Spine malformation complex in 3 diverse syndromic entities

PubMed Central

Kaissi, Ali Al; van Egmond-Fröhlich, Andreas; Ryabykh, Sergey; Ochirov, Polina; Kenis, Vladimir; Hofstaetter, Jochen G.; Grill, Franz; Ganger, Rudolf; Kircher, Susanne Gerit

2016-01-01

Abstract Rationale: Clinical and radiographic phenotypic characterizations were the base line tool of diagnosis in 3 syndromic disorders in which congenital cervico-thoracic kyphosis was the major deformity. Patients concerns: Directing maximal care toward the radiographic analysis is not only the axial malformation but also toward the appendicular abnormalities was our main concern. We fully documented the diversity of the spine phenotypic malformation complex via the clinical and radiographic phenotypes. Diagnoses: We established the diagnosis via phenotypic/genotypic confirmation in 3 diverse syndromic entities namely acampomelic campomelic dysplasia, Larsen syndrome and Morquio syndrome type A (mucopolysaccharidosis type IV A). Interventions: Surgical interventions have been carried out in the Larsen syndrome and Morquio syndrome type A, resepectively. Outcomes: The earliest the diagnosis is, the better the results are. The necessity to diagnose children in their first year of life has many folds, firstly the management would be in favor of the child's growth and development and secondly, the prognosis could be clearer to the family and the medical staff as well. Our current paper is to sensitize paediatricians, physicians and orthopedic surgeons regarding the necessity to detect the aetiological understanding in every child who manifests a constellation of malformation complex. Lesons: Scoliosis and kyphosis/kyphoscoliosis are not a diagnosis in themselves. Such deformities are mostly a symptom complex correlated to dozens of types of syndromic associations. The rate curve progression and the final severity of congenital spine tilting are related to 3 factors: (a) the type of vertebral malformation present, (b) the patient's phenotype, and (c) the diagnosis. PMID:27977582

Klippel-Feil syndrome and Dandy-Walker malformation.

PubMed

Karaman, A; Kahveci, H

2011-01-01

The Klippel-Feil deformity is a complex of osseous and visceral anomalies, which include low hairline, platybasia, fused cervical vertebrae with a short neck, and deafness. Associated central nervous system abnormalities include occipital cephalocele, Chiari I malformation, syrinx, microcephaly, and hydrocephalus. Herein, we report a case with Klippel-Feil syndrome and Dandy-Walker malformation.

Morning glory disk anomaly with ipsilateral capillary hemangioma, agenesis of the internal carotid artery, and Horner syndrome: a variant of PHACES syndrome?

PubMed

Puvanachandra, Narman; Heran, Manraj K; Lyons, Christopher J

2008-10-01

We describe a 6-week-old girl with a right upper lid capillary hemangioma, ipsilateral morning glory disk anomaly, microphthalmos, Mittendorf dot, and Horner syndrome. The ipsilateral internal carotid artery was also found to be absent. To our knowledge, this is the first patient to be reported with this group of findings. We suggest that this represents an overlap between morning glory disk and intracranial vascular abnormalities, a recognized association, and PHACES syndrome (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye, and sternal abnormalities). We discuss the common embryological basis for these abnormalities, which point to a widespread but highly variable disorder of mesodermal differentiation.

Mutations in KPTN Cause Macrocephaly, Neurodevelopmental Delay, and Seizures

PubMed Central

Baple, Emma L.; Maroofian, Reza; Chioza, Barry A.; Izadi, Maryam; Cross, Harold E.; Al-Turki, Saeed; Barwick, Katy; Skrzypiec, Anna; Pawlak, Robert; Wagner, Karin; Coblentz, Roselyn; Zainy, Tala; Patton, Michael A.; Mansour, Sahar; Rich, Phillip; Qualmann, Britta; Hurles, Matt E.; Kessels, Michael M.; Crosby, Andrew H.

2014-01-01

The proper development of neuronal circuits during neuromorphogenesis and neuronal-network formation is critically dependent on a coordinated and intricate series of molecular and cellular cues and responses. Although the cortical actin cytoskeleton is known to play a key role in neuromorphogenesis, relatively little is known about the specific molecules important for this process. Using linkage analysis and whole-exome sequencing on samples from families from the Amish community of Ohio, we have demonstrated that mutations in KPTN, encoding kaptin, cause a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures. Our immunofluorescence analyses in primary neuronal cell cultures showed that endogenous and GFP-tagged kaptin associates with dynamic actin cytoskeletal structures and that this association is lost upon introduction of the identified mutations. Taken together, our studies have identified kaptin alterations responsible for macrocephaly and neurodevelopmental delay and define kaptin as a molecule crucial for normal human neuromorphogenesis. PMID:24239382

Usher syndrome associated with a variant of Dandy-Walker malformation.

PubMed

Simsek, Tulay; Ozdamar, Yasemin; Simsek, Enver; Men, Gamze

2010-05-21

Three cases of Usher syndrome associated with a variant of Dandy-Walker malformation in three siblings from consanguineous Turkish parents are described. The siblings had retinitis pigmentosa and hearing loss. Two of the siblings also had mental retardation, which is not a constant finding in Usher syndrome. Dandy-Walker malformation might have contributed to the mental retardation in two of these patients and might be a coincidental finding with Usher syndrome. Copyright 2010, SLACK Incorporated.

Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and seizures.

PubMed

Baple, Emma L; Maroofian, Reza; Chioza, Barry A; Izadi, Maryam; Cross, Harold E; Al-Turki, Saeed; Barwick, Katy; Skrzypiec, Anna; Pawlak, Robert; Wagner, Karin; Coblentz, Roselyn; Zainy, Tala; Patton, Michael A; Mansour, Sahar; Rich, Phillip; Qualmann, Britta; Hurles, Matt E; Kessels, Michael M; Crosby, Andrew H

2014-01-02

The proper development of neuronal circuits during neuromorphogenesis and neuronal-network formation is critically dependent on a coordinated and intricate series of molecular and cellular cues and responses. Although the cortical actin cytoskeleton is known to play a key role in neuromorphogenesis, relatively little is known about the specific molecules important for this process. Using linkage analysis and whole-exome sequencing on samples from families from the Amish community of Ohio, we have demonstrated that mutations in KPTN, encoding kaptin, cause a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures. Our immunofluorescence analyses in primary neuronal cell cultures showed that endogenous and GFP-tagged kaptin associates with dynamic actin cytoskeletal structures and that this association is lost upon introduction of the identified mutations. Taken together, our studies have identified kaptin alterations responsible for macrocephaly and neurodevelopmental delay and define kaptin as a molecule crucial for normal human neuromorphogenesis. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

[Capillary leak syndrome disclosing Ofuji's papuloerythroderma].

PubMed

Carsuzaa, F; Pierre, C; Morand, J J; Farnarier, C; Marrot, F; Kaplanski, G

1996-01-01

Capillary leak syndrome is a specific entity among syndromes with capillary hyperpermeability. Endothelial cell activation is related to the higt level of adhesion molecules (sICAM-1, sVCAM-&, sCD62E) possibly due to several cytokines (IL-2, TNF ...). An 84-year-old woman was hospitalized for erythroderma. Ofujui papuloerythroderma was diagnosed and edema was attributed to capillary leak. A kinetic study of several cytokines and adhesion molecules sCD62E, sVCAM-1 and sICAM-1 was done. Outcome was favorable with corticopuvatherapy. The capillary leak syndrome reported here is simlar to that described in other erythrodermas with or without lymphoma. The keratinocyte would be activated by the CD4 T lymphocyte via the gamma-interferon mediator. The T cell secretes cytokines (interleukin-1, tumor necrosis factor ...) which activates the endothelium and increases vascular permeability. The level of adhesion molecules and changes observed during the episode of edema demonstrated the endothelial activation.

Thromboembolism and congenital malformations: from Duane syndrome to thalidomide embryopathy.

PubMed

Parsa, Cameron F; Robert, Matthieu P

2013-04-01

To propose a pathophysiologic mechanism to unify a variety of disparate sporadic congenital malformations. Inductive and deductive analyses to correlate malformation laterality with asymmetries in thoracic anatomy, critical analysis of malformations with female predominance, and concepts of hydrodynamic pressure gradients in vascular growth were applied to the ensuing development of guiding tissue scaffolds for cellular proliferation, differentiation, and apoptosis. Duane syndrome may develop following a focal vascular insult to the sixth nerve trunk with axonal degeneration, allowing for substitutive innervation from third nerve axons to the lateral rectus muscle. Causative fibrin clots may originate from the venous system and paradoxically migrate through physiological right-to left shunts, or they may arise directly from the heart. Hence, the unilateral, left-sided, and female predominance of Duane syndrome results from the asymmetry in the thoracic anatomy and from thrombosis risk factors. Embolic occlusions may also alter local hemodynamic pressure gradients, leading to the compensatory enlargement and persistence of the fetal vasculature and may dysregulate tissue growth. Within the eye, this results in forms of Peters anomaly, unilateral congenital cataracts, and the morning glory disc anomaly, all in the vascular territory of the carotid arteries that also share a propensity for left-sided involvement in girls. Most aberrant misinnervation phenomena (eg, jaw-winking syndrome, crocodile tear syndrome, Brown syndrome, and congenital fibrosis syndrome) and, by extrapolation, the hypoplasia or dysgenesis of noncephalic anatomical structures (including limbs) may be similarly explained. Such malformations will occur more frequently under thrombogenic conditions, such as those induced by thalidomide. Fibrin emboli and focal hypoperfusion may explain the development of many sporadic congenital malformations.

Congenital Auricular Malformations: Description of Anomalies and Syndromes.

PubMed

Bartel-Friedrich, Sylva

2015-12-01

Half of the malformations in the ear, nose, and throat region affect the ear. Malformations of the external ear (pinna or auricle with external auditory canal [EAC]) are collectively termed microtia. Microtia is a congenital anomaly that ranges in severity from mild structural abnormalities to complete absence of the external ear (anotia). Microtia occurs more frequently in males (∼2 or 3:1), is predominantly unilateral (∼70-90%), and more often involves the right ear (∼60%). The reported prevalence varies geographically from 0.83 to 17.4 per 10,000 births. Microtia may be genetic (with family history, spontaneous mutations) or acquired. Malformations of the external ear can also involve the middle ear and/or inner ear. Microtia may be an isolated birth defect, but associated anomalies or syndromes are described in 20 to 60% of cases, depending on study design. These generally fit within the oculo-auriculo-vertebral spectrum; defects are located most frequently in the facial skeleton, facial soft tissues, heart, and vertebral column, or comprise a syndrome (e.g., Treacher Collins syndrome). Diagnostic investigation of microtia includes clinical examination, audiologic testing, genetic analysis and, especially in higher grade malformations with EAC deformities, computed tomography (CT) or cone-beam CT for the planning of surgery and rehabilitation procedures, including implantation of hearing aids. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Significance of Macrocephaly or Enlarging Head Circumference in Infants With the Triad

PubMed Central

Miller, David; Barnes, Patrick; Miller, Marvin

2015-01-01

Abstract Infants with the triad (neurologic dysfunction, subdural hematoma [SDH], and retinal hemorrhage) are often diagnosed as victims of shaken baby syndrome. Medical conditions/predisposing factors to developing the triad are often dismissed: short falls, birth-related SDH that enlarges, macrocephaly, sinus/cortical vein thrombosis, and others. Six infants with the triad are described in which child abuse was diagnosed, but parents denied wrongdoing. All 6 had either macrocephaly or enlarging head circumference, which suggested medical explanations. Three infants incurred short falls, 1 had a difficult delivery in which there was likely a rebleed of a birth-related SDH, 1 had a spontaneous SDH associated with increased extra-axial fluid spaces, and 1 had a sinus thrombosis. Following legal proceedings, all 6 infants were returned to their parents, and there has been no child maltreatment in follow-up, suggesting child abuse never happened. The results indicate that alternative medical explanations for causing the triad should be considered and that macrocephaly or an enlarging head circumference raises the possibility of a medical explanation. PMID:25893912

Low-flow vascular malformations of the head and neck: clinicopathology and image guided therapy.

PubMed

Love, Zachary; Hsu, Daniel Pierce

2012-11-01

Low-flow vascular malformations are congenital lesions secondary to errors in the development of veins, capillaries or lymphatics. The majority of these lesions are sporadic although association with heritable syndromes does occur. Patients with these lesions should be treated and evaluated by a multidisciplinary team comprising medical, radiologic and surgical subspecialties. Percutaneous image guided sclerotherapy is gaining acceptance as a firstline treatment of low-flow vascular malformations.

Spine malformation complex in 3 diverse syndromic entities: Case reports.

PubMed

Kaissi, Ali Al; van Egmond-Fröhlich, Andreas; Ryabykh, Sergey; Ochirov, Polina; Kenis, Vladimir; Hofstaetter, Jochen G; Grill, Franz; Ganger, Rudolf; Kircher, Susanne Gerit

2016-12-01

Clinical and radiographic phenotypic characterizations were the base line tool of diagnosis in 3 syndromic disorders in which congenital cervico-thoracic kyphosis was the major deformity. Directing maximal care toward the radiographic analysis is not only the axial malformation but also toward the appendicular abnormalities was our main concern. We fully documented the diversity of the spine phenotypic malformation complex via the clinical and radiographic phenotypes. We established the diagnosis via phenotypic/genotypic confirmation in 3 diverse syndromic entities namely acampomelic campomelic dysplasia, Larsen syndrome and Morquio syndrome type A (mucopolysaccharidosis type IV A). Surgical interventions have been carried out in the Larsen syndrome and Morquio syndrome type A, resepectively. The earliest the diagnosis is, the better the results are. The necessity to diagnose children in their first year of life has many folds, firstly the management would be in favor of the child's growth and development and secondly, the prognosis could be clearer to the family and the medical staff as well. Our current paper is to sensitize paediatricians, physicians and orthopedic surgeons regarding the necessity to detect the aetiological understanding in every child who manifests a constellation of malformation complex. Scoliosis and kyphosis/kyphoscoliosis are not a diagnosis in themselves. Such deformities are mostly a symptom complex correlated to dozens of types of syndromic associations. The rate curve progression and the final severity of congenital spine tilting are related to 3 factors: (a) the type of vertebral malformation present, (b) the patient's phenotype, and (c) the diagnosis.

Familial Dandy-Walker malformation associated with macrocephaly, facial anomalies, developmental delay, and brain stem dysgenesis: prenatal diagnosis and postnatal outcome in brothers. A new syndrome?

PubMed

Chitayat, D; Moore, L; Del Bigio, M R; MacGregor, D; Ben-Zeev, B; Hodgkinson, K; Deck, J; Stothers, T; Ritchie, S; Toi, A

1994-10-01

Brothers are reported with an apparently new constellation of manifestations including Dandy-Walker complex (DWC), migrational brain disorder, macrocephaly, and facial anomalies. The first brother presented at birth, the second was detected prenatally with DWC and the pregnancy terminated. Fetal brain histopathology showed DWC associated with brainstem dysgenesis. Inheritance is likely autosomal or X-linked recessive. An extensive review of the differential diagnosis of DWC is provided.

Cyclical vomiting syndrome secondary to a Chiari I malformation-a case report.

PubMed

White, William L; Bagga, Veejay; Campbell, David I; Hart, Anthony R; Ushewokunze, Shungu

2017-12-01

Cyclical vomiting syndrome is a disorder characterised by recurrent episodes of profuse vomiting. There are no cases in the literature on the management of children with presenting with cyclical vomiting syndrome and a Chiari malformation type I. We report the case of a 12-year-old child diagnosed with cyclical vomiting syndrome and a Chiari malformation type I. The patient received symptomatic relief following a craniocervical decompression.

Arteriovenous Malformations

MedlinePlus

Arteriovenous malformations (AVMs) are defects in your vascular system. The vascular system includes arteries, veins, and capillaries. Arteries carry blood away from the heart to other organs; veins carry blood back to the heart. Capillaries connect the arteries and veins. An ...

Fatal Primary Capillary Leak Syndrome in a Late Preterm Newborn.

PubMed

Kulihova, Katarina; Prochazkova, Martina; Semberova, Jana; Janota, Jan

2016-10-01

Primary capillary leak syndrome is a rare disease of unknown etiology, characterized by episodes of vascular collapse and plasma extravasation, which may lead to multiple organ failure. Primary capillary leak is extremely rare in children. The authors report a case of a late preterm newborn with fatal capillary leak syndrome of unknown etiology, manifesting as hypotension unresponsive to treatment, extravasation leading to generalised edema, disseminated intravascular coagulation and finally, multiple organ dysfunction syndrome. Aggressive volumotherapy and a combination of inotropes and high doses of terlipressin did not influence systemic vascular collapse and plasma extravasation. The newborn developed multiple organ failure and died on day 27 of life. Investigations performed failed to reveal any specific cause of capillary leak. This is the first report of a fatal primary capillary leak syndrome in a newborn.

Proteus syndrome: A rare cause of gigantic limb.

PubMed

Chakrabarti, Nandini; Chattopadhyay, Chandan; Bhuban, Majhi; Pal, Salil Kumar

2014-04-01

A congenital disorder with variable manifestations, including partial gigantism of the hands and feet with hypertrophy of soles, nevi, hemihypertrophy, gynecomastia, macrocephaly and other skull abnormalities, and abdominal lipomatosis. The cause is unknown, although a genetic origin, generally of autosomal-dominant transmission, has been conjectured. Symptoms can be treated, but there is no known cure. We present the case of a young male with grotesque overgrowth of the right lower limb, splenomegaly and multiple nevi. Angiography revealed venous malformation within the limb. The findings are in conformity to the criteria for the Proteus syndrome.

Multiple cavernous malformations presenting in a patient with Poland syndrome: A case report

PubMed Central

2011-01-01

Introduction Poland syndrome is a congenital disorder related to chest and hand anomalies on one side of the body. Its etiology remains unclear, with an ipsilateral vascular alteration (of unknown origin) to the subclavian artery in early embryogenesis being the currently accepted theory. Cavernous malformations are vascular hamartomas, which have been linked to a genetic etiology, particularly in familial cases, which commonly present with multiple lesions. Our case report is the first to describe multiple cavernous malformations associated with Poland syndrome, further supporting the vascular etiology theory, but pointing to a genetic rather than a mechanistic factor disrupting blood flow in the corresponding vessels. Case presentation A 41-year-old Caucasian man with Poland syndrome on the right side of his body presented to our hospital with a secondary generalized seizure and was found to have multiple cavernous malformations distributed in his brain, cerebellum, and brain stem, with a predominance of lesions in the left hemisphere. Conclusion The distribution of cavernous malformations in the left hemisphere and the right-sided Poland syndrome in our patient could not be explained by a mechanistic disruption of one of the subclavian arteries. A genetic alteration, as in familial cavernous malformations, would be a more appropriate etiologic diagnosis of Poland syndrome in our patient. Further genetic and pathological studies of the involved blood vessels in patients with Poland syndrome could lead to a better understanding of the disease. PMID:21933407

Oral-facial-digital syndrome type 1 with hypothalamic hamartoma and Dandy-Walker malformation.

PubMed

Azukizawa, Takayuki; Yamamoto, Masahito; Narumiya, Seirou; Takano, Tomoyuki

2013-04-01

We report a 1-year-old girl with oral-facial-digital syndrome type 1 with multiple malformations of the oral cavity, face, digits, and central nervous system, including agenesis of the corpus callosum, the presence of intracerebral cysts, and agenesis of the cerebellar vermis, which is associated with the subarachnoid space separating the medial sides of the cerebellar hemispheres. This child also had a hypothalamic hamartoma and a Dandy-Walker malformation, which have not been reported previously. The clinical features, including cerebral malformations, in several types of oral-facial-digital syndrome, overlap with each other. Further accumulation of new case reports and identification of new genetic mutations in oral-facial-digital syndrome may provide novel and important insights into the genetic mechanisms of this syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening.

PubMed

Marchese, Maria; Conti, Valerio; Valvo, Giulia; Moro, Francesca; Muratori, Filippo; Tancredi, Raffaella; Santorelli, Filippo M; Guerrini, Renzo; Sicca, Federico

2014-02-27

With a complex and extremely high clinical and genetic heterogeneity, autism spectrum disorders (ASD) are better dissected if one takes into account specific endophenotypes. Comorbidity of ASD with epilepsy (or paroxysmal EEG) has long been described and seems to have strong genetic background. Macrocephaly also represents a well-known endophenotype in subgroups of ASD individuals, which suggests pathogenic mechanisms accelerating brain growth in early development and predisposing to the disorder. We attempted to estimate the association of gene variants with neurodevelopmental disorders in patients with autism-epilepsy phenotype (AEP) and cranial overgrowth, analyzing two genes previously reported to be associated with autism and macrocephaly. We analyzed the coding sequences and exon-intron boundaries of GLIALCAM, encoding an IgG-like cell adhesion protein, in 81 individuals with Autism Spectrum Disorders, either with or without comorbid epilepsy, paroxysmal EEG and/or macrocephaly, and the PTEN gene in the subsample with macrocephaly. Among 81 individuals with ASD, 31 had concurrent macrocephaly. Head circumference, moreover, was over the 99.7th percentile ("extreme" macrocephaly) in 6/31 (19%) patients. Whilst we detected in GLIALCAM several single nucleotide variants without clear pathogenic effects, we found a novel PTEN heterozygous frameshift mutation in one case with "extreme" macrocephaly, autism, intellectual disability and seizures. We did not find a clear association between GLIALCAM mutations and AEP-macrocephaly comorbidity. The identification of a novel frameshift variant of PTEN in a patient with "extreme" macrocephaly, autism, intellectual disability and seizures, confirms this gene as a major candidate in the ASD-macrocephaly endophenotype. The concurrence of epilepsy in the same patient also suggests that PTEN, and the downstream signaling pathway, might deserve to be investigated in autism-epilepsy comorbidity. Working on clinical

Chiari I malformation as part of the Floating-Harbor syndrome?

PubMed

Kurzbuch, Arthur R; Magdum, Shailendra

2016-12-01

We report the first case of a patient diagnosed with Floating-Harbor syndrome (FHS) and Chiari I malformation. The 3-year-old girl was of proportional short stature, had delay of language development, conductive hearing loss and a high threshold of pain. Diagnosis of Chiari I malformation may be difficult in FHS patients who present with communication problems. Clinicians following patients with FHS should be aware of a possible relation between FHS and Chiari I malformation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Magnetic Resonance Imaging of An Adult with the Dandy-Walker Syndrome

PubMed Central

Stovall, Joyce M.; Venkatesh, Ramachandran

1988-01-01

A 30-year-old retired veteran was asymptomatic for two decades; he had carried out normal everyday living activities and was self-supporting. It was not until he was struck by an automobile, which resulted in head trauma, that the Dandy-Walker syndrome was incidentally discovered by computed tomography. Most patients with the Dandy-Walker syndrome or malformation are infants and seldom live into adulthood. Therefore, this patient is one of the very few patients with this malformation who remained in a state of cerebrospinal fluid compensation and lived to adulthood. The head trauma he received in the accident is believed to have activated neurological deficits, visual impairment, and diplopia. Although magnetic resonance imaging revealed severe hydrocephalus and lobar holoprosencephaly, the patient had no symptoms of increased intracranial pressure and no craniofacial deformities except for macrocephaly, and was capable of performing everyday living activities adequately. ImagesFigure 1Figure 2Figure 3 PMID:3249328

Microcephaly and Macrocephaly in Autism.

ERIC Educational Resources Information Center

Fombonne, Eric; Roge, Bernadette; Claverie, Jacques; Courty, Stephanie; Fremolle, Jeanne

1999-01-01

Analysis of data from 126 children with autism found macrocephaly (head circumstance microcephaly (head circumference <3rd centile) was found in 15.1%. Microcephaly was significantly associated with the presence of medical disorders. (Author/DB)

[Cutaneous larva migrans syndrome on a malformed foot (a case report)].

PubMed

Benbella, Imane; Khalki, Hanane; Lahmadi, Khalid; Kouara, Sara; Abbadi, Abderrahim; Er-Rami, Mohammed

2016-01-01

Cutaneous larva migrans syndrome is a subcutaneous dermatitis caused by hookworms' larvae, originating from animals in parasitic impasse in humans. Transcutaneous infestation is favored by contact with contaminated soil. We report the case of a 15-month-old child, native of Guinea - Bissau, suffering from cutaneous larva migrans syndrome on a malformed foot. This malformation in the form of a syndactyly, associated with a tumefaction of the foot cause a delay in the standing position. Besides, the fact that the child never wears shoes because of the sick foot is another factor contributing to the patient's infestation by the larvae of the nematode.

[Hemangiomas and vascular malformations of the head and neck].

PubMed

Hassmann-Poznańska, Elibieta; Kurzyna, Agnieszka

2006-01-01

This paper presents the review of current knowledge regarding vascular lesions of the head and neck. For many years the term hemangioma was used to describe all vascular lesions. Mulliken and Glowacki classified congenital vascular lesions and recognized two distinct entities, hemangiomas-vascular tumors and vascular malformations. Hemangiomas are usually not present at birth, proliferate during first year of life and then involute. They are composed of proliferating endothelial cells. Vascular malformations are always present at birth although not always apparent, increase slowly in size throughout whole life and never involute. They enlarge by hypertrophy of malformed vessels. Vascular malformations can be further subdivided according to the type of involved vessels as arterial, arteriovenous, venous, capillary or lymphatic. Accurate diagnosis of hemangiomas and vascular malformations remains a challenge for physicians. Although majority of hemangiomas are self limiting lesions some of them may develop complications such as; ulceration, airway obstruction, ophthalmic complications, psychosocial consequences. Segmental hemangiomas are associated with the risk of structural anomalies such as those that occur in PHACE syndrome. Clinical presentation and forms of treatment of various forms of vascular malformations are presented. Vascular malformations have to be treated according to their histopathology and location, as well as their hemodynamic features shown by radiological examinations.

Genetic Modifiers of the Physical Malformations in Velo-Cardio-Facial Syndrome/DiGeorge Syndrome

ERIC Educational Resources Information Center

Aggarwal, Vimla S.; Morrow, Bernice E.

2008-01-01

Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), the most common micro-deletion disorder in humans, is characterized by craniofacial, parathyroid, and thymic defects as well as cardiac outflow tract malformations. Most patients have a similar hemizygous 3 million base pair deletion on 22q11.2. Studies in mouse have shown that "Tbx1", a…

Tetraphocomelia with the Waardenburg syndrome and multiple malformations.

PubMed

Wu, Hue-Tsi; Wainwright, Helen; Beighton, Peter

2009-04-01

A male infant delivered spontaneously at the 29th week of pregnancy had gross tetraphocomelia and features of the Waardenburg syndrome. There were no relevant factors in the pregnancy nor family history. It is possible that microdeletions or contiguous gene defects are involved in the pathogenesis of these malformations.

Safety and Efficacy Study of Sirolimus in Complicated Vascular Anomalies

ClinicalTrials.gov

2015-02-03

Kaposiform Hemangioendotheliomas; Tufted Angioma; Capillary Venous Lymphatic Malformation; Venous Lymphatic Malformation; Microcystic Lymphatic Malformation; Mucocutaneous Lymphangiomatosis and Thrombocytopenia; Capillary Lymphatic Arterial Venous Malformations; PTEN Overgrowth Syndrome With Vascular Anomaly; Lymphangiectasia Syndromes

Mutations in STRA6 Cause a Broad Spectrum of Malformations Including Anophthalmia, Congenital Heart Defects, Diaphragmatic Hernia, Alveolar Capillary Dysplasia, Lung Hypoplasia, and Mental Retardation

PubMed Central

Pasutto, Francesca; Sticht, Heinrich; Hammersen, Gerhard; Gillessen-Kaesbach, Gabriele; FitzPatrick, David R.; Nürnberg, Gudrun; Brasch, Frank; Schirmer-Zimmermann, Heidemarie; Tolmie, John L.; Chitayat, David; Houge, Gunnar; Fernández-Martínez, Lorena; Keating, Sarah; Mortier, Geert; Hennekam, Raoul C. M.; von der Wense, Axel; Slavotinek, Anne; Meinecke, Peter; Bitoun, Pierre; Becker, Christian; Nürnberg, Peter; Reis, André; Rauch, Anita

2007-01-01

We observed two unrelated consanguineous families with malformation syndromes sharing anophthalmia and distinct eyebrows as common signs, but differing for alveolar capillary dysplasia or complex congenital heart defect in one and diaphragmatic hernia in the other family. Homozygosity mapping revealed linkage to a common locus on chromosome 15, and pathogenic homozygous mutations were identified in STRA6, a member of a large group of “stimulated by retinoic acid” genes encoding novel transmembrane proteins, transcription factors, and secreted signaling molecules or proteins of largely unknown function. Subsequently, homozygous STRA6 mutations were also demonstrated in 3 of 13 patients chosen on the basis of significant phenotypic overlap to the original cases. While a homozygous deletion generating a premature stop codon (p.G50AfsX22) led to absence of the immunoreactive protein in patient’s fibroblast culture, structural analysis of three missense mutations (P90L, P293L, and T321P) suggested significant effects on the geometry of the loops connecting the transmembrane helices of STRA6. Two further variations in the C-terminus (T644M and R655C) alter specific functional sites, an SH2-binding motif and a phosphorylation site, respectively. STRA6 mutations thus define a pleiotropic malformation syndrome representing the first human phenotype associated with mutations in a gene from the “STRA” group. PMID:17273977

Clival Malformations in CHARGE Syndrome.

PubMed

Mahdi, E S; Whitehead, M T

2018-06-01

CHARGE syndrome is a multisystemic congenital disorder, most commonly including coloboma, heart malformations, choanal atresia, developmental delay, and genital and ear anomalies. The diagnostic criteria for CHARGE syndrome have been refined with time. However, limited reports describe skull base and craniocervical junction abnormalities. Recently, a coronal clival cleft has been identified in association with CHARGE syndrome. The aim of our study was to assess the prevalence of clival pathology in CHARGE syndrome. In this retrospective study, the CT/MR imaging data base at a single academic children's hospital was queried for the phrase "CHARGE syndrome" during a 17-year period (2001-2017). Electronic medical records were reviewed to confirm the diagnosis. Images were assessed for skull base anomalies, specifically clival hypoplasia and dysplasia. The search yielded 42 examinations (21 CTs and 21 MRIs) from 15 distinct patients (mean age, 4.1 ± 5.6 years; range, 2 days to 19 years). CHARGE syndrome diagnosis was confirmed either by clinical and genetic testing ( n = 6) or by clinical diagnosis only ( n = 9). A coronal clival cleft was identified in 87% of patients (37 examinations, n = 13 patients), either partial (53%) or complete (33%). Clival hypoplasia without clefting was present in all 5 examinations from the remaining 2 patients. Clival pathology is universal in CHARGE syndrome. Coronal clival clefts are extremely common, representing a useful additional diagnostic finding. Detection of a clival cleft should alert the radiologist to examine the palate, choana, eyes, ears, and olfactory centers for other signs of CHARGE syndrome. © 2018 by American Journal of Neuroradiology.

Megalencephaly, polymicrogyria and ribbon-like band heterotopia: A new cortical malformation.

PubMed

Kobayashi, Yu; Magara, Shinichi; Okazaki, Kenichi; Komatsubara, Takao; Saitsu, Hirotomo; Matsumoto, Naomichi; Kato, Mitsuhiro; Tohyama, Jun

2016-11-01

Megalencephalic polymicrogyria syndromes include megalencephaly-capillary malformation and megalencephaly-polymicrogyria-polydactyly-hydrocephalus. Recent genetic studies have identified that genes in the PI3K-AKT pathway are involved in the pathogenesis of these disorders. Herein, we report a patient who presented with developmental delay, epilepsy and peculiar neuroimaging findings of megalencephaly, polymicrogyria, and symmetrical band heterotopia in the periventricular region. The heterotopias exhibited inhomogeneous signals with undulatory mixtures of gray and white matter, resembling ribbon-like heterotopia, with a predominance in the temporal to occipital regions. These neuroradiological findings were not consistent with those in known megalencephalic polymicrogyria syndromes. No genetic abnormality was identified through whole-exome sequencing. The neuroimaging findings of this patient may represent a novel cortical malformation involving megalencephaly with polymicrogyria and ribbon-like band heterotopia. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Seckel's syndrome and malformations of cortical development: report of three new cases and review of the literature.

PubMed

Capovilla, G; Lorenzetti, M E; Montagnini, A; Borgatti, R; Piccinelli, P; Giordano, L; Accorsi, P; Caudana, R

2001-05-01

Seckel's syndrome is a rare form of primordial dwarfism, characterized by peculiar facial appearance. In the past, this condition was overdiagnosed, and most attention was given to the facial and skeletal features to define more precise diagnostic criteria. The presence of mental retardation and neurologic signs is one of the peculiar features of this syndrome, but only recently were rare cases of malformation of cortical development described, as documented by magnetic resonance imaging (MRI). Here, we present three new cases of Seckel's syndrome showing different malformations of cortical development (one gyral hypoplasia, one macrogyria and partial corpus callosum agenesis, and one bilateral opercular macrogyria). We hypothesize that the different types of clinical expression of our patients could be explained by different malformation of cortical development types. We think that MRI studies could be performed in malformative syndromes because of the possible correlations between type and extent of the lesion and the clinical picture of any individual case.

[Vascular malformations in the Williams-Beuren syndrome: report of three new cases].

PubMed

Sator, Hicham; Rhouni, Fatima Ezzahra; Benjouad, Ibitihale; Rhouni, Fatima Ezzahra; Benjouad, Ibitihale; Dafiri, Rachida; Chat, Latifa

2016-01-01

The Williams-Beuren syndrome is a rare genetic disease. It combines classically specific facial dysmorphism, cardiovascular malformations and specific neuropsychological profile. We report three cases of Williams-Beuren syndrome in children with particular emphasis on vascular abnormalities observed on CT angiography and MR angiography.

[Aicardi syndrome with Dandy-Walker type malformation].

PubMed

Laguado-Herrera, Yuly V; Manrique-Hernández, Edgar F; Peñaloza-Mantilla, Camilo A; Quintero-Gómez, David A; Contreras-García, Gustavo A; Sandoval-Martínez, Diana K

2015-07-16

Aicardi syndrome (OMIM 304050) was first described in 1965. Its classic triad consists of infantile spasms, partial or total agenesis of the corpus callosum and ocular disorders, such as chorioretinal lacunae. It has been posited that it is due to a mechanism involving X-linked dominant inheritance. We report the case of a full-term female, with no pathological familial history or parental consanguinity, with a prenatal diagnosis of Dandy-Walker type malformation, who presented convulsions, coloboma of the optic nerve, thoracic vertebral block with presence of scoliosis, transfontanellar ultrasound imaging showing agenesis of the corpus callosum and karyotype 46,XX. She was diagnosed with Aicardi syndrome and died at the age of one and a half months. The autopsy revealed supratentorial hydrocephalus with the presence of choroid plexus papilloma, a cyst in the posterior fossa (fourth ventricle), hypoplasia of the cerebellar vermis, agenesis of the left hemisphere of the corpus callosum and cerebellum, characteristic facial features of the syndrome, ogival palate, pectus excavatum, scoliosis, paraovarian cyst and hepatomegaly. Few cases of an association between the pathology and the presence of Dandy-Walker malformation have been described. We report a new case of the association, bearing in mind that the related disorders, mainly agenesis or hypoplasia of the corpus callosum, suggest the existence of an underlying genetic component. A study of the search for the aetiology must be focused on evaluating those genes that are related with neurodevelopment and its activation in the organogenesis stage. The definitive diagnosis establishes the prognosis, management and genetic counselling of the family.

De Novo 3q22.3q24 Microdeletion in a Patient With Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome, Dandy-Walker Malformation, and Wisconsin Syndrome.

PubMed

Ramineni, Anand; Coman, David

2016-01-01

Interstitial deletions affecting the long arm of chromosome 3 have been associated with a broad phenotype. This has included the features of blepharophimosis-ptosis-epicanthus inversus syndrome, Dandy-Walker malformation, and the rare Wisconsin syndrome. The authors report a young female patient presenting with features consistent with all 3 of these syndromes. This has occurred in the context of a de novo 3q22.3q24 microdeletion including FOXL2 , ZIC1 , and ZIC4 . This patient provides further evidence for the role of ZIC1 and ZIC4 in Dandy-Walker malformation and is the third reported case of Dandy-Walker malformation to have associated corpus callosum thinning. This patient is also only the seventh to be reported with the rare Wisconsin syndrome phenotype.

Ear malformations, hearing loss and hearing rehabilitation in children with Treacher Collins syndrome.

PubMed

Rosa, Francisco; Coutinho, Miguel Bebiano; Ferreira, João Pinto; Sousa, Cecilia Almeida

2016-01-01

The aim of this study was to assess the main ear malformations, hearing loss and auditory rehabilitation in children with Treacher Collins syndrome. We performed a retrospective study of 9 children with Treacher Collins syndrome treated in a central hospital between January 2003 and January 2013. This study showed a high incidence of malformations of the outer and middle ear, such as microtia, atresia or stenosis of the external auditory canal, hypoplastic middle ear cavity, dysmorphic or missing ossicular chain. Most patients had bilateral hearing loss of moderate or high degree. In the individuals studied, there was functional improvement in patients with bone-anchored hearing aids in relation to conventional hearing aids by bone conduction. Treacher Collins syndrome is characterized by bilateral malformations of the outer and middle ear. Hearing rehabilitation in these children is of utmost importance, and bone-anchored hearing aids is the method of choice. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Magnetic Resonance Imaging of Malformations of Midbrain-Hindbrain.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Castillo, Mauricio

2016-01-01

We aim to review the magnetic resonance imaging appearance of malformations of midbrain and hindbrain. These can be classified as predominantly cerebellar malformations, combined cerebellar and brain stem malformations, and predominantly brain stem malformations. The diagnostic criteria for the majority of these morphological malformations are based on neuroimaging findings. The predominantly cerebellar malformations include predominantly vermian hypoplasia seen in Dandy-Walker malformation and rhombencephalosynapsis, global cerebellar hypoplasia reported in lissencephaly and microlissencephaly, and unilateral cerebellar hypoplasia seen in PHACES, vanishing cerebellum, and cerebellar cleft. Cerebellar dysplasias are seen in Chudley-McCullough syndrome, associated with LAMA1 mutations and GPR56 mutations; Lhermitte-Duclos disease; and focal cerebellar dysplasias. Cerebellar hyperplasias are seen in megalencephaly-related syndromes and hemimegalencephaly with ipsilateral cerebellomegaly. Cerebellar and brain stem malformations include tubulinopathies, Joubert syndrome, cobblestone malformations, pontocerebellar hypoplasias, and congenital disorders of glycosylation type Ia. Predominantly brain stem malformations include congenital innervation dysgenesis syndrome, pontine tegmental cap dysplasia, diencephalic-mesencephalic junction dysplasia, disconnection syndrome, and pontine clefts.

De Novo 3q22.3q24 Microdeletion in a Patient With Blepharophimosis–Ptosis–Epicanthus Inversus Syndrome, Dandy-Walker Malformation, and Wisconsin Syndrome

PubMed Central

Ramineni, Anand

2016-01-01

Interstitial deletions affecting the long arm of chromosome 3 have been associated with a broad phenotype. This has included the features of blepharophimosis–ptosis–epicanthus inversus syndrome, Dandy-Walker malformation, and the rare Wisconsin syndrome. The authors report a young female patient presenting with features consistent with all 3 of these syndromes. This has occurred in the context of a de novo 3q22.3q24 microdeletion including FOXL2, ZIC1, and ZIC4. This patient provides further evidence for the role of ZIC1 and ZIC4 in Dandy-Walker malformation and is the third reported case of Dandy-Walker malformation to have associated corpus callosum thinning. This patient is also only the seventh to be reported with the rare Wisconsin syndrome phenotype. PMID:28503614

Anterior Mesencephalic Cap Dysplasia: Novel Brain Stem Malformative Features Associated with Joubert Syndrome.

PubMed

Arrigoni, F; Romaniello, R; Peruzzo, D; De Luca, A; Parazzini, C; Valente, E M; Borgatti, R; Triulzi, F

2017-12-01

In Joubert syndrome, the "molar tooth" sign can be associated with several additional supra- and infratentorial malformations. Here we report on 3 subjects (2 siblings, 8-14 years of age) with Joubert syndrome, showing an abnormal thick bulging of the anterior profile of the mesencephalon causing a complete obliteration of the interpeduncular fossa. DTI revealed that the abnormal tissue consisted of an ectopic white matter tract with a laterolateral transverse orientation. Tractographic reconstructions support the hypothesis of impaired axonal guidance mechanisms responsible for the malformation. The 2 siblings were compound heterozygous for 2 missense variants in the TMEM67 gene, while no mutations in a panel of 120 ciliary genes were detected in the third patient. The name "anterior mesencephalic cap dysplasia," referring to the peculiar aspect of the mesencephalon on sagittal MR imaging, is proposed for this new malformative feature. © 2017 by American Journal of Neuroradiology.

[Malformation syndromes in the spanish literature: The first descriptions].

PubMed

García Nieto, V; Zafra Anta, M; Bassat, Q; de Arana Amurrio, J I; Fernández Menéndez, J M; Fernández Teijeiro, J J; Gorrotxategi Gorrotxategi, P J; Ponte Hernando, F

2013-12-01

Malformation or dysmorphic syndromes are conditions that are defined by the combination of a set of major and minor malformations that generally have a genetic origin. We investigated the early Spanish descriptions of a large number of sydromes. We started the study from the definition in a classic treatise on the subject. Among the 60 selected syndromes studied, at least two articles of each syndrome among those published in Spain and for the first time were listed in the Spanish Medical Index. For years prior to 1970, it expanded The search was expanded to PubMed, for the years before 1970. We collected 64 articles that referred to 58 syndromes. Four articles were written during the first half of the twentieth century. Almost half of the works (n=30) appeared in the 1970's. The papers were published in ten Spanish pediatric, nine Spanish non-pediatric, three pediatric non-Spanish and two non-Spanish non-pediatric Journals. The Journals with the most articles published were Anales de Pediatría y Revista Española de Pediatría. The hospitals where the articles originate more often were Hospital La Paz, Madrid and Hospital Clinic, Barcelona. The rest of the works were written in 30 pediatric hospitals and two more in non-Spanish hospitals. The number of authors increased with the passage of time. Although there were potential limitations, we have identified what may be the first descriptions of 58 syndromes, among the 60 chosen initially. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Beckwith-Wiedemann syndrome and Chiari I malformation--a case-based review of central nervous system involvement in hemihypertrophy syndromes.

PubMed

Udayakumaran, Suhas; Onyia, Chiazor U

2015-05-01

Beckwith-Wiedemann syndrome (BWS) is an unusual complex of abnormalities that includes mainly omphalocele, macroglossia, gigantism, visceromegaly, and neonatal hypoglycemia. Type I Chiari malformation, on the other hand, is defined as ectopia of the cerebellar tonsils below the plane of the foramen magnum. Only one case of association of BWS with Chiari I malformation has been previously reported in the literature. Several conditions involving congenital hemihypertrophy have been previously reported in association with Type I Chiari malformation. The pathophysiological mechanism for most of these associations is thought to be quite complex and still remains unclear. However, the presence of tonsillar herniation in BWS has been explained by Tubbs and Oakes in the only one existing case report of BWS with Type I Chiari malformation in the literature, to be due to associated hemihypertrophy of the skull base. We additionally suggest that cerebellar hypertrophy may also contribute to the tonsillar herniation and fourth ventricular outlet obstruction. We now report our recent experience on this association following a review of the literature on association of other hemihypertrophy syndromes with the central nervous system anomalies. We believe that a common pathogenesis of Type I Chiari malformation occurs in conditions of hemihypertrophy including BWS, probably secondary to dysmorphology involving the posterior cranial fossa, and is not just an associated finding.

Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome)

PubMed Central

Pruszewicz, Antoni; Wiskirska-Woźnica, Bożena; Wojnowski, Waldemar; Czerniejewska, Hanna; Jackowska, Joanna; Jarmuż, Małgorzata; Szyfter, Krzysztof; Leszczyńska, Małgorzata

2014-01-01

Patient: Female, 6 Final Diagnosis: Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome) Symptoms: — Medication: — Clinical Procedure: — Specialty: Otolaryngology Objective: Congenital defects Background: Communication process disorders are very frequent in rare cases of chromosomal aberrations (deletions, insertions, and trisomies) such as Down syndrome (trisomy 21), Turner syndrome, Edwards syndrome (trisomy 18), or Patau syndrome (trisomy 13). Sometimes phenotype may delusively correspond to the characteristic features of a given syndrome, but genotype tests do not confirm its presence. Case Report: We present the case of a 6-year-old girl admitted to the Clinic of Phoniatrics and Audiology for the assessment of communication in the course of congenital malformations with phenotype characteristic for trisomy 18 (Edwards syndrome). Immediately upon birth, dysmorphic changes suggesting trisomy 18 (Edwards syndrome) were observed, but trisomy 18 was excluded after karyotype test results were normal (46, XX). Conclusions: Disturbed articulation was diagnosed: deformed linguo-dental and palatal sounds, interdental realization with flat tongue of the /s/, /z/, /c/, /dz/, /ś/, /ź/, /ć/, /dz/ sounds (sigmatismus interdentalis). Hearing loss was confirmed. PMID:24478819

Abernethy malformation associated with Caroli's syndrome in a patient with a PKHD1 mutation: a case report.

PubMed

Mi, Xiao-Xiao; Li, Xiao-Guang; Wang, Zi-Rong; Lin, Ling; Xu, Chun-Hai; Shi, Jun-Ping

2017-08-16

Abernethy malformation is a rare congenital anomaly characterised by the partial or complete absence of the portal vein and the subsequent development of an extrahepatic portosystemic shunt. Caroli's disease is a rare congenital condition characterised by non-obstructive saccular intrahepatic bile duct dilation. Caroli's disease combined with congenital hepatic fibrosis and/or renal cystic disease is referred to - Caroli's syndrome. The combination of Abernethy malformation and Caroli's syndrome has not been reported previously. We present the case of a 23-year-old female who was found to have both type II Abernethy malformation and Caroli's syndrome. Radiological imaging was performed, including computed tomography with three-dimensional reconstruction and magnetic resonance imaging with (magnetic resonance cholangiopancreatography (MRCP), which revealed a side-to-side portocaval shunt, intrahepatic bile duct dilation, congenital hepatic fibrosis, and renal cysts. In addition, PKHD1 (polycystic kidney and hepatic disease 1) gene mutational analysis revealed a paternally inherited heterozygous missense mutation (c.1877A > G, p.Lys626Arg). A liver biopsy confirmed the pathological features of Caroli's syndrome. To our knowledge, this is the first reported case of a patient with both type II Abernethy malformation and Caroli's syndrome diagnosed using a comprehensive approach that included imaging, mutational analysis, and liver biopsy. Additionally, this is the second reported case to date of an Asian patient presenting with liver and renal disorders with the same paternally inherited PKHD1 missense mutation.

Dandy-Walker malformation with postaxial polydactly: a new case of Pierquin syndrome.

PubMed

Passalacqua, Cristóbal A; Villegas, Victor P; Aracena, Mariana I; Mellado, Cecilia X

2013-04-01

The combination of Dandy-Walker malformation, other central nervous system anomalies, and postaxial polydactyly has been reported previously in two pairs of siblings. We propose the name 'Pierquin syndrome' for this combination and we report a new patient with this disorder.

Vascular malformations: an update.

PubMed

Gloviczki, Peter; Duncan, Audra; Kalra, Manju; Oderich, Gustavo; Ricotta, Joseph; Bower, Thomas; McKusick, Michael; Bjarnason, Haraldur; Driscoll, David

2009-06-01

Vascular malformations occur as a result of an arrest in the development of the vascular system. The modified Hamburg classification distinguishes arterial, venous, arteriovenous, capillary, lymphatic, and mixed vascular malformations. Each malformation is further subdivided based on anatomy and on the time when arrest in development of the embryogenesis occurred; malformations can be truncular or extratruncular. Progress in the last decade in management has been significant because of improvements in open surgical procedures and perfection of percutaneous and hybrid endovascular interventions and devices, such as balloons, stents, and stent-grafts. There has been increasing use of embolization for the treatment of malformations with coils, other particles, glue, or with endovascular placement of occlusive plugs. Absolute alcohol, detergent liquids, or foam have been used for sclerotherapy with improved efficacy. The agents are delivered percutaneously or through a catheter placed either into the feeding arteries or the draining veins. This review aims to aid vascular and endovascular specialists in staying familiar with vascular malformations. These specialists need to be able to evaluate the patients, perform treatment if appropriate, or refer complex cases to multidisciplinary vascular malformation clinics and vascular centers.

Developmental outcomes of Down syndrome and Dandy-Walker malformation

PubMed Central

Love, Kaitlin; Huddleston, Lillie; Olney, Pat; Wrubel, David; Visootsak, Jeannie

2012-01-01

Dandy-Walker syndrome (DWS), or Dandy-Walker complex, is a congenital brain malformation of the posterior fossa, typically resulting in developmental delay and cognitive disability. The co-occurrence of Down syndrome (DS) and DWS is relatively uncommon; thus, its impact on developmental outcomes has not been fully elucidated. Herein, we report a case of a 37-month-old child with DS and DWS, who is functioning at the following age-equivalent: gross motor at a 9-mo level, fine motor 6 mo, expressive language 14 mo, receptive language 9 mo. As such, it is important to determine how the DWS influences developmental outcomes, and appreciate the importance of early interventional therapy. PMID:22866020

Malformation syndromes caused by disorders of cholesterol synthesis

PubMed Central

Porter, Forbes D.; Herman, Gail E.

2011-01-01

Cholesterol homeostasis is critical for normal growth and development. In addition to being a major membrane lipid, cholesterol has multiple biological functions. These roles include being a precursor molecule for the synthesis of steroid hormones, neuroactive steroids, oxysterols, and bile acids. Cholesterol is also essential for the proper maturation and signaling of hedgehog proteins, and thus cholesterol is critical for embryonic development. After birth, most tissues can obtain cholesterol from either endogenous synthesis or exogenous dietary sources, but prior to birth, the human fetal tissues are dependent on endogenous synthesis. Due to the blood-brain barrier, brain tissue cannot utilize dietary or peripherally produced cholesterol. Generally, inborn errors of cholesterol synthesis lead to both a deficiency of cholesterol and increased levels of potentially bioactive or toxic precursor sterols. Over the past couple of decades, a number of human malformation syndromes have been shown to be due to inborn errors of cholesterol synthesis. Herein, we will review clinical and basic science aspects of Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis, HEM dysplasia, X-linked dominant chondrodysplasia punctata, Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects Syndrome, sterol-C-4 methyloxidase-like deficiency, and Antley-Bixler syndrome. PMID:20929975

Subtelomeric deletions of chromosome 6p: molecular and cytogenetic characterization of three new cases with phenotypic overlap with Ritscher-Schinzel (3C) syndrome.

PubMed

Descipio, Cheryl; Schneider, Lori; Young, Terri L; Wasserman, Nora; Yaeger, Dinah; Lu, Fengmin; Wheeler, Patricia G; Williams, Marc S; Bason, Lynn; Jukofsky, Lori; Menon, Ammini; Geschwindt, Ryan; Chudley, Albert E; Saraiva, Jorge; Schinzel, Albert A G L; Guichet, Agnes; Dobyns, William E; Toutain, Annick; Spinner, Nancy B; Krantz, Ian D

2005-04-01

We have identified six children in three families with subtelomeric deletions of 6p25 and a recognizable phenotype consisting of ptosis, posterior embryotoxon, optic nerve abnormalities, mild glaucoma, Dandy-Walker malformation, hydrocephalus, atrial septal defect, patent ductus arteriosus, and mild mental retardation. There is considerable clinical overlap between these children and individuals with the Ritscher-Schinzel (or cranio-cerebello-cardiac (3C)) syndrome (OMIM #220210). Clinical features of 3C syndrome include craniofacial anomalies (macrocephaly, prominent forehead and occiput, foramina parietalia, hypertelorism, down-slanting palpebral fissures, ocular colobomas, depressed nasal bridge, narrow or cleft palate, and low-set ears), cerebellar malformations (variable manifestations of a Dandy-Walker malformation with moderate mental retardation), and cardiac defects (primarily septal defects). Since the original report, over 25 patients with 3C syndrome have been reported. Recessive inheritance has been postulated based on recurrence in siblings born to unaffected parents and parental consanguinity in two familial cases. Molecular and cytogenetic mapping of the 6p deletions in these three families with subtelomeric deletions of chromosome 6p have defined a 1.3 Mb minimally deleted critical region. To determine if 6p deletions are common in 3C syndrome, we analyzed seven unrelated individuals with 3C syndrome for deletions of this region. Three forkhead genes (FOXF1 and FOXQ1 from within the critical region, and FOXC1 proximal to this region) were evaluated as potential candidate disease genes for this disorder. No deletions or disease-causing mutations were identified.

PHACE syndrome misdiagnosed as a port-wine stain

PubMed Central

Thomson, Jason; Greig, Aina; Lloyd, Claire; Morrison, Danny; Flohr, Carsten

2015-01-01

We present the case of a boy born with a large macular, segmental vascular anomaly over the left face, initially diagnosed as a capillary malformation (port-wine stain) by the postnatal paediatric team. The vascular anomaly in the face then grew rapidly during the first few weeks of life and started to occlude the left eye, causing parental concerns about the infant's vision. A dermatological opinion established that the lesion was a segmental infantile haemangioma (IH). This, in combination with the posterior fossa malformation previously detected on antenatal scanning and confirmed by an MRI postnatally, satisfied the criteria for Posterior fossa abnormalities, Haemangiomas, Arterial abnormalities, Cardiac abnormalities and Eye abnormalities (PHACE) syndrome: a rare cutaneous neurovascular syndrome. This case highlights the diagnostic challenge posed by early phenotypes of haemangiomas as well as the importance of correctly diagnosing PHACE syndrome. PMID:26177999

Capillary Leak Syndrome Following Snakebite Envenomation

PubMed Central

Udayabhaskaran, V.; Arun Thomas, E. T.; Shaji, Bhagya

2017-01-01

Capillary leak syndrome is a unique complication that follows Russell's viper envenomation. This syndrome has a very high fatality rate and is characterized by parotid swelling, chemosis, periorbital edema, hypotension, albuminuria, hypoalbuminemia, and hemoconcentration. This syndrome is frequently recognized from the southern parts of India, especially from the state of Kerala. It has been postulated that a vascular apoptosis inducing component of Russell's viper venom that is not neutralized by the commercially available anti-snake venom (ASV) is responsible for this complication as it occurs even after adequate doses of ASV administration in most cases. Acute kidney injury often requiring dialysis is invariably present in all patients because of reduced renal perfusion and ischemic acute tubular necrosis as a result of hypotension. Management mainly involves aggressive fluid resuscitation to maintain adequate tissue perfusion. There are no other proven effective treatment modalities, except a few reports of successful treatment with plasmapheresis. Methylprednisolone pulse therapy, terbutaline, aminophylline, and intravenous immunoglobulin are other treatment modalities tried. PMID:29142382

Syndrome de larva migrans cutanée sur pied malformé (à propos d'un cas)

PubMed Central

Benbella, Imane; Khalki, Hanane; Lahmadi, Khalid; Kouara, Sara; Abbadi, Abderrahim; Er-rami, Mohammed

2016-01-01

Le syndrome de larva migrans cutanée est une dermite sous cutanée causée par des larves d'ankylostomes d'animaux en impasse parasitaire chez l'homme. L'infestation transcutanée est favorisée par le contact avec le sol contaminé par les larves du parasite. Nous rapportons le cas d'un nourrisson de 15 mois, originaire de Guinée-Bissau, atteint d'un syndrome de larva migrans cutanée sur un pied malformé. Cette malformation sous forme d'une syndactylie associée à une tuméfaction du pied, était à l'origine d'un retard d'acquisition de la station debout. De même, on a rapporté une notion de pieds nus, vue la difficulté de chausser le pied malformé du patient. Tous ces facteurs auraient contribués à favoriser l'infestation du malade par les larves du nématode. PMID:27217876

Human genetics and molecular mechanisms of vein of Galen malformation.

PubMed

Duran, Daniel; Karschnia, Philipp; Gaillard, Jonathan R; Karimy, Jason K; Youngblood, Mark W; DiLuna, Michael L; Matouk, Charles C; Aagaard-Kienitz, Beverly; Smith, Edward R; Orbach, Darren B; Rodesch, Georges; Berenstein, Alejandro; Gunel, Murat; Kahle, Kristopher T

2018-04-01

Vein of Galen malformations (VOGMs) are rare developmental cerebrovascular lesions characterized by fistulas between the choroidal circulation and the median prosencephalic vein. Although the treatment of VOGMs has greatly benefited from advances in endovascular therapy, including technical innovation in interventional neuroradiology, many patients are recalcitrant to procedural intervention or lack accessibility to specialized care centers, highlighting the need for improved screening, diagnostics, and therapeutics. A fundamental obstacle to identifying novel targets is the limited understanding of VOGM molecular pathophysiology, including its human genetics, and the lack of an adequate VOGM animal model. Herein, the known human mutations associated with VOGMs are reviewed to provide a framework for future gene discovery. Gene mutations have been identified in 2 Mendelian syndromes of which VOGM is an infrequent but associated phenotype: capillary malformation-arteriovenous malformation syndrome ( RASA1) and hereditary hemorrhagic telangiectasia ( ENG and ACVRL1). However, these mutations probably represent only a small fraction of all VOGM cases. Traditional genetic approaches have been limited in their ability to identify additional causative genes for VOGM because kindreds are rare, limited in patient number, and/or seem to have sporadic inheritance patterns, attributable in part to incomplete penetrance and phenotypic variability. The authors hypothesize that the apparent sporadic occurrence of VOGM may frequently be attributable to de novo mutation or incomplete penetrance of rare transmitted variants. Collaboration among treating physicians, patients' families, and investigators using next-generation sequencing could lead to the discovery of novel genes for VOGM. This could improve the understanding of normal vascular biology, elucidate the pathogenesis of VOGM and possibly other more common arteriovenous malformation subtypes, and pave the way for advances

PHACE syndrome misdiagnosed as a port-wine stain.

PubMed

Thomson, Jason; Greig, Aina; Lloyd, Claire; Morrison, Danny; Flohr, Carsten

2015-07-15

We present the case of a boy born with a large macular, segmental vascular anomaly over the left face, initially diagnosed as a capillary malformation (port-wine stain) by the postnatal paediatric team. The vascular anomaly in the face then grew rapidly during the first few weeks of life and started to occlude the left eye, causing parental concerns about the infant's vision. A dermatological opinion established that the lesion was a segmental infantile haemangioma (IH). This, in combination with the posterior fossa malformation previously detected on antenatal scanning and confirmed by an MRI postnatally, satisfied the criteria for Posterior fossa abnormalities, Haemangiomas, Arterial abnormalities, Cardiac abnormalities and Eye abnormalities (PHACE) syndrome: a rare cutaneous neurovascular syndrome. This case highlights the diagnostic challenge posed by early phenotypes of haemangiomas as well as the importance of correctly diagnosing PHACE syndrome. 2015 BMJ Publishing Group Ltd.

Volumetric and Voxel-Based Morphometry Findings in Autism Subjects With and Without Macrocephaly

PubMed Central

Bigler, Erin D.; Abildskov, Tracy J.; Petrie, Jo Ann; Johnson, Michael; Lange, Nicholas; Chipman, Jonathan; Lu, Jeffrey; McMahon, William; Lainhart, Janet E.

2015-01-01

This study sought to replicate Herbert et al. (2003a), which found increased overall white matter (WM) volume in subjects with autism, even after controlling for head size differences. To avoid the possibility that greater WM volume in autism is merely an epiphenomena of macrocephaly over-representation associated with the disorder, the current study included control subjects with benign macrocephaly. The control group also included subjects with a reading disability to insure cognitive heterogeneity. WM volume in autism was significantly larger, even when controlling for brain volume, rate of macrocephaly, and other demographic variables. Autism and controls differed little on whole-brain WM voxel-based morphometry (VBM) analyses suggesting that the overall increase in WM volume was non-localized. Autism subjects exhibited a differential pattern of IQ relationships with brain volumetry findings from controls. Current theories of brain overgrowth and their importance in the development of autism are discussed in the context of these findings. PMID:20446133

Middle and inner ear malformations in mutation-proven branchio-oculo-facial (BOF) syndrome: case series and review of the literature.

PubMed

Carter, Melissa T; Blaser, Susan; Papsin, Blake; Meschino, Wendy; Reardon, Willie; Klatt, Regan; Babul-Hirji, Riyana; Milunsky, Jeff; Chitayat, David

2012-08-01

Hearing impairment is common in individuals with branchio-oculo-facial (BOF) syndrome. The majority of described individuals have conductive hearing impairment due to malformed ossicles and/or external canal stenosis or atresia, although a sensorineural component to the hearing impairment in BOF syndrome is increasingly being reported. Sophisticated computed tomography (CT) of the temporal bone has revealed middle and inner ear malformations in three previous reports. We present middle and inner ear abnormalities in three additional individuals with mutation-proven BOF syndrome. We suggest that temporal bone CT imaging be included in the medical workup of a child with BOF syndrome, in order to guide management. Copyright © 2012 Wiley Periodicals, Inc.

Gigantism of the lower limb in Klippel-Trenaunay syndrome: anatomy of the lateral marginal vein.

PubMed

Abdul-Rahman, N R; Mohammad, K F; Ibrahim, S

2009-06-01

The Klippel-Trenaunay syndrome is a combination of venous and capillary malformations associated with soft tissue and/or bony limb hypertrophy, with or without lymphatic malformations. Although persistent foetal veins are rare, the persistence of the lateral marginal vein is a common association in this syndrome. It results in venous hypertension, which gives rise to venous varicosities, which are commonly seen in this syndrome. This is a case report of a 28-year-old man with Klippel-Trenaunay syndrome, with persistence of the lateral marginal vein, affecting his right lower limb. He was treated with an above-knee amputation. The amputated limb was dissected to demonstrate the anatomy of the lateral marginal vein. To the best of the authors' knowledge, the gross anatomy of the lateral marginal vein has not been previously reported.

CLOVES syndrome: review of a PIK3CA-related overgrowth spectrum (PROS).

PubMed

Martinez-Lopez, A; Blasco-Morente, G; Perez-Lopez, I; Herrera-Garcia, J D; Luque-Valenzuela, M; Sanchez-Cano, D; Lopez-Gutierrez, J C; Ruiz-Villaverde, R; Tercedor-Sanchez, J

2017-01-01

Overgrowth syndromes are characterized by global or localized disproportionate growth associated with other anomalies, including vascular malformations and neurological and/or visceral disorders. CLOVES (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal naevi, Scoliosis/Skeletal and spinal anomalies) is an overgrowth syndrome caused by mosaic activating mutation in gene PIK3CA, which gives rise to abnormal PI3K-AKT-mTOR pathway activation. These mutations are responsible for the clinical manifestations of the syndrome, which include low- and high-flow vascular malformations, thoracic lipomatous hyperplasia, asymmetric growth, and visceral and neurological disorders. These common anomalies are illustrated with figures from two personal cases. Identification of the clinical and genetic characteristics of CLOVES syndrome is crucial for the differential diagnosis with other overgrowth syndromes, such as Proteus or Klippel-Trenaunay (K-T) syndromes, and for the therapeutic management of the different anomalies. In this context, a new entity comprising different syndromes with phenotypic mutations in PIK3CA has been proposed, designated PIK3CA-related overgrowth spectrum (PROS), with the aim of facilitating clinical management and establishing appropriate genetic study criteria. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sleep disturbance: a forgotten syndrome in patients with Chiari I malformation.

PubMed

Ferré Masó, A; Poca, M A; de la Calzada, M D; Solana, E; Romero Tomás, O; Sahuquillo, J

2014-06-01

Chiari type I malformation (CM-I) is characterised by caudal ectopia of the cerebellar tonsils through the foramen magnum. This is associated with brain stem, high spinal cord, and cranial nerve compression phenomena. The most frequent symptoms are occipital headaches and dizziness. Less well-known symptoms are sleep disorders and nocturnal respiratory abnormalities. MEDLINE and information from patients evaluated at the Neurosurgery and Clinical Neurophysiology Departments at Hospital Universitario Vall d'Hebron. Review article based on data obtained from MEDLINE articles since 1966, using combinations of the following keywords: «Chiari malformation» or «Arnold-Chiari malformation» and «sleep apnea» or «sleep disorders». CM-I patients show a higher prevalence of sleep disorders than that observed in the general population. Some studies report a 50% prevalence of sleep apnea-hypopnea syndrome (SAHS), probably associated with sudden death in some cases. These results support analysing sleep respiratory parameters in theses patients. Identifying SAHS symptoms may help optimise treatment, thereby improving quality of life and prognosis. Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Growth hormone deficiency and pituitary malformation in a recurrent Cat-Eye syndrome: a family report.

PubMed

Jedraszak, Guillaume; Braun, Karine; Receveur, Aline; Decamp, Matthieu; Andrieux, Joris; Rabbind Singh, Amrathlal; Copin, Henri; Bremond-Gignac, Dominique; Mathieu, Michèle; Rochette, Jacques; Morin, Gilles

2015-10-01

Growth hormone deficiency affects roughly between one in 3000 and one in 4000 children with most instances of growth hormone deficiency being idiopathic. Growth hormone deficiency can also be associated with genetic diseases or chromosome abnormalities. Association of growth hormone deficiency together with hypothalamic-pituitary axis malformation and Cat-Eye syndrome is a very rare condition. We report a family with two brothers presenting with growth delay due to a growth hormone deficiency associated with a polymalformation syndrome. They both displayed pre-auricular pits and tags, imperforate anus and Duane retraction syndrome. Both parents and a third unaffected son displayed normal growth pattern. Cerebral MRI showed a hypothalamic-pituitary axis malformation in the two affected brothers. Cytogenetic studies revealed a type I small supernumerary marker chromosome derived from chromosome 22 resulting in a tetrasomy 22pter-22q11.21 characteristic of the Cat-Eye syndrome. The small supernumerary marker chromosome was present in the two affected sons and the mother in a mosaic state. Patients with short stature due to growth hormone deficiency should be evaluated for chromosomal abnormality. Family study should not be underestimated. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Craniofacial and dental malformations in Costello syndrome: A detailed evaluation using multi-detector row computed tomography.

PubMed

Takahashi, Masashi; Ohashi, Hirofumi

2013-06-01

Costello syndrome is a rare multiple congenital anomaly syndrome caused by heterozygous germline HRAS mutations, which is characterized by intellectual disability, growth retardation, distinctive facies, loose skin, cardiomyopathy and a preposition to malignancies. Although teeth abnormalities have been encountered in nearly two-thirds of the patients in literature, the evaluation tended to be limited to the extent which can be obtained from physical examination. We investigated detailed craniofacial, oral and dental findings in four patients with Costello syndrome. In this study, images reconstructed by multi-detector row computed tomography (MDCT) were used as substitutes for dental cast study and panoramic and lateral cephalometric radiograph studies to evaluate dental arches, tooth size, relationships between craniofacial and dental structures, and hypodontia. All four patients showed true/relative macrocephaly with facial bone hypoplasia and gingival hypertrophy. Occlusal attrition, malocclusion, small dental arches, microdontia, and convex face were noted in three patients. In addition, one patient showed dental caries, conic tooth and gingivitis, and another patient showed hypodontia. Our study suggests that craniofacial and dental abnormalities are common in Costello syndrome patients and comprehensive dental care should be provided from early infancy. To our knowledge, this is the first study of thorough craniofacial and dental evaluation by using MDCT in Costello syndrome. MDCT is a useful tool for precise evaluation of craniofacial and oral manifestations in patients with congenital anomaly/intellectual disability syndromes. © 2012 The Authors. Congenital Anomalies © 2012 Japanese Teratology Society.

Duodenal atresia in an infant with triple-X syndrome: a new associated malformation in 47,XXX.

PubMed

Rolle, Udo; Linse, Barbara; Glasow, Simone; Sandig, Klaus Rainer; Richter, Thomas; Till, Holger

2007-08-01

An association between the triple-X syndrome (47,XXX) and gastrointestinal malformations is extremely rare. Most 47,XXX patients present with a normal phenotype, but genitourinary malformations have been described. We report a case of a child with 47,XXX and duodenal atresia. Antenatal ultrasound scan showed a dilated fetal stomach and upper part of the duodenum (double bubble phenomenon) at 31 weeks of gestation in a 31-year-old woman with polyhydramnion. The amniotic fluid karyotype showed 47,XXX. After a scheduled delivery, duodenal atresia was confirmed and treated with duodeno-duodenostomy. The possible association of gastrointestinal and genitourinary tract anomalies requires a detailed postnatal clinical investigation and ultrasonographic examination of the abdomen, retroperitoneum, and pelvis on all triple-X syndrome patients. 2007 Wiley-Liss, Inc.

Sulphonated phthalocyanine induced caudal malformative syndrome in the chick embryo.

PubMed

Sandor, S; Prelipceanu, O; Checiu, I

1985-01-01

Sulphonated phthalocyanine (Pht.) has been tested for its possible noxious effect on the developing chick embryo. When injected into the subembryonic cavity of 40-45 hours incubated chick embryos (mainly 10-20 somite pairs), Pht. induces a highly reproducible caudal malformative syndrome (trunk and taillessness, various anomalies of the limbs). The main effect is--in about 15% of the malformed specimens--associated with unilateral microphthalmy and, less frequently, with coelosomy. Microscopically developmental disturbances of the caudal axial organs, of the mesonephros and of the limbs are observed. The initial pathological changes, at microscopic level, are necrosis and hemorrhages in the caudal axial and paraxial area. The allantois is poorly developed or even absent. Skeletal changes involve anomalies of the ribs and of the vertebral column and total or partial absence of the pelvic girdle bones. The high mortality, mainly during the first week, is due--first of all--to the developmental disturbances including the poor development or absence of the allantois. Control experiments with CuCl2 suggest the ethiological role of Cu. Pathogenetic aspects are discussed.

Sotos syndrome (cerebral gigantism): analysis of 8 cases.

PubMed

Melo, Débora Gusmão; Acosta, Angelina Xavier; Salles, Maria Aparecida de Almeida; Pina-Neto, João Monteiro de; Castro, José Daniel Vieira de; Santos, Antonio Carlos

2002-06-01

Sotos syndrome or cerebral gigantism is characterized by macrocephaly, overgrowth, mental retardation and central nervous system abnormalities. Congenital heart defects may be present. We report 8 patients with this syndrome and relate their clinical features, neuroimaging and echocardiographic findings.

Congenital Vascular Malformation

MedlinePlus

... also be effective for small, localized birthmarks (port wine stains). Patients with a rare venous malformation (Kleppel–Trenaunay Syndrome) of the limbs, frequently benefit from elastic garments and bandages used for com- ...

Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly

PubMed Central

Hobert, Judith A; Embacher, Rebecca; Mester, Jessica L; Frazier, Thomas W; Eng, Charis

2014-01-01

Unlike some other childhood neurodevelopmental disorders, no diagnostic biochemical marker has been identified in all individuals with an autism spectrum disorder (ASD). This deficit likely results from genetic heterogeneity among the population. Therefore, we evaluated a subset of individuals with ASDs, specifically, individuals with or without macrocephaly in the presence or absence of PTEN mutations. We sought to determine if amino or organic acid markers could be used to identify individuals with ASDs with or without macrocephaly in the presence or absence of PTEN mutations, and to establish the degree of macrocephaly in individuals with ASDs and PTEN mutation. Urine, blood and occipital–frontal circumference (OFC) measurements were collected from 69 individuals meeting DSM-IV-TR criteria. Urine and plasma samples were subjected to amino and organic acid analyses. PTEN was Sanger-sequenced from germline genomic DNA. Germline PTEN mutations were identified in 27% (6/22) of the macrocephalic ASD population. All six PTEN mutation-positive individuals were macrocephalic with average OFC+4.35 standard deviations (SDs) above the mean. No common biochemical abnormalities were identified in macrocephalic ASD individuals with or without PTEN mutations. In contrast, among the collective ASD population, elevation of urine aspartic acid (87% 54/62), plasma taurine (69% 46/67) and reduction of plasma cystine (72% 46/64) were observed. PTEN sequencing should be carried out for all individuals with ASDs and macrocephaly with OFC ≥2SDs above the mean. A proportion of individuals with ASDs may have an underlying disorder in sulfur amino acid metabolism. PMID:23695273

Macrocephaly in infancy: benign enlargement of the subarachnoid spaces and subdural collections.

PubMed

Tucker, Jacqueline; Choudhary, Arabinda Kumar; Piatt, Joseph

2016-07-01

OBJECTIVE Benign enlargement of the subarachnoid spaces (BESS) is a common finding on imaging studies indicated by macrocephaly in infancy. This finding has been associated with the presence of subdural fluid collections that are sometimes construed as suggestive of abusive head injury. The prevalence of BESS among infants with macrocephaly and the prevalence of subdural collections among infants with BESS are both poorly defined. The goal of this study was to determine the relative frequencies of BESS, hydrocephalus, and subdural collections in a large consecutive series of imaging studies performed for macrocephaly and to determine the prevalence of subdural fluid collections among patients with BESS. METHODS A text search of radiology requisitions identified studies performed for macrocephaly in patients ≤ 2 years of age. Studies of patients with hydrocephalus or acute trauma were excluded. Studies that demonstrated hydrocephalus or chronic subdural hematoma not previously recognized but responsible for macrocephaly were noted but not investigated further. The remaining studies were reviewed for the presence of incidental subdural collections and for measurement of the depth of the subarachnoid space. A 3-point scale was used to grade BESS: Grade 0, < 5 mm; Grade 1, 5-9 mm; and Grade 2, ≥ 10 mm. RESULTS After exclusions, there were 538 studies, including 7 cases of hydrocephalus (1.3%) and 1 large, bilateral chronic subdural hematoma (0.2%). There were incidental subdural collections in 21 cases (3.9%). Two hundred sixty-five studies (49.2%) exhibited Grade 1 BESS, and 46 studies (8.6%) exhibited Grade 2 BESS. The prevalence of incidental subdural collections among studies with BESS was 18 of 311 (5.8%). The presence of BESS was associated with a greater prevalence of subdural collections, and higher grades of BESS were associated with increasing prevalence of subdural collections. After controlling for imaging modality, the odds ratio of the association of

Anatomic Malformations of the Middle and Inner Ear in 22q11.2 Deletion Syndrome: Case Series and Literature Review.

PubMed

Verheij, E; Elden, L; Crowley, T B; Pameijer, F A; Zackai, E H; McDonald-McGinn, D M; Thomeer, H G X M

2018-05-01

The 22q11.2 deletion syndrome is characterized by a heterogenic phenotype, including hearing loss. The underlying cause of hearing loss, especially sensorineural hearing loss, is not yet clear. Therefore, our objective was to describe anatomic malformations in the middle and inner ear in patients with 22q11.2 deletion syndrome. A retrospective case series was conducted in 2 tertiary referral centers. All patients with 22q11.2 deletion syndrome who had undergone CT or MR imaging of the temporal bones were included. Radiologic images were evaluated on predetermined parameters, including abnormalities of the ossicular chain, cochlea, semicircular canals, and vestibule. There were 26 patients (52 ears) with a CT or MR imaging scan available. A dense stapes superstructure was found in 18 ears (36%), an incomplete partition type II was suspected in 12 cochleas (23%), the lateral semicircular canal was malformed with a small bony island in 17 ears (33%), and the lateral semicircular canal and vestibule were fused to a single cavity in 15 ears (29%). Middle and inner ear abnormalities were frequently encountered in our cohort, including malformations of the lateral semicircular canal. © 2018 by American Journal of Neuroradiology.

Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism.

PubMed

Yeung, Kit San; Tso, Winnie Wan Yee; Ip, Janice Jing Kun; Mak, Christopher Chun Yu; Leung, Gordon Ka Chun; Tsang, Mandy Ho Yin; Ying, Dingge; Pei, Steven Lim Cho; Lee, So Lun; Yang, Wanling; Chung, Brian Hon-Yin

2017-01-01

Macrocephaly, which is defined as a head circumference greater than or equal to + 2 standard deviations, is a feature commonly observed in children with developmental delay and/or autism spectrum disorder. Although PTEN is a well-known gene identified in patients with this syndromic presentation, other genes in the PI3K-AKT-mTOR signalling pathway have also recently been suggested to have important roles. The aim of this study is to characterise the mutation spectrum of this group of patients. We performed whole-exome sequencing of 21 patients with macrocephaly and developmental delay/autism spectrum disorder. Sources of genomic DNA included blood, buccal mucosa and saliva. Germline mutations were validated by Sanger sequencing, whereas somatic mutations were validated by droplet digital PCR. We identified ten pathogenic/likely pathogenic mutations in PTEN ( n  = 4), PIK3CA ( n  = 3), MTOR ( n  = 1) and PPP2R5D ( n  = 2) in ten patients. An additional PTEN mutation, which was classified as variant of unknown significance, was identified in a patient with a pathogenic PTEN mutation, making him harbour bi-allelic germline PTEN mutations. Two patients harboured somatic PIK3CA mutations, and the level of somatic mosaicism in blood DNA was low. Patients who tested positive for mutations in the PI3K-AKT-mTOR pathway had a lower developmental quotient than the rest of the cohort (DQ = 62.8 vs. 76.1, p = 0.021). Their dysmorphic features were non-specific, except for macrocephaly. Among the ten patients with identified mutations, brain magnetic resonance imaging was performed in nine, all of whom showed megalencephaly. We identified mutations in the PI3K-AKT-mTOR signalling pathway in nearly half of our patients with macrocephaly and developmental delay/autism spectrum disorder. These patients have subtle dysmorphic features and mild developmental issues. Clinically, patients with germline mutations are difficult to distinguish from patients with somatic

Associated malformations among infants with anophthalmia and microphthalmia.

PubMed

Stoll, Claude; Dott, Beatrice; Alembik, Yves; Roth, Marie-Paule

2012-03-01

Infants with anophthalmia and microphthalmia frequently have other associated congenital anomalies. The reported frequency and types of associated malformations vary among different studies. The purpose of this investigation was to assess the frequency and types of associated malformations among infants with anophthalmia and microphthalmia in a geographically well defined population from 1979 to 2004 of 346,831 consecutive births. Of the 87 infants with anophthalmia and microphthalmia born during this period (prevalence at birth, 2.5 per 10,000), 90% had associated malformations. Infants with associated malformation were divided into recognizable conditions (22 infants [25%] with chromosomal and 15 infants [17%] with nonchromosomal conditions), and nonrecognizable conditions (41 infants [47%] with multiple malformations). Trisomies 13 and 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, CHARGE syndrome, Meckel-Gruber syndrome, and VACTERL association were most often present in recognizable nonchromosomal conditions. Malformations in the musculoskeletal, cardiovascular, and central nervous systems were the most common other anomalies in infants with multiple malformations and nonrecognizable conditions. The frequency of associated malformations in infants with anophthalmia or microphthalmia emphasizes the need for a thorough investigation of these infants. Routine screening for other malformations-especially musculoskeletal, cardiac, and central nervous system anomalies-may need to be considered in infants with anophthalmia or microphthalmia, and referral of these infants for genetics evaluation and counseling seems warranted. Copyright © 2012 Wiley Periodicals, Inc.

Oral-facial-digital syndrome type IX in a patient with Dandy-Walker malformation.

PubMed Central

Nagai, K; Nagao, M; Nagao, M; Yanai, S; Minagawa, K; Takahashi, Y; Takekoshi, Y; Ishizaka, A; Matsuzono, Y; Kobayashi, O; Itagaki, T

1998-01-01

We report a girl with oral, facial, and digital anomalies including multiple alveolar frenula, lobulated tongue with nodules, a posterior cleft palate, hypertelorism, a prominent forehead with a large anterior fontanelle, and postaxial polydactyly in both hands and the right foot, features compatible with the oral-facial-digital syndrome (OFDS). In addition, she had bilateral microphthalmia, optic disc coloboma, and retinal degeneration with partial detachment, thus establishing a diagnosis of OFDS type IX. Dandy-Walker malformation and retrobulbar cysts were observed on MRI. These additional malformations have not been reported in OFDS type IX. The frequent apnoeic spells which occurred immediately after birth were relieved after cystoperitoneal shunt implantation for hydrocephalus. Considering our case and previous reports of OFDS type IX, including two male sibs, a boy born to consanguineous parents, and three females, inheritance is probably autosomal recessive. Images PMID:9598735

Posterior reversible encephalopathy syndrome in a patient with a Chiari I malformation

PubMed Central

Hansberry, David R.; Agarwal, Nitin; Tomei, Krystal L.; Goldstein, Ira M.

2013-01-01

Background: The authors describe a unique case of a patient who developed posterior reversible encephalopathy syndrome (PRES) following postoperative treatment of a Chiari I malformation. Case Decsription: A 25-year-old female presented with complaints of left upper and lower extremity paresthesias and gait disturbances. A magnetic resonance imaging (MRI) of the brain and cervical spine showed a Chiari I malformation with tonsillar descent beyond the level of the C1 lamina. She underwent a suboccipital craniectomy and C1 laminectomy with cerebellar tonsillar cauterization and duraplasty. Postoperatively, an MRI showed bilateral acute infarcts of the cerebellar vermis. She was initially treated for cerebellar ischemia with hypertensive therapy with a subsequent decline in her neurologic status and generalized tonic–clonic seizure. Further workup showed evidence of PRES. After weaning pressors, the patient had a significant progressive improvement in her mental status. Conclusion: Although the mechanism of PRES remains controversial given its diverse clinical presentation, several theories implicate hypertension and steroid use as causative agents. PMID:24232171

Malformations of the middle and inner ear on CT imaging in 22q11 deletion syndrome.

PubMed

Loos, Elke; Verhaert, Nicolas; Willaert, Annelore; Devriendt, Koenraad; Swillen, Ann; Hermans, Robert; Op de Beeck, Katya; Hens, Greet

2016-11-01

The 22q11 deletion syndrome (22q11DS), the most frequent microdeletion syndrome in humans, presents with a large variety of abnormalities. A common abnormality is hearing impairment. The exact pathophysiological explanation of the observed hearing loss remains largely unknown. The aim of this study was to analyze the middle and inner ear malformations as seen on computer tomographic imaging in patients with 22q11DS. We retrospectively reviewed the charts of 11 22q11DS patients who had undergone a CT of the temporal bone in the past. Of the 22 examined ears, two showed an abnormal malleus and incus, 10 presented with a dense stapes superstructure, and three ears had an abnormal orientation of the stapes. With regard to the inner ear, 12 ears showed an incomplete partition type II with a normal vestibular aqueduct. In four ears the vestibule and lateral semicircular canal were composed of a single cavity, in 14 ears the vestibule was too wide, and three ears had a broadened lateral semicircular canal. These findings suggest that malformations of the stapes, cochlea, vestibule, and lateral semicircular canal are frequent in 22q11DS. To our knowledge, the current study involves the largest case series describing middle and inner ear malformations in 22q11DS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Phosphatase and tensin homolog (PTEN) gene mutations and autism: literature review and a case report of a patient with Cowden syndrome, autistic disorder, and epilepsy.

PubMed

Conti, Sara; Condò, Maria; Posar, Annio; Mari, Francesca; Resta, Nicoletta; Renieri, Alessandra; Neri, Iria; Patrizi, Annalisa; Parmeggiani, Antonia

2012-03-01

Phosphatase and tensin homolog (PTEN) gene mutations are associated with a spectrum of clinical disorders characterized by skin lesions, macrocephaly, hamartomatous overgrowth of tissues, and an increased risk of cancers. Autism has rarely been described in association with these variable clinical features. At present, 24 patients with phosphatase and tensin homolog gene mutation, autism, macrocephaly, and some clinical findings described in phosphatase and tensin homolog syndromes have been reported in the literature. We describe a 14-year-old boy with autistic disorder, focal epilepsy, severe and progressive macrocephaly, and multiple papular skin lesions and palmoplantar punctate keratoses, characteristic of Cowden syndrome. The boy has a de novo phosphatase and tensin homolog gene mutation. Our patient is the first case described to present a typical Cowden syndrome and autism associated with epilepsy.

[Coexistence of female sexual organ malformation and urinary tract anomalies].

PubMed

Rzymski, P; Szpakowska-Rzymska, I; el Yubi, R; Wilczak, M; Sajdak, S; Opala, T

2001-02-01

The aim of the study was to estimate the correlation between sexual organs and urinary tract malformation. The retrospective analysis of clinical data obtained from 50 patients with sexual organs anomalies diagnosed in the Academic Gynaecological Centre between 1992-1999 was performed. Material included 24 patients with the Meyer-Rokitansky-Küster-Hauser syndrome and 26 with other sexual organs' malformations. Frequency of urinary tract anomalies was 42%, 11 patients with Meyer-Rokitansky-Küster-Hauser syndrome and 11 with other malformations. The gravity of urinary tract anomalies showed no statistical significant difference dependent on the type and symmetry of genital malformation. Urinary tract anomalies were more frequent in cases of asymmetric genital malformation and the difference was statistically significant. Intravenous urography proofed to be more sensitive than ultrasonography in diagnosing urinary tract anomalies.

Intravenous Immunoglobulins Improve Survival in Monoclonal Gammopathy-Associated Systemic Capillary-Leak Syndrome.

PubMed

Pineton de Chambrun, Marc; Gousseff, Marie; Mauhin, Wladimir; Lega, Jean-Christophe; Lambert, Marc; Rivière, Sophie; Dossier, Antoine; Ruivard, Marc; Lhote, François; Blaison, Gilles; Alric, Laurent; Agard, Christian; Saadoun, David; Graveleau, Julie; Soubrier, Martin; Lucchini-Lecomte, Marie-Josée; Christides, Christine; Bosseray, Annick; Levesque, Hervé; Viallard, Jean-François; Tieulie, Nathalie; Lovey, Pierre-Yves; Le Moal, Sylvie; Bibes, Béatrice; Malizia, Giuseppe; Abgueguen, Pierre; Lifermann, François; Ninet, Jacques; Hatron, Pierre-Yves; Amoura, Zahir

2017-10-01

Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome. We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality. We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first

Somatic GNAQ Mutation is Enriched in Brain Endothelial Cells in Sturge-Weber Syndrome.

PubMed

Huang, Lan; Couto, Javier A; Pinto, Anna; Alexandrescu, Sanda; Madsen, Joseph R; Greene, Arin K; Sahin, Mustafa; Bischoff, Joyce

2017-02-01

Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by facial and extracraniofacial capillary malformations and capillary-venule malformations in the leptomeninges. A somatic mosaic mutation in GNAQ (c.548G>A; p.R183Q) was found in SWS brain and skin capillary malformations. Our laboratory showed endothelial cells in skin capillary malformations are enriched for the GNAQ mutation. The purpose of this study is to determine whether the GNAQ mutation is also enriched in endothelial cells in affected SWS brain. Two human SWS brain specimens were fractionated by fluorescence-activated cell sorting into hematopoietic (CD45), endothelial (CD31, VE-Cadherin, and vascular endothelial growth factor receptor 2), and perivascular (platelet-derived growth factor receptor beta) cells and cells negative for all markers. The sorted cell populations were analyzed for GNAQ p.R183Q mutation by droplet digital polymerase chain reaction. SWS patient-derived brain endothelial cells were selected by anti-CD31-coated magnetic beads and cultured in endothelial growth medium in vitro. The GNAQ p.R183Q mutation was present in brain endothelial cells in two SWS specimens, with mutant allelic frequencies of 34.7% and 24.0%. Cells negative for all markers also harbored the GNAQ mutation. The mutant allelic frequencies in these unidentified cells were 9.2% and 8.4%. SWS patient-derived brain endothelial cells with mutant allelic frequencies of 14.7% and 21% survived and proliferated in vitro. Our study provides evidence that GNAQ p.R183Q mutation is enriched in endothelial cells in SWS brain lesions and thereby reveals endothelial cells as a source of aberrant Gαq signaling. This will help to understand the pathophysiology of SWS, to discover biomarkers for predicting cerebral involvement, and to develop therapeutic targets to prevent neurological impairments in SWS. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetics Home Reference: capillary malformation-arteriovenous malformation syndrome

MedlinePlus

... JB, Enjolras O, Cordisco MR, Burrows PE, Clapuyt P, Hammer F, Dubois J, Baselga E, Brancati F, Carder R, Quintal JM, Dallapiccola B, Fischer G, Frieden IJ, Garzon M, Harper J, Johnson-Patel J, Labrèze C, Martorell L, Paltiel HJ, Pohl ...

Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor.

PubMed

Tarpey, Patrick S; Raymond, F Lucy; O'Meara, Sarah; Edkins, Sarah; Teague, Jon; Butler, Adam; Dicks, Ed; Stevens, Claire; Tofts, Calli; Avis, Tim; Barthorpe, Syd; Buck, Gemma; Cole, Jennifer; Gray, Kristian; Halliday, Kelly; Harrison, Rachel; Hills, Katy; Jenkinson, Andrew; Jones, David; Menzies, Andrew; Mironenko, Tatiana; Perry, Janet; Raine, Keiran; Richardson, David; Shepherd, Rebecca; Small, Alexandra; Varian, Jennifer; West, Sofie; Widaa, Sara; Mallya, Uma; Moon, Jenny; Luo, Ying; Holder, Susan; Smithson, Sarah F; Hurst, Jane A; Clayton-Smith, Jill; Kerr, Bronwyn; Boyle, Jackie; Shaw, Marie; Vandeleur, Lucianne; Rodriguez, Jayson; Slaugh, Rachel; Easton, Douglas F; Wooster, Richard; Bobrow, Martin; Srivastava, Anand K; Stevenson, Roger E; Schwartz, Charles E; Turner, Gillian; Gecz, Jozef; Futreal, P Andrew; Stratton, Michael R; Partington, Michael

2007-02-01

We have identified three truncating, two splice-site, and three missense variants at conserved amino acids in the CUL4B gene on Xq24 in 8 of 250 families with X-linked mental retardation (XLMR). During affected subjects' adolescence, a syndrome emerged with delayed puberty, hypogonadism, relative macrocephaly, moderate short stature, central obesity, unprovoked aggressive outbursts, fine intention tremor, pes cavus, and abnormalities of the toes. This syndrome was first described by Cazebas et al., in a family that was included in our study and that carried a CUL4B missense variant. CUL4B is a ubiquitin E3 ligase subunit implicated in the regulation of several biological processes, and CUL4B is the first XLMR gene that encodes an E3 ubiquitin ligase. The relatively high frequency of CUL4B mutations in this series indicates that it is one of the most commonly mutated genes underlying XLMR and suggests that its introduction into clinical diagnostics should be a high priority.

Brief Report: Macrocephaly Phenotype and Psychiatric Comorbidity in a Clinical Sample of Mexican Children and Adolescents with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Albores-Gallo, Lilia; Fritsche-García, Laura; Miranda-Aguirre, Arturo Pabel; Avila-Acosta, Montserrat

2017-01-01

Autism spectrum disorders (ASD) may present with macrocephaly. Few studies have analyzed the association with psychiatric comorbidity. Participants were 94 children with any ASD with an age range from 2 to 16 years (Mdn 6 years), 82% were boys. It was found that 20% of the sample had macrocephaly and 1% microcephaly. There was no association…

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.

Dandy-Walker Malformation Presenting with Psychological Manifestations

PubMed Central

Dahanayake, Dulangi Maneksha Amerasinghe

2016-01-01

Dandy-Walker malformation, which is a congenital malformation of the cerebellum, is documented in literature to be associated with psychotic symptoms, obsessive compulsive symptoms, mood symptoms, hyperactivity, and impulsive behavior. The pathogenesis of psychiatric symptoms in Dandy-Walker malformation is thought to be due to disruption of the corticocerebellar tracts, resulting in what is known as cerebellar cognitive affective syndrome. We present a case of Dandy-Walker malformation presenting with psychiatric symptoms. This case highlights the necessity to be aware of psychiatric manifestations of cerebellar disease as it has an impact on the diagnosis and treatment. PMID:27493822

Dandy-Walker Malformation Presenting with Psychological Manifestations.

PubMed

Rohanachandra, Yasodha Maheshi; Dahanayake, Dulangi Maneksha Amerasinghe; Wijetunge, Swarna

2016-01-01

Dandy-Walker malformation, which is a congenital malformation of the cerebellum, is documented in literature to be associated with psychotic symptoms, obsessive compulsive symptoms, mood symptoms, hyperactivity, and impulsive behavior. The pathogenesis of psychiatric symptoms in Dandy-Walker malformation is thought to be due to disruption of the corticocerebellar tracts, resulting in what is known as cerebellar cognitive affective syndrome. We present a case of Dandy-Walker malformation presenting with psychiatric symptoms. This case highlights the necessity to be aware of psychiatric manifestations of cerebellar disease as it has an impact on the diagnosis and treatment.

Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

PubMed

Woods, C G; Stricker, S; Seemann, P; Stern, R; Cox, J; Sherridan, E; Roberts, E; Springell, K; Scott, S; Karbani, G; Sharif, S M; Toomes, C; Bond, J; Kumar, D; Al-Gazali, L; Mundlos, S

2006-08-01

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development.

Mutations in WNT7A Cause a Range of Limb Malformations, Including Fuhrmann Syndrome and Al-Awadi/Raas-Rothschild/Schinzel Phocomelia Syndrome

PubMed Central

Woods, C. G.; Stricker, S.; Seemann, P.; Stern, R.; Cox, J.; Sherridan, E.; Roberts, E.; Springell, K.; Scott, S.; Karbani, G.; Sharif, S. M.; Toomes, C.; Bond, J.; Kumar, D.; Al-Gazali, L.; Mundlos, S.

2006-01-01

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development. PMID:16826533

Laser treatment of oral vascular malformations

NASA Astrophysics Data System (ADS)

Romeo, U.; Gaimari, G.; Mohsen, M.; Tenore, G.; Palaia, G.

2014-01-01

Oral Vascular Malformations (OVM) are congenital anomalies characterized by morph-structural and/or functional changes of nature in severity and extension. OVM can affect any type of vessels arterial, venous or lymphatic and any capillary or anatomical. They are divided into two categories: low and high flow. In this study were treated 40 patients with OVM with a range size from 2 mm to 44 mm; they were subjected to clinical examination supported by Colour-Doppler Ultrasound instrumental examination and only for doubt cases the Magnetic Resonance Imaging (MRI) was prescribed. Only low flow venous and capillary malformations were treated by GaAlAs laser (Wiser®, Lambda, Brindole,Italy, 980nm) and KTP laser (SmartLite®, DEKA, Florence, Italy, 532nm) with two different techniques: the Transmucosal Thermophotocoagulation (TMT) and the Intralesional Photocoagulation (ILP). These techniques permitted a good control of haemostasis, avoiding bleeding both during surgery and in the postoperative. It is obtained an excellent and good healing respectively in 10% and 60% of cases, a moderate and poor resolution respectively in 22.5% and 7.5% of cases. A clear diagnosis allowed the management of Venous malformations (VM) by laser devices with wavelengths highly absorbed in haemoglobin in safety and efficacy and according to the principles of minimal invasive surgery. The aim of this study was to verify if the laser is effective in the treatment of OVM for the purpose of the clinical findings and the postoperative course. The Authors concluded that the laser can be considered the "gold standard" for treating OVM.

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

PubMed

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

2017-04-01

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

A longitudinal study of hearing and middle ear status of individuals with cleft palate with and without additional malformations/syndromes.

PubMed

Flynn, Traci; Persson, Christina; Moller, Claes; Lohmander, Anette; Magnusson, Lennart

2014-09-01

Objective : To describe and compare the middle ear status and hearing sensitivity in adolescence with isolated cleft palate plus additional malformations and/or syndromes with those with only an isolated cleft palate. Design : Retrospective and longitudinal. Two groups of individuals with isolated cleft palate were compared. Participants : A cohort of individuals born over 4 years in the western region of Sweden. The cohort was divided into one group with isolated cleft palate (n = 31; ICP) and one group with isolated cleft palate plus additional malformations and/or syndromes (n = 37; ICP+). Methods : Middle ear status and hearing thresholds were collected from the medical records at 7, 10, 13, and 16 years of age, examined, and compared within and between groups over time. Results : The ICP+ group demonstrated a significantly higher prevalence of abnormal middle ear status and elevated hearing thresholds as compared with the ICP group. As the individuals aged, the prevalence of abnormal middle ear status decreased. The hearing levels in both groups decreased in the low to middle frequencies as individuals aged; however, the hearing in the high frequencies did not. Conclusions : Individuals with cleft palate need to be followed routinely for middle ear status and hearing thresholds to ensure optimal audiological rehabilitation, with particular attention to those with additional malformations and/or syndromes.

Rare association between cystic fibrosis, Chiari I malformation, and hydrocephalus in a baby: a case report and review of the literature

PubMed Central

2011-01-01

Introduction Cystic fibrosis, an epithelial cell transport disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator gene, is not generally associated with malformations of the central nervous system. We review eight previously published reports detailing an infrequent association between cystic fibrosis and Chiari I malformation. Case presentation To the best of our knowledge, our report describes only the ninth case of a baby presenting with a new diagnosis of cystic fibrosis and Chiari I malformation, in this case in a 10-month-old, full-term Caucasian baby boy from the United States of America. Neurosurgical consultation was obtained for associated developmental delay, macrocephaly, bulging anterior fontanel, and papilledema. An MRI scan demonstrated an extensive Chiari I malformation with effacement of the fourth ventricle, obliteration of the outlets of the fourth ventricle and triventricular hydrocephalus without aqueductal stenosis. Our patient was taken to the operating room for ventriculoperitoneal shunt placement. Conclusions It is possible that the cystic fibrosis transmembrane conductance regulator gene may play a previously unrecognized role in central nervous system development; alternatively, this central nervous system abnormality may have been acquired due to constant valsalva from recurrent coughing or wheezing or metabolic and electrolyte imbalances that occur characteristically in cystic fibrosis. PMID:21838874

[Anatomy and malformations of the posterior cranial fossa].

PubMed

Struffert, T

2016-11-01

Many important structures are located in the confined space within the posterior cranial fossa. This article describes the main aspects of the anatomy. As a uniform classification of malformations of the posterior cranial fossa does not exist the main syndromes, such as Chiari malformations, zerebellar hypoplasia and dysplasia are discussed separately.

Chiari malformation and central sleep apnea syndrome: efficacy of treatment with adaptive servo-ventilation*

PubMed Central

do Vale, Jorge Marques; Silva, Eloísa; Pereira, Isabel Gil; Marques, Catarina; Sanchez-Serrano, Amparo; Torres, António Simões

2014-01-01

The Chiari malformation type I (CM-I) has been associated with sleep-disordered breathing, especially central sleep apnea syndrome. We report the case of a 44-year-old female with CM-I who was referred to our sleep laboratory for suspected sleep apnea. The patient had undergone decompressive surgery 3 years prior. An arterial blood gas analysis showed hypercapnia. Polysomnography showed a respiratory disturbance index of 108 events/h, and all were central apnea events. Treatment with adaptive servo-ventilation was initiated, and central apnea was resolved. This report demonstrates the efficacy of servo-ventilation in the treatment of central sleep apnea syndrome associated with alveolar hypoventilation in a CM-I patient with a history of decompressive surgery. PMID:25410846

Extensive intracranial calcification of pseudo-TORCH syndrome with features of Dandy–Walker malformation

PubMed Central

Patnaik, Ashis; Mishra, Sudhansu Sekhar; Das, Srikanta

2017-01-01

Pseudo-TORCH syndrome or congenital infection-like syndrome is a group of conditions which resemble congenital infections such as those caused by toxoplasmosis, rubella, cytomegalovirus (CMV), herpes (TORCH) group of organisms, clinico-radiologically, but serological tests are negative for the organisms. One of the variety shows features such as microcephaly, extensive intracranial calcification showing gross resemblance to congenital CMV infection, making its other name as microcephaly intracranial calcification syndrome (MICS). Dandy–Walker malformation (DWM), in addition to posterior fossa large cyst, cerebellar vermis hypoplasia, and hydrocephalus is often associated with agenesis of the corpus callosum and callosal lipomas, dysplasia of the brainstem, and cerebellar hypoplasia or dysgenesis. But radiological features of DWM with microcephaly and intracranial calcification are very unusual and have been rarely reported in the literature.[1] We report a case of infant showing clinical features suggestive of congenital CMV infection with negative serology and radiological imaging suggestive of DWM with extensive intracranial calcification. Pseudo-TORCH syndrome with radiological features of DWM is a congenital developmental abnormality. Inspite of hydrocephalus, it does not require cerebrospinal fluid (CSF) diversionary procedure due to lack of increased intracranial pressure. Conservative management for seizure disorder is the optimal therapy. PMID:28761539

Extensive intracranial calcification of pseudo-TORCH syndrome with features of Dandy-Walker malformation.

PubMed

Patnaik, Ashis; Mishra, Sudhansu Sekhar; Das, Srikanta

2017-01-01

Pseudo-TORCH syndrome or congenital infection-like syndrome is a group of conditions which resemble congenital infections such as those caused by toxoplasmosis, rubella, cytomegalovirus (CMV), herpes (TORCH) group of organisms, clinico-radiologically, but serological tests are negative for the organisms. One of the variety shows features such as microcephaly, extensive intracranial calcification showing gross resemblance to congenital CMV infection, making its other name as microcephaly intracranial calcification syndrome (MICS). Dandy-Walker malformation (DWM), in addition to posterior fossa large cyst, cerebellar vermis hypoplasia, and hydrocephalus is often associated with agenesis of the corpus callosum and callosal lipomas, dysplasia of the brainstem, and cerebellar hypoplasia or dysgenesis. But radiological features of DWM with microcephaly and intracranial calcification are very unusual and have been rarely reported in the literature.[1] We report a case of infant showing clinical features suggestive of congenital CMV infection with negative serology and radiological imaging suggestive of DWM with extensive intracranial calcification. Pseudo-TORCH syndrome with radiological features of DWM is a congenital developmental abnormality. Inspite of hydrocephalus, it does not require cerebrospinal fluid (CSF) diversionary procedure due to lack of increased intracranial pressure. Conservative management for seizure disorder is the optimal therapy.

Congenital extrahepatic portosystemic shunts (Abernethy malformation): a histopathologic evaluation.

PubMed

Lisovsky, Mikhail; Konstas, Angelos A; Misdraji, Joseph

2011-09-01

Congenital extrahepatic portosystemic shunt, also known as Abernethy malformation, is a rare malformation in which intestinal and splenic venous blood bypasses the liver and drains into systemic veins. Aside from the complete or near-complete absence of portal veins, other histologic features of Abernethy malformation have not been evaluated in the literature. The goal of this study was to detail the hepatic histopathology in 5 patients with Abernethy malformation diagnosed at our institution. Paraffin-embedded tissue sections from 1 explant, 2 liver tumor resections, and 2 liver biopsies were evaluated using hematoxylin and eosin stains, reticulin, elastic, and trichrome stains, and immunohistochemistry for D2-40. Histologic findings included absence of portal veins in small portal tracts, absent or hypoplastic portal veins in medium-sized and large-sized portal tracts, isolated capillaries and arterioles in the lobules, hypertrophy of hepatic artery branches, remodeling of the liver architecture, and nodular regenerative hyperplasia in 1 case. Two patients had hepatocellular carcinoma without cirrhosis, and 2 had focal nodular hyperplasia. In addition to loss of portal veins, Abernethy malformation is characterized by multiple abnormalities due to remodeling of the hepatic vasculature. Abernethy malformation may also be associated with hepatocellular carcinoma and focal nodular hyperplasia in some patients.

Dandy-Walker Malformation and Down Syndrome Association: Good Developmental Outcome and Successful Endoscopic Treatment of Hydrocephalus

PubMed Central

Nigri, Flavio; Cabral, Isaias Fiuza; da Silva, Raquel Tavares Boy; Pereira, Heloisa Viscaíno; Ribeiro, Carlos Roberto Telles

2014-01-01

The association of Down syndrome (DS) with Dandy Walker malformation (DWM) is extremely rare, with only 3 cases reported to date. All cases reported have shown a bad life expectancy and a bad developmental outcome. The present case reveals the possibility of a good prognosis. A 19-month-old male patient had successful endoscopic hydrocephalus treatment and a good developmental outcome. He probably had a better outcome because of good DS and DWM prognostic parameters. Our patient suffered from a DWM with vermis identification of 2 fissures and 3 lobes and a DS with a well-preserved tonus, which was not associated with other congenital systemic defects. We may conclude that the prognosis of DS-DWM association may separately depend on the degree of clinical and neurological involvement of each malformation. PMID:24932176

Dandy-walker malformation and down syndrome association: good developmental outcome and successful endoscopic treatment of hydrocephalus.

PubMed

Nigri, Flavio; Cabral, Isaias Fiuza; da Silva, Raquel Tavares Boy; Pereira, Heloisa Viscaíno; Ribeiro, Carlos Roberto Telles

2014-05-01

The association of Down syndrome (DS) with Dandy Walker malformation (DWM) is extremely rare, with only 3 cases reported to date. All cases reported have shown a bad life expectancy and a bad developmental outcome. The present case reveals the possibility of a good prognosis. A 19-month-old male patient had successful endoscopic hydrocephalus treatment and a good developmental outcome. He probably had a better outcome because of good DS and DWM prognostic parameters. Our patient suffered from a DWM with vermis identification of 2 fissures and 3 lobes and a DS with a well-preserved tonus, which was not associated with other congenital systemic defects. We may conclude that the prognosis of DS-DWM association may separately depend on the degree of clinical and neurological involvement of each malformation.

Biology of vascular malformations of the brain.

PubMed

Leblanc, Gabrielle G; Golanov, Eugene; Awad, Issam A; Young, William L

2009-12-01

This review discusses recent research on the genetic, molecular, cellular, and developmental mechanisms underlying the etiology of vascular malformations of the brain (VMBs), including cerebral cavernous malformation, sporadic brain arteriovenous malformation, and the arteriovenous malformations of hereditary hemorrhagic telangiectasia. Summary of Review- The identification of gene mutations and genetic risk factors associated with cerebral cavernous malformation, hereditary hemorrhagic telangiectasia, and sporadic arteriovenous malformation has enabled the development of animal models for these diseases and provided new insights into their etiology. All of the genes associated with VMBs to date have known or plausible roles in angiogenesis and vascular remodeling. Recent work suggests that the angiogenic process most severely disrupted by VMB gene mutation is that of vascular stabilization, the process whereby vascular endothelial cells form capillary tubes, strengthen their intercellular junctions, and recruit smooth muscle cells to the vessel wall. In addition, there is now good evidence that in some cases, cerebral cavernous malformation lesion formation involves a genetic 2-hit mechanism in which a germline mutation in one copy of a cerebral cavernous malformation gene is followed by a somatic mutation in the other copy. There is also increasing evidence that environmental second hits can produce lesions when there is a mutation to a single allele of a VMB gene. Recent findings begin to explain how mutations in VMB genes render vessels vulnerable to rupture when challenged with other inauspicious genetic or environmental factors and have suggested candidate therapeutics. Understanding of the cellular mechanisms of VMB formation and progression in humans has lagged behind that in animal models. New knowledge of lesion biology will spur new translational work. Several well-established clinical and genetic database efforts are already in place, and further

"Serpentine-like syndrome"-A very rare multiple malformation syndrome characterised by brachioesophagus and vertebral anomalies.

PubMed

Beleza-Meireles, Ana; Steenhaut, Patricia; Hocq, Catheline; Clapuyt, Philippe; Bernard, Pierre; Debauche, Christian; Sznajer, Yves

2017-02-01

"Serpentine-like syndrome" is a severe and rare association of multiple congenital malformations, characterised by brachioesophagus, secondary intrathoracic stomach, and vertebral anomalies. Other associated anomalies have been described, such as malposition and herniation of abdominal organs. We report the natural history of a baby girl born at 29 weeks of gestation with intra uterine growth restriction, short neck, large rachischisis from cervical to thoracic spine, a very short oesophagus, thoracic stomach associated with a midline diaphragmatic hernia, malrotated gut and median cleft lip. Most of these anomalies were detected antenatally. Molecular karyotype was normal. She died at age 12 days. To our knowledge, the present patient represents the 8th report of a case of "Serpentine-like syndrome". Brachioesophagus and congenital vertebral anomalies, in particular rachischisis, are the cardinal features of this condition. All reported cases have been sporadic and the cause is still unknown. We believe that the specificity of the presentation as well as the similarities between available descriptions of patients suggests a common, yet to identify, molecular cause, possibly involving a developmental "toolkit"/homeobox gene or related pathways. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Antenatal hemorrhage of a cervical lymphatic malformation presenting as a draining neck mass: An unusual presentation.

PubMed

Haricharan, R N; Nawaz, M; Bettolli, M; Ferretti, E

2014-01-01

Lymphatic malformations in the neck can present as large fetal neck masses causing airway obstructions with potential perinatal demise and can pose a therapeutic challenge. We present a rare case of prenatally diagnosed large fetal neck mass with features of lymphatic malformation with intralesional hemorrhage of uncertain origin. Postnatal evaluation showed a complex cystic-solid lesion eroding through the skin with an open wound that made it clinically hard to differentiate from a teratoma. Given that malignancy could not be completely ruled out, surgery was favored. Final pathology showed a complex lymphatic malformation with intralesional hemorrhage, despite having no associated capillary, venous or arterial malformations.

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.

Nailfold capillary morphological characteristics of hand-arm vibration syndrome: a cross-sectional study

PubMed Central

Chen, QingSong; Chen, GuiPing; Xiao, Bin; Lin, HanSheng; Qu, HongYing; Zhang, DanYing; Shi, MaoGong; Lang, Li; Yang, Bei; Yan, MaoSheng

2016-01-01

Objective The purpose of this study was to investigate the characteristics of nailfold capillaroscopy associated with hand-arm vibration syndrome (HAVS). Methods In total, 113 male gold miners were recruited: 35 workers who were chronically exposed to vibration and developed vibration-induced white finger were defined as the HAVS group, 39 workers who were exposed to vibration but did not have HAVS were classified as the vibration-exposed controls (VEC) group, and 39 workers without vibration exposure were categorised as the non-VEC (NVEC) group. Video capillaroscopy was used to capture images of the 2nd, 3rd and 4th fingers of both hands. The following nailfold capillary characteristics were included: number of capillaries/mm, avascular areas, haemorrhages and enlarged capillaries. The experiments were carried out in the same winter. All characteristics were evaluated under blinded conditions. Results Significant differences in all morphological characteristics existed between the groups (p<0.05). Avascular areas in the HAVS, VEC and NVEC groups appeared in 74.3%, 43.6% and 25.0% of participants, respectively. A higher percentage of participants had haemorrhages in the HAVS group (65.7%) compared with the other groups (VEC: 7.7% and NVEC: 7.5%). The number of capillaries/mm, input limb width, output limb width, apical width, and ratio of output limb and input limb all had more than 70% sensitivity or specificity of their cut-off value. Conclusions Nailfold capillary characteristics, especially the number of capillaries/mm, avascular areas, haemorrhages, output limb width, input limb width and apical width alterations, revealed significant associations with HAVS. PMID:27888176

[Sturge-Weber syndrome].

PubMed

Maruani, Annabel

2010-04-01

Facial port-wine stains are capillary malformations, which can reveal, very rarely, Sturge-Weber syndrome (SWS). SWS is a severe neurocutaneous syndrome, which involves a facial port-wine stain reaching the first branch of trigeminal nerve (V1), ophthalmologic abnormalities (especially congenital glaucoma) and neurologic signs (seizure, mental retardation, hemiparesis). Neuroimaging (CT-scan/angio-magnetic resonance imaging [MRI]) provides the diagnosis of SWS, when it shows ipsilateral leptomeningeal angioma; the best age to perform the exam is not established. Extension to superior eyelid, to other territories of trigeminal nerve (V2, V3) or to the contralateral hemiface is statistically associated to SWS. When a new-born has a facial port-wine stain reaching V1, ophthalmologic examination must be performed in the first months of life, as well as neuroimaging (at the age of 6-12 months, earlier in case of neurologic signs); a treatment of the port-wine stain by pulsed dye laser must also be considered. (c) 2010. Published by Elsevier Masson SAS.

NCAM2 deletion in a boy with macrocephaly and autism: Cause, association or predisposition?

PubMed

Scholz, Caroline; Steinemann, Doris; Mälzer, Madeleine; Roy, Mandy; Arslan-Kirchner, Mine; Illig, Thomas; Schmidtke, Jörg; Stuhrmann, Manfred

2016-10-01

We report on an 8-year-old boy with autism spectrum disorder (ASD), speech delay, behavioural problems, disturbed sleep and macrosomia including macrocephaly carrying a microdeletion that contains the entire NCAM2 gene and no other functional genes. Other family members with the microdeletion show a large skull circumference but do not exhibit any symptoms of autism spectrum disorder. Among many ASD-candidate genes, NCAM2 has been assumed to play a pivotal role in the development of ASD because of its function in the outgrowth and bundling of neurites. Our reported case raises the questions whether the NCAM2-deletion is the true cause of the ASD or only a risk factor and whether there might be any connection in NCAM2 with skull-size autism spectrum disorder, macrocephaly, neural cell adhesion molecule 2 protein (NCAM2), array comparative genomic hybridization (microarray). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Arnold-Chiari malformation in Noonan syndrome and other syndromes of the RAS/MAPK pathway].

PubMed

Ejarque, Ismael; Millán-Salvador, José M; Oltra, Silvestre; Pesudo-Martínez, José V; Beneyto, Magdalena; Pérez-Aytés, Antonio

2015-05-01

Noonan syndrome (NS) and other syndromes with a similar phenotype, such as LEOPARD, cardiofaciocutaneous, Costello and Legius, are associated to mutations in genes included in the RAS/MAPK pathway (RASopathies), which is an important signalling pathway related to cell proliferation. Tonsillar descent into the upper cervical spinal canal, known as Arnold-Chiari malformation (ACM), has been reported in patients with NS and this has led some researchers to suggest that ACM could be part of the phenotypic spectrum of NS. We report two cases of NS and ACM. Case 1: 29-year-old female with Noonan phenotype who underwent surgery at the age of nine years due to pulmonary valve stenosis. At the age of 27, she presented symptomatic ACM that required surgical decompression. She presented the c.922A>G (N308D) mutation in the gene PTPN that belongs to the RAS/MAPK pathway. Case 2: a 10-year-old female with Noonan phenotype and asymptomatic ACM detected in magnetic resonance imaging of the brain. She was a carrier of the c.923A>G (N308S) mutation in gene PTPN11. Six patients with this association have been found in the literature, four with the Noonan phenotype and two with LEOPARD. Our two patients provide supplementary evidence that backs up the hypothesis by which ACM would be part of the phenotypic spectrum of NS. The small number of reported cases of patients with this association does not allow us to draw up recommendations about when and how often neuroimaging studies should be performed; a careful neurological examination, however, should be included in the anticipatory health guidelines in syndromes involving the RAS/MAPK pathway.

The five-year survival of children with Down syndrome in Norway 1994-2009 differed by associated congenital heart defects and extracardiac malformations.

PubMed

Brodwall, Kristoffer; Greve, Gottfried; Leirgul, Elisabeth; Klungsøyr, Kari; Holmstrøm, Henrik; Vollset, Stein Emil; Øyen, Nina

2018-05-01

We investigated the prevalence of Down syndrome in a nationwide birth cohort, focusing on congenital heart defects (CHDs), their associations with extracardiac malformations (ECM) and survival. National registers were used to identify Norwegian births (1994-2009) and deaths (1994-2014) and updated with hospital diagnoses. We estimated birth defect frequencies in Down syndrome and the general population, the association between CHDs and ECM and hazard ratios for death from different combinations of CHDs and ECM. Down syndrome was found in 1672 of 953 450 births (17.6 per 10 000). Of the 1251 live births (13.3 per 10 000), 58% had CHD and 9% ECM. CHDs were associated with oesophageal atresia (p = 0.02) and Hirschsprung's disease (p = 0.03) but with no other malformations. The five-year survival for Down syndrome increased from 91.8% (1994-1999) to 95.8% (2000-2009) (p = 0.006), and overall survival was 92.0% with CHD and 97.4% without. Compared with Down syndrome children without CHD or ECM, the five-year mortality was similar for those with nonsevere CHDs, without or with ECM, but 4-7 times higher in those with severe CHDs without ECM and 13-28 times higher in those with severe CHDs and ECM. Down syndrome childhood survival improved, but mortality remained high with severe CHDs and extracardiac defects. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Brainstem conundrum: the Chiari I malformation.

PubMed

Mueller, D

2001-04-01

To describe the Chairi I Malformation in relation to the anatomy of the brain and spinal cord, the common manifestations of the condition, diagnostic considerations, and management for the primary care provider. Extensive review of the world-wide scientific literature on the condition, supplemented with actual case studies. The adult Chairi I Malformation is an insidious congenital brainstem anomaly that consists of caudal displacement of the cerebellar tonsils, brainstem and fourth ventricle into the upper cervical space, resulting in overcrowding of the posterior fossa. Due to the vague, and often ambiguous presenting symptoms of Chiari I Malformation, many patients are misdiagnosed with conditions such as multiple sclerosis, fibromyalgia, chronic fatigue syndrome, or psychiatric disorders. Patients frequently experience symptoms months to years prior to accurate diagnosis and often incur irreversible neurologic deficits.

Loss of function mutations in EPHB4 are responsible for vein of Galen aneurysmal malformation.

PubMed

Vivanti, Alexandre; Ozanne, Augustin; Grondin, Cynthia; Saliou, Guillaume; Quevarec, Loic; Maurey, Helène; Aubourg, Patrick; Benachi, Alexandra; Gut, Marta; Gut, Ivo; Martinovic, Jelena; Sénat, Marie Victoire; Tawk, Marcel; Melki, Judith

2018-04-01

See Meschia (doi:10.1093/brain/awy066) for a scientific commentary on this article.Vein of Galen aneurysmal malformation is a congenital anomaly of the cerebral vasculature representing 30% of all paediatric vascular malformations. We conducted whole exome sequencing in 19 unrelated patients presenting this malformation and subsequently screened candidate genes in a cohort of 32 additional patients using either targeted exome or Sanger sequencing. In a cohort of 51 patients, we found five affected individuals with heterozygous mutations in EPHB4 including de novo frameshift (p.His191Alafs*32) or inherited deleterious splice or missense mutations predicted to be pathogenic by in silico tools. Knockdown of ephb4 in zebrafish embryos leads to specific anomalies of dorsal cranial vessels including the dorsal longitudinal vein, which is the orthologue of the median prosencephalic vein and the embryonic precursor of the vein of Galen. This model allowed us to investigate EPHB4 loss-of-function mutations in this disease by the ability to rescue the brain vascular defect in knockdown zebrafish co-injected with wild-type, but not truncated EPHB4, mimicking the p.His191Alafs mutation. Our data showed that in both species, loss of function mutations of EPHB4 result in specific and similar brain vascular development anomalies. Recently, EPHB4 germline mutations have been reported in non-immune hydrops fetalis and in cutaneous capillary malformation-arteriovenous malformation. Here, we show that EPHB4 mutations are also responsible for vein of Galen aneurysmal malformation, indicating that heterozygous germline mutations of EPHB4 result in a large clinical spectrum. The identification of EPHB4 pathogenic mutations in patients presenting capillary malformation or vein of Galen aneurysmal malformation should lead to careful follow-up of pregnancy of carriers for early detection of anomaly of the cerebral vasculature in order to propose optimal neonatal care. Endovascular

Cerebrospinal fluid leakage and Chiari I malformation with Gorham's disease of the skull base: A case report.

PubMed

Nagashima, Hiroaki; Mizukawa, Katsu; Taniguchi, Masaaki; Yamamoto, Yusuke; Kohmura, Eiji

Gorham's syndrome is a rare bone disorder characterized by massive osteolysis of unknown etiology. There are no reports of comorbidity involving cerebrospinal fluid (CSF) leakage and Chiari I malformation with Gorham's syndrome. Here, we report an unusual case of an acute presyrinx state complicated by bacterial meningitis due to CSF leakage and Chiari I malformation associated with Gorham's disease of the skull base. A 25-year-old woman with Chiari I malformation associated with Gorham's syndrome presented with aggressive paresthesia following bacterial meningitis. Axial magnetic resonance imaging (MRI) and computed tomography (CT) cisternography revealed CSF leakage in the right petrous apex. A presyrinx state was diagnosed based on the clinical symptoms and MRI findings. With resolution of the bacterial meningitis, the spinal edema and tonsillar ectopia also improved. Surgical repair of the CSF leakage was performed by an endoscopic endonasal transsphenoidal approach to prevent recurrence of meningitis. The postoperative course was uneventful. Skull base osteolysis in Gorham's syndrome may induce Chiari I malformation and CSF leakage. We should pay attention to acute progression of clinical symptoms because Gorham's syndrome may predispose to development of Chiari I malformation and may be complicated by CSF leakage. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Nailfold capillary morphological characteristics of hand-arm vibration syndrome: a cross-sectional study.

PubMed

Chen, QingSong; Chen, GuiPing; Xiao, Bin; Lin, HanSheng; Qu, HongYing; Zhang, DanYing; Shi, MaoGong; Lang, Li; Yang, Bei; Yan, MaoSheng

2016-11-25

The purpose of this study was to investigate the characteristics of nailfold capillaroscopy associated with hand-arm vibration syndrome (HAVS). In total, 113 male gold miners were recruited: 35 workers who were chronically exposed to vibration and developed vibration-induced white finger were defined as the HAVS group, 39 workers who were exposed to vibration but did not have HAVS were classified as the vibration-exposed controls (VEC) group, and 39 workers without vibration exposure were categorised as the non-VEC (NVEC) group. Video capillaroscopy was used to capture images of the 2nd, 3rd and 4th fingers of both hands. The following nailfold capillary characteristics were included: number of capillaries/mm, avascular areas, haemorrhages and enlarged capillaries. The experiments were carried out in the same winter. All characteristics were evaluated under blinded conditions. Significant differences in all morphological characteristics existed between the groups (p<0.05). Avascular areas in the HAVS, VEC and NVEC groups appeared in 74.3%, 43.6% and 25.0% of participants, respectively. A higher percentage of participants had haemorrhages in the HAVS group (65.7%) compared with the other groups (VEC: 7.7% and NVEC: 7.5%). The number of capillaries/mm, input limb width, output limb width, apical width, and ratio of output limb and input limb all had more than 70% sensitivity or specificity of their cut-off value. Nailfold capillary characteristics, especially the number of capillaries/mm, avascular areas, haemorrhages, output limb width, input limb width and apical width alterations, revealed significant associations with HAVS. 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/.

Fiber 1.56-1.9 μm lasers in treatment of vascular malformations in children and adults

NASA Astrophysics Data System (ADS)

Abushkin, Ivan A.; Privalov, Valeriy A.; Lappa, Alexander V.; Minaev, Vladimir P.

2013-03-01

A few new low invasive fiber laser technologies for treatment of 1) capillary malformations (port-wine stains), 2) venous, arterial, and arteriovenous malformations, 3) lymphatic malformations of 3 types: micro, small and large-cystic lymphangiomas are presented in this work. There were applied 1.56 μm laser distant photocoagulation, 1.56 μm laser endovascular thermotherapy, 1.9 μm laser instant ablation, 1.9 μm laser interstitial thermotherapy, and 1.9 μm laser excision. The technologies were applied to about 300 patients. Good clinical and esthetic results have been achieved in great majority cases.

Congenital nephrotic syndrome.

PubMed

Hamed, Radi Ma

2003-01-01

The congenital nephrotic syndrome (CNS) is an uncommon disorder with onset of the nephrotic syndrome usually in the first three months of life. Several different diseases may cause the syndrome. These may be inherited, sporadic, acquired or part of a general malformation syndrome. The clinical course is marked by failure to thrive, recurrent life threatening bacterial infections, and early death from sepsis and/or uremia. A characteristic phenotype may be seen in children with CNS. The majority of reported cases of CNS are of the Finnish type (CNF). Although the role of the glomerular basement membrane has been emphasized as the barrier for retaining plasma proteins, recent studies have clearly shown that the slit diaphragm is the structure most likely to be the barrier in the glomerular capillary wall. The gene (NPHS1) was shown to encode a novel protein that was termed nephrin, due to its specific location in the kidney filter barrier, where it seems to form a highly organized filter structure. Nephrin is a transmembrane protein that probably forms the main building block of an isoporous zipper-like slit diaphragm filter structure. Defects in nephrin lead to the abnormal or absent slit diaphragm resulting in massive proteinuria and renal failure.

[Advances in genetics of congenital malformation of external and middle ear].

PubMed

Wang, Dayong; Wang, Qiuju

2013-05-01

Congenital malformation of external and middle ear is a common disease in ENT department, and the incidence of this disease is second only to cleft lip and palate in the whole congenital malformations of the head and face. The external and middle ear malformations may occur separately, or as an important ear symptom of the systemic syndrome. We systematically review and analysis the genetic research progress of congenital malformation of external and middle ear, which would be helpful to understand the mechanism of external and middle ear development, and to provide clues for the further discovery of new virulence genes.

Exclusion of the Sonic Hedgehog gene as responsible for Currarino syndrome and anorectal malformations with sacral hypodevelopment.

PubMed

Seri, M; Martucciello, G; Paleari, L; Bolino, A; Priolo, M; Salemi, G; Forabosco, P; Caroli, F; Cusano, R; Tocco, T; Lerone, M; Cama, A; Torre, M; Guys, J M; Romeo, G; Jasonni, V

1999-01-01

Anorectal malformations (ARMs) are common congenital anomalies that account for 1:4 digestive malformations. ARM patients show different degrees of sacral hypodevelopment while the hemisacrum is characteristic of the Currarino syndrome (CS). Cases of CS present an association of ARM, hemisacrum and presacral mass. A gene responsible for CS has recently been mapped in 7q36. Among the genes localized in this critical region, sonic hedgehog (SHH) was thought to represent a candidate gene for CS as well as for ARM with different levels of sacral hypodevelopment according to its role in the differentiation of midline mesoderm. By linkage analysis we confirmed the critical region in one large family with recurrence of CS. In addition, the screening of SHH in 7 CS and in 15 sporadic ARM patients with sacral hypodevelopment allowed us to exclude its role in the pathogenesis of these disorders.

[Focus on Dandy-Walker malformation].

PubMed

Klein, O; Pierre-Kahn, A

2006-09-01

The aim of this review is to summarize our knowledge about Dandy-Walker malformation (DWM) and introduce recent notions about its prognosis. DWM is a malformation associating hypoplasia of the vermis, pseudocystic fourth ventricle, upward displacement of the tentorium, torcular and lateral sinuses and anterio-posterior enlargement of the posterior fossa. It is frequently associated with genetic anomalies, brain malformations (anomalies of gyration, grey matter heterotopias, meningoceles, corpus callosum agenesis...) or systemic malformations (heart, orthopedic, intestinal, urogenital and facial anomalies). It is also part of many syndromes. Its rarity, the difficulty of its diagnosis, the fact that the malformation is mainly known through hospitalized patients, mainly from neurosurgical departments, have made its definition variable and prevents us from having an accurate knowledge of its natural history and prognosis. Hydrocephalus, so frequent in neurosurgical series that some have included it in the definition, is actually rare as has been seen in prenatal series. Treatment, when necessary, is still controversial, the main options remaining cyst fenestration, ventriculo- and/or cystoperitoneal shunts and more recently endoscopic third ventriculostomy. The prognosis, commonly said to be unpredictable, is actually foreseeable after scrutinous observation of the brain anatomy, and mainly of the vermis. A cerebellar vermis with three groups of lobes and two main fissures, as identified on MRI T2 sagittal views, not only has the greatest chance to not be associated with other malformation but also to have a favorable neurocognitive outcome. On the contrary, a deeply dysgenetic vermis with only two or one recognizable lobes is not only constantly associated with other brain malformation but also with poor prognosis. This is a recent advance that may be important for those involved in prenatal counselling.

Exercise training dose differentially alters muscle and heart capillary density and metabolic functions in an obese rat with metabolic syndrome.

PubMed

Machado, Marcus Vinicius; Vieira, Aline Bomfim; da Conceição, Fabiana Gomes; Nascimento, Alessandro Rodrigues; da Nóbrega, Antonio Claudio Lucas; Tibirica, Eduardo

2017-12-01

What is the central question of this study? Regular exercise is recommended as a non-pharmacological approach for the prevention and treatment of metabolic syndrome. However, the impact of different combinations of intensity, duration and frequency of exercise on metabolic syndrome and microvascular density has not been reported. What is the main finding and its importance? We provide evidence on the impact of aerobic exercise dose on metabolic and microvascular alterations in an experimental model of metabolic syndrome induced by high-fat diet. We found that the exercise frequency and duration were the main factors affecting anthropometric and metabolic parameters and microvascular density in the skeletal muscle. Exercise intensity was related only to microvascular density in the heart. We evaluated the effect of the frequency, duration and intensity of exercise training on metabolic parameters and structural capillary density in obese rats with metabolic syndrome. Wistar-Kyoto rats were fed either a standard commercial diet (CON) or a high-fat diet (HFD). Animals that received the HFD were randomly separated into either a sedentary (SED) group or eight different exercise groups that varied according to the frequency, duration and intensity of training. After 12 weeks of aerobic exercise training, the body composition, aerobic capacity, haemodynamic variables, metabolic parameters and capillary density in the heart and skeletal muscle were evaluated. All the exercise training groups showed reduced resting systolic blood pressure and heart rate and normalized fasting glucose. The minimal amount of exercise (90 min per week) produced little effect on metabolic syndrome parameters. A moderate amount of exercise (150 min per week) was required to reduce body weight and improve capillary density. However, only the high amount of exercise (300 min per week) significantly reduced the amount of body fat depots. The three-way ANOVA showed a main effect of exercise

[The case of completed pregnancy of the patient with Dandy-Walker malformation].

PubMed

Beliaeva, E V; Lapshina, L V; Shaposhnikova, E V; Molgachev, A A

2018-01-01

Dandy-Walker malformation is a rare disease of the central nervous system pathology (congenital malformations of the fossa cranii posterior). The key features of this syndrome are an enlargement of the fourth ventricle; complete absence of the cerebellar vermis, the posterior midline area of cerebellar cortex responsible for coordination of the axial musculature; and cyst formation near the internal base of the skull. Pregnant patients with Dandy-Walker malformation are at high risk and are managed by multidisciplinary teams including neurologists and obstetricians. We present a case report of full-term pregnancy and uncomplicated delivery in a women with Dandy-Walker malformation.

Genetically diagnosed Birt-Hogg-Dubé syndrome and familial cerebral cavernous malformations in the same individual: a case report.

PubMed

Whitworth, James; Stausbøl-Grøn, Brian; Skytte, Anne-Bine

2017-01-01

When faced with an unusual clinical feature in a patient with a Mendelian disorder, the clinician may entertain the possibilities of either the feature representing a novel manifestation of that disorder or the co-existence of a different inherited condition. Here we describe an individual with a submandibular oncocytoma, pulmonary bullae and renal cysts as well as multiple cerebral cavernous malformations and haemangiomas. Genetic investigations revealed constitutional mutations in FLCN, associated with Birt-Hogg-Dubé syndrome (BHD) and CCM2, associated with familial cerebral cavernous malformation. Intracranial vascular pathologies (but not cerebral cavernous malformation) have recently been described in a number of individuals with BHD (Kapoor et al. in Fam Cancer 14:595-597, 10.1007/s10689-015-9807-y , 2015) but it is not yet clear whether they represent a genuine part of that conditions' phenotypic spectrum. We suggest that in such instances of potentially novel clinical features, more extensive genetic testing to consider co-existing conditions should be considered where available. The increased use of next generation sequencing applications in diagnostic settings is likely to lead more cases such as this being revealed.

Anesthetic management of Costello syndrome: a case report.

PubMed

Williams, Christol

2014-04-01

Costello syndrome is a rare genetic disorder with an estimated 300 medical cases worldwide. Typical features that characterize this syndrome include short stature, macrocephaly, developmental delay, loose skin folds, distinctive coarse facial features, and multiorgan system anomalies. The following case report discusses the anesthetic management for a 3-year-old boy undergoing general anesthesia for a scheduled dental restoration, hydrocelectomy, inguinal hernia repair, and bilateral myringotomy with placement of pressure equalization tubes. A scarcity of literature for the anesthetic management of Costello syndrome (also known as faciocutaneoskeletal syndrome) exists. Utilizing an overview of the pertinent literature, clinical practice recommendations are suggested for the anesthetic implications of managing a pediatric patient with this rare syndrome.

Ischaemic Strokes in Patients with Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia: Associations with Iron Deficiency and Platelets

PubMed Central

Shovlin, Claire L.; Chamali, Basel; Santhirapala, Vatshalan; Livesey, John A.; Angus, Gillian; Manning, Richard; Laffan, Michael A.; Meek, John; Tighe, Hannah C.; Jackson, James E.

2014-01-01

Background Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke. Methodology 497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies. Principal Findings Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0

Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report.

PubMed

Lei, Hongen; Guan, Xing; Han, Hu; Qian, Xiaosong; Zhou, Xiaoguang; Zhang, Xiaodong; Tian, Long

2018-06-01

Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder characterized by a triad of cutaneous port wine capillary malformations, varicose veins, and hemihypertrophy of bone and soft tissues. To report on a rare case of KTS in an adult man manifested by painless urethral bleeding during penile erection briefly review the clinical presentation and management of the genitourinary forms of this syndrome. On presentation, the clinical features of this patient, including medical history, signs and symptoms, and imaging examinations, were recorded. After diagnosis and initial treatment, a literature review of the urethral features of KTS was performed and is discussed in this report. A 35-year-old man with KTS presented with painless urethral bleeding during penile erection that was associated with posterior urethral vascular malformations. The coagulation method was used to treat the malformation, and no urethral bleeding or gross hematuria occurred during a postoperative follow-up period of 6 months. This case demonstrates that coagulation therapy and careful follow-up can be adequate treatment approaches for urethral features of KTS. However, the long-term efficacy of coagulation for this disorder should be investigated further. Lei H, Guan X, Han H, et al. Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report. Sex Med 2018;6:180-183. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Klippel-Trenaunay syndrome complicated by ascites and vaginal lymphatic drainage in adolescence: a case report.

PubMed

Scribner, Dennis R; Lara-Torre, Eduardo; Heineck, Robert J; Weiss, Patrice M

2012-12-01

Klippel-Trenaunay syndrome is a rare disease characterized by capillary malformationsand soft tissue and bony hypertrophy and atypical varicosities. Management of this syndrome is focused primarily on treatment of the complications that arise from these malformations. Ascites and lymphedema are two of the more common complications in these patients. A 15-year-old female with Klippel-Trenaunay syndrome presented with chylous ascites, vaginal drainage, and unilateral lower extremity lymphedema. Treatment included dilation, hysteroscopy and curettage, and laparoscopic evacuation of abdomino-pelvic ascites with resolution of symptoms for 32 months. Repeat laparoscopic drainage was successful and remains symptom free after 12 months. Vaginal drainage of chylous ascites is a rare complication from Klippel-Trenaunay syndrome and can be successfully managed by techniques to remove abdomino-pelvic ascites. Copyright © 2012 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

[Cutaneous hemangiomas and vascular malformations and associated pathology (Pascual-Castroviejo type II syndrome). Study of 41 patients].

PubMed

Pascual-Castroviejo, I; Pascual-Pascual, S I; Velázquez-Fragua, R; García, L; López-Gutiérrez, J C; Viaño-López, J; Martínez, V; Palencia, R

To describe the clinical, diagnostic and therapeutic features of this angiomatous neurocutaneous syndrome, which is the most frequent one, and to report a personal series of 41 patients. Forty one patients--31 females and 10 males--were studied during childhood and then, several patients were followed during many years, which allowed us to learn about the evolution of the abnormalities. The cutaneous lesions were classified as hemangiomas in 30 patients (73%) and as vascular malformations in 11 patients (27%). A cerebellar anomaly (unilateral hemispheric hypoplasia and Dandy-Walker malformation) was seen in 13 patients (31.5%) cerebral cortical dysplasia in 4 patients (10%), aortic arch coarctation in 6 patients (15%), and congenital cardiopathy in 5 patients (12%). The most frequent abnormalities were intracranial and/or extracranial vascular malformations. Persistence of the trigeminal artery was observed in 7 patients (17%), absence or severe hypoplasia of an internal carotid artery in 13 patients (32%), absence of a vertebral artery in 7 patients (17%), hypoplasia of intracranial arteries in 6 patients (15%) and aneurysmal enlargement of carotid or vertebral arteries in 5 patients (12%). Also were observed 4 patients (10%) with intracranial hemangioma, 2 (5%) with hemangioma in mediastinum, and 3 (7.5%) with intestinal hemangioma, all of which disappeared during the first years of life. Aneurysmal enlargement of the carotid and vertebral arteries and intracranial branches also disappeared after a process of progressive narrowing of the arterial lumen that caused complete obstruction of these arteries. At the same time the cutaneous hemangioma regressed. During this process, collateral vascularization through branches of the external carotid artery and of the non-affected branches of the contralateral intracranial arteries developed. This neurocutaneous syndrome is the most frequent one and it is associated with several types of vascular and non

Genetics Home Reference: microcephaly-capillary malformation syndrome

MedlinePlus

... A, Isidor B, David A, Smyser CD, Paciorkowski AR, Willing M, Woulfe J, Das S, Beaulieu CL, Marcadier ... Free article on PubMed Central Mirzaa GM, Paciorkowski AR, Smyser CD, Willing MC, Lind AC, Dobyns WB. ...

Inner ear abnormalities in patients with Goldenhar syndrome.

PubMed

Bisdas, Sotirios; Lenarz, Minoo; Lenarz, Thomas; Becker, Hartmut

2005-05-01

The objective of this study is to investigate the inner ear malformations in patients with Goldenhar syndrome and to hypothesize the potential embryopathogenesis of these malformations. Retrospective case review. Tertiary referral center. Fourteen patients with Goldenhar syndrome. Each patient underwent hearing tests and high-resolution computed tomography (CT) of the temporal bone. In six patients, magnetic resonance imaging of the temporal bone also was performed. Among the 14 patients with Goldenhar syndrome, 13 had outer and middle ear anomalies and 5 (36%) had inner ear malformations, including one case of common cavity. Our observations regarding inner ear anomalies in Goldenhar syndrome correlate with the reported cases in the literature and may help to hypothesize the embryological origin of these malformations, which can caused by an early developmental arrest in the fourth gestational week. Specialists evaluating patients with Goldenhar syndrome should be aware of the possibility of inner ear malformations, which could be diagnosed earlier with appropriate imaging studies.

Perinatal features of the RASopathies: Noonan syndrome, cardiofaciocutaneous syndrome and Costello syndrome.

PubMed

Myers, Angela; Bernstein, Jonathan A; Brennan, Marie-Luise; Curry, Cynthia; Esplin, Edward D; Fisher, Jamie; Homeyer, Margaret; Manning, Melanie A; Muller, Eric A; Niemi, Anna-Kaisa; Seaver, Laurie H; Hintz, Susan R; Hudgins, Louanne

2014-11-01

The RASopathies are a family of developmental disorders caused by heritable defects of the RAS/MAPK signaling pathway. While the postnatal presentation of this group of disorders is well known, the prenatal and neonatal findings are less widely recognized. We report on the perinatal presentation of 10 patients with Noonan syndrome (NS), nine with Cardiofaciocutaneous syndrome (CFCS) and three with Costello syndrome (CS), in conjunction with the results of a comprehensive literature review. The majority of perinatal findings in NS, CS, and CFCS are shared: polyhydramnios; prematurity; lymphatic dysplasia; macrosomia; relative macrocephaly; respiratory distress; hypotonia, as well as cardiac and renal anomalies. In contrast, fetal arrhythmia and neonatal hypoglycemia are relatively specific to CS. NS, CS, and CFCS should all be considered as a possible diagnosis in pregnancies with a normal karyotype and ultrasound findings of a RASopathy. Recognition of the common perinatal findings of these disorders should facilitate both their prenatal and neonatal diagnosis. © 2014 Wiley Periodicals, Inc.

Dandy-Walker malformation: analysis of 19 cases.

PubMed

Alexiou, George A; Sfakianos, George; Prodromou, Neofytos

2010-02-01

Dandy-Walker malformation is a congenital disorder that involves the cerebellum and fourth ventricle. Regarding treatment, there is still controversy over the optimum surgical management. In the current study, we present 19 consecutive cases of Dandy-Walker malformation diagnosed between January 1992 and January 2008 that were treated in our institute. All patients presented with hydrocephalus at the time of diagnosis and were treated surgically. Combined drainage of the ventricular system and posterior fossa cyst, using a 3-way connector was performed in 5 patients. Posterior fossa cyst drainage alone was performed in 10 patients and the remaining 4 patients were treated by ventricular drainage alone. All patients improved after treatment. Dandy-Walker malformation is a developmental abnormality of the central nervous system associated with various brain and extracranial abnormalities. Surgical treatment remains controversial, whereas prognosis varies greatly according to the severity of syndrome and associated comorbidities.

Two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: Clinical homogeneity but also unreported malformations.

PubMed

Barraza-García, Jimena; Iván Rivera-Pedroza, Carlos; Salamanca, Luis; Belinchón, Alberta; López-González, Vanesa; Sentchordi-Montané, Lucía; del Pozo, Ángela; Santos-Simarro, Fernando; Campos-Barros, Ángel; Lapunzina, Pablo; Guillén-Navarro, Encarna; González-Casado, Isabel; García-Miñaur, Sixto; Heath, Karen E

2016-01-01

Primordial dwarfism encompasses rare conditions characterized by severe intrauterine growth retardation and growth deficiency throughout life. Recently, three POC1A mutations have been reported in six families with the primordial dwarfism, SOFT syndrome (Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis). Using a custom-designed Next-generation sequencing skeletal dysplasia panel, we have identified two novel homozygous POC1A mutations in two individuals with primordial dwarfism. The severe growth retardation and the facial profiles are strikingly similar between our patients and those described previously. However, one of our patients was diagnosed with severe foramen magnum stenosis and subglottic tracheal stenosis, malformations not previously associated with this syndrome. Our findings confirm that POC1A mutations cause SOFT syndrome and that mutations in this gene should be considered in patients with severe pre- and postnatal short stature, symmetric shortening of long bones, triangular facies, sparse hair and short, thickened distal phalanges. © 2015 Wiley Periodicals, Inc.

Idiopathic Systemic Capillary Leak Syndrome (Clarkson's Disease): The Mayo Clinic Experience

PubMed Central

Kapoor, Prashant; Greipp, Patricia T.; Schaefer, Eric W.; Mandrekar, Sumithra J.; Kamal, Arif H.; Gonzalez-Paz, Natalia C.; Kumar, Shaji; Greipp, Philip R.

2010-01-01

OBJECTIVE: To determine clinical features, natural history, and outcome of a well-defined cohort of 25 consecutive patients with idiopathic systemic capillary leak syndrome (SCLS) evaluated at a tertiary care center. PATIENTS AND METHODS: Records of patients diagnosed as having SCLS from November 1, 1981, through April 30, 2008, were reviewed. Descriptive statistics were used to analyze patient demographics, clinical features, complications, and therapeutic interventions. RESULTS: Of the 34 patients whose records were reviewed, 25 fulfilled all diagnostic criteria for SCLS. The median age at diagnosis of SCLS was 44 years. Median follow-up of surviving patients was 4.9 years, and median time to diagnosis from symptom onset was 1.1 years (interquartile range, 0.5-4.1 years). Flulike illness or myalgia was reported by 14 patients (56%) at onset of an acute attack of SCLS, and rhabdomyolysis developed in 9 patients (36%). Patients with a greater decrease in albumin level had a higher likelihood of developing rhabdomyolysis (p=.03). Monoclonal gammopathy, predominantly of the IgG-κ type, was found in 19 patients (76%). The progression rate to multiple myeloma was 0.7% per person-year of follow-up. The overall response rate to the different therapies was 76%, and 24% of patients sustained durable (>2 years) complete remission. The estimated 5-year overall survival rate was 76% (95% confidence interval, 59%-97%). CONCLUSION: Systemic capillary leak syndrome, a rare disease that occurs in those of middle age, is usually diagnosed after a considerable delay from onset of symptoms. The degree of albumin decrement during an attack correlates with development of rhabdomyolysis. A reduction in the frequency and/or the severity of attacks was seen in nearly three-fourths of patients who were offered empirical therapies. The rate of progression to multiple myeloma appears to be comparable to that of monoclonal gammopathy of undetermined significance. PMID:20634497

The presentation and management of complex female genital malformations.

PubMed

Acién, Pedro; Acién, Maribel

2016-01-01

Common uterine anomalies are important owing to their impact on fertility, and complex mesonephric anomalies and certain Müllerian malformations are particularly important because they cause serious clinical symptoms and affect woman's quality of life, in addition to creating fertility problems. In these cases of complex female genital tract malformations, a correct diagnosis is essential to avoid inappropriate and/or unnecessary surgery. Therefore, acquiring and applying the appropriate embryological knowledge, management and therapy is a challenge for gynaecologists. Here, we considered complex malformations to be obstructive anomalies and/or those associated with cloacal and urogenital sinus anomalies, urinary and/or extragenital anomalies, or other clinical implications or symptoms creating a difficult differential diagnosis. A diligent and comprehensive search of PubMed and Scopus was performed for all studies published from 1 January 2011 to 15 April 2015 (then updated up to September 2015) using the following search terms: 'management' in combination with either 'female genital malformations' or 'female genital tract anomalies' or 'Müllerian anomalies'. The MeSH terms 'renal agenesis', 'hydrocolpos', 'obstructed hemivagina' 'cervicovaginal agenesis or atresia', 'vaginal agenesis or atresia', 'Herlyn-Werner-Wunderlich syndrome', 'uterine duplication' and 'cloacal anomalies' were also used to compile a list of all publications containing these terms since 2011. The basic embryological considerations for understanding female genitourinary malformations were also revealed. Based on our experience and the updated literature review, we studied the definition and classification of the complex malformations, and we analysed the clinical presentation and different therapeutic strategies for each anomaly, including the embryological and clinical classification of female genitourinary malformations. From 755 search retrieved references, 230 articles were analysed and

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 developmental and genetic classification for midbrain-hindbrain malformations

PubMed Central

Millen, Kathleen J.; Dobyns, William B.

2009-01-01

Advances in neuroimaging, developmental biology and molecular genetics have increased the understanding of developmental disorders affecting the midbrain and hindbrain, both as isolated anomalies and as part of larger malformation syndromes. However, the understanding of these malformations and their relationships with other malformations, within the central nervous system and in the rest of the body, remains limited. A new classification system is proposed, based wherever possible, upon embryology and genetics. Proposed categories include: (i) malformations secondary to early anteroposterior and dorsoventral patterning defects, or to misspecification of mid-hindbrain germinal zones; (ii) malformations associated with later generalized developmental disorders that significantly affect the brainstem and cerebellum (and have a pathogenesis that is at least partly understood); (iii) localized brain malformations that significantly affect the brain stem and cerebellum (pathogenesis partly or largely understood, includes local proliferation, cell specification, migration and axonal guidance); and (iv) combined hypoplasia and atrophy of putative prenatal onset degenerative disorders. Pertinent embryology is discussed and the classification is justified. This classification will prove useful for both physicians who diagnose and treat patients with these disorders and for clinical scientists who wish to understand better the perturbations of developmental processes that produce them. Importantly, both the classification and its framework remain flexible enough to be easily modified when new embryologic processes are described or new malformations discovered. PMID:19933510

Congenital capillary proliferation of the kidney: a distinctive renal vascular lesion of childhood.

PubMed

Cajaiba, Mariana M; North, Paula E; Gong, Shunyou; Dickman, Paul S; Mroczek-Musulman, Elizabeth; Sauer, David A; Perlman, Elizabeth J

2017-08-01

Renal vascular lesions (RVL) are rare, and their morphological spectrum remains largely unknown, particularly in children. In this study, we characterize the clinicopathological features of RVL in a cohort of 12 children. Seven lesions were classified as previously recognized entities: vascular malformations (4), papillary endothelial hyperplasia (2), and pyogenic granuloma (lobular capillary hemangioma; 1). An eighth lesion showed nonspecific findings, which were interpreted as reactive during our review. The remaining 4 cases presented either prenatally, at birth, or shortly after birth and were morphologically similar. These were characterized by a peculiar pattern of capillary proliferation with entrapment of native renal structures, variable amounts of extramedullary hematopoiesis and reactive lymphocytes, foci of infarction and hemorrhage, and the presence of feeding and draining vessels at their periphery. To our knowledge, this represents a previously undescribed congenital vascular lesion involving the kidney, which we have descriptively and provisionally termed congenital capillary proliferation of the kidney (CCPK). While it is unclear whether CCPK represents a malformation or neoplastic proliferation, it shows overlapping features with congenital hemangioma of the liver (solitary congenital hepatic hemangioma) and congenital nonprogressive hemangioma (CNH) of the skin and soft tissue, suggesting a possible common pathogenesis among these 3 entities. Copyright © 2017 Elsevier Inc. All rights reserved.

[Nephrourologic pathology in girls with Turner syndrome].

PubMed

Di Pinto, Diana; Balestracci, Alejandro; Dujovne, Noelia; de Palma, Isabel; Adragna, Marta; Delgado, Norma

2010-08-01

Nephrourologic malformations in Turner syndrome are frequent, its diagnosis and follow-up is important in order to diminish the morbidity of this disease. The aim of this retrospective study was to analyze the nephrourologic pathology in 72 girls with Turner syndrome followed between 1989 and 2008 at Garrahan Hospital. The prevalence of nephrourologic involvement was 33% (24 patients). The most frequent findings were urinary system malformations, isolated (10 pacientes, 42%) or associated with renal malformations (9 patients, 37%); 5 patients (21%) had only renal malformations. Fifty percent of patients developed complications (8 urinary tract infection, 2 proteinuria and 2 arterial hypertension); however, none progressed to chronic renal failure. The prevalence of nephrourologic involvement was 33% and a half of these girls developed complications, our findings show the need of routine nephrological follow-up of girls with Turner syndrome and nephrourologic malformations.

Dandy-Walker syndrome and chromosomal abnormalities.

PubMed

Imataka, George; Yamanouchi, Hideo; Arisaka, Osamu

2007-12-01

Dandy-Walker syndrome (DWS) is a brain malformation of unknown etiology, but several reports have been published indicating that there is a causal relationship to various types of chromosomal abnormalities and malformation syndromes. In the present article, we present a bibliographical survey of several previously issued reports on chromosomal abnormalities associated with DWS, including our case of DWS found in trisomy 18. There are various types of chromosomal abnormalities associated with DWS; most of them are reported in chromosome 3, 9, 13 and 18. We also summarize some other chromosomal abnormalities and various congenital malformation syndromes.

Severe capillary leak syndrome after inner ear decompression sickness in a recreational scuba diver.

PubMed

Gempp, Emmanuel; Lacroix, Guillaume; Cournac, Jean-Marie; Louge, Pierre

2013-07-01

Post-decompression shock with plasma volume deficit is a very rare event that has been observed under extreme conditions of hypobaric and hyperbaric exposure in aviators and professional divers. We report a case of severe hypovolemic shock due to extravasation of plasma in a recreational scuba diver presenting with inner ear decompression sickness. Impaired endothelial function can lead to capillary leak with hemoconcentration and hypotension in severe cases. This report suggests that decompression-induced circulating bubbles may have triggered the endothelial damage, activating the classic inflammatory pathway of increased vascular permeability. This observation highlights the need for an accurate diagnosis of this potentially life-threatening condition at the initial presentation in the Emergency Department after a diving-related injury. An elevated hematocrit in a diver should raise the suspicion for the potential development of capillary leak syndrome requiring specific treatment using albumin infusion as primary fluid replacement. Copyright © 2013 Elsevier Inc. All rights reserved.

Hereditary hemorrhagic telangiectasia patient presenting with brain abscess due to silent pulmonary arteriovenous malformation.

PubMed

Themistocleous, Marios; Giakoumettis, Dimitrios; Mitsios, Andreas; Anagnostopoulos, Christos; Kalyvas, Aristoteles; Koutsarnakis, Christos

2016-01-01

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant inherited disease that is usually complicated by visceral vascular malformations. Patients harboring such malformations are at increased risk of brain abscess formation, which despite advances in diagnostic and surgical methods remains a life threatening medical emergency with high mortality and morbidity rates. In the present report we describe a case of cerebral abscess due to silent pulmonary arteriovenous malformation (AVM) in a young patient previously undiagnosed for hereditary hemorrhagic telangiectasia syndrome (HHT).

Retrospective single center study of the efficacy of large spot 532 nm laser for the treatment of facial capillary malformations in 44 patients with the use of three-dimensional image analysis.

PubMed

Kwiek, Bartłomiej; Rożalski, Michał; Kowalewski, Cezary; Ambroziak, Marcin

2017-10-01

We wanted to asses the efficacy of large spot 532 nm laser for the treatment of facial capillary malformations with the use of three-dimensional (3D) image analysis. Retrospective single center study on previously non-treated patients with facial capillary malformations (CM) was performed. A total of 44 consecutive Caucasian patients aged 5-66 were included. Patients had 3D photography performed before and after and had at least one single session of treatment with 532 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser with contact cooling, fluencies ranging from 8 to 11.5 J/cm 2 , pulse duration ranging from 5 to 9 milliseconds and spot size ranging from 5 to 10 mm. Objective analysis of percentage improvement based on 3D digital assessment of combined color and area improvement (global clearance effect [GCE]) were performed. Median maximal improvement achieved during the treatment (GCE max ) was 70.4%. Mean number of laser procedures required to achieve this improvement was 7.1 (ranging from 2 to 14)). Improvement of minimum 25% (GCE 25) was achieved by all patients, of minimum 50% (GCE 50) by 77.3%, of minimum 75% (GCE 75) by 38.6%, and of minimum 90% (GCE 90) by 13.64. Large spot 532 nm laser is highly effective in the treatment of facial CM. 3D color and area image analysis provides an objective method to compare different methods of facial CM treatment in future studies. Lasers Surg. Med. 49:743-749, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Dandy-Walker Malformation: is the 'tail sign' the key sign?

PubMed

Bernardo, Silvia; Vinci, Valeria; Saldari, Matteo; Servadei, Francesca; Silvestri, Evelina; Giancotti, Antonella; Aliberti, Camilla; Porpora, Maria Grazia; Triulzi, Fabio; Rizzo, Giuseppe; Catalano, Carlo; Manganaro, Lucia

2015-12-01

The study aims to demonstrate the value of the 'tail sign' in the assessment of Dandy-Walker malformation. A total of 31 fetal magnetic resonance imaging (MRI), performed before 24 weeks of gestation after second-line ultrasound examination between May 2013 and September 2014, were examined retrospectively. All MRI examinations were performed using a 1.5 Tesla magnet without maternal sedation. Magnetic resonance imaging diagnosed 15/31 cases of Dandy-Walker malformation, 6/31 of vermian partial caudal agenesis, 2/31 of vermian hypoplasia, 4/31 of vermian malrotation, 2/31 of Walker-Warburg syndrome, 1/31 of Blake pouch cyst and 1/31 of rhombencephalosynapsis. All data were compared with fetopsy results, fetal MRI after the 30th week or postnatal MRI; the follow-up depended on the maternal decision to terminate or continue pregnancy. In our review study, we found the presence of the 'tail sign'; this sign was visible only in Dandy-Walker malformation and Walker-Warburg syndrome. The 'tail sign' could be helpful in the difficult differential diagnosis between Dandy-Walker, vermian malrotation, vermian hypoplasia and vermian partial agenesis. © 2015 John Wiley & Sons, Ltd.

Neuroimaging of Dandy-Walker malformation: new concepts.

PubMed

Correa, Gustavo Gumz; Amaral, Lázaro Faria; Vedolin, Leonardo Modesti

2011-12-01

Dandy-Walker malformation (DWM) is the most common human cerebellar malformation, characterized by hypoplasia of the cerebellar vermis, cystic dilation of the fourth ventricle, and an enlarged posterior fossa with upward displacement of the lateral sinuses, tentorium, and torcular. Although its pathogenesis is not completely understood, there are several genetic loci related to DWM as well as syndromic malformations and congenital infections. Dandy-Walker malformation is associated with other central nervous system abnormalities, including dysgenesis of corpus callosum, ectopic brain tissue, holoprosencephaly, and neural tube defects. Hydrocephalus plays an important role in the development of symptoms and neurological outcome in patients with DWM, and the aim of surgical treatment is usually the control of hydrocephalus and the posterior fossa cyst. Imaging modalities, especially magnetic resonance imaging, are crucial for the diagnosis of DWM and distinguishing this disorder from other cystic posterior fossa lesions. Persistent Blake's cyst is seen as a retrocerebellar fluid collection with cerebrospinal fluid signal intensity and a median line communication with the fourth ventricle, commonly associated with hydrocephalus. Mega cisterna magna presents as an extraaxial fluid collection posteroinferior to an intact cerebellum. Retrocerebellar arachnoid cysts frequently compress the cerebellar hemispheres and the fourth ventricle. Patients with DWM show an enlarged posterior fossa filled with a cystic structure that communicates freely with the fourth ventricle and hypoplastic vermis. Comprehension of hindbrain embryology is of utmost importance for understanding the cerebellar malformations, including DWM, and other related entities.

Acute Respiratory Distress Syndrome after Onyx Embolization of Arteriovenous Malformation

PubMed Central

Tawil, Isaac; Carlson, Andrew P.; Taylor, Christopher L.

2011-01-01

Purpose. We report a case of a 60-year-old male who underwent sequential Onyx embolizations of a cerebral arteriovenous malformation (AVM) which we implicate as the most likely etiology of subsequent acute respiratory distress syndrome (ARDS). Methods. Case report and literature review. Results. Shortly after the second Onyx embolization procedure, the patient declined from respiratory failure secondary to pulmonary edema. Clinical entities typically responsible for pulmonary edema including cardiac failure, renal failure, iatrogenic volume overload, negative-pressure pulmonary edema, and infectious etiologies were evaluated and excluded. The patient required mechanical ventilatory support for several days, delaying operative resection. The patient met clinical and radiographic criteria for ARDS. After excluding other etiologies of ARDS, we postulate that ARDS developed as a result of Onyx administration. The Onyx copolymer is dissolved in dimethyl sulfoxide (DMSO), a solvent excreted through the lungs and has been implicated in transient pulmonary side effects. Additionally, a direct toxic effect of the Onyx copolymer is postulated. Conclusion. Onyx embolization and DMSO toxicity are implicated as the etiology of ARDS given the lack of other inciting factors and the close temporal relationship. A strong physiologic rationale provides further support. Clinicians should consider this uncommon but important complication. PMID:21687580

[Neuropsychiatric symptoms in Sotos syndrome. Case report and review of the literature].

PubMed

Kessler, Holger; Kraft, Susanne

2008-01-01

Sotos syndrome, or cerebral gigantism, is a rare genetic syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial gestalt and learning difficulties. It is caused by mutations or deletions of the NSD-1 gene. Most cases are sporadic. Apart from a number of physical abnormalities that are commonly present, a high prevalence of cognitive, emotional and behavioural problems in children with Sotos syndrome can be assumed. However, there has been almost no literature about psychiatric symptoms in adults with Sotos syndrome so far; one case of psychosis was reported. In the present case, the authors present psychopathological features of an adult patient with Sotos syndrom who developed - among other things - psychotic symptoms.

A Novel Rasopathy Caused by Recurrent De Novo Missense Mutations In PPP1CB Closely Resembles Noonan Syndrome with Loose Anagen Hair

PubMed Central

Gripp, Karen W.; Aldinger, Kimberly A.; Bennett, James T.; Baker, Laura; Tusi, Jessica; Powell-Hamilton, Nina; Stabley, Deborah; Sol-Church, Katia; Timms, Andrew E.; Dobyns, William B.

2016-01-01

Noonan syndrome is a rasopathy caused by mutations in multiple genes encoding components of the RAS/MAPK pathway. Despite its variable phenotype, limited genotype-phenotype correlations exist. Noonan syndrome with loose anagen hair (NS-LAH) is characterized by its distinctive hair anomalies, developmental differences and structural brain abnormalities and is caused by a single recurrent missense SHOC2 mutation. SHOC2 forms a complex with protein phosphatase 1 (PP1C). Protein phosphatases counterbalance kinases and control activation of signaling proteins, such as the mitogen activated protein kinases of the RAS/MAPK pathway. Here we report four patients with de novo missense mutations in protein phosphatase 1 catalytic subunit beta (PPP1CB), sharing a recognizable phenotype. Three individuals had the recurrent PPP1CB c.146G>C, p.Pro49Arg mutation, the fourth had a c.166G>C, p.Ala56Pro change. All had relative or absolute macrocephaly, low-set and posteriorly angulated ears and developmental delay. Slow growing and/or sparse hair and/or an unruly hair texture was present in all. Three individuals had feeding difficulties requiring feeding tubes. One of two males had cryptorchidism, another had pectus excavatum. Short stature was present in three. A female with the recurrent mutation had a Dandy-Walker malformation and optic nerve hypoplasia. Mild ventriculomegaly occurred in all, cerebellar tonsillar ectopia was seen in two and progressed to Chiari 1 malformation in one individual. Based on the combination of phenotypic findings and PPP1CB’s effect on RAF dephosphorylation within the RAS/MAPK pathway, this novel condition can be considered a rasopathy, most similar to NS-LAH. Collectively, these mutations meet the standardized criteria for pathogenicity. PMID:27264673

A novel rasopathy caused by recurrent de novo missense mutations in PPP1CB closely resembles Noonan syndrome with loose anagen hair.

PubMed

Gripp, Karen W; Aldinger, Kimberly A; Bennett, James T; Baker, Laura; Tusi, Jessica; Powell-Hamilton, Nina; Stabley, Deborah; Sol-Church, Katia; Timms, Andrew E; Dobyns, William B

2016-09-01

Noonan syndrome is a rasopathy caused by mutations in multiple genes encoding components of the RAS/MAPK pathway. Despite its variable phenotype, limited genotype-phenotype correlations exist. Noonan syndrome with loose anagen hair (NS-LAH) is characterized by its distinctive hair anomalies, developmental differences, and structural brain abnormalities and is caused by a single recurrent missense SHOC2 mutation. SHOC2 forms a complex with protein phosphatase 1 (PP1C). Protein phosphatases counterbalance kinases and control activation of signaling proteins, such as the mitogen-activated protein kinases of the RAS/MAPK pathway. Here we report four patients with de novo missense mutations in protein phosphatase one catalytic subunit beta (PPP1CB), sharing a recognizable phenotype. Three individuals had the recurrent PPP1CB c.146G>C, p.Pro49Arg mutation, the fourth had a c.166G>C, p.Ala56Pro change. All had relative or absolute macrocephaly, low-set and posteriorly angulated ears, and developmental delay. Slow growing and/or sparse hair and/or an unruly hair texture was present in all. Three individuals had feeding difficulties requiring feeding tubes. One of two males had cryptorchidism, another had pectus excavatum. Short stature was present in three. A female with the recurrent mutation had a Dandy-Walker malformation and optic nerve hypoplasia. Mild ventriculomegaly occurred in all, cerebellar tonsillar ectopia was seen in two and progressed to Chiari 1 malformation in one individual. Based on the combination of phenotypic findings and PPP1CB's effect on RAF dephosphorylation within the RAS/MAPK pathway, this novel condition can be considered a rasopathy, most similar to NS-LAH. Collectively, these mutations meet the standardized criteria for pathogenicity. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Contribution of Rare Copy Number Variants to Isolated Human Malformations

PubMed Central

Serra-Juhé, Clara; Rodríguez-Santiago, Benjamín; Cuscó, Ivon; Vendrell, Teresa; Camats, Núria; Torán, Núria; Pérez-Jurado, Luis A.

2012-01-01

Background Congenital malformations are present in approximately 2–3% of liveborn babies and 20% of stillborn fetuses. The mechanisms underlying the majority of sporadic and isolated congenital malformations are poorly understood, although it is hypothesized that the accumulation of rare genetic, genomic and epigenetic variants converge to deregulate developmental networks. Methodology/Principal Findings We selected samples from 95 fetuses with congenital malformations not ascribed to a specific syndrome (68 with isolated malformations, 27 with multiple malformations). Karyotyping and Multiplex Ligation-dependent Probe Amplification (MLPA) discarded recurrent genomic and cytogenetic rearrangements. DNA extracted from the affected tissue (46%) or from lung or liver (54%) was analyzed by molecular karyotyping. Validations and inheritance were obtained by MLPA. We identified 22 rare copy number variants (CNV) [>100 kb, either absent (n = 7) or very uncommon (n = 15, <1/2,000) in the control population] in 20/95 fetuses with congenital malformations (21%), including 11 deletions and 11 duplications. One of the 9 tested rearrangements was de novo while the remaining were inherited from a healthy parent. The highest frequency was observed in fetuses with heart hypoplasia (8/17, 62.5%), with two events previously related with the phenotype. Double events hitting candidate genes were detected in two samples with brain malformations. Globally, the burden of deletions was significantly higher in fetuses with malformations compared to controls. Conclusions/Significance Our data reveal a significant contribution of rare deletion-type CNV, mostly inherited but also de novo, to human congenital malformations, especially heart hypoplasia, and reinforce the hypothesis of a multifactorial etiology in most cases. PMID:23056206

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

Chiari-like Malformation.

PubMed

Loughin, Catherine A

2016-03-01

Chiari-like malformation is a condition of the craniocervical junction in which there is a mismatch of the structures of the caudal cranial fossa causing the cerebellum to herniate into the foramen magnum. This herniation can lead to fluid buildup in the spinal cord, also known as syringomyelia. Pain is the most common clinical sign followed by scratching. Other neurologic signs noted are facial nerve deficits, seizures, vestibular syndrome, ataxia, menace deficit, proprioceptive deficits, head tremor, temporal muscle atrophy, and multifocal central nervous system signs. MRI is the diagnostic of choice, but computed tomography can also be used. Copyright © 2016 Elsevier Inc. All rights reserved.

Chiari Malformation

MedlinePlus

... Staying Safe Videos for Educators Search English Español Chiari Malformation KidsHealth / For Parents / Chiari Malformation What's in this ... balance problems, and other symptoms. What Is a Chiari Malformation? Normally, the cerebellum sits at the back of ...

Prospective long-term follow up of children with anorectal malformation: growth and development until 5years of age.

PubMed

van den Hondel, Desiree; Sloots, Cornelius E J; Gischler, Saskia J; Meeussen, Conny J H M; Wijnen, Rene M H; IJsselstijn, Hanneke

2013-04-01

To evaluate growth and development in children with anorectal malformations and to analyze effects of type of malformation and comorbidities. Non-syndromal children with anorectal malformations were prospectively evaluated at 0.5, 1, 2, and 5 years. Biometrics were obtained at all visits. Mental and psychomotor function development was determined. 108 children (59% male) were included. 49% had a high malformation, and 46% had ≥ 1 additional major comorbidity. All growth parameters were below the norm at all ages (p<0.01), irrespective of type of malformation. Children with ≥ 1 additional major anomaly had lower height at all ages; at 5 years, mean (95% CI) height was -1.83 (-2.7 to -1.1) and -0.70 (-1.3 to -0.1) in children with and without comorbidities, respectively (p=0.019). Mental development was normal, irrespective of the type of malformation or comorbidities. Motor development was delayed at all ages. At 5 years, motor development (n=30) was normal in 70%, borderline in 23%, and 7% had definitive motor problems (p=0.043). Non-syndromal children with anorectal malformations are at risk for growth impairment, especially those with additional major comorbidity. Mental development is normal. Motor development is slightly impaired. Supportive care should focus on growth, dietary management, and motor development besides defecation problems. Copyright © 2013 Elsevier Inc. All rights reserved.

Unusual Association: Cerebral Arteriovenous Malformation and Chiari Type I Malformation.

PubMed

Ogul, Hayri; Kantarci, Mecit

2017-06-01

Cerebral arteriovenous malformation (AVM) is a common type of cerebral vascular malformation. The imaging findings are enlarged vessels, thrombosed sinuses, and hemorrhage or gliosis on adjacent brain parenchyma. Magnetic resonance (MR) imaging can be used safely for diagnosis. Chiari type I malformation is characterized by a caudal descent of the cerebellar tonsil. Coincidence of cerebral AVM and Chiari type I malformation is very rare. In this paper, the authors report MR imaging findings of a patient with coincidence of cerebral AVM and Chiari type I malformation.

[The genetic background for the eye malformations anophthalmia and microphthalmia].

PubMed

Roos, Laura Sønderberg; Grønskov, Karen; Jensen, Hanne; Tümer, Zeynep

2012-03-12

Anophthalmia and microphthalmia (AO/MO) are rare congenital eye malformations, in which the eyeball is apparently absent or smaller than normal, which causes various degrees of visual impairment. Over 200 different AO/MO-related syndromes have been described, but the genetic background is unknown in many cases. The aim of this article is to give an overview of AO/MO, focusing on the genetic background. It is illustrated that the future identification of new AO/MO related genes will benefit in the genetic counseling of AO/MO patients, and in the understanding of eye development and congenital eye malformations.

Amphibian malformations

USGS Publications Warehouse

,

1998-01-01

Frog malformations have been reported from 42 states. The broad geographic distribution of these malformations warrants national attention. Scientists at the USGS National Wildlife Health Center in Madison, Wisconsin are studying this problem in an effort to document its scope and to determine the causes of the observed malformations.

Prospective pilot study on combined use of pulsed dye laser and 1% topical rapamycin for treatment of nonfacial cutaneous capillary malformation.

PubMed

Doh, Eun Jin; Ohn, Jungyoon; Kim, Min Ji; Kim, Young Gull; Cho, Soyun

2017-11-01

The regeneration or revascularization of blood vessels after pulsed dye laser (PDL) treatment is one of the causes of treatment failures of cutaneous capillary malformations (CM). Recently, topical administration of rapamycin was introduced as a possible adjunctive therapeutic option to minimize postlaser revascularization in facial CM. We evaluated the effect of combined use of 1% topical rapamycin with PDL compared to PDL alone in cutaneous CM of trunk or extremities and tried to identify the optimal duration of topical rapamycin application. Three adjacent areas of cutaneous CM that had never been treated before were selected in each patient and underwent the following regimens: (A) PDL + vehicle for 8 weeks post-PDL; (B) PDL + topical rapamycin for 1-week post-PDL and (C) PDL + topical rapamycin for 8 weeks post-PDL. Each test site was treated by PDL for two sessions with 8 weeks interval. Only one of six patients showed clinical improvement with combined rapamycin treatment. Overall, there was no statistically significant difference in erythema and blanching rate among PDL alone and combined rapamycin regimens. One percent topical rapamycin does not seem to be effective as a treatment modality for cutaneous CM of trunk or extremities.

Miscarriage, stillbirth and congenital malformation in the offspring of UK veterans of the first Gulf war.

PubMed

Doyle, Pat; Maconochie, Noreen; Davies, Graham; Maconochie, Ian; Pelerin, Margo; Prior, Susan; Lewis, Samantha

2004-02-01

To assess whether the offspring of UK veterans of the first Gulf war are at increased risk of fetal death or congenital malformation. This was a retrospective reproductive cohort study of UK Gulf war veterans and a demographically similar comparison group who were in service at the time but were not deployed to the Gulf. Reproductive history was collected by means of a validated postal questionnaire between 1998 and 2001. In all, 27 959 pregnancies reported by men and 861 pregnancies reported by women were conceived after the first Gulf war and before November 1997. The risk of reported miscarriage was higher among pregnancies fathered by Gulf war veterans than by non-Gulf war veterans (OR = 1.4, 95% CI: 1.3, 1.5). Stillbirth risk was similar in both groups. Male Gulf war veterans reported a higher proportion of offspring with any type of malformation than the comparison cohort (OR = 1.5, 95% CI: 1.3, 1.7). Examination by type of malformation revealed some evidence for increased risk of malformations of the genital system, urinary system (renal and urinary tract), and 'other' defects of the digestive system, musculo-skeletal system, and non-chromosomal (non-syndrome) anomalies. These associations were weakened when analyses were restricted to clinically confirmed conditions. There was little or no evidence of increased risk for other structural malformations, specific syndromes, and chromosomal anomalies. Among female veterans, no effect of Gulf war service was found on the risk of miscarriage. The numbers of stillbirths and malformations reported by women were too small to allow meaningful analyses. We found no evidence for a link between paternal deployment to the Gulf war and increased risk of stillbirth, chromosomal malformations, or congenital syndromes. Associations were found between fathers' service in the Gulf war and increased risk of miscarriage and less well-defined malformations, but these findings need to be interpreted with caution as such outcomes

Ectrodactyly-ectodermal dysplasia clefting syndrome (EEC syndrome).

PubMed

Koul, Monika; Dwivedi, Rahul; Upadhyay, Vinod

2014-01-01

Ectrodactyly-ectodermal dysplasia- clefting syndrome (also k/a. split hand- split foot malformation /split hand-split foot ectodermal dysplasia- cleft syndrome/ectodermal dysplasia cleft lip/cleft palate syndrome) a rare form of ectodermal dysplasia, is an autosomal dominant disorder inherited as a genetic trait and characterized by a triad of (i) ectrodactyly, (ii) ectodermal dysplasia and, (iii) & facial clefts.

Use of External Cephalic Version and Amnioreduction in the Delivery of a Fetal Demise with Macrocephaly Secondary to Massive Intracranial Teratoma.

PubMed

Blitz, Matthew J; Greeley, Elizabeth; Tam, Hima Tam; Rochelson, Burton

2015-04-01

Introduction Congenital intracranial tumors are rare and often incidentally diagnosed on routine ultrasound. We report a case of a fetal demise with a massive intracranial teratoma at 25 weeks of gestation and the management of her delivery in the setting of macrocephaly, breech presentation, and polyhydramnios. Case A 31-year-old G3P1011 woman at 25 weeks' gestation presented with a recent fetal demise and a fetal intracranial tumor first identified at 16 weeks' gestational age. The patient had declined termination of pregnancy. Biometry was consistent with 24 weeks' gestation, except for a head circumference of 394.4 mm consistent with 39 weeks' gestation. The fetus was in a breech presentation. An external cephalic version (ECV) was successfully performed under epidural anesthesia and an amnioreduction was then performed to stabilize the fetal position. Immediate induction of labor and vaginal delivery followed. Discussion ECV and amnioreduction may help facilitate delivery in cases of fetal demise complicated by macrocephaly, malpresentation, and polyhydramnios.

Vascular anomalies and the growth of limbs: a review.

PubMed

Enjolras, Odile; Chapot, René; Merland, Jean Jacques

2004-11-01

Growth of the limb in a child can be impaired, with the coexistence of a vascular malformation. In these vascular bone syndromes, altered growth is manifest as overgrowth or hypotrophy. The vascular malformation is usually complex and gets progressively worse with time. The two types of vascular anomalies in limbs, fast-flow and slow-flow, can be associated with limb length discrepancies. The fast-flow vascular malformations together with arteriovenous fistulae are part of Parkes Weber syndrome, characterized by congenital red cutaneous staining, hypertrophy in girth and increasing of limb length, lymphedema, increasing skin alterations due to a distal vascular steal, and pain, all of which develop during childhood. Treatment is generally conservative. An affected lower extremity can be complicated by pelvic tilting and scoliosis because leg length discrepancy may reach 10 cm. To avoid such a course, stapling epiphysiodesis of the knee cartilages is often performed, but this orthopedic procedure may augment the worsening of the arterial venous malformation in the limb. Therefore, less aggressive orthopedic management is preferable. Slow-flow vascular anomalies associated with limb growth alteration include (1) a diffuse capillary malformation (port-wine stain) with congenital hypertrophy of the involved extremity which is non-progressive; (2) purely venous malformations invading skin, muscles and joints, with pain, functional impairment, a chronic localized intravascular coagulopathy requiring distinctive management, and usually a slight undergrowth of the affected extremity and progressing amyotrophy; (3) the triad of a port-wine stain, anomalous veins and overgrowth of the limb, often known as Klippel-Trenaunay syndrome, which requires orthopedic management to decide the optimal timing for epiphysiodesis (i.e. when leg length discrepancy is >2.5 cm). Varicose veins are sometimes surgically removed after ultrasonographic and Doppler evaluation has confirmed a

Dandy-Walker malformation, genitourinary abnormalities, and intellectual disability in two families.

PubMed

Zaki, Maha S; Masri, Amira; Gregor, Anne; Gleeson, Joseph G; Rosti, Rasim Ozgur

2015-11-01

We report on two families, each with documented consanguinity and two affected with overlapping features of Dandy-Walker malformation, genitourinary abnormalities, intellectual disability, and hearing deficit. This phenotype shares similar findings with many well-known syndromes. However, the clinical findings of this syndrome categorize this as a new syndrome as compared with the phenotype of already established syndromes. Due to parental consanguinity, occurrence in siblings of both genders and the absence of manifestations in obligate carrier parents, an autosomal recessive pattern of inheritance is more likely. The authors believe that these families suggest a novel autosomal recessive cerebello-genital syndrome. Array CGH analyses of an affected did not show pathological deletions or duplications. © 2015 Wiley Periodicals, Inc.

Dandy–Walker Malformation, Genitourinary Abnormalities, and Intellectual Disability in Two Families

PubMed Central

Gregor, Anne; Gleeson, Joseph G.; Rosti, Rasim Ozgur

2016-01-01

We report on two families, each with documented consanguinity and two affected with overlapping features of Dandy-Walker malformation, genitourinary abnormalities, intellectual disability, and hearing deficit. This phenotype shares similar findings with many well-known syndromes. However, the clinical findings of this syndrome categorize this as a new syndrome as compared with the phenotype of already established syndromes. Due to parental consanguinity, occurrence in siblings of both genders and the absence of manifestations in obligate carrier parents, an autosomal recessive pattern of inheritance is more likely. The authors believe that these families suggest a novel autosomal recessive cerebello–genital syndrome. Array CGH analyses of an affected did not show pathological deletions or duplications. PMID:26109232

[PHACES syndrome].

PubMed

Morcillo Azcárate, J; Bernabeu-Wittel, J; Fernández-Pineda, I; Conejo-Mir, M D; Tuduri Limousin, I; Aspiazu Salinas, D A; de Agustín Asensio, J C

2010-04-01

PHACES syndrome associates a segmental facial hemangioma with cerebral malformations, aortic branches/cranial arteries anomalies, cardiac defects, eye anomalies or ventral wall defects. The aim of this study is to analyze our experience with this syndrome. Retrospective study of the cases seen at our unit in the last year. We treat 4 cases; 3 girls and 1 child. Besides the segmental hemangioma they presented: 3 vascular cerebral malformations; 2 structural cardiopathies; 2 cerebral malformations, 1 microftalmia. We did not find ventral wall defects. A case received treatment with two cycles of metilprednisolone i.v. and oral prednisone, with favourable course; two cases received initial treatment with oral prednisone continued of oral propanolol in rising pattern up to 2 mg/kg/day, Obtaining both the detention of the tumour growth and regression of the lesion, with very good tolerance. A 7-year-old patient has been treated with colouring pulse laser for her residual lesions. When we see a segmental facial hemangioma we must perform a wide diagnostic study in order to discard a PHACES syndrome. Multidisciplinar approach to the patient by a wide expert's group gets an earlier diagnose and improves the outcome. Propranolol is a promising therapeutic alternative.

Idiopathic systemic capillary leak syndrome in children.

PubMed

Hsu, Peter; Xie, Zhihui; Frith, Katie; Wong, Melanie; Kakakios, Alyson; Stone, Kelly D; Druey, Kirk M

2015-03-01

Adult subjects with systemic capillary leak syndrome (SCLS) present with acute and recurrent episodes of vascular leak manifesting as severe hypotension, hypoalbuminemia, hemoconcentration, and generalized edema. We studied clinical disease characteristics, serum cytokine profiles, and treatment modalities in a cohort of children with documented SCLS. Six children with SCLS were recruited from the United States, Australia, Canada, and Italy. Serum cytokines from SCLS subjects and a group of 10 healthy children were analyzed. Children with SCLS (aged 5-11 years old) presented with at least 1 acute, severe episode of hypotension, hypoalbuminemia, and hemoconcentration in the absence of underlying causes for these abnormalities. In contrast to what is observed in adult SCLS, identifiable infectious triggers precipitated most episodes in these children, and none of them had a monoclonal gammopathy. We found elevated levels of chemokine (C-C motif) ligand 2 (CCL2), interleukin-8, and tumor necrosis factor α in baseline SCLS sera compared with the control group. All patients are alive and well on prophylactic therapy, with 4 patients receiving intravenous or subcutaneous immunoglobulins at regular intervals. The clinical manifestations of pediatric and adult SCLS are similar, with the notable exceptions of frequent association with infections and the lack of monoclonal gammopathy. Prophylactic medication, including high dose immunoglobulins or theophylline plus verapamil, appears to be safe and efficacious therapy for SCLS in children. Copyright © 2015 by the American Academy of Pediatrics.

Magnetic resonance imaging features of complex Chiari malformation variant of Chiari 1 malformation.

PubMed

Moore, Hannah E; Moore, Kevin R

2014-11-01

Complex Chiari malformation is a subgroup of Chiari 1 malformation with distinct imaging features. Children with complex Chiari malformation are reported to have a more severe clinical phenotype and sometimes require more extensive surgical treatment than those with uncomplicated Chiari 1 malformation. We describe reported MR imaging features of complex Chiari malformation and evaluate the utility of craniometric parameters and qualitative anatomical observations for distinguishing complex Chiari malformation from uncomplicated Chiari 1 malformation. We conducted a retrospective search of the institutional imaging database using the keywords "Chiari" and "Chiari 1" to identify children imaged during the 2006-2011 time period. Children with Chiari 2 malformation were excluded after imaging review. We used the first available diagnostic brain or cervical spine MR study for data measurement. Standard measurements and observations were made of obex level (mm), cerebellar tonsillar descent (mm), perpendicular distance to basion-C2 line (pB-C2, mm), craniocervical angle (degrees), clivus length, and presence or absence of syringohydromyelia, basilar invagination and congenital craniovertebral junction osseous anomalies. After imaging review, we accessed the institutional health care clinical database to determine whether each subject clinically met criteria for Chiari 1 malformation or complex Chiari malformation. Obex level and craniocervical angle measurements showed statistically significant differences between the populations with complex Chiari malformation and uncomplicated Chiari 1 malformation. Cerebellar tonsillar descent and perpendicular distance to basion-C2 line measurements trended toward but did not meet statistical significance. Odontoid retroflexion, craniovertebral junction osseous anomalies, and syringohydromyelia were all observed proportionally more often in children with complex Chiari malformation than in those with Chiari 1 malformation

α1β1 Integrin/Rac1-Dependent Mesangial Invasion of Glomerular Capillaries in Alport Syndrome

PubMed Central

Zallocchi, Marisa; Johnson, Brianna M.; Meehan, Daniel T.; Delimont, Duane; Cosgrove, Dominic

2014-01-01

Alport syndrome, hereditary glomerulonephritis with hearing loss, results from mutations in type IV collagen COL4A3, COL4A4, or COL4A5 genes. The mechanism for delayed glomerular disease onset is unknown. Comparative analysis of Alport mice and CD151 knockout mice revealed progressive accumulation of laminin 211 in the glomerular basement membrane. We show mesangial processes invading the capillary loops of both models as well as in human Alport glomeruli, as the likely source of this laminin. l-NAME salt–induced hypertension accelerated mesangial cell process invasion. Cultured mesangial cells showed reduced migratory potential when treated with either integrin-linked kinase inhibitor or Rac1 inhibitor, or by deletion of integrin α1. Treatment of Alport mice with Rac1 inhibitor or deletion of integrin α1 reduced mesangial cell process invasion of the glomerular capillary tuft. Laminin α2–deficient Alport mice show reduced mesangial process invasion, and cultured laminin α2–null cells showed reduced migratory potential, indicating a functional role for mesangial laminins in progression of Alport glomerular pathogenesis. Collectively, these findings predict a role for biomechanical insult in the induction of integrin α1β1–dependent Rac1-mediated mesangial cell process invasion of the glomerular capillary tuft as an initiation mechanism of Alport glomerular pathology. PMID:23911822

Histopathological features of Proteus syndrome.

PubMed

Hoey, S E H; Eastwood, D; Monsell, F; Kangesu, L; Harper, J I; Sebire, N J

2008-05-01

Proteus syndrome is a rare, sporadic overgrowth disorder for which the underlying genetic defect remains unknown. Although the clinical course is well-described there is no systematic histopathological description of the lesional pathology. To describe the histopathological features encountered in a series of patients with Proteus syndrome from a single centre. Patients with Proteus syndrome who had undergone therapeutic surgical resection or biopsy were identified from a database and the histopathological findings were reviewed, with particular regard to descriptive features of the underlying tissue abnormality. There were 18 surgical specimens from nine patients, median age 4 years (range 1-9), classified into four main categories: soft-tissue swellings (lipomatous lesions), vascular anomalies (vascular malformation and haemangioma), macrodactyly (hamartomatous overgrowth) and others (sebaceous naevus and nonspecific features). In all cases, the clinical features of overgrowth were due to increased amounts of disorganized tissue, indicating a hamartomatous-type defect in which normal tissue constituents were present, but with an abnormal distribution and architecture. Vascular malformations represented a prominent category of lesions, accounting for 50% of the specimens, predominantly comprising lymphatic and lymphovascular malformations. No malignancy or cytological atypia was identified in any case. The histopathological features of lesions resected from children with Proteus syndrome predominantly include hamartomatous mixed connective tissue lesions, benign neoplasms such as lipomata, and lymphatic-rich vascular malformations.

Rare DNA copy number variants in cardiovascular malformations with extracardiac abnormalities

USDA-ARS?s Scientific Manuscript database

Clinically significant cardiovascular malformations (CVMs) occur in 5-8 per 1000 live births. Recurrent copy number variations (CNVs) are among the known causes of syndromic CVMs, accounting for an important fraction of cases. We hypothesized that many additional rare CNVs also cause CVMs and can be...

Effect of Gastrointestinal Malformations on the Outcomes of Patients With Congenital Heart Disease.

PubMed

Mery, Carlos M; De León, Luis E; Rodriguez, J Rubén; Nieto, R Michael; Zhang, Wei; Adachi, Iki; Heinle, Jeffrey S; Kane, Lauren C; McKenzie, E Dean; Fraser, Charles D

2017-11-01

The goal of this study was to assess the effect of associated gastrointestinal malformations (GI) on the outcomes of patients undergoing congenital heart operations. Neonates and infants with thoracic (esophageal atresia, tracheoesophageal fistula) and abdominal (duodenal stenosis/atresia, imperforate anus, Hirschsprung disease) GI malformations undergoing congenital heart operations between 1995 and 2015 were included. Two control groups were created, one for each group. Patients were matched by diagnosis, procedure, history of prematurity, presence of genetic syndrome, and a propensity score including weight and year of operation. The cohort included 383 patients: 52 (14%) with thoracic GI malformations and 98 (25%) thoracic GI controls, 80 (21%) with abdominal GI malformations and 153 (40%) abdominal GI controls. Median follow-up was 6 years (range, 16 days to 20 years). Patients with thoracic GI malformations had longer length of stay (p < 0.001), longer intubation times (p = 0.002), and higher perioperative death (p = 0.015) than controls. There was a tendency for worse overall survival than controls, mainly explained by the higher risk of early death (p = 0.06). No difference was found in outcomes between patients with abdominal GI malformations and controls. Patients with thoracic GI malformations have worse perioperative outcomes than controls, but their long-term survival does not seem to be significantly different. Abdominal GI malformations do not have a significant effect on outcomes. The presence of GI malformations should likely not preclude patients from undergoing congenital heart operations, but careful family counseling is necessary, especially for thoracic GI malformations. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Is Dandy-Walker malformation associated with "distal 13q deletion syndrome"? Findings in a fetus supporting previous observations.

PubMed

Alanay, Yasemin; Aktaş, Dilek; Utine, Eda; Talim, Beril; Onderoğlu, Lütfü; Cağlar, Melda; Tunçbilek, Ergül

2005-07-30

We report on a fetus with a large deletion of the distal part of the long arm of chromosome 13, (del(13)(q14 --> qter)) congenital anomalies of the urinary system, lungs and extremities, and Dandy-Walker malformation (DWM). Although DWM has been associated with many chromosomal abnormalities and genetic syndromes, its relation to the distal 13q has been demonstrated recently. In 2002, McCormack et al., described two patients with deletions of the long arm of chromosome 13 who had multiple congenital abnormalities along with holoprosencephaly (HPE) and DWM. The phenotypic features and autopsy findings of a fetus with "distal 13q deletion syndrome" at 22 weeks gestation are discussed and comparison with the previous two cases is made. The findings support the previous hypothesis suggesting that haploinsufficiency at a locus within 13q22-33 due to microdeletions may be responsible for isolated DWM in some of the patients. Detailed examination of 13q (13q22-33) by means of conventional and molecular cytogenetic methods is necessary in cases with DWM. Copyright 2005 Wiley-Liss, Inc.

Recognition and management of idiopathic systemic capillary leak syndrome: an evidence-based review.

PubMed

Baloch, Noor Ul-Ain; Bikak, Marvi; Rehman, Abdul; Rahman, Omar

2018-05-01

Idiopathic systemic capillary leak syndrome (SCLS) is a unique disorder characterized by episodes of massive systemic leak of intravascular fluid leading to volume depletion and shock. A typical attack of SCLS consists of prodromal, leak and post-leak phases. Complications, such as compartment syndrome and pulmonary edema, usually develop during the leak and post-leak phases respectively. Judicious intravenous hydration and early use of vasopressors is the cornerstone of management in such cases. Areas covered: The purpose of the present review is to provide an up-to-date, evidence-based review of our understanding of SCLS and its management in the light of currently available evidence. Idiopathic SCLS was first described in 1960 and, since then, more than 250 cases have been reported. A large number of cases have been reported over the past one decade, most likely due to improved recognition. In the acute care setting, most patients with SCLS are managed as per the Surviving Sepsis guidelines and receive aggressive volume resuscitation - which is not the optimal management strategy for such patients. There is a need to raise awareness amongst physicians and clinicians in order to improve recognition of this disorder and ensure its appropriate management.

Arteriovenous malformations of the uterus.

PubMed

Cura, M; Martinez, N; Cura, A; Dalsaso, T J; Elmerhi, F

2009-09-01

Arterial venous malformations (AVM) of the uterus are uncommon entities and should be considered in patients who present with profuse genital bleeding. There are two types of uterine AVM: acquired and congenital. Acquired uterine AVMs are conformed by communications between the uterine arteries and the myometrial veins, and are caused by an iatrogenic event or a pathological condition. Congenital AVMs are the result of abnormal development of primitive vessels that result in connections between pelvic arteries and veins in the uterus without an interconnecting capillary bed. Ultrasonography is a noninvasive diagnostic method able to demonstrate and characterize AVMs of the uterus. AVM in the pelvis may be noted incidentally by computed tomography (CT) of the pelvis, and magnetic resonance imaging (MRI) is frequently used to confirm and further characterize the sonographic findings of uterine AVM. Catheter angiography and embolization are very effective in defining the vascular anatomy and treating uterine vascular abnormalities.

Jarcho-Levin syndrome presenting with diaphragmatic hernia.

PubMed

Onay, O S; Kinik, S T; Otgün, Y; Arda, I S; Varan, B

2008-08-01

Jarcho-Levin syndrome (spondylothoracic or spondylocostal dysostosis) is an eponym that is used to define individuals with a short neck, short trunk, and short stature and multiple vertebral anomalies. The prognosis is directly related to respiratory complications. Reported findings associated with Jarcho-Levin syndrome include congenital heart defects, abdominal wall malformations, genitourinary malformations, upper limb anomalies, and neural tube defects. We report on a 6-day-old girl who presented with an incomplete form of Jarcho-Levin syndrome with late-presenting congenital diaphragmatic hernia and congenital heart disease.

Clinical, Genetic and Environmental Factors Associated with Congenital Vertebral Malformations

PubMed Central

Giampietro, P.F.; Raggio, C.L.; Blank, R.D.; McCarty, C.; Broeckel, U.; Pickart, M.A.

2013-01-01

Congenital vertebral malformations (CVM) pose a significant health problem because they can be associated with spinal deformities, such as congenital scoliosis and kyphosis, in addition to various syndromes and other congenital malformations. Additional information remains to be learned regarding the natural history of congenital scoliosis and related health problems. Although significant progress has been made in understanding the process of somite formation, which gives rise to vertebral bodies, there is a wide gap in our understanding of how genetic factors contribute to CVM development. Maternal diabetes during pregnancy most commonly contributes to the occurrence of CVM, followed by other factors such as hypoxia and anticonvulsant medications. This review highlights several emerging clinical issues related to CVM, including pulmonary and orthopedic outcome in congenital scoliosis. Recent breakthroughs in genetics related to gene and environment interactions associated with CVM development are discussed. The Klippel-Feil syndrome which is associated with cervical segmentation abnormalities is illustrated as an example in which animal models, such as the zebrafish, can be utilized to provide functional evidence of pathogenicity of identified mutations. PMID:23653580

The Dandy-Walker malformation. A review of 40 cases.

PubMed

Hirsch, J F; Pierre-Kahn, A; Renier, D; Sainte-Rose, C; Hoppe-Hirsch, E

1984-09-01

Forty cases of Dandy-Walker malformation referred to the Hôpital Necker Enfants-Malades between 1969 and 1982 have been reviewed. The incidence of the malformation in hydrocephalus was 2.4%. There was a slight, statistically insignificant, female prevalence. Hydrocephalus should not be included in the definition of the syndrome. In 80% of the cases, it was actually a post-natal complication of the malformation and most often developed within 3 months after birth. In 80% of the cases, a communication, although insufficient, was found between the dilated 4th ventricle and the subarachnoid space. Since this communication is probably established through the foramina of Luschka, the definition of the Dandy-Walker malformation should only include atresia of the foramen of Magendie. Associated brain and systemic malformations were numerous. Among facial anomalies, facial angiomas were found in 10% of our cases. The association of facial and cardiovascular anomalies favors the hypothesis that the onset of the malformation occurs between the formation and the migration of the cells of the neural crest (that is, between the 3rd and the 4th post-ovulatory week, earlier than previously thought). Except in selected patients, membrane excision has a high rate of failure and should be abandoned. Cyst-peritoneal shunting avoids the risk of an entrapped fourth ventricle and is presently the best surgical procedure. The overall mortality in this series was 12.5%. Intelligence quotients were over 80 in 60% of the patients. Other studies will be necessary to understand why the communication between the fourth ventricle and the subarachnoid spaