities have drawbacks. In this study, the authors define normal pediatric craniofacial form and craniofacial asymmetry using stereophotogrammetric images, which capture a densely sampled set of points on the form. After institutional review board approval, normal, healthy children (n = 533) with no known craniofacial abnormalities were recruited at well-child visits to undergo full head stereophotogrammetric imaging. The children's ages ranged from 0 to 18 years. A symmetric three-dimensional template was registered and scaled to each individual scan using 25 manually placed landmarks. The template was deformed to each subject's three-dimensional scan using a thin-plate spline algorithm and closest point matching. Age-based normal facial models were derived. Mean facial asymmetry and statistical characteristics of the population were calculated. The mean head asymmetry across all pediatric subjects was 1.5 ± 0.5 mm (range, 0.46 to 4.78 mm), and the mean facial asymmetry was 1.2 ± 0.6 mm (range, 0.4 to 5.4 mm). There were no significant differences in the mean head or facial asymmetry with age, sex, or race. Understanding the "normal" form and baseline distribution of asymmetry is an important anthropomorphic foundation. The authors present a method to quantify normal craniofacial form and baseline asymmetry in a large pediatric sample. The authors found that the normal pediatric craniofacial form is asymmetric, and does not change in magnitude with age, sex, or race.

Applications of Computer Technology in Complex Craniofacial Reconstruction.

PubMed

Day, Kristopher M; Gabrick, Kyle S; Sargent, Larry A

2018-03-01

To demonstrate our use of advanced 3-dimensional (3D) computer technology in the analysis, virtual surgical planning (VSP), 3D modeling (3DM), and treatment of complex congenital and acquired craniofacial deformities. We present a series of craniofacial defects treated at a tertiary craniofacial referral center utilizing state-of-the-art 3D computer technology. All patients treated at our center using computer-assisted VSP, prefabricated custom-designed 3DMs, and/or 3D printed custom implants (3DPCI) in the reconstruction of craniofacial defects were included in this analysis. We describe the use of 3D computer technology to precisely analyze, plan, and reconstruct 31 craniofacial deformities/syndromes caused by: Pierre-Robin (7), Treacher Collins (5), Apert's (2), Pfeiffer (2), Crouzon (1) Syndromes, craniosynostosis (6), hemifacial microsomia (2), micrognathia (2), multiple facial clefts (1), and trauma (3). In select cases where the available bone was insufficient for skeletal reconstruction, 3DPCIs were fabricated using 3D printing. We used VSP in 30, 3DMs in all 31, distraction osteogenesis in 16, and 3DPCIs in 13 cases. Utilizing these technologies, the above complex craniofacial defects were corrected without significant complications and with excellent aesthetic results. Modern 3D technology allows the surgeon to better analyze complex craniofacial deformities, precisely plan surgical correction with computer simulation of results, customize osteotomies, plan distractions, and print 3DPCI, as needed. The use of advanced 3D computer technology can be applied safely and potentially improve aesthetic and functional outcomes after complex craniofacial reconstruction. These techniques warrant further study and may be reproducible in various centers of care.

Cognitive-Behavioral Therapy for Adolescent Body Dysmorphic Disorder

ERIC Educational Resources Information Center

Greenberg, Jennifer L.; Markowitz, Sarah; Petronko, Michael R.; Taylor, Caitlin E.; Wilhelm, Sabine; Wilson, G. Terence

2010-01-01

The onset of appearance-related concerns associated with body dysmorphic disorder (BDD) typically occurs in adolescence, and these concerns are often severe enough to interfere with normal development and psychosocial functioning. Cognitive behavioral therapy (CBT) is an effective treatment for adults with BDD. However, no treatment studies…

['Barbie Doll Syndrome'. A case report of body dysmorphic disorder].

PubMed

Gruber, Maria; Jahn, Rebecca; Stolba, Karin; Ossege, Michael

2018-03-01

This case report aims to present a 37-year-old women striving to shape her body like a Barbie doll of which she has been fascinated since childhood. She could hardly tolerate any deviation from this beauty ideal. She has been admitted to the psychosomatic ward due to an eating disorder. The ICD-10 and DSM-5 criteria were established for axis I disorders and the German version of the SCID II interview (for DSM-4) was applied for axis II disorders. Additionally, the "modified Yale-Brown Obsessive Compulsive Scale for body dysmorphic disorder" was carried out. The diagnosis of dysmorphophobia (ICD-10: F45.21) or body dysmorphic disorder (DSM-5: 300.7) and bulimia nervosa (ICD-10: F50.2; DSM-5: 307.51) was confirmed. The patient fulfilled criteria of an avoidant, depressive and histrionic personality disorder. Psychopharmacological treatment with Fluoxetine was started and the patient participated in an intensive inpatient psychosomatic program. The body image, self-concept and the sense of shame were therapeutic key topics. The present case report focuses on body dysmorphic disorder as a distinctive entity with high prevalence. Diagnostic criteria of different classification systems were contrasted and comorbidity with eating disorders was discussed. In clinical praxis, body dysmorphic disorder remains underdiagnosed, especially when cooccurring with an eating disorder. However, the correct diagnosis could be relevant for therapy planning.

Hysteroscopic outpatient metroplasty to expand dysmorphic uteri (HOME-DU technique): a pilot study.

PubMed

Di Spiezio Sardo, A; Florio, P; Nazzaro, G; Spinelli, M; Paladini, D; Di Carlo, C; Nappi, C

2015-02-01

The new classification system of uterine anomalies from the European Society of Human Reproduction and Embryology and the European Society for Gynaecological Endoscopy defines T-shaped and tubular-shaped infantilis uteri as 'dysmorphic'. Such malformations have been proven to be associated with poor reproductive performance. A prospective observational study was conducted with 30 infertile women with dysmorphic uterus who underwent the novel Hysteroscopic Outpatient Metroplasty to Expand Dysmorphic Uteri (HOME-DU ) technique. Incisions are made on the uterine walls with a 5 Fr bipolar electrode. The procedure was conducted in outpatients under conscious sedation, using a 5-mm office hysteroscope. The technique was successful in all cases without complications. A net increase of uterine volume was found, as measured at hysteroscopy and three-dimensional transvaginal ultrasound (P < 0.001). Uterine morphology improved in all patients but one. At mean follow-up of 15 months, clinical pregnancy rate was 57% and term delivery rate 65%. These early data support HOME-DU as safe and effective in expanding the volume and normalizing the appearance of the uterine cavity of dysmorphic uteri. Although the cohort was small, pregnancy and live births outcomes were favourable in this poor-prognosis group, implying desirable benefits, which should be compared with other techniques. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Cerebro-facio-thoracic dysplasia (Pascual-Castroviejo syndrome): Identification of a novel mutation, use of facial recognition analysis, and review of the literature

PubMed Central

Tender, Jennifer A.F.; Ferreira, Carlos R.

2018-01-01

BACKGROUND: Cerebro-facio-thoracic dysplasia (CFTD) is a rare, autosomal recessive disorder characterized by facial dysmorphism, cognitive impairment and distinct skeletal anomalies and has been linked to the TMCO1 defect syndrome. OBJECTIVE: To describe two siblings with features consistent with CFTD with a novel homozygous p.Arg114* pathogenic variant in the TMCO1 gene. METHODS: We conducted a literature review and summarized the clinical features and laboratory results of two siblings with a novel pathogenic variant in the TMCO1 gene. Facial recognition analysis was utilized to assess the specificity of facial traits. CONCLUSION: The novel homozygous p.Arg114* pathogenic variant in the TMCO1 gene is responsible for the clinical features of CFTD in two siblings. Facial recognition analysis allows unambiguous distinction of this syndrome against controls. PMID:29682451

Neurological presentation of three patients with 22q11 deletion (CATCH 22 syndrome).

PubMed

Roubertie, A; Semprino, M; Chaze, A M; Rivier, F; Humbertclaude, V; Cheminal, R; Lefort, G; Echenne, B

2001-12-01

Chromosome 22q11 deletion (CATCH 22 syndrome or velocardiofacial syndrome) is one of the most frequent chromosomal syndromes. Neurological features other than cognitive disorders are probably the least-described part of the expanding phenotype of the 22q11 deletion. We report the neurological features of three unrelated children with a de novo deletion: one patient with an autistic disorder, a second patient with hypocalcaemic neonatal seizures and unusual persistent epileptic focus at electroencephalographic follow-up, and a third patient with atypical absence epilepsy. These observations enlarge the clinical and neurological spectrum of the 22q11 deletion. Awareness of such cases is necessary, and a diagnosis of the 22q11 deletion should be suspected in children with common neurological features associated with severe or mild dysmorphism. Diagnosis of the 22q11 deletion should be confirmed by fluorescence in situ hybridization analysis associated with standard chromosomal analysis.

Modular Cognitive-Behavioral Therapy for Body Dysmorphic Disorder

ERIC Educational Resources Information Center

Wilhelm, Sabine; Phillips, Katharine A.; Fama, Jeanne M.; Greenberg, Jennifer L.; Steketee, Gail

2011-01-01

This study pilot tested a newly developed modular cognitive-behavioral therapy (CBT) treatment manual for body dysmorphic disorder (BDD). We tested feasibility, acceptability, and treatment outcome in a sample of 12 adults with primary BDD. Treatment was delivered in weekly individual sessions over 18 or 22 weeks. Standardized clinician ratings…

Visual processing in anorexia nervosa and body dysmorphic disorder: similarities, differences, and future research directions

PubMed Central

Madsen, Sarah K.; Bohon, Cara; Feusner, Jamie D.

2013-01-01

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are psychiatric disorders that involve distortion of the experience of one’s physical appearance. In AN, individuals believe that they are overweight, perceive their body as “fat,” and are preoccupied with maintaining a low body weight. In BDD, individuals are preoccupied with misperceived defects in physical appearance, most often of the face. Distorted visual perception may contribute to these cardinal symptoms, and may be a common underlying phenotype. This review surveys the current literature on visual processing in AN and BDD, addressing lower- to higher-order stages of visual information processing and perception. We focus on peer-reviewed studies of AN and BDD that address ophthalmologic abnormalities, basic neural processing of visual input, integration of visual input with other systems, neuropsychological tests of visual processing, and representations of whole percepts (such as images of faces, bodies, and other objects). The literature suggests a pattern in both groups of over-attention to detail, reduced processing of global features, and a tendency to focus on symptom-specific details in their own images (body parts in AN, facial features in BDD), with cognitive strategy at least partially mediating the abnormalities. Visuospatial abnormalities were also evident when viewing images of others and for non-appearance related stimuli. Unfortunately no study has directly compared AN and BDD, and most studies were not designed to disentangle disease-related emotional responses from lower-order visual processing. We make recommendations for future studies to improve the understanding of visual processing abnormalities in AN and BDD. PMID:23810196

Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD).

PubMed

Wozniak, Jeffrey R; Mueller, Bryon A; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lim, Kelvin O; Riley, Edward P; Sowell, Elizabeth R

2017-10-01

Consistent with well-documented structural and microstructural abnormalities in prenatal alcohol exposure (PAE), recent studies suggest that functional connectivity (FC) may also be disrupted. We evaluated whole-brain FC in a large multi-site sample, examined its cognitive correlates, and explored its potential to objectively identify neurodevelopmental abnormality in individuals without definitive dysmorphic features. Included were 75 children with PAE and 68 controls from four sites. All participants had documented heavy prenatal alcohol exposure. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Resting-state FC was examined using whole-brain graph theory metrics to characterize each individual's connectivity. Although whole-brain FC metrics did not discriminate prenatally-exposed from unexposed overall, atypical FC (> 1 standard deviation from the grand mean) was significantly more common (2.7 times) in the PAE group vs. In a subset of 55 individuals (PAE and controls) whose dysmorphology examination could not definitively characterize them as either Fetal Alcohol Syndrome (FAS) or non-FAS, atypical FC was seen in 27 % of the PAE group, but 0 % of controls. Across participants, a 1 % difference in local network efficiency was associated with a 36 point difference in global cognitive functioning. Whole-brain FC metrics have potential to identify individuals with objective neurodevelopmental abnormalities from prenatal alcohol exposure. When applied to individuals unable to be classified as FAS or non-FAS from dysmorphology alone, these measures separate prenatally-exposed from non-exposed with high specificity.

Body Dysmorphic Disorder: Some Key Issues for DSM-V

PubMed Central

Phillips, Katharine A.; Wilhelm, Sabine; Koran, Lorrin M.; Didie, Elizabeth R.; Fallon, Brian A.; Feusner, Jamie; Stein, Dan J.

2014-01-01

Body dysmorphic disorder (BDD), a distressing or impairing preoccupation with an imagined or slight defect in appearance, has been described for more than a century and increasingly studied over the past several decades. This paper provides a focused review of issues pertaining to BDD that are relevant to DSM-V. The review presents a number of options and preliminary recommendations to be considered for DSM-V: 1) Criterion A may benefit from some rewording, without changing its focus or meaning; 2) Potential disadvantages of adding a new criterion to reflect BDD compulsive behaviors seem to outweigh potential advantages, but adding such a criterion remains an option that can be considered; 3) A clinical significance criterion seems necessary for BDD to differentiate it from normal appearance concerns; 4) BDD and eating disorders have some overlapping features and need to be differentiated; some minor changes to DSM-IV’s criterion C are suggested; 5) BDD should not be broadened to include body integrity identity disorder (apotemnophilia) or olfactory reference syndrome; 6) There is no compelling evidence for including diagnostic features or subtypes that are specific to gender-related, age-related, or cultural manifestations of BDD; 7) Adding muscle dysmorphia as a specifier may have clinical utility; and 8) The ICD-10 criteria for hypochondriacal disorder are not suitable for BDD, and there is no empirical evidence that BDD and hypochondriasis are the same disorder. The issue of how BDD’s delusional variant should be classified in DSM-V is briefly discussed and will be addressed more extensively in a separate paper. PMID:20533368

Refinement of the deletion in 8q22.2-q22.3: the minimum deletion size at 8q22.3 related to intellectual disability and epilepsy.

PubMed

Kuroda, Yukiko; Ohashi, Ikuko; Saito, Toshiyuki; Nagai, Jun-ichi; Ida, Kazumi; Naruto, Takuya; Iai, Mizue; Kurosawa, Kenji

2014-08-01

Kuechler et al. [2011] reported five patients with interstitial deletions in 8q22.2-q22.3 who had intellectual disability, epilepsy, and dysmorphic features. We report on a new patient with the smallest overlapping de novo deletion in 8q22.3 and refined the phenotype. The proposita was an 8-year-old girl, who developed seizures at 10 months, and her epileptic seizure became severe and difficult to control with antiepileptic drugs. She also exhibited developmental delay and walked alone at 24 months. She was referred to us for evaluation for developmental delay and epilepsy at the age of 8 years. She had intellectual disability (IQ 37 at 7 years) and autistic behavior, and spoke two word sentences at 8 years. She had mild dysmorphic features, including telecanthus and thick vermilion of the lips. Array comparative genomic hybridization detected a 1.36 Mb deletion in 8q22.3 that encompassed RRM2B and NCALD, which encode the small subunit of p53-inducible ribonucleotide reductase and neurocalcin delta in the neuronal calcium sensor family of calcium-binding proteins, respectively. The minimum overlapping region between the present and previously reported patients is considered to be a critical region for the phenotype of the deletion in 8q22.3. We suggest that the deletion in 8q22.3 may represent a clinically recognizable condition, which is characterized by intellectual disability and epilepsy. © 2014 Wiley Periodicals, Inc.

A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations.

PubMed

Iype, Thomas; Alakbarzade, Vafa; Iype, Mary; Singh, Royana; Sreekantan-Nair, Ajith; Chioza, Barry A; Mohapatra, Tribhuvan M; Baple, Emma L; Patton, Michael A; Warner, Thomas T; Proukakis, Christos; Kulkarni, Abhi; Crosby, Andrew H

2015-11-10

The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance. We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features. We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals.

Body dysmorphic disorder: some key issues for DSM-V.

PubMed

Phillips, Katharine A; Wilhelm, Sabine; Koran, Lorrin M; Didie, Elizabeth R; Fallon, Brian A; Feusner, Jamie; Stein, Dan J

2010-06-01

Body dysmorphic disorder (BDD), a distressing or impairing preoccupation with an imagined or slight defect in appearance, has been described for more than a century and increasingly studied over the past several decades. This article provides a focused review of issues pertaining to BDD that are relevant to DSM-V. The review presents a number of options and preliminary recommendations to be considered for DSM-V: (1) Criterion A may benefit from some rewording, without changing its focus or meaning; (2) There are both advantages and disadvantages to adding a new criterion to reflect compulsive BDD behaviors; this possible addition requires further consideration; (3) A clinical significance criterion seems necessary for BDD to differentiate it from normal appearance concerns; (4) BDD and eating disorders have some overlapping features and need to be differentiated; some minor changes to DSM-IV's criterion C are suggested; (5) BDD should not be broadened to include body integrity identity disorder (apotemnophilia) or olfactory reference syndrome; (6) There is no compelling evidence for including diagnostic features or subtypes that are specific to gender-related, age-related, or cultural manifestations of BDD; (7) Adding muscle dysmorphia as a specifier may have clinical utility; and (8) The ICD-10 criteria for hypochondriacal disorder are not suitable for BDD, and there is no empirical evidence that BDD and hypochondriasis are the same disorder. The issue of how BDD's delusional variant should be classified in DSM-V is briefly discussed and will be addressed more extensively in a separate article. (c) 2010 Wiley-Liss, Inc.

Antimicrobial surfaces for craniofacial implants: state of the art.

PubMed

Actis, Lisa; Gaviria, Laura; Guda, Teja; Ong, Joo L

2013-04-01

In an attempt to regain function and aesthetics in the craniofacial region, different biomaterials, including titanium, hydroxyapatite, biodegradable polymers and composites, have been widely used as a result of the loss of craniofacial bone. Although these materials presented favorable success rates, osseointegration and antibacterial properties are often hard to achieve. Although bone-implant interactions are highly dependent on the implant's surface characteristics, infections following traumatic craniofacial injuries are common. As such, poor osseointegration and infections are two of the many causes of implant failure. Further, as increasingly complex dental repairs are attempted, the likelihood of infection in these implants has also been on the rise. For these reasons, the treatment of craniofacial bone defects and dental repairs for long-term success remains a challenge. Various approaches to reduce the rate of infection and improve osseointegration have been investigated. Furthermore, recent and planned tissue engineering developments are aimed at improving the implants' physical and biological properties by improving their surfaces in order to develop craniofacial bone substitutes that will restore, maintain and improve tissue function. In this review, the commonly used biomaterials for craniofacial bone restoration and dental repair, as well as surface modification techniques, antibacterial surfaces and coatings are discussed.

Exploring the Medical and Psychosocial Concerns of Adolescents and Young Adults With Craniofacial Microsomia: A Qualitative Study.

PubMed

Hamilton, Kayla V; Ormond, Kelly E; Moscarello, Tia; Bruce, Janine S; Bereknyei Merrell, Sylvia; Chang, Kay W; Bernstein, Jonathan A

2018-01-01

This study explores the experiences of adolescents and young adults with craniofacial microsomia, including the impact of growing up with this craniofacial condition on daily life and sense of self. The results may guide future research on optimally supporting individuals with craniofacial microsomia during this critical life phase. Participants were recruited through a craniofacial center, online patient support groups, and social media sites. Eleven individual semistructured interviews with participants between 12 and 22 years old were conducted by a single interviewer, transcribed, iteratively coded, and thematically analyzed. Five themes were evident in the data: (1) impact on personal growth and character development, (2) negative psychosocial impact, (3) deciding to hide or reveal the condition, (4) desire to make personal surgical decisions, and (5) struggles with hearing loss. We identified both medical and psychosocial concerns prevalent among adolescents with craniofacial microsomia. Although adolescents with craniofacial microsomia exhibit considerable resilience, the challenges they face impact their sense of self and should be addressed through psychosocial support and counseling. Further research should investigate the potential benefit of the wider use of hearing aids, as well as the involvement of patients in decision-making about reconstructive ear surgery.

Adult psychological functioning of individuals born with craniofacial anomalies.

PubMed

Sarwer, D B; Bartlett, S P; Whitaker, L A; Paige, K T; Pertschuk, M J; Wadden, T A

1999-02-01

This study represents an initial investigation into the adult psychological functioning of individuals born with craniofacial disfigurement. A total of 24 men and women born with a craniofacial anomaly completed paper and pencil measures of body image dissatisfaction, self-esteem, quality of life, and experiences of discrimination. An age- and gender-matched control group of 24 non-facially disfigured adults also completed the measures. As expected, craniofacially disfigured adults reported greater dissatisfaction with their facial appearance than did the control group. Craniofacially disfigured adults also reported significantly lower levels of self-esteem and quality of life. Dissatisfaction with facial appearance, self-esteem, and quality of life were related to self-ratings of physical attractiveness. More than one-third of craniofacially disfigured adults (38 percent) reported experiences of discrimination in employment or social settings. Among disfigured adults, psychological functioning was not related to number of surgeries, although the degree of residual facial deformity was related to increased dissatisfaction with facial appearance and greater experiences of discrimination. Results suggest that adults who were born with craniofacial disfigurement, as compared with non-facially disfigured adults, experience greater dissatisfaction with facial appearance and lower self-esteem and quality of life; however, these experiences do not seem to be universal.

Anteverted internal auditory canal as an inner ear anomaly in patients with craniofacial microsomia.

PubMed

L'Heureux-Lebeau, Bénédicte; Saliba, Issam

2014-09-01

Craniofacial microsomia involves structure of the first and second branchial arches. A wide range of ear anomalies, affecting external, middle and inner ear, has been described in association with this condition. We report three cases of anteverted internal auditory canal in patients presenting craniofacial microsomia. This unique internal auditory canal orientation was found on high-resolution computed tomography of the temporal bones. This internal auditory canal anomaly is yet unreported in craniofacial anomalies. Copyright © 2014. Published by Elsevier Ireland Ltd.

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

Hegman, K.; Spikes, A.S.; Orr-Urteger, A.

A genetic evaluation was requested for a 6 week old infant with multiple congenital malformations including mild craniofacial anomalies, truncal hypotonia, hypospadias and a VSD. Blood obtained for chromosome analysis revealed an abnormal chromosome 4. Paternal chromosome analysis showed a 46,XY,inv ins(3;4)(p21.32;q25q21.2),inv(4)(p15.3q21.3) karyotype. Therefore, the proband`s chromosome 4 was the unbalanced product of this insertional translocation from the father resulting in partial monosomy 4q. Additionally, the derivative 4 had a pericentric inversion which was also seen in the father`s chromosome 4. During genetic counseling, the proband`s 2 year-old brother was evaluated. Although he was not felt to be dysmorphic, hemore » was described as having impulsive behavior. Chromosome analysis on this child revealed 46,XY,der(3)inv ins(3;4)(p21.32;q25q21.2)pat. This karyotype results in partial trisomy 4q. FISH using two-color {open_quotes}painting{close_quotes} probes for chromosomes 3 and 4 confirmed the G-banded interpretation in this family. The segregation seen in this family was due to adjacent I segregation with both reciprocal products observed in the two children. Few patients with partial 4q trisomy or partial 4q monosomy have been described in the literature. This family revealed both possible unbalanced products from adjacent I segregation with partial 4q monosomy showing multiple congenital anomalies and partial 4q trisomy showing very few phenotypic abnormalities.« less

Mice Haploinsufficient for Ets1 and Fli1 Display Middle Ear Abnormalities and Model Aspects of Jacobsen Syndrome.

PubMed

Carpinelli, Marina R; Kruse, Elizabeth A; Arhatari, Benedicta D; Debrincat, Marlyse A; Ogier, Jacqueline M; Bories, Jean-Christophe; Kile, Benjamin T; Burt, Rachel A

2015-07-01

E26 transformation-specific 1 (ETS1) and friend leukemia integration 1 (FLI1) are members of the ETS family of transcription factors, of which there are 28 in humans. Both genes are hemizygous in Jacobsen syndrome, an 11q contiguous gene deletion disorder involving thrombocytopenia, facial dysmorphism, growth and mental retardation, malformation of the heart and other organs, and hearing impairment associated with recurrent ear infections. To determine whether any of these defects are because of hemizygosity for ETS1 and FLI1, we characterized the phenotype of mice heterozygous for mutant alleles of Ets1 and Fli1. Fli1(+/-) mice displayed mild thrombocytopenia, as did Ets1(+/-)Fli1(+/-) animals. Fli1(+/-) and Ets1(+/-)Fli1(+/-) mice also displayed craniofacial abnormalities, including a small middle ear cavity, short nasal bone, and malformed interface between the nasal bone process and cartilaginous nasal septum. They exhibited hearing impairment, otitis media, fusions of ossicles to the middle ear wall, and deformed stapes. Hearing impairment was more penetrant and stapes malformations were more severe in Ets1(+/-)Fli1(+/-) mice than in Fli1(+/-) mice, indicating partial functional redundancy of these transcription factors during auditory development. Our findings indicate that the short nose, otitis media, and hearing impairment in Jacobsen syndrome are likely because of hemizygosity for ETS1 and FLI1. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Rapamycin Prevents Seizures After Depletion of STRADA in a Rare Neurodevelopmental Disorder

PubMed Central

Parker, Whitney E.; Orlova, Ksenia A.; Parker, William H.; Birnbaum, Jacqueline F.; Krymskaya, Vera P.; Goncharov, Dmitry A.; Baybis, Marianna; Helfferich, Jelte; Okochi, Kei; Strauss, Kevin A.; Crino, Peter B.

2013-01-01

A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heterotopic neurons in subcortical white matter and subependymal regions. PMSE is caused by a homozygous deletion of exons 9 to 13 of the LYK5/STRADA gene, which encodes the pseudokinase STRADA, an upstream inhibitor of mammalian target of rapamycin complex 1 (mTORC1). We show that disrupted pathfinding in migrating mouse neural progenitor cells in vitro caused by STRADA depletion is prevented by mTORC1 inhibition with rapamycin or inhibition of its downstream effector p70 S6 kinase (p70S6K) with the drug PF-4708671 (p70S6Ki). We demonstrate that rapamycin can rescue aberrant cortical lamination and heterotopia associated with STRADA depletion in the mouse cerebral cortex. Constitutive mTORC1 signaling and a migration defect observed in fibroblasts from patients with PMSE were also prevented by mTORC1 inhibition. On the basis of these preclinical findings, we treated five PMSE patients with sirolimus (rapamycin) without complication and observed a reduction in seizure frequency and an improvement in receptive language. Our findings demonstrate a mechanistic link between STRADA loss and mTORC1 hyperactivity in PMSE, and suggest that mTORC1 inhibition may be a potential treatment for PMSE as well as other mTOR-associated neurodevelopmental disorders. PMID:23616120

Unilateral agenesis of internal carotid artery associated with congenital combined pituitary hormone deficiency and pituitary stalk interruption without HESX1, LHX4 or OTX2 mutation: a case report.

PubMed

Lamine, Faïza; Kanoun, Faouzi; Chihaoui, Melika; Saveanu, Alexandru; Menif, Emna; Barlier, Anne; Enjalbert, Alain; Brue, Thierry; Slimane, Hédia

2012-12-01

Agenesis of internal carotid artery (ICA) is an unusual finding in subjects with congenital Combined Pituitary hormone deficiency (CPHD) with only nine cases being reported to date but to our best knowledge none of them was genetically investigated. A 10-years old girl presented with severe growth failure (height 103 cm) with substantial bone age delay (3 years). She had no history of perinatal insults or familial CPHD. There was no evidence of mental retardation or craniofacial dysmorphism or ophtalmological abnormalities. She was first diagnosed with GH and TSH deficiency. Cerebral magnetic resonance imaging (MRI) showed hypoplastic anterior pituitary, flat sella turcica, absent pituitary stalk with ectopic posterior pituitary as well as agenesis of the left ICA and the left carotid canal. Genomic analysis of pituitary transcription factor HESX1, LHX4 and OTX2 showed no mutations. Treatment with GH and thyroxine was started. The patient remained free of neurovascular symptoms for 5 years but she presented at the age of 15 years with delayed puberty related to an evolving gonadotropin deficiency. ICA agenesis associated with CPHD is unusual and is often asymptomatic in children. Since the CPHD with pituitary stalk interruption cannot be due to HESX1, LHX4 or OTX2 mutation in our case, other pathogenetic mechanisms may be responsible for CPHD associated with unilateral ICA agenesis.

76 FR 38193 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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2011-06-29

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76 FR 28793 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

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2011-05-18

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75 FR 52537 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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2010-08-26

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Ultrasonic measurement of facial tissue depth in a Northern Chinese Han population.

PubMed

Jia, Linpei; Qi, Baiyu; Yang, Jingyan; Zhang, Weiguang; Lu, Yingqiang; Zhang, Hong-Liang

2016-02-01

In forensic anthropology, facial soft tissue depth measurement is crucial for craniofacial reconstruction technology, which is based on the morphological features of human faces to rebuild appearances of decedents, helps forensic scientists to identify the nameless bone. We measured the facial tissue depth of 135 young subjects from northern China whereby revealing the relationship among tissue depth, sex and BMI as well as providing data for craniofacial reconstruction in forensic science. All the volunteers are healthy medical students including 64 males and 71 females. Ultrasound was used to measure 19 points across the face evenly distributed in 6 regions including the eye, nose, mouth, cheek, jaw and chin. Our results indicate that tissue thickness at 11 points of females and 11 points of males are related to BMI. A majority of points are thicker in females than those of males. Further comparisons with data of American and European population show an apparent diversity in both genders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The old and new face of craniofacial research: How animal models inform human craniofacial genetic and clinical data.

PubMed

Van Otterloo, Eric; Williams, Trevor; Artinger, Kristin Bruk

2016-07-15

The craniofacial skeletal structures that comprise the human head develop from multiple tissues that converge to form the bones and cartilage of the face. Because of their complex development and morphogenesis, many human birth defects arise due to disruptions in these cellular populations. Thus, determining how these structures normally develop is vital if we are to gain a deeper understanding of craniofacial birth defects and devise treatment and prevention options. In this review, we will focus on how animal model systems have been used historically and in an ongoing context to enhance our understanding of human craniofacial development. We do this by first highlighting "animal to man" approaches; that is, how animal models are being utilized to understand fundamental mechanisms of craniofacial development. We discuss emerging technologies, including high throughput sequencing and genome editing, and new animal repository resources, and how their application can revolutionize the future of animal models in craniofacial research. Secondly, we highlight "man to animal" approaches, including the current use of animal models to test the function of candidate human disease variants. Specifically, we outline a common workflow deployed after discovery of a potentially disease causing variant based on a select set of recent examples in which human mutations are investigated in vivo using animal models. Collectively, these topics will provide a pipeline for the use of animal models in understanding human craniofacial development and disease for clinical geneticist and basic researchers alike. Copyright © 2016 Elsevier Inc. All rights reserved.

Altered Astrocyte-Neuron Interactions and Epileptogenesis in Tuberous Sclerosis Complex Disorder

DTIC Science & Technology

2013-06-01

mouse brain Phospho-S6 staining revealed a striking dysmorphic appearance and increased cell size in the TSC1CKO cortex (Figs. 3). These enlarged...TSC1CKO mice. B A 11 6. Increased cell size of TSC1CKO astrocytes Increased numbers of astrocytes, many with enlarged and dysmorphic shapes, have

Cognitive-Behavioral Body Image Therapy for Body Dysmorphic Disorder.

ERIC Educational Resources Information Center

Rosen, James C.; And Others

1995-01-01

Randomly assigned 54 body dysmorphic disorder (BDD) subjects to cognitive behavior therapy or no treatment. BDD symptoms were significantly decreased in therapy subjects and the disorder was eliminated in 82 percent of cases at posttreatment and 77 percent at follow-up. Subjects' overall psychological symptoms and self-esteem also improved. (RJM)

Clinical Application of a Behavioral Model for the Treatment of Body Dysmorphic Disorder

ERIC Educational Resources Information Center

Rabinowitz, Dena; Neziroglu, Fugen; Roberts, Marty

2007-01-01

Body dysmorphic disorder (BDD) is characterized by an obsessive concern over a perceived flaw in bodily appearance. If a minor flaw does exist, the patient displays unwarranted distress. This preoccupation typically leads to compulsive behaviors, such as mirror checking or mirror avoiding, camouflaging, and seeking reassurance from others…

Body Dysmorphic Disorder: Easing the Distress of Distortion.

ERIC Educational Resources Information Center

Fore, Cynthia M.

People who suffer from body dysmorphic disorder believe that their body is defected and that this defect makes them ugly. Their distorted body image can be precipitated by many internal and external factors and as a result of their imagined defect, these normal-appearing individuals exhibit self-defeating behaviors. The disorder can lead to the…

Childhood Abuse and Neglect in Body Dysmorphic Disorder

ERIC Educational Resources Information Center

Didie, Elizabeth R.; Tortolani, Christina C.; Pope, Courtney G.; Menard, William; Fay, Christina; Phillips, Katharine A.

2006-01-01

Objective: No published studies have examined childhood abuse and neglect in body dysmorphic disorder (BDD). This study examined the prevalence and clinical correlates of abuse and neglect in individuals with this disorder. Methods: Seventy-five subjects (69.3% female, mean age = 35.4 +/- 12.0) with DSM-IV BDD completed the Childhood Trauma…

[Prevalence of depression and body dysmorphic disorder in patients before functional rhinosurgery].

PubMed

Bender, M; Rustige, L; Lindemann, J

2014-11-01

Psychiatric disorders are known to influence the result of many surgical procedures. Body dysmorphic disorder (BDD) is found in many patients undergoing plastic surgery. The prevalence before functional rhinosurgery has not been examined so far. The aim of this study was to determine the prevalence of depression and BDD before functional rhinosurgery. 201 patients were prospectively examined with a questionnaire before functional rhinosurgery. Beck-Depression-Index was used to rate depression, the PISA body dsymorphic symptom scale was used to evaluate the likelihood that a patient suffers from body dysmoprhic disorder. 186 patients returned a complete questionnaire. In 33.9% showed a mild or strong indication for a body dysmorphic disorder. Patients who were planned to undergo septorhinoplasty had a significantly higher scores in the PISA-scale compared to patients before septoplasty. 1.7% patients were depressive without a significant difference between the planned surgical procedure. Many patients before functional septorhinoplasty show signs of body dysmorphic disorder. Whether this influences the subjective clinical outcome needs to be evaluated in further studies. © Georg Thieme Verlag KG Stuttgart · New York.

Pygmoid Australomelanesian Homo sapiens skeletal remains from Liang Bua, Flores: Population affinities and pathological abnormalities

PubMed Central

Jacob, T.; Indriati, E.; Soejono, R. P.; Hsü, K.; Frayer, D. W.; Eckhardt, R. B.; Kuperavage, A. J.; Thorne, A.; Henneberg, M.

2006-01-01

Liang Bua 1 (LB1) exhibits marked craniofacial and postcranial asymmetries and other indicators of abnormal growth and development. Anomalies aside, 140 cranial features place LB1 within modern human ranges of variation, resembling Australomelanesian populations. Mandibular and dental features of LB1 and LB6/1 either show no substantial deviation from modern Homo sapiens or share features (receding chins and rotated premolars) with Rampasasa pygmies now living near Liang Bua Cave. We propose that LB1 is drawn from an earlier pygmy H. sapiens population but individually shows signs of a developmental abnormality, including microcephaly. Additional mandibular and postcranial remains from the site share small body size but not microcephaly. PMID:16938848

77 FR 59199 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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2013-07-02

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Craniofacial morphology of Homo floresiensis: description, taxonomic affinities, and evolutionary implication.

PubMed

Kaifu, Yousuke; Baba, Hisao; Sutikna, Thomas; Morwood, Michael J; Kubo, Daisuke; Saptomo, E Wahyu; Jatmiko; Awe, Rokhus Due; Djubiantono, Tony

2011-12-01

This paper describes in detail the external morphology of LB1/1, the nearly complete and only known cranium of Homo floresiensis. Comparisons were made with a large sample of early groups of the genus Homo to assess primitive, derived, and unique craniofacial traits of LB1 and discuss its evolution. Principal cranial shape differences between H. floresiensis and Homo sapiens are also explored metrically. The LB1 specimen exhibits a marked reductive trend in its facial skeleton, which is comparable to the H. sapiens condition and is probably associated with reduced masticatory stresses. However, LB1 is craniometrically different from H. sapiens showing an extremely small overall cranial size, and the combination of a primitive low and anteriorly narrow vault shape, a relatively prognathic face, a rounded oval foramen that is greatly separated anteriorly from the carotid canal/jugular foramen, and a unique, tall orbital shape. Whereas the neurocranium of LB1 is as small as that of some Homo habilis specimens, it exhibits laterally expanded parietals, a weak suprameatal crest, a moderately flexed occipital, a marked facial reduction, and many other derived features that characterize post-habilis Homo. Other craniofacial characteristics of LB1 include, for example, a relatively narrow frontal squama with flattened right and left sides, a marked frontal keel, posteriorly divergent temporal lines, a posteriorly flexed anteromedial corner of the mandibular fossa, a bulbous lateral end of the supraorbital torus, and a forward protruding maxillary body with a distinct infraorbital sulcus. LB1 is most similar to early Javanese Homo erectus from Sangiran and Trinil in these and other aspects. We conclude that the craniofacial morphology of LB1 is consistent with the hypothesis that H. floresiensis evolved from early Javanese H. erectus with dramatic island dwarfism. However, further field discoveries of early hominin skeletal remains from Flores and detailed analyses of the finds are needed to understand the evolutionary history of this endemic hominin species. Copyright © 2011 Elsevier Ltd. All rights reserved.

Musculocontractural Ehlers–Danlos syndrome and neurocristopathies: dermatan sulfate is required for Xenopus neural crest cells to migrate and adhere to fibronectin

PubMed Central

Gouignard, Nadège; Maccarana, Marco; Strate, Ina; von Stedingk, Kristoffer; Malmström, Anders

2016-01-01

ABSTRACT Of all live births with congenital anomalies, approximately one-third exhibit deformities of the head and face. Most craniofacial disorders are associated with defects in a migratory stem and progenitor cell population, which is designated the neural crest (NC). Musculocontractural Ehlers–Danlos syndrome (MCEDS) is a heritable connective tissue disorder with distinct craniofacial features; this syndrome comprises multiple congenital malformations that are caused by dysfunction of dermatan sulfate (DS) biosynthetic enzymes, including DS epimerase-1 (DS-epi1; also known as DSE). Studies in mice have extended our understanding of DS-epi1 in connective tissue maintenance; however, its role in fetal development is not understood. We demonstrate that DS-epi1 is important for the generation of isolated iduronic acid residues in chondroitin sulfate (CS)/DS proteoglycans in early Xenopus embryos. The knockdown of DS-epi1 does not affect the formation of early NC progenitors; however, it impairs the correct activation of transcription factors involved in the epithelial–mesenchymal transition (EMT) and reduces the extent of NC cell migration, which leads to a decrease in NC-derived craniofacial skeleton, melanocytes and dorsal fin structures. Transplantation experiments demonstrate a tissue-autonomous role for DS-epi1 in cranial NC cell migration in vivo. Cranial NC explant and single-cell cultures indicate a requirement of DS-epi1 in cell adhesion, spreading and extension of polarized cell processes on fibronectin. Thus, our work indicates a functional link between DS and NC cell migration. We conclude that NC defects in the EMT and cell migration might account for the craniofacial anomalies and other congenital malformations in MCEDS, which might facilitate the diagnosis and development of therapies for this distressing condition. Moreover, the presented correlations between human DS-epi1 expression and gene sets of mesenchymal character, invasion and metastasis in neuroblastoma and malignant melanoma suggest an association between DS and NC-derived cancers. PMID:27101845

Musculocontractural Ehlers-Danlos syndrome and neurocristopathies: dermatan sulfate is required for Xenopus neural crest cells to migrate and adhere to fibronectin.

PubMed

Gouignard, Nadège; Maccarana, Marco; Strate, Ina; von Stedingk, Kristoffer; Malmström, Anders; Pera, Edgar M

2016-06-01

Of all live births with congenital anomalies, approximately one-third exhibit deformities of the head and face. Most craniofacial disorders are associated with defects in a migratory stem and progenitor cell population, which is designated the neural crest (NC). Musculocontractural Ehlers-Danlos syndrome (MCEDS) is a heritable connective tissue disorder with distinct craniofacial features; this syndrome comprises multiple congenital malformations that are caused by dysfunction of dermatan sulfate (DS) biosynthetic enzymes, including DS epimerase-1 (DS-epi1; also known as DSE). Studies in mice have extended our understanding of DS-epi1 in connective tissue maintenance; however, its role in fetal development is not understood. We demonstrate that DS-epi1 is important for the generation of isolated iduronic acid residues in chondroitin sulfate (CS)/DS proteoglycans in early Xenopus embryos. The knockdown of DS-epi1 does not affect the formation of early NC progenitors; however, it impairs the correct activation of transcription factors involved in the epithelial-mesenchymal transition (EMT) and reduces the extent of NC cell migration, which leads to a decrease in NC-derived craniofacial skeleton, melanocytes and dorsal fin structures. Transplantation experiments demonstrate a tissue-autonomous role for DS-epi1 in cranial NC cell migration in vivo Cranial NC explant and single-cell cultures indicate a requirement of DS-epi1 in cell adhesion, spreading and extension of polarized cell processes on fibronectin. Thus, our work indicates a functional link between DS and NC cell migration. We conclude that NC defects in the EMT and cell migration might account for the craniofacial anomalies and other congenital malformations in MCEDS, which might facilitate the diagnosis and development of therapies for this distressing condition. Moreover, the presented correlations between human DS-epi1 expression and gene sets of mesenchymal character, invasion and metastasis in neuroblastoma and malignant melanoma suggest an association between DS and NC-derived cancers. © 2016. Published by The Company of Biologists Ltd.

Sex-specific differences of craniofacial traits in Croatia: the impact of environment in a small geographic area.

PubMed

Buretic-Tomljanovic, Alena; Giacometti, Jasminka; Ostojic, Sasa; Kapovic, Miljenko

2007-01-01

Craniometric variation in humans reflects different genetic and environmental influences. Long-term climatic adaptation is less likely to show an impact on size and shape variation in a small local area than at the global level. The aim of this work was to assess the contribution of the particular environmental factors to body height and craniofacial variability in a small geographic area of Croatia. A total of 632 subjects, aged 18-21, participated in the survey. Body height, head length, head breadth, head height, head circumference, cephalic index, morphological face height, face breadth, and facial index were analysed regarding geographic, climatic and dietary conditions in different regions of the country, and correlated with the specific climatic variables (cumulative multiyear sunshine duration, cumulative multiyear average precipitation, multiyear average air temperatures) and calcium concentrations in drinking water. Significant differences between groups classified according to geographic, climatic or dietary affiliation, and the impact of the environmental predictors on the variation in the investigated traits were assessed using multiple forward stepwise regression analyses. Higher body height measures in both sexes were significantly correlated with Mediterranean diet type. Mediterranean diet type also contributed to higher head length and head circumference measures in females. Cephalic index values correlated to geographic regions in both sexes, showing an increase from southern to eastern Croatia. In the same direction, head length significantly decreased in males and head breadth increased in females. Mediterranean climate was associated with higher and narrower faces in females. The analysis of the particular climatic variables did not reveal a significant influence on body height in either sex. Concurrently, climatic features influenced all craniofacial traits in females and only head length and facial index in males. Mediterranean climate, characterized by higher average sunshine duration, higher average precipitation and higher average air temperatures, was associated with longer, higher and narrower skulls, higher head circumference, lower cephalic index, and higher and narrower faces (lower facial index). Calcium concentrations in drinking water did not correlate significantly with any dependent variable. A significant effect of environmental factors on body height and craniofacial variability was found in Croatian young adult population. This effect was more pronounced in females, revealing sex-specific craniofacial differentiation. However, the impact of environment was low and may explain only 1.0-7.32% variation of the investigated traits.

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The society for craniofacial genetics and developmental biology 38th annual meeting.

PubMed

Taneyhill, Lisa A; Hoover-Fong, Julie; Lozanoff, Scott; Marcucio, Ralph; Richtsmeier, Joan T; Trainor, Paul A

2016-07-01

The mission of the Society for Craniofacial Genetics and Developmental Biology (SCGDB) is to promote education, research, and communication about normal and abnormal development of the tissues and organs of the head. The SCGDB welcomes as members undergraduate students, graduate students, post doctoral researchers, clinicians, orthodontists, scientists, and academicians who share an interest in craniofacial biology. Each year our members come together to share their novel findings, build upon, and challenge current knowledge of craniofacial biology. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Orthognathic Surgery in Craniofacial Microsomia: Treatment Algorithm

PubMed Central

Valladares, Salvador; Torrealba, Ramón; Nuñez, Marcelo; Uribe, Francisca

2015-01-01

Summary: Craniofacial microsomia is a broad term that covers a variety of craniofacial malformation conditions that are caused by alterations in the derivatives of the first and second pharyngeal arches. In general terms, diverse therapeutic alternatives are proposed according to the growth stage and the severity of the alteration. When craniofacial growth has concluded, conventional orthognathic surgery (Le Fort I osteotomy, bilateral sagittal split osteotomy, and genioplasty) provides good alternatives for MI and MIIA type cases. Reconstruction of the mandibular ramus and temporomandibular joint before orthognathic surgery is the indicated treatment for cases MIIB and MIII. The goal of this article is to establish a surgical treatment algorithm for orthognathic surgery on patients with craniofacial microsomia, analyzing the points that allow the ideal treatment for each patient to be chosen. PMID:25674375

Partial craniofacial duplication: a review of the literature and case report.

PubMed

Costa, Melinda A; Borzabadi-Farahani, Ali; Lara-Sanchez, Pedro A; Schweitzer, Daniela; Jacobson, Lia; Clarke, Noreen; Hammoudeh, Jeffery; Urata, Mark M; Magee, William P

2014-06-01

Diprosopus (Greek; di-, "two" + prosopon, "face"), or craniofacial duplication, is a rare craniofacial anomaly referring to the complete duplication of facial structures. Partial craniofacial duplication describes a broad spectrum of congenital anomalies, including duplications of the oral cavity. This paper describes a 15 month-old female with a duplicated oral cavity, mandible, and maxilla. A Tessier type 7 cleft, midline meningocele, and duplicated hypophysis were also present. The preoperative evaluation, surgical approach, postoperative results, and a review of the literature are presented. The surgical approach was designed to preserve facial nerve innervation to the reconstructed cheek and mouth. The duplicated mandible and maxilla were excised and the remaining left maxilla was bone grafted. Soft tissue repair included closure of the Tessier type VII cleft. Craniofacial duplication remains a rare entity that is more common in females. The pathophysiology remains incompletely characterized, but is postulated to be due to duplication of the notochord, as well as duplication of mandibular growth centres. While diprosopus is a severe deformity often associated with anencephaly, patients with partial duplication typically benefit from surgical treatment. Managing craniofacial duplication requires a detailed preoperative evaluation as well as a comprehensive, staged treatment plan. Long-term follow up is needed appropriately to address ongoing craniofacial deformity. Published by Elsevier Ltd.

Identification of novel craniofacial regulatory domains located far upstream of SOX9 and disrupted in Pierre Robin sequence

PubMed Central

Gordon, Christopher T.; Attanasio, Catia; Bhatia, Shipra; Benko, Sabina; Ansari, Morad; Tan, Tiong Y.; Munnich, Arnold; Pennacchio, Len A.; Abadie, Véronique; Temple, I. Karen; Goldenberg, Alice; van Heyningen, Veronica; Amiel, Jeanne; FitzPatrick, David; Kleinjan, Dirk A.; Visel, Axel; Lyonnet, Stanislas

2015-01-01

Mutations in the coding sequence of SOX9 cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions and duplications within a ~2 Mb region upstream of SOX9 can recapitulate the CD-DSD phenotype fully or partially, suggesting the existence of an unusually large cis-regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus for isolated PRS at ~1.2-1.5 Mb upstream of SOX9 has been previously reported. The craniofacial regulatory potential within this locus, and within the greater genomic domain surrounding SOX9, remains poorly defined. We report two novel deletions upstream of SOX9 in families with PRS, allowing refinement of the regions harbouring candidate craniofacial regulatory elements. In parallel, ChIP-Seq for p300 binding sites in mouse craniofacial tissue led to the identification of several novel craniofacial enhancers at the SOX9 locus, which were validated in transgenic reporter mice and zebrafish. Notably, some of the functionally validated elements fall within the PRS deletions. These studies suggest that multiple non-coding elements contribute to the craniofacial regulation of SOX9 expression, and that their disruption results in PRS. PMID:24934569

The fusion of craniofacial reconstruction and microsurgery: a functional and aesthetic approach.

PubMed

Broyles, Justin M; Abt, Nicholas B; Shridharani, Sachin M; Bojovic, Branko; Rodriguez, Eduardo D; Dorafshar, Amir H

2014-10-01

Reconstruction of large, composite defects in the craniofacial region has evolved significantly over the past half century. During this time, there have been significant advances in craniofacial and microsurgical surgery. These contributions have often been in parallel; however, over the past 10 years, these two disciplines have begun to overlap more frequently, and the techniques of one have been used to advance the other. In the current review, the authors aim to describe the available options for free tissue reconstruction in craniofacial surgery. A review of microsurgical reconstructive options of aesthetic units within the craniofacial region was undertaken with attention directed toward surgeon flap preference. Anatomical areas analyzed included scalp, calvaria, forehead, frontal sinus, nose, maxilla and midface, periorbita, mandible, lip, and tongue. Although certain flaps such as the ulnar forearm flap and lateral circumflex femoral artery-based flaps were used in multiple reconstructive sites, each anatomical location possesses a unique array of flaps to maximize outcomes. Craniofacial surgery, like plastic surgery, has made tremendous advancements in the past 40 years. With innovations in technology, flap design, and training, microsurgery has become safer, faster, and more commonplace than at any time in history. Reconstructive microsurgery allows the surgeon to be creative in this approach, and free tissue transfer has become a mainstay of modern craniofacial reconstruction.

A complex chromosomal rearrangement involving chromosomes 2, 5, and X in autism spectrum disorder.

PubMed

Griesi-Oliveira, Karina; Moreira, Danielle de Paula; Davis-Wright, Nicole; Sanders, Stephan; Mason, Christopher; Orabona, Guilherme Müller; Vadasz, Estevão; Bertola, Débora Romeo; State, Matthew W; Passos-Bueno, Maria Rita

2012-07-01

Here, we describe a female patient with autism spectrum disorder and dysmorphic features that harbors a complex genetic alteration, involving a de novo balanced translocation t(2;X)(q11;q24), a 5q11 segmental trisomy and a maternally inherited isodisomy on chromosome 5. All the possibly damaging genetic effects of such alterations are discussed. In light of recent findings on ASD genetic causes, the hypothesis that all these alterations might be acting in orchestration and contributing to the phenotype is also considered. Copyright © 2012 Wiley Periodicals, Inc.

How many breaks do we need to CATCH on 22q11?

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

Dallapiccola, B.; Pizzuti, A.; Novelli, G.

1996-07-01

The major clinical manifestations of DiGeorge syndrome (DGS; MIM 188400), which reflect developmental abnormalities of the 3d and 4th pharyngeal pouch derivatives, include thymus- and parathyroid-gland aplasia or hypoplasia and conotruncal cardiac malformations. The additional dysmorphic facial features, such as hypertelorism, cleft lip and palate, bifid uvula, and small/low-set ears, which are also common, presumably reflect the same defect. The DGS phenotype has been associated with chromosome abnormalities and, sometimes, is the effect of teratogenic agents such as retinoic acid and alcohol. 53 refs., 1 fig.

Focal giant cell cardiomyopathy with Beckwith-Wiedemann syndrome.

PubMed

Kapur, S; Kuehl, K S; Midgely, F M; Chandra, R S

1985-01-01

Cardiac involvement in Beckwith-Wiedemann syndrome is mostly limited to mild cardiomegaly. Although these patients have visceromegaly, macroglossia, gigantism, and adrenal cytomegaly, no significant myocardial changes have been described. An infant with dysmorphic features of this syndrome had supraventricular tachycardia since birth. Nodular lesions were present in the right atrium. Morphologically these lesions were composed of hypertrophic myocardial fibers admixed with multinucleated giant cells of myogenic origin. The exact nature of these lesions remains undetermined. It is postulated that hypertrophic myocardial cells may represent cardiac cytomegaly as a manifestation of the accelerated growth potential of cells seen with this syndrome.

[Prader-Willi syndrome].

PubMed

Beccaria, L; Bosio, L; Benzi, F; Bregani, P; Achutegui, I; Chiumello, G; Livieri, C; Trifirò, G; de Toni, T; Iughetti, L; Ragusa, L; Salvatoni, A; Tonini, G; Corrias, A; Crinò, A

1999-01-01

Prader-Willi syndrome (PWS) is the most frequent cause of secondary obesity, characterized by neonatal hypotonia, dysmorphic facies, acromicria, hypogonadism, stunted growth, obesity, behavioural disturbances and cognitive impairment. Clinical diagnosis is confirmed by alteration of imprinted genes on the proximal long arm of chromosome 15 (15q11-13) for deletion, translocation, uniparental disomy for maternal chromosome 15 or imprinting center defect. Methylation test is the most reliable test for diagnosis. This issue explains diagnostic tests, clinical, metabolic, endocrinological features, and the most frequent complications observed in this syndrome. Precocious diagnosis and multidisciplinary approach allow in these patients to prevent the severe obesity and linked complications.

[Mutation analysis of FGFR3 gene in a family featuring hereditary dwarfism].

PubMed

Zhang, Qiong; Jiang, Hai-ou; Quan, Qing-li; Li, Jun; He, Ting; Huang, Xue-shuang

2011-12-01

To investigate the clinical symptoms and potential mutation in FGFR3 gene for a family featuring hereditary dwarfism in order to attain diagnosis and provide prenatal diagnosis. Five patients and two unaffected relatives from the family, in addition with 100 healthy controls, were recruited. Genome DNA was extracted. Exons 10 and 13 of the FGFR3 gene were amplified using polymerase chain reaction (PCR). PCR products were sequenced in both directions. All patients had similar features including short stature, short limbs, lumbar hyperlordosis but normal craniofacial features. A heterozygous mutation G1620T (N540K) was identified in the cDNA from all patients but not in the unaffected relatives and 100 control subjects. A heterozygous G380R mutation was excluded. The hereditary dwarfism featured by this family has been caused by hypochondroplasia (HCH) due to a N540K mutation in the FGFR3 gene.

Clinical spectrum of KIAA2022 pathogenic variants in males: Case report of two boys with KIAA2022 pathogenic variants and review of the literature.

PubMed

Lorenzo, Melissa; Stolte-Dijkstra, Irene; van Rheenen, Patrick; Smith, Ronald Garth; Scheers, Tom; Walia, Jagdeep S

2018-06-01

KIAA2022 is an X-linked intellectual disability (XLID) syndrome affecting males more severely than females. Few males with KIAA2022 variants and XLID have been reported. We present a clinical report of two unrelated males, with two nonsense KIAA2022 pathogenic variants, with profound intellectual disabilities, limited language development, strikingly similar autistic behavior, delay in motor milestones, and postnatal growth restriction. Patient 1, 19-years-old, has long ears, deeply set eyes with keratoconus, strabismus, a narrow forehead, anteverted nares, café-au-lait spots, macroglossia, thick vermilion of the upper and lower lips, and prognathism. He has gastroesophageal reflux, constipation with delayed rectosigmoid colonic transit time, difficulty regulating temperature, several musculoskeletal issues, and a history of one grand mal seizure. Patient 2, 10-years-old, has mild dysmorphic features, therapy resistant vomiting with diminished motility of the stomach, mild constipation, cortical visual impairment with intermittent strabismus, axial hypotonia, difficulty regulating temperature, and cutaneous mastocytosis. Genetic testing identified KIAA2022 variant c.652C > T(p.Arg218*) in Patient 1, and a novel nonsense de novo variant c.2707G > T(p.Glu903*) in Patient 2. We also summarized features of all reported males with KIAA2022 variants to date. This report not only adds knowledge of a novel pathogenic variant to the KIAA2022 variant database, but also likely extends the spectrum by describing novel dysmorphic features and medical conditions including macroglossia, café-au-lait spots, keratoconus, severe cutaneous mastocytosis, and motility problems of the GI tract, which may help physicians involved in the care of patients with this syndrome. Lastly, we describe the power of social media in bringing families with rare medical conditions together. © 2018 Wiley Periodicals, Inc.

30-year International Pediatric Craniofacial Surgery Partnership: Evolution from the “Third World” Forward

PubMed Central

Swanson, Jordan W.; Skirpan, Jan; Stanek, Beata; Kowalczyk, Maciej

2016-01-01

Background: Craniofacial diseases constitute an important component of the surgical disease burden in low- and middle-income countries. The consideration to introduce craniofacial surgery into such settings poses different questions, risks, and challenges compared with cleft or other forms of plastic surgery. We report the evolution, innovations, and challenges of a 30-year international craniofacial surgery partnership. Methods: We retrospectively report a partnership between surgeons at the Uniwersytecki Szpital Dzieciecy in Krakow, Poland, and a North American craniofacial surgeon. We studied patient conditions, treatment patterns, and associated complications, as well as program advancements and limitations as perceived by surgeons, patient families, and hospital administrators. Results: Since partnership inception in 1986, the complexity of cases performed increased gradually, with the first intracranial case performed in 1995. In the most recent 10-year period (2006–2015), 85 patients have been evaluated, with most common diagnoses of Apert syndrome, Crouzon syndrome, and single-suture craniosynostosis. In the same period, 55 major surgical procedures have been undertaken, with LeFort III midface distraction, posterior vault distraction, and frontoorbital advancement performed most frequently. Key innovations have been the employment of craniofacial distraction osteogenesis, the use of Internet communication and digital photography, and increased understanding of how craniofacial morphology may improve in the absence of surgical intervention. Ongoing challenges include prohibitive training pathways for pediatric plastic surgeons, difficulty in coordinating care with surgeons in other institutions, and limited medical and material resources. Conclusion: Safe craniofacial surgery can be introduced and sustained in a resource-limited setting through an international partnership. PMID:27200233

The Relationship between Body Dysmorphic Disorder Behaviors and the Acquired Capability for Suicide

ERIC Educational Resources Information Center

Witte, Tracy K.; Didie, Elizabeth R.; Menard, William; Phillips, Katharine A.

2012-01-01

In a sample of 200 individuals diagnosed with body dysmorphic disorder (BDD), we utilized the interpersonal-psychological theory for suicide as a framework to examine BDD behaviors that might be associated with suicide risk, insofar as they might increase the acquired capability for suicide. We predicted that physically painful BDD behaviors…

A Cognitive-Behavioral Treatment Approach for Body Dysmorphic Disorder

ERIC Educational Resources Information Center

Wilhelm, Sabine; Buhlmann, Ulrike; Hayward, Laura C.; Greenberg, Jennifer L.; Dimaite, Ruta

2010-01-01

Although body dysmorphic disorder (BDD) has been described in the literature for more than a century, there has been only a limited focus on the development of cognitive behavioral treatments for BDD. Our case report provides a detailed description of a course of cognitive behavioral treatment (CBT) for an individual with BDD. The patient was…

Body Dysmorphic Disorder and Other Clinically Significant Body Image Concerns in Adolescent Psychiatric Inpatients: Prevalence and Clinical Characteristics

ERIC Educational Resources Information Center

Dyl, Jennifer; Kittler, Jennifer; Phillips, Katharine A.; Hunt, Jeffrey I.

2006-01-01

Background: This study assessed prevalence and clinical correlates of body dysmorphic disorder (BDD), eating disorders (ED), and other clinically significant body image concerns in 208 consecutively admitted adolescent inpatients. It was hypothesized that adolescents with BDD would have higher levels of depression, anxiety, and suicidality.…

[Body dysmorphic disorder and aesthetic surgery: A systematic review].

PubMed

Kerfant, N; Henry, A-S; Ta, P; Trimaille, A; Philandrianos, C; Hu, W

2015-12-01

Patients suffering from body dysmorphic disorder (BDD) are preoccupied with an imagined or minor defect in appearance that causes significant distress and impairment in social and occupational functioning. Despite a rate of up to 15% of BDD patients reported in cosmetic surgery settings, there is no consensus on the best management for these patients. The main purpose of this article was to conduct a literature review on BDD and cosmetic surgery. Properly trained healthcare professionals in recognizing and diagnosing this pathology is essential for the delivery of quality psychiatric care while taking into account the high prevalence of body dysmorphic disorder patients in cosmetic surgery and the poor outcome of these patients following cosmetic procedures. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

75 FR 82033 - National Institute of Dental and Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... Dental and Craniofacial Research Council. The meeting will be open to the public as indicated below, with... Committee: National Advisory Dental and Craniofacial Research Council. Date: January 24, 2011. Open: 8:30 a...

78 FR 65348 - National Institute of Dental & Craniofacial Research; Amended Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Dental and Craniofacial Research Special Emphasis Panel, October 21, 2013, 9:00 a.m...

75 FR 55592 - National Institute of Dental & Craniofacial Research; Amended Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Advisory Dental and Craniofacial Research Council, September 27, 2010, 8:30 a.m. to September 27...

78 FR 65343 - National Institute of Dental & Craniofacial Research; Amended Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Dental and Craniofacial Research Special Emphasis Panel, October 7, 2013, 10:00 a.m...

Zebrafish Craniofacial Development: A Window into Early Patterning

PubMed Central

Mork, Lindsey; Crump, Gage

2016-01-01

The formation of the face and skull involves a complex series of developmental events mediated by cells derived from the neural crest, endoderm, mesoderm, and ectoderm. Although vertebrates boast an enormous diversity of adult facial morphologies, the fundamental signaling pathways and cellular events that sculpt the nascent craniofacial skeleton in the embryo have proven to be highly conserved from fish to man. The zebrafish Danio rerio, a small freshwater cyprinid fish from eastern India, has served as a popular model of craniofacial development since the 1990s. Unique strengths of the zebrafish model include a simplified skeleton during larval stages, access to rapidly developing embryos for live imaging, and amenability to transgenesis and complex genetics. In this chapter, we describe the anatomy of the zebrafish craniofacial skeleton; its applications as models for the mammalian jaw, middle ear, palate, and cranial sutures; the superior imaging technology available in fish that has provided unprecedented insights into the dynamics of facial morphogenesis; the use of the zebrafish to decipher the genetic underpinnings of craniofacial biology; and finally a glimpse into the most promising future applications of zebrafish craniofacial research. PMID:26589928

The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival

PubMed Central

Dworkin, Sebastian; Boglev, Yeliz; Owens, Harley; Goldie, Stephen J.

2016-01-01

Craniofacial defects (CFD) are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog (Shh), a vertebrate orthologue of Drosophila hedgehog, is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla) and lower jaw (mandible). PMID:29615588

The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival.

PubMed

Dworkin, Sebastian; Boglev, Yeliz; Owens, Harley; Goldie, Stephen J

2016-08-03

Craniofacial defects (CFD) are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog ( Shh ), a vertebrate orthologue of Drosophila hedgehog , is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla) and lower jaw (mandible).

Involuntary craniofacial lingual movements in intensive care-acquired quadriplegia.

PubMed

Cartagena, A M; Jog, M; Young, G B

2012-02-01

The syndrome of involuntary craniofacial lingual movements in the setting of acute intensive care-acquired quadriplegia (critical illness neuromyopathy) following sepsis-associated encephalopathy has not been previously described. We suggest a localization and treatment for this disabling condition. Three patients (2 female) from our center were quadriplegic from critical illness neuromyopathy when they developed involuntary craniofacial lingual movements following sepsis-associated encephalopathy. Extensive investigations failed to identify an etiology for the abnormal movements. Movements were of large amplitude, of moderate speed, and semi-rhythmic in the jaw, tongue, and palate, persistent and extremely bothersome to all patients. Injection with Botulinum toxin type A was very beneficial. Involuntary craniofacial lingual movements in the setting of flaccid quadriplegia following sepsis-associated encephalopathy are consistent with focal craniofacial brainstem myoclonus and constitutes a new syndrome. Botulinum toxin type A treatment maybe helpful in treatment.

Set shifting and visuospatial organization deficits in body dysmorphic disorder.

PubMed

Greenberg, Jennifer L; Weingarden, Hilary; Reuman, Lillian; Abrams, Dylan; Mothi, Suraj S; Wilhelm, Sabine

2017-11-24

Individuals with body dysmorphic disorder (BDD) over-attend to perceived defect(s) in their physical appearance, often becoming "stuck" obsessing about perceived flaws and engaging in rituals to hide flaws. These symptoms suggest that individuals with BDD may experience deficits in underlying neurocognitive functions, such as set-shifting and visuospatial organization. These deficits have been implicated as risk and maintenance factors in disorders with similarities to BDD but have been minimally investigated in BDD. The present study examined differences in neurocognitive functions among BDD participants (n = 20) compared to healthy controls (HCs; n = 20). Participants completed neuropsychological assessments measuring set-shifting (Cambridge Neuropsychological Test Automated Battery Intra-Extra Dimensional Set Shift [IED] task) and visuospatial organization and memory (Rey-Osterrieth Complex Figure Test [ROCF]). Results revealed a set-shifting deficit among BDD participants compared to HCs on the IED. On the ROCF, BDD participants exhibited deficits in visuospatial organization compared to HCs, but they did not differ in visuospatial memory compared to HCs. Results did not change when accounting for depression severity. Findings highlight neurocognitive deficits as potential endophenotype markers of clinical features (i.e., delusionality). Understanding neuropsychological deficits may clarify similarities and differences between BDD and related disorders and may guide targets for BDD treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

De novo partial duplication 7(q11.2{r_arrow}q21.2) in a dysmorphic, developmentally retarded boy

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

Ross, M.; Pinsky, L.; Teebi, A.

Chromosomal abnormalities involving chromosome 7q are rare; we report a case of partial duplication 7q. The propositus was born at 34 weeks by cesarian section, decided because of oligohydramnios, severe intrauterine growth retardation and fetal immobility. At birth, the baby was under the 5th percentile for height, weight and head circumference and had dysmorphic features, including slight asymmetry of the face, bilateral epicanthus, hypoplastic nasal bridge, short globular nose, asymmetrical dysplastic ears, fifth finger clinodactyly, short second and fifth toe. Ultrasound examination showed atrial and ventricular septal defects. At 18 months, the child had a fracture of the femur, secondarymore » to a minor trauma; skeletal X-rays showed generalized osteoporosis and normal healing. The karyotype with GTG-banding showed a de novo partial duplication of the long arm of chromosome 7 (46,XX,dup(7)(q11.23{r_arrow}q21.2)). Fluorescence in situ hybridization with a painting probe specific for chromosome 7 confirmed the intra-chromosomal rearrangement. The patient`s phenotype and his chromosomal abnormality do not match the previously reported cases of partial trisomy 7q. This case confirms the importance of FISH for the delineation of the chromosomal inbalance in structural chromosomal aberrations.« less

A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

PubMed

Dunkerton, Sophie; Field, Matthew; Cho, Vicki; Bertram, Edward; Whittle, Belinda; Groves, Alexandra; Goel, Himanshu

2015-09-01

Growth deficiency, psychomotor delay, and facial dysmorphism was originally described in a male patient in 1989 by Wiedemann et al. and later in 2000 by Steiner et al. Wiedemann-Steiner syndrome (WSS) has since been described only a few times in the literature, with the phenotypic spectrum both expanding and becoming more delineated with each patient reported. We report on the clinical and molecular features of monozygotic twins with a de novo mutation in KMT2A. Single nucleotide polymorphism (SNP) microarray was done on both twins and whole-exome sequencing was done using both parents and one of the affected twins. SNP microarray confirmed that they were monozygotic twins. A de novo heterozygous variant (p. Arg1083*) in the KMT2A gene was identified through whole-exome sequencing, confirming the diagnosis of WSS. In this study, we have identified a de novo mutation in KMT2A associated with psychomotor developmental delay, facial dysmorphism, short stature, hypertrichosis cubiti, and small kidneys. This finding in monozygotic twins gives specificity to the WSS. The description of more cases of WSS is needed for further delineation of this condition. Small kidneys with normal function have not been described in this condition in the medical literature before. © 2015 Wiley Periodicals, Inc.

A comprehensive analysis of craniofacial trauma.

PubMed

Hussain, K; Wijetunge, D B; Grubnic, S; Jackson, I T

1994-01-01

A review of the literature identified a need for a prospective study of the complete range of craniofacial trauma. The aims of this study were to determine the incidence, etiology, and mechanisms of craniofacial and associated injuries, enabling a greater understanding of their range and magnitude. Nine hundred fifty consecutive patients seen at an urban university hospital with any degree of craniofacial trauma were prospectively investigated. Craniofacial trauma was found to be very common at all ages. The causes were directly related to age, sex, and alcohol consumption, and determine the type and severity of injury. The commonest cause of soft-tissue injury was falls, whereas that of fractures was interpersonal violence. Falls accounted for most of the injuries in children and the elderly, whereas interpersonal violence was mainly responsible for those occurring in patients aged 15 to 50 years. Interpersonal violence mostly involved young male adults: fights occurring mainly between strangers who had consumed excessive amounts of alcohol. Women were usually assaulted by assailants known to them, their partners. Pedestrians showed a propensity to sustain cranial fractures, whereas motor vehicle occupants tended to sustain midfacial fractures and bicyclists mandibular fractures. Pedestrians incurred the severest injuries of all road users, and a significant proportion of road user collisions involved bicyclists. Sports were responsible for a significant proportion of craniofacial injuries in youths and young adults. Craniofacial soft-tissue injuries overall occurred most frequently on the forehead, nose, lips, and chin, and a method for their classification is proposed. The commonest craniofacial fracture was that of the nasal bones (45%), followed by cranial bones (24%), mandible (13%), zygoma (13%), orbital blow-out (3%), and maxilla (2%). The incidence of craniofacial trauma can be greatly reduced by improvements in interior home design, school education in alcohol abuse and handling potentially hostile situations (especially for men), improvement in automotive safety devices and compliance by motor vehicle occupants, and utilization of full-face helmets by bicyclists and motorcyclists.

Contribution of jaw muscle size and craniofacial morphology to human bite force magnitude.

PubMed

Raadsheer, M C; van Eijden, T M; van Ginkel, F C; Prahl-Andersen, B

1999-01-01

The existence of an interaction among bite force magnitude, jaw muscle size (e.g., cross-sectional area, thickness), and craniofacial morphology is widely accepted. Bite force magnitude depends on the size of the jaw muscles and the lever arm lengths of bite force and muscle forces, which in turn are dictated by craniofacial morphology. In this study, the relative contributions of craniofacial morphology and jaw muscle thickness to the bite force magnitude were studied. In 121 adult individuals, both magnitude and direction of the maximal voluntary bite force were registered. Craniofacial dimensions were measured by anthropometrics and from lateral radiographs. The thicknesses of the masseter, temporal, and digastric muscles were registered by ultrasonography. After a factor analysis was applied to the anthropometric and cephalometric dimensions, the correlation between bite force magnitude, on the one hand, and the "craniofacial factors" and jaw muscle thicknesses, on the other, was assessed by stepwise multiple regression. Fifty-eight percent of the bite force variance could be explained. From the jaw muscles, only the thickness of the masseter muscle correlated significantly with bite force magnitude. Bite force magnitude also correlated significantly positively with vertical and transverse facial dimensions and the inclination of the midface, and significantly negatively with mandibular inclination and occlusal plane inclination. The contribution of the masseter muscle to the variation in bite force magnitude was higher than that of the craniofacial factors.

Biomaterials and biologics in craniofacial reconstruction.

PubMed

Engstrand, Thomas

2012-01-01

Complications related to surgery, including infection, wound dehiscence, and implant protrusion, are costly and may cause severe morbidity to patients. The choice of implants materials is critical for a successful outcome, particularly in craniofacial reconstructions. This review discusses the potential benefits and drawbacks of biologically active materials used for craniofacial bone repair as alternatives to inert implant prostheses.

Body dysmorphic disorder.

PubMed

Fang, Angela; Matheny, Natalie L; Wilhelm, Sabine

2014-09-01

Body dysmorphic disorder (BDD) can be a severe and often debilitating psychiatric disorder that has been largely under-recognized and underdiagnosed. Pharmacologic and nonpharmacologic treatment options are available but limited. This review aims to provide an updated overview of the psychopathology and epidemiology of BDD, with an emphasis on current pharmacologic and nonpharmacologic treatment options for BDD. Copyright © 2014 Elsevier Inc. All rights reserved.

Relative relationships of general shame and body shame with body dysmorphic phenomenology and psychosocial outcomes.

PubMed

Weingarden, Hilary; Renshaw, Keith D; Davidson, Eliza; Wilhelm, Sabine

2017-07-01

Body Dysmorphic Disorder (BDD) is characterized by a preoccupation with a perceived flaw in appearance and repetitive avoidance behaviors. BDD involves severe psychosocial outcomes (e.g., depression, suicidality, functional impairment). Identifying correlates of BDD symptoms and outcomes can inform treatment. Shame, a painful emotion felt in response to critical self-judgment, may be one key correlate. However, research on shame in BDD is scarce and previous studies have not distinguished general shame from body shame. This study examines the relative relationships between body shame and general shame with body dysmorphic phenomenology and psychosocial outcomes. Participants ( N = 184) were recruited online via BDD organizations and completed a survey. Path analysis was used to examine associations between body and general shame with 1) body dysmorphic phenomenology and 2) depression severity, suicide risk, and functional impairment. Both types of shame were differentially related to outcomes. Body shame was more strongly related to phenomenology, whereas general shame was more strongly related to psychosocial outcomes. Thus, it may be important for BDD treatment to focus on reducing both general and body shame. Further research should evaluate whether current treatments adequately address and reduce general and body shame, and whether addressing shame promotes better treatment outcomes.

Psychological Aspects of Cosmetic Surgery among Females: A Media Literacy Training Intervention

PubMed Central

Khazir, Zahra; Dehdari, Tahereh; Majdabad, Mahmood Mahmoodi; Tehrani, Said Pournaghash

2016-01-01

Introduction: The present study examined the favorable attitude of a sample of female university students regarding elective cosmetic surgery, body dysmorphic disorder, self-esteem and body dissatisfaction following a media literacy training intervention. Methods: This study was a quasi-experimental type. The study sample included 140 female university students who were allocated to either the intervention (n=70) or the control group (n=70). Attitude toward cosmetic surgery, body dysmorphic disorder, self-esteem and, body satisfaction was measured in both groups before the intervention and 4 weeks later. Four media literacy training sessions were conducted over 4 weeks for the intervention group. The data was analyzed through analysis of covariance, student’s paired-samples t test, and Pearson correlation. Results: Our findings showed that favorable attitude, body dysmorphic disorder and body dissatisfaction scores were significantly lower (p<0.05) in the intervention group than the control group. Furthermore, self-esteem score increased significantly in the intervention group. Conclusions: Our results underscores the importance of media literacy intervention in decreasing female’s favorable attitude towards elective cosmetic surgery, body dysmorphic disorder and body dissatisfaction as well as increasing self-esteem. PMID:26383204

Molecular cytogenetic studies in structural abnormalities of chromosome 13

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

Lozzio, C.B.; Bamberger, E.; Anderson, I.

1994-09-01

A partial trisomy 13 was detected prenatally in an amniocentesis performed due to the following ultrasound abnormalities: open sacral neural tube defect (NTD), a flattened cerebellum, and lumbar/thoracic hemivertebrae. Elevated AFP and positive acetylcholinesterase in amniotic fluid confirmed the open NTD. Chromosome analysis showed an extra acrocentric chromosome marker. FISH analysis with the painting probe 13 showed that most of the marker was derived from this chromosome. Chromosomes on the parents revealed that the mother had a balanced reciprocal translocation t(2;13)(q23;q21). Dual labeling with painting chromosomes 2 and 13 on cells from the mother and from the amniotic fluid identifiedmore » the marker as a der(13)t(2;13)(p23;q21). Thus, the fetus had a partial trisomy 13 and a small partial trisomy 2p. The maternal grandfather was found to be a carrier for this translocation. Fetal demise occurred a 29 weeks of gestation. The fetus had open lumbar NTD and showed dysmorphic features, overlapping fingers and imperforate anus. This woman had a subsequent pregnancy and chorionic villi sample showed that this fetus was normal. Another case with an abnormal chromosome 13 was a newborn with partial monosomy 13 due to the presence of a ring chromosome 13. This infant had severe intrauterine growth retardation, oligohydramnios, dysmorphic features and multiple congenital microphthalmia, congenital heart disease, absent thumbs and toes and cervical vertebral anomalies. Chromosome studies in blood and skin fibroblast cultures showed that one chromosome 3 was replaced by a ring chromosome of various sizes. This ring was confirmed to be derived from chromosome 13 using the centromeric 21/13 probe.« less

Homozygous loss of function BRCA1 variant causing a Fanconi-anemia-like phenotype, a clinical report and review of previous patients.

PubMed

Freire, Bruna L; Homma, Thais K; Funari, Mariana F A; Lerario, Antônio M; Leal, Aline M; Velloso, Elvira D R P; Malaquias, Alexsandra C; Jorge, Alexander A L

2018-03-01

Fanconi Anemia (FA) is a rare and heterogeneous genetic syndrome. It is associated with short stature, bone marrow failure, high predisposition to cancer, microcephaly and congenital malformation. Many genes have been associated with FA. Previously, two adult patients with biallelic pathogenic variant in Breast Cancer 1 gene (BRCA1) had been identified in Fanconi Anemia-like condition. The proband was a 2.5 year-old girl with severe short stature, microcephaly, neurodevelopmental delay, congenital heart disease and dysmorphic features. Her parents were third degree cousins. Routine screening tests for short stature was normal. We conducted whole exome sequencing (WES) of the proband and used an analysis pipeline to identify rare nonsynonymous genetic variants that cause short stature. We identified a homozygous loss-of-function BRCA1 mutation (c.2709T > A; p. Cys903*), which promotes the loss of critical domains of the protein. Cytogenetic study with DEB showed an increased chromosomal breakage. We screened heterozygous parents of the index case for cancer and we detected, in her mother, a metastatic adenocarcinoma in an axillar lymph node with probable primary site in the breast. It is possible to consolidate the FA-like phenotype associated with biallelic loss-of-function BRCA1, characterized by microcephaly, short stature, developmental delay, dysmorphic face features and cancer predisposition. In our case, the WES allowed to establish the genetic cause of short stature in the context of a chromosome instability syndrome. An identification of BRCA1 mutations in our patient allowed precise genetic counseling and also triggered cancer screening for the patient and her family members. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Analysis of an In-Service Examination for Core Pediatric Craniofacial Surgery Knowledge.

PubMed

Silvestre, Jason; Chang, Benjamin; Taylor, Jesse A

2016-01-01

Little is known about designing an effective residency curriculum for pediatric craniofacial surgery. This study elucidates the pediatric craniofacial curriculum of the Plastic Surgery In-Service Training Examination (PSITE) to facilitate knowledge acquisition during residency. Approximately, 6 consecutive PSITEs were reviewed for pediatric craniofacial questions (2010-2015). Subjects were categorized according to topics on the American Board of Plastic Surgery written board examination. Questions were categorized using an educational taxonomy model. Answer references were categorized by source and publication lag. Of 1174 PSITE questions, 147 tested pediatric craniofacial topics (12.5%). Questions appeared predominately in the Craniomaxillofacial section (83.0%, p < 0.001). The annual representation was stable more than 6 years (range: 10.2%-14.4%, p = 0.842). Question taxonomy favored interpretation (45.6%) and decision-making (40.8%) over recall (13.6%, p < 0.001) skills, and 41 questions had an associated image (27.9%) and most were photographic (76.7%, p < 0.001). The most frequently tested categories on the American Board of Plastic Surgery written examination content outline were craniofacial anomalies (23.5%), benign and malignant tumors (17.6%), and cleft lip and palate (12.5%). Overall, 80 unique journals were cited 304 times with a mean publication lag of 9.4 ± 10.9 years. Plastic and Reconstructive Surgery (34.5%) was the most cited journal (p < 0.001). These data may assist in designating core knowledge competency in pediatric craniofacial surgery for plastic surgery residents. A further understanding of PSITE utility for core knowledge competency in pediatric craniofacial surgery would be the focus of future work. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Correlations of frontal lip-line canting with craniofacial morphology and muscular activity.

PubMed

Cho, Jin-Hyoung; Kim, Eun-Jung; Kim, Byeong-Chae; Cho, Ki-Hyun; Lee, Ki-Heon; Hwang, Hyeon-Shik

2007-09-01

The purpose of this study was to investigate factors affecting lip-line canting by using musculoskeletal analyses. Fifty-six adults with lip-line canting were selected as subjects. They were divided into 3 groups according to the changes of lip line during smiling: increasing (group I), decreasing (group D), and minimal (group M). Lip-line canting at rest was correlated to craniofacial morphology and muscular activity: Regarding craniofacial morphology, various craniofacial measurements in lateral and frontal cephalograms were used, including inclination of the tongue blade placed across both first molars. The zygomaticus major was the focus of the measurement of muscular activity affecting lip-line canting, and its activity during smiling was evaluated by using a needle electrode. In group I, lip-line canting at rest showed a significant correlation with the right-left (R/L) difference of muscular activity, but no significant correlation with the measurements of craniofacial morphology. In group D, lip-line canting showed a positive correlation with the measurements of craniofacial morphology, such as the inclination of the tongue blade, and a negative correlation with the R/L difference of muscular activity. In group M, lip-line canting showed no significant correlation with the R/L difference of muscular activity, but a significant correlation with inclination of the tongue blade. The results indicate that lip-line canting is caused by craniofacial morphology when the change of lip-line canting during smiling is minimal, whereas lip-line canting is affected by the R/L difference of muscular activity in addition to craniofacial morphology when the cant of lip line markedly changes during smiling. The findings suggest that the cause of lip-line canting can be identified easily by the change of canting during smiling, without complicated musculoskeletal analyses.

Cleft Palate-Craniofacial Journal 50th anniversary editorial board commentary: anatomy, basic sciences, and genetics--then and now.

PubMed

Mooney, Mark P; Cooper, Gregory M; Marazita, Mary L

2014-05-01

To celebrate the 50th year of the Cleft Palate-Craniofacial Journal we look back to where we started in 1964 and where we are now, and we speculate about directions for the future in a "Then and Now" editorial series. This editorial examines changing trends and perspectives in anatomical, basic science, and genetic studies published in this 50-year interval. In volume 1 there were 45 total papers, seven (16%) of which were peer-reviewed basic science and genetic articles published: four in anatomy, three in craniofacial biology, and none in genetics. In contrast, in volume 50, of 113 articles there were 47 (42%) peer-reviewed basic science and genetic articles published: 30 in anatomy, five in craniofacial biology, and 12 in genetics. Topical analysis of published manuscripts then and now reveal that similar topics in anatomy and craniofacial biology are still being researched today (e.g., phenotypic variability, optimal timing of surgery, presurgical orthopedics, bone grafting); whereas, most of the more recent papers use advanced technology to address old questions. In contrast, genetic publications have clearly increased in frequency during the last 50 years, which parallels advances in the field during this time. However, all of us have noticed that the more "cutting-edge" papers in these areas are not being submitted for publication to the journal, but instead to discipline-specific journals. Concerted efforts are therefore indicated to attract and publish these cutting-edge papers in order to keep the Cleft Palate-Craniofacial Journal in the forefront of orofacial cleft and craniofacial anomaly research and to provide a valuable service to American Cleft Palate-Craniofacial Association members.

Assessing Species-specific Contributions To Craniofacial Development Using Quail-duck Chimeras

PubMed Central

Fish, Jennifer L.; Schneider, Richard A.

2014-01-01

The generation of chimeric embryos is a widespread and powerful approach to study cell fates, tissue interactions, and species-specific contributions to the histological and morphological development of vertebrate embryos. In particular, the use of chimeric embryos has established the importance of neural crest in directing the species-specific morphology of the craniofacial complex. The method described herein utilizes two avian species, duck and quail, with remarkably different craniofacial morphology. This method greatly facilitates the investigation of molecular and cellular regulation of species-specific pattern in the craniofacial complex. Experiments in quail and duck chimeric embryos have already revealed neural crest-mediated tissue interactions and cell-autonomous behaviors that regulate species-specific pattern in the craniofacial skeleton, musculature, and integument. The great diversity of neural crest derivatives suggests significant potential for future applications of the quail-duck chimeric system to understanding vertebrate development, disease, and evolution. PMID:24962088

An Adult Case of Chromosome 22q11.2 Deletion Syndrome Associated with a High-positioned Right Aortic Arch

PubMed Central

Hoshino, Yoichi; Machida, Moriya; Shimano, Shun-ichi; Taya, Teizo

2017-01-01

Chromosome 22q11.2 deletion syndrome (22q11.2 DS) has a very wide phenotypic spectrum that includes dysmorphic features, cardiac anomalies, and hypocalcemia arising from hypoparathyroidism. We herein describe an adult case of 22q11.2 DS with associated hypoparathyroidism and anomalies of the aortic arch. Because the patient had been diagnosed with primary hypoparathyroidism at another hospital, a diagnosis of 22q11.2 DS had been overlooked. A chest X-ray examination revealed widening of the mediastinum caused by a high-positioned right aortic arch, and we subsequently confirmed a diagnosis of 22q11.2 DS using fluorescence in situ hybridization. Because primary hypoparathyroidism is a rare disorder, physicians should be aware of the variable phenotypic features of 22q11.2 DS. PMID:28381757

Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis: a new X linked contiguous gene deletion syndrome?

PubMed Central

Jonsson, J J; Renieri, A; Gallagher, P G; Kashtan, C E; Cherniske, E M; Bruttini, M; Piccini, M; Vitelli, F; Ballabio, A; Pober, B R

1998-01-01

We describe a family with four members, a mother, two sons, and a daughter, who show clinical features consistent with X linked Alport syndrome. The two males presented with additional features including mental retardation, dysmorphic facies with marked midface hypoplasia, and elliptocytosis. The elliptocytosis was not associated with any detectable abnormalities in red cell membrane proteins; red cell membrane stability and rigidity was normal on ektacytometry. Molecular characterisation suggests a submicroscopic X chromosome deletion encompassing the entire COL4A5 gene. We propose that the additional abnormalities found in the affected males of this family are attributable to deletion or disruption of X linked recessive genes adjacent to the COL4A5 gene and that this constellation of findings may represent a new X linked contiguous gene deletion syndrome. Images PMID:9598718

75 FR 13561 - National Institute of Dental & Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... & Craniofacial Research; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as... Craniofacial Research Council. The meeting will be open to the public as indicated below, with attendance... set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended. The grant applications...

78 FR 50066 - National Institute of Dental and Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... and Craniofacial Research; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory... National Advisory Dental and Craniofacial Research Council. The meeting will be open to the public as... accordance with the provisions set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended...

Msx homeobox gene family and craniofacial development.

PubMed

Alappat, Sylvia; Zhang, Zun Yi; Chen, Yi Ping

2003-12-01

Vertebrate Msx genes are unlinked, homeobox-containing genes that bear homology to the Drosophila muscle segment homeobox gene. These genes are expressed at multiple sites of tissue-tissue interactions during vertebrate embryonic development. Inductive interactions mediated by the Msx genes are essential for normal craniofacial, limb and ectodermal organ morphogenesis, and are also essential to survival in mice, as manifested by the phenotypic abnormalities shown in knockout mice and in humans. This review summarizes studies on the expression, regulation, and functional analysis of Msx genes that bear relevance to craniofacial development in humans and mice. Key words: Msx genes, craniofacial, tooth, cleft palate, suture, development, transcription factor, signaling molecule.

Customized Polymethyl Methacrylate Implants for the Reconstruction of Craniofacial Osseous Defects

PubMed Central

Fernandes da Silva, André Luis; Borba, Alexandre Meireles; Simão, Niverso Rodrigues; Pedro, Fábio Luis Miranda

2014-01-01

Craniofacial defects represent alterations in the anatomy and morphology of the cranial vault and the facial bones that potentially affect an individual's psychological and social well-being. Although a variety of techniques and restorative procedures have been described for the reconstruction of the affected area, polymethyl methacrylate (PMMA), a biocompatible and nondegradable acrylic resin-based implant, is the most widely used alloplastic material for such craniomaxillofacial reconstruction. The aim of this study was to describe a technique for aesthetic and functional preoperative customized reconstruction of craniofacial bone defects from a small series of patients offered by the Brazilian public health system. Three adult male patients attended consultation with chief complaints directly related to their individual craniofacial bone defects. With the aid of multislice computed tomography scans and subsequent fabrication of the three-dimensional craniofacial prototype, custom-made PMMA implants were fabricated preoperatively. Under general anesthesia, with access to the craniofacial defects with a coronal approach, the PMMA implants were adapted and fixated to the facial skeleton with titanium plates and screws. Postoperative evaluation demonstrated uneventful recovery and an excellent aesthetic result. Customized prefabricated PMMA implants manufactured over the rapid prototyping models proved to be effective and feasible. PMID:25093139

Customized polymethyl methacrylate implants for the reconstruction of craniofacial osseous defects.

PubMed

Fernandes da Silva, André Luis; Borba, Alexandre Meireles; Simão, Niverso Rodrigues; Pedro, Fábio Luis Miranda; Borges, Alvaro Henrique; Miloro, Michael

2014-01-01

Craniofacial defects represent alterations in the anatomy and morphology of the cranial vault and the facial bones that potentially affect an individual's psychological and social well-being. Although a variety of techniques and restorative procedures have been described for the reconstruction of the affected area, polymethyl methacrylate (PMMA), a biocompatible and nondegradable acrylic resin-based implant, is the most widely used alloplastic material for such craniomaxillofacial reconstruction. The aim of this study was to describe a technique for aesthetic and functional preoperative customized reconstruction of craniofacial bone defects from a small series of patients offered by the Brazilian public health system. Three adult male patients attended consultation with chief complaints directly related to their individual craniofacial bone defects. With the aid of multislice computed tomography scans and subsequent fabrication of the three-dimensional craniofacial prototype, custom-made PMMA implants were fabricated preoperatively. Under general anesthesia, with access to the craniofacial defects with a coronal approach, the PMMA implants were adapted and fixated to the facial skeleton with titanium plates and screws. Postoperative evaluation demonstrated uneventful recovery and an excellent aesthetic result. Customized prefabricated PMMA implants manufactured over the rapid prototyping models proved to be effective and feasible.

Concurrent cervical and craniofacial pain. A review of empiric and basic science evidence.

PubMed

Browne, P A; Clark, G T; Kuboki, T; Adachi, N Y

1998-12-01

Because many patients present themselves for treatment with both craniofacial and craniocervical pain, 2 questions arise: (1) What are the sensory and motor consequences of dysfunction in either of these areas on the other? (2) Do craniofacial and craniocervical pain have a similar cause? These questions formed the impetus for this review article. The phenomenon of concurrent pain in craniofacial and cervical structures is considered, and clinical reports and opinions are presented regarding theories of cervical-to-craniofacial and craniofacial-to-cervical pain referral. Because pain referral between these 2 areas requires anatomic and functional connectivity between trigeminally and cervically innervated structures, basic neurophysiologic and neuroanatomic literature is reviewed. The published data clearly demonstrate neurophysiologic and structural convergence of cervical sensory and muscle afferent inputs onto trigeminal subnucleus caudalis nociceptive and non-nociceptive neurons. Moreover, changes in metabolic activity and blood flow in the brainstem and cervical dorsal horn of the spinal cord in both monkeys and cats have been demonstrated after electric stimulation of the V1-innervated superior sagittal sinus. In conclusion, the animal experimental data support the findings of human empiric and experimental studies, which suggest that strong connectivity exists between trigeminal and cervical motor and sensory responses.

PAX3 gene deletion detected by microarray analysis in a girl with hearing loss.

PubMed

Drozniewska, Malgorzata; Haus, Olga

2014-01-01

Deletions of the PAX3 gene have been rarely reported in the literature. Mutations of this gene are a common cause of Waardenburg syndrome type 1 and 3. We report a 16 year old female presenting hearing loss and normal intellectual development, without major features of Waardenburg syndrome type 1, and without family history of the syndrome. Her phenotype, however, overlaps with features of craniofacial-deafness-hand syndrome. Microarray analysis showed ~862 kb de novo deletion at 2q36.1 including PAX3. The above findings suggest that the rearrangement found in our patient appeared de novo and with high probability is a cause of her phenotype.

Roberts-SC phocomelia syndrome.

PubMed

Maheshwari, A; Kumar, P; Dutta, S; Narang, A

2001-06-01

A severely growth retarded baby was born at 38 weeks gestation. He had multiple craniofacial anomalies, microbrachycephaly, phocomelia in the upper limbs and renal cysts visible on ultrasound. He died of recurrent apneas. The autopsy showed left sided multicystic dysplastic kidney and absence of one testis. Cytogenetic studies did not reveal any abnormality. The phenotypic features match those described in the Roberts-SC phocomelia syndrome. A literature review revealed that 50% of these patients have chromosomal defects and antenatal detection is possible on ultrasound and by chromosome analysis of the amniocytes.

[Cryptorchidism with didymo-epididymal dissociation and Robinow's syndrome: 2 case reports].

PubMed

Fabbro, M A; D'Agostino, S; Costa, L; Musi, L; Cappellari, F

1997-01-01

Two brothers of normal not consanguineous parents, with bilateral intrabdominal cryptorchidism, were admitted to our Institution. Both children had short stature, limb and hand malformations and craniofacial patterns of Robinow syndrome. During the orchidopexy, bilateral epididymal and vasal abnormalities were found in both of them. This anomaly associated with Robinow syndrome has never been reported before. These two cases provides the Authors with the opportunity of reviewing clinical features, genetics and radiological patterns of this rare syndrome.

Heritability of Craniofacial Structures in Normal Subjects and Patients with Sleep Apnea

PubMed Central

Chi, Luqi; Comyn, Francois-Louis; Keenan, Brendan T.; Cater, Jacqueline; Maislin, Greg; Pack, Allan I.; Schwab, Richard J.

2014-01-01

Objectives: Accumulating evidence has shown that there is a genetic contribution to obstructive sleep apnea (OSA).The objectives were to use magnetic resonance imaging (MRI) cephalometry to (1) confirm heritability of craniofacial risk factors for OSA previously shown by cephalometrics; and (2) examine the heritability of new craniofacial structures that are measurable with MRI. Design: A sib pair “quad” design examining apneics, apneic siblings, controls, and control siblings. The study design used exact matching on ethnicity and sex, frequency matching on age, and statistical control for differences in age, sex, ethnicity, height, and weight. Setting: Academic medical center. Patients: We examined 55 apneic probands (apnea-hypopnea index [AHI]: 46.8 ± 33.5 events/h), 55 proband siblings (AHI: 11.1 ± 15.9 events/h), 55 controls (AHI: 2.2 ± 1.7 events/h), and 55 control siblings (AHI: 4.1 ± 4.0 events/h). Interventions: N/A. Measurements and Results: Five independent domains reflecting different aspects of the craniofacial structure were examined. We confirmed heritability of sella–nasion–subspinale (38%, P = 0.002), saddle angle (55%, P < 0.0001), mandibular length (24%, P = 0.02) and lower facial height (33%, P = 0.006) previously measured by cephalometry. In addition, the current study added new insights by demonstrating significant heritability of mandibular width (30%, P = 0.005), maxillary width (47%, P < 0.0001), distance from the hyoid bone to the retropogonion (36%, P = 0.0018) and size of the oropharyngeal space (31%, P = 0.004). Finally, our data indicate that heritability of the craniofacial structures is similar in normal patients and those with apnea. Conclusions: The data support our a priori hypothesis that the craniofacial structures that have been associated with obstructive sleep apnea (OSA) are heritable. We have demonstrated heritability for several intermediate craniofacial phenotypes for OSA. Thus, we believe that future studies should be able to identify genes associated with these intermediate craniofacial phenotypes. Citation: Chi L, Comyn FL, Keenan BT, Cater J, Maislin G, Pack AI, Schwab RJ. Heritability of craniofacial structures in normal subjects and patients with sleep apnea. SLEEP 2014;37(10):1689-1698. PMID:25197806

Prevalence of and associations between body dysmorphic concerns, obsessive beliefs and social anxiety.

PubMed

Barahmand, Usha; Shahbazi, Zeynab

2015-03-01

Physical attractiveness has been of concern in different cultures and at different times. Physical attractiveness can influence one's thoughts and actions, and concerns regarding body image can be destructive, giving rise to psychological problems. The purpose of the present study was to determine the prevalence of body dysmorphic concerns, related sex differences and comorbidity with social anxiety and obsessive beliefs. Using a stratified and cluster sampling procedure, 1,200 males and females were randomly selected. Self-report measures on body image, social anxiety and obsessive beliefs were distributed of which 843 completed questionnaires (54.9% males and 45.1% females) were returned (return rate of 70.25%). Therefore, data pertaining to 463 males and 380 females ranging in age from 17 to 20 years with a mean age of 18.12 years (SD = 1.06) were analyzed. Findings suggest a prevalence rate of 19.1% for body dysmorphic disorder, 23.6% for social anxiety and 8.8% for obsessive beliefs. Both social anxiety and obsessive beliefs were found to be comorbid with body dysmorphic concerns. The percentage of individuals reporting comorbid social anxiety (12.9%) was greater than that of those reporting comorbid obsessive beliefs (6.4%). Males with body dysmorphic concerns reported more obsessive beliefs (8.2% versus 4.1%), while their female counterparts reported more social anxiety (23.4% versus 4.2%). In males, body image concerns appear to be more cognitive in quality, while in females, body image concerns seem more emotional in tone. As the measures used do not yield formal diagnoses, findings should be viewed with caution. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

The drive for muscle leanness: a complex case with features of muscle dysmorphia and eating disorder not otherwise specified.

PubMed

Cafri, G; Blevins, N; Thompson, J K

2006-12-01

Muscle dysmorphia has been described as a subtype of body dysmorphic disorder in which an individual experiences severe body image disturbance related to muscularity. The current case is of a 20-year-old man who describes a history of muscle dysmorphia in which the nature of the body image concern is related to leanness (i.e., muscularity in the absence of body fat), as opposed to increasing muscle mass, which is how muscle dysmorphia has typically been characterized in the literature. The case illustrates the need to consider this additional facet of body image when diagnosing muscle dysmorphia.

Robinow syndrome: phenotypic variability in a family with a novel intragenic ROR2 mutation.

PubMed

Brunetti-Pierri, Nicola; Del Gaudio, Daniela; Peters, Hartmut; Justino, Henri; Ott, Claus-Eric; Mundlos, Stefan; Bacino, Carlos A

2008-11-01

Robinow syndrome comprises dysmorphic facial features, short stature, brachymesomelia, segmental spine defects, and genital hypoplasia. The range of severity in this disorder is broad. We report on the clinical and molecular findings of two sib pairs from the same extended family with Robinow syndrome due to a novel intragenic ROR2 deletion involving exons 6 and 7 that could not be detected by sequencing. The affected individuals exhibited variability with respect to the cleft lip, cleft palate, and cardiac findings and for the presence in one of the patients of syringomyelia, which has not been previously reported in Robinow syndrome. Copyright 2008 Wiley-Liss, Inc.

[Laron syndrome: Presentation, treatment and prognosis].

PubMed

Latrech, Hanane; Polak, Michel

2016-01-01

Laron syndrome is a rare cause of short stature due to an abnormality of growth hormone receptor (GHR). It is characterized by poor phenotype-genotype correlation and geographic predilection essentially in the Mediterranean rim, the Middle East and Indian subcontinent. This syndrome corresponds to an endogenous and exogenous complete insensitivity of GH and manifests by early hypoglycemia, an extremely severe short stature and dysmorphic features contrasting with high levels of circulating GH. To date, treatment with recombinant IGF1 is the only treatment option that has improved the terrible prognosis in these patients but does not actually realize the conditions for genuine replacement therapy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Trisomy 2q11.2-->q21.1 resulting from an unbalanced insertion in two generations.

PubMed Central

Glass, I A; Stormer, P; Oei, P T; Hacking, E; Cotter, P D

1998-01-01

In this communication, we describe two cases of proximal 2q trisomy (2q11.2--> q21.1) resulting from an interchromosomal insertion. The chromosomal origin of the insertion was confirmed by fluorescence in situ hybridisation. An unbalanced karyotype, 46,XX,der(8) ,ins(8;2) (p21.3; q21.1q11.2), was found in the proband and her mother, who both have mild mental retardation, short stature, dysmorphic features, insulin dependent diabetes mellitus, and a psychotic illness. This family is a rare example of direct transmission of a partial autosomal trisomy. Images PMID:9598728

Insulin dependent diabetes mellitus (IDDM) and autoimmune thyroiditis in a boy with a ring chromosome 18: additional evidence of autoimmunity or IDDM gene(s) on chromosome 18.

PubMed

Dacou-Voutetakis, C; Sertedaki, A; Maniatis-Christidis, M; Sarri, C; Karadima, G; Petersen, M B; Xaidara, A; Kanariou, M; Nicolaidou, P

1999-02-01

A 4 year 3 month old boy with insulin dependent diabetes mellitus (IDDM), autoimmune thyroiditis, slight mental retardation, facial dysmorphism, and a de novo ring chromosome 18 (deletion 18q22.3-18qter) is described. This unique association of defects could represent a chance association. Alternatively, the clinical features could be the result of the chromosomal aberration. If so, one could speculate that a gene or genes on chromosome 18 might act as a suppressor or activator of the autoimmune process by itself or in concert with other IDDM loci.

A malformed child with a recombinant chromosome 7, rec(7) dup p, derived from a maternal pericentric inversion inv(7)(p15q36).

PubMed Central

Delicado, A; Escribano, E; Lopez Pajares, I; Diaz de Bustamante, A; Carrasco, S

1991-01-01

We report a child with facial dysmorphic features, hypoplasia of the external genitalia, intestinal malrotation, congenital cardiac defect, and minor limb anomalies. Chromosome studies showed a recombinant chromosome 7, rec(7) dup p, resulting from a maternal pericentric inversion inv(7)(p15 q36). Thus, this child had partial trisomy 7p in addition to a small distal monosomy 7. The clinical findings are compared with those found in previous reports of trisomy 7p. Finally, some general principles for genetic counselling are discussed. Images PMID:2002483

Novel case of paternal paracentric inversion causing partial trisomy 13 and review of the literature.

PubMed

Douglas, Chad; Smith, Stephen A; Rohena, Luis

2017-06-01

Partial trisomies have often been reported secondary to inversion mutations. These occurrences are most frequently associated with pericentric inversions. In this report, we describe the first documented case of partial trisomy 13 secondary to a parental paracentric inversion, in this case a paternal paracentric 13q inversion. Our Patient exhibits a variety of clinical findings including global developmental delay with intellectual disability, sensorineural hearing loss, bilateral congenital polar cataracts with associated foveal and optic nerve hypoplasia, right retinal detachment, atrial septal defect, absence of corpus callosum, celiac disease, microcephaly, as well as other dysmorphic features. © 2017 Wiley Periodicals, Inc.

Wnt signaling regulates pulp volume and dentin thickness

PubMed Central

Lim, Won Hee; Liu, Bo; Cheng, Du; Hunter, Daniel J; Zhong, Zhendong; Ramos, Daniel M; Williams, Bart O; Sharpe, Paul T; Bardet, Claire; Mah, Su-jung; Helms, Jill A

2015-01-01

Odontoblasts, cementoblasts, ameloblasts and osteoblasts all form mineralized tissues in the craniofacial complex, and all these cell types exhibit active Wnt signaling during postnatal life. We set out to understand the functions of this Wnt signaling, by evaluating the phenotypes of mice in which the essential Wnt chaperone protein, Wingless was eliminated. The deletion of Wls was restricted to cells expressing Osteocalcin, which in addition to osteoblasts includes odontoblasts, cementoblasts, and ameloblasts. Dentin, cementum, enamel, and bone all formed in OCN-Cre;Wlsfl/fl mice but their homeostasis was dramatically affected. The most notable feature was a significant increase in dentin volume and density. We attribute this gain in dentin volume to a Wnt-mediated mis-regulation of Runx2. Normally, Wnt signaling stimulates Runx2, which in turn inhibits DSP; this inhibition must be relieved for odontoblasts to differentiate. In OCN-Cre;Wlsfl/fl mice, Wnt pathway activation is reduced and Runx2 levels decline. The Runx2-mediated repression of DSP is relieved and odontoblast differentiation is accordingly enhanced. This study demonstrates the importance of Wnt signaling in the homeostasis of mineralized tissues of the craniofacial complex. PMID:23996396

Three-Dimensional Printing: Custom-Made Implants for Craniomaxillofacial Reconstructive Surgery

PubMed Central

Matias, Mariana; Zenha, Horácio; Costa, Horácio

2017-01-01

Craniomaxillofacial reconstructive surgery is a challenging field. First it aims to restore primary functions and second to preserve craniofacial anatomical features like symmetry and harmony. Three-dimensional (3D) printed biomodels have been widely adopted in medical fields by providing tactile feedback and a superior appreciation of visuospatial relationship between anatomical structures. Craniomaxillofacial reconstructive surgery was one of the first areas to implement 3D printing technology in their practice. Biomodeling has been used in craniofacial reconstruction of traumatic injuries, congenital disorders, tumor removal, iatrogenic injuries (e.g., decompressive craniectomies), orthognathic surgery, and implantology. 3D printing has proven to improve and enable an optimization of preoperative planning, develop intraoperative guidance tools, reduce operative time, and significantly improve the biofunctional and the aesthetic outcome. This technology has also shown great potential in enriching the teaching of medical students and surgical residents. The aim of this review is to present the current status of 3D printing technology and its practical and innovative applications, specifically in craniomaxillofacial reconstructive surgery, illustrated with two clinical cases where the 3D printing technology was successfully used. PMID:28523082

Craniofacial Anomalies And Biostereometrics

NASA Astrophysics Data System (ADS)

Christiansen, Richard L.

1980-07-01

Man's oral-facial structures are vital for the functions of breathing, mastication, swallowing, vision, and communication. When defective development of these tissues occurs, function becomes impaired and the anatomic features of the afflicted individual will frequently deviate from the norm. This error of form and function will classify the individual as being physically and psychosocially handicapped. The successful habilitation regimen of the handicapped person depends on the accurate analysis of both craniofacial anatomy and physiology of these individuals, as well as psychological implications of the disfigurement. Biostereometrics can contribute to the establishment of operationally valid measures for assessing the severity of the handicapping conditions. The heterogeneous nature of diverse disfigurement suggest that an improved classification of malformations would be beneficial. Three-dimensional analysis may also have significant influence on the accuracy of the diagnosis, and the establishment of a biologically sound treatment plan. Biostereometrics will contribute more fully if the three-dimensional surface analysis can be coordinated with a study of 1) the underlying skeletal structures, and 2) the operational musculature. Increased communication between the stereometric experts and the biological scientists should accelerate the application of this technique to the health problem.

Disorders with similar clinical phenotypes reveal underlying genetic interaction: SATB2 acts as an activator of the UPF3B gene

PubMed Central

Leoyklang, Petcharat; Suphapeetiporn, Kanya; Srichomthong, Chalurmpon; Tongkobpetch, Siraprapa; Fietze, Stefanie; Dorward, Heidi; Cullinane, Andrew R.; Gahl, William A.; Huizing, Marjan; Shotelersuk, Vorasuk

2014-01-01

Two syndromic cognitive impairment disorders have very similar craniofacial dysmorphisms. One is caused by mutations of SATB2, a transcription regulator, and the other by heterozygous mutations leading to premature stop codons in UPF3B, encoding a member of the nonsense-mediated mRNA decay complex. Here we demonstrate that the products of these two causative genes function in the same pathway. We show that the SATB2 nonsense mutation in our patient leads to a truncated protein that localizes to the nucleus, forms a dimer with wild-type SATB2 and interferes with its normal activity. This suggests that the SATB2 nonsense mutation has a dominant negative effect. The patient’s leukocytes had significantly decreased UPF3B mRNA compared to controls. This effect was replicated both in vitro, where siRNA knockdown of SATB2 in HEK293 cells resulted in decreased UPF3B expression, and in vivo, where embryonic tissue of Satb2 knock-out mice showed significantly decreased Upf3b expression. Furthermore, chromatin immunoprecipitation demonstrates that SATB2 binds to the UPF3B promoter, and a luciferase reporter assay confirmed that SATB2 expression significantly activates gene transcription using the UPF3B promoter. These findings indicate that SATB2 acts as an activator UPF3B expression through binding to its promoter. This study emphasizes the value of recognizing disorders with similar clinical phenotypes to explore underlying mechanisms of genetic interaction. PMID:23925499

Trisomy 15 mosaicism and uniparental disomy (UPD) in a liveborn infant

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

Milunsky, J.M.; Wyandt, H.E.; Amos, J.A.

We describe a liveborn infant with UPD in association with trisomy 15 mosaicism. Third trimester amniocentesis was performed for suspected IUGR. Results revealed 46,XX/47,XX,+15. The infant initially had respiratory distress and fed poorly. Symmetrical growth retardation, craniofacial dysmorphism, excess nuchal folds, a heart murmur, hypermobile joints, minor limb abnormalities, absent spontaneous movement and an abnormal cry were noted. Further study showed complex heart defects, including VSD and PDA, a left choroid plexus cyst, 13 ribs bilaterally, abnormal optic discs, abnormal visual evoked potentials and abnormal auditory brain stem responses. The infant died at 6 weeks of life from cardio-respiratory complications.more » Blood chromosomes were normal, 46,XX in 100 cells. Parental blood chromosomes were normal. Skin biopsy revealed 46,XX/47,XX,+15 in 40/50 (80%) cells as did autopsy lung tissue. Molecular analysis of the infant`s blood revealed maternal uniparental heterodisomy for chromosome 15 in the 46,XX cell line. Microsatellite analysis demonstrated that the extra chromosome originated from a maternal meiosis I nondisjunction. To our knowledge, this is the first liveborn infant with mosaic trisomy 15 and UPD in the diploid cells. Trisomy 15, heretofore, has been regarded as nonviable, even in mosaic form. While maternal UPD is associated with the Prader-Willi syndrome phenotype, mosaicism for trisomy 15 has been reported only when confined to the placenta. UPD in this case generally complicated prediction of the phenotype and raises the question whether all cases with UPD 15 should have more than one tissue studied to determine undetected trisomy 15.« less

Ocular Manifestations of Oblique Facial Clefts

PubMed Central

Ortube, Maria Carolina; Dipple, Katrina; Setoguchi, Yoshio; Kawamoto, Henry K.; Demer, Joseph L.

2014-01-01

Introduction In the Tessier classification, craniofacial clefts are numbered from 0 to 14 and extend along constant axes through the eyebrows, eyelids, maxilla, nostrils, and the lips. We studied a patient with bilateral cleft 10 associated with ocular abnormalities. Method Clinical report with orbital and cranial computed tomography. Results After pregnancy complicated by oligohydramnios, digoxin, and lisinopril exposure, a boy was born with facial and ocular dysmorphism. Examination at age 26 months showed bilateral epibulbar dermoids, covering half the corneal surface, and unilateral morning glory anomaly of the optic nerve. Ductions of the right eye were normal, but the left eye had severely impaired ductions in all directions, left hypotropia, and esotropia. Under anesthesia, the left eye could not be rotated freely in any direction. Bilateral Tessier cleft number 10 was implicated by the presence of colobomata of the middle third of the upper eyelids and eyebrows. As the cleft continued into the hairline, there was marked anterior scalp alopecia. Computed x-ray tomography showed a left middle cranial fossa arachnoid cyst and calcification of the reflected tendon of the superior oblique muscle, trochlea, and underlying sclera, with downward and lateral globe displacement. Discussion Tessier 10 clefts are very rare and usually associated with encephalocele. Bilateral 10 clefts have not been reported previously. In this case, there was coexisting unilateral morning glory anomaly and arachnoid cyst of the left middle cranial fossa but no encephalocele. Conclusions Bilateral Tessier facial cleft 10 may be associated with alopecia, morning glory anomaly, epibulbar dermoids, arachnoid cyst, and restrictive strabismus. PMID:20856062

Presence of muscle dysmorphia symptomology among male weightlifters.

PubMed

Hildebrandt, Tom; Schlundt, David; Langenbucher, James; Chung, Tammy

2006-01-01

Limited research exists on muscle dysmorphia (MD) in men and in nonclinical populations. The current study evaluated types of body image disturbance among 237 male weightlifters. Latent class analysis of 8 measures of body image disturbance revealed 5 independent types of respondents: Dysmorphic, Muscle Concerned, Fat Concerned, Normal Behavioral, and Normal. One-way analysis of variance of independent measures of body image disturbance and associated psychopathology confirmed significant differences between groups. The Dysmorphic group reported a pattern of body image disturbance consistent with MD by displaying a high overall level of body image disturbance, symptoms of associated psychopathology, steroid use, and appearance-controlling behavior. Findings generally supported classifying MD as a subtype of body dysmorphic disorder and an obsessive-compulsive spectrum disorder. Implications for studying body image disturbance in male weightlifters, and further evaluation of the MD diagnostic criteria are discussed.

Pediatric considerations in craniofacial trauma.

PubMed

Koch, Bernadette L

2014-08-01

In many respects, craniofacial trauma in children is akin to that in adults. The appearance of fractures and associated injuries is frequently similar. However, the frequencies of different types of fractures and patterns of injury in younger children vary depending on the age of the child. In addition, there are unique aspects that must be considered when imaging the posttraumatic pediatric face. Some of these are based on normal growth and development of the skull base and craniofacial structures, and others on the varying etiologies and mechanisms of craniofacial injury in children, such as injuries related to toppled furniture, nonaccidental trauma, all-terrain vehicle accidents, and impalement injuries. Copyright © 2014 Elsevier Inc. All rights reserved.

[Observational study of craniofacial growth and development in Mexican children].

PubMed

Fijikami, T K; Cedeño Pacheco, E

1991-01-01

The election of a investigation about craniofacial growing and development in Mexican children, was done due to a lack of national information in this rubric and as a fundamental part of the "growing and development in the scholastic" module of the Universidad Autónoma Metropolitana-Xochimilco, which work hypothesis was that "craniofacial growing and development in Mexican, 6 to 12 children in Xochimilco area are due to nutritional deficiency, second dentition eruption delay and dental maloclution "which was totality confirmed in a 100 Mexican facial characteristic children field work study, with cephalometric studies which permit to determine the craniofacial growing standard. This study was corroborated with a 40 children, 4 years later follow up.

Advances in Bioprinting Technologies for Craniofacial Reconstruction.

PubMed

Visscher, Dafydd O; Farré-Guasch, Elisabet; Helder, Marco N; Gibbs, Susan; Forouzanfar, Tymour; van Zuijlen, Paul P; Wolff, Jan

2016-09-01

Recent developments in craniofacial reconstruction have shown important advances in both the materials and methods used. While autogenous tissue is still considered to be the gold standard for these reconstructions, the harvesting procedure remains tedious and in many cases causes significant donor site morbidity. These limitations have subsequently led to the development of less invasive techniques such as 3D bioprinting that could offer possibilities to manufacture patient-tailored bioactive tissue constructs for craniofacial reconstruction. Here, we discuss the current technological and (pre)clinical advances of 3D bioprinting for use in craniofacial reconstruction and highlight the challenges that need to be addressed in the coming years. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation.

PubMed

Sakai, Daisuke; Dixon, Jill; Achilleos, Annita; Dixon, Michael; Trainor, Paul A

2016-01-21

Craniofacial anomalies account for approximately one-third of all birth defects and are a significant cause of infant mortality. Since the majority of the bones, cartilage and connective tissues that comprise the head and face are derived from a multipotent migratory progenitor cell population called the neural crest, craniofacial disorders are typically attributed to defects in neural crest cell development. Treacher Collins syndrome (TCS) is a disorder of craniofacial development and although TCS arises primarily through autosomal dominant mutations in TCOF1, no clear genotype-phenotype correlation has been documented. Here we show that Tcof1 haploinsufficiency results in oxidative stress-induced DNA damage and neuroepithelial cell death. Consistent with this discovery, maternal treatment with antioxidants minimizes cell death in the neuroepithelium and substantially ameliorates or prevents the pathogenesis of craniofacial anomalies in Tcof1(+/-) mice. Thus maternal antioxidant dietary supplementation may provide an avenue for protection against the pathogenesis of TCS and similar neurocristopathies.

Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation

PubMed Central

Sakai, Daisuke; Dixon, Jill; Achilleos, Annita; Dixon, Michael; Trainor, Paul A.

2016-01-01

Craniofacial anomalies account for approximately one-third of all birth defects and are a significant cause of infant mortality. Since the majority of the bones, cartilage and connective tissues that comprise the head and face are derived from a multipotent migratory progenitor cell population called the neural crest, craniofacial disorders are typically attributed to defects in neural crest cell development. Treacher Collins syndrome (TCS) is a disorder of craniofacial development and although TCS arises primarily through autosomal dominant mutations in TCOF1, no clear genotype–phenotype correlation has been documented. Here we show that Tcof1 haploinsufficiency results in oxidative stress-induced DNA damage and neuroepithelial cell death. Consistent with this discovery, maternal treatment with antioxidants minimizes cell death in the neuroepithelium and substantially ameliorates or prevents the pathogenesis of craniofacial anomalies in Tcof1+/− mice. Thus maternal antioxidant dietary supplementation may provide an avenue for protection against the pathogenesis of TCS and similar neurocristopathies. PMID:26792133

Sleep disorders and chronic craniofacial pain: Characteristics and management possibilities.

PubMed

Almoznino, Galit; Benoliel, Rafael; Sharav, Yair; Haviv, Yaron

2017-06-01

Chronic craniofacial pain involves the head, face and oral cavity and is associated with significant morbidity and high levels of health care utilization. A bidirectional relationship is suggested in the literature for poor sleep and pain, and craniofacial pain and sleep are reciprocally related. We review this relationship and discuss management options. Part I reviews the relationship between pain and sleep disorders in the context of four diagnostic categories of chronic craniofacial pain: 1) primary headaches: migraines, tension-type headache (TTH), trigeminal autonomic cephalalgias (TACs) and hypnic headache, 2) secondary headaches: sleep apnea headache, 3) temporomandibular joint disorders (TMD) and 4) painful cranial neuropathies: trigeminal neuralgia, post-herpetic trigeminal neuropathy, painful post-traumatic trigeminal neuropathy (PTTN) and burning mouth syndrome (BMS). Part II discusses the management of patients with chronic craniofacial pain and sleep disorders addressing the factors that modulate the pain experience as well as sleep disorders and including both non-pharmacological and pharmacological modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomaterials for Craniofacial Bone Engineering

PubMed Central

Tevlin, R.; McArdle, A.; Atashroo, D.; Walmsley, G.G.; Senarath-Yapa, K.; Zielins, E.R.; Paik, K.J.; Longaker, M.T.; Wan, D.C.

2014-01-01

Conditions such as congenital anomalies, cancers, and trauma can all result in devastating deficits of bone in the craniofacial skeleton. This can lead to significant alteration in function and appearance that may have significant implications for patients. In addition, large bone defects in this area can pose serious clinical dilemmas, which prove difficult to remedy, even with current gold standard surgical treatments. The craniofacial skeleton is complex and serves important functional demands. The necessity to develop new approaches for craniofacial reconstruction arises from the fact that traditional therapeutic modalities, such as autologous bone grafting, present myriad limitations and carry with them the potential for significant complications. While the optimal bone construct for tissue regeneration remains to be elucidated, much progress has been made in the past decade. Advances in tissue engineering have led to innovative scaffold design, complemented by progress in the understanding of stem cell–based therapy and growth factor enhancement of the healing cascade. This review focuses on the role of biomaterials for craniofacial bone engineering, highlighting key advances in scaffold design and development. PMID:25139365

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

Noda, Kazuo, E-mail: knoda@kuhp.kyoto-u.ac.jp; Nakamura, Tomoyuki; Komatsu, Yoshihiro

Craniofacial sutures govern the shape of the craniofacial skeleton during postnatal development. The differentiation of suture mesenchymal cells to osteoblasts is precisely regulated in part by signaling through cell surface receptors that interact with extracellular proteins. Here we report that fibulin-5, a key extracellular matrix protein, is important for craniofacial skeletal development in mice. Fibulin-5 is deposited as a fibrous matrix in cranial neural crest-derived mesenchymal tissues, including craniofacial sutures. Fibulin-5-null mice show decreased premaxillary bone outgrowth during postnatal stages. While premaxillo-maxillary suture mesenchymal cells in fibulin-5-null mice were capable of differentiating into osteoblasts, suture cells in mutant mice weremore » less proliferative. Our study provides the first evidence that fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis. - Highlights: • Fibulin-5 is deposited in cranial neural crest-derived mesenchymal tissues. • Fibulin-5-null mice show decreased premaxillary bone growth during postnatal stage. • Fibulin-5 is indispensable for facial suture mesenchymal cell proliferation.« less

Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

PubMed Central

Gaihre, Bipin; Uswatta, Suren; Jayasuriya, Ambalangodage C.

2017-01-01

Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies. PMID:29156629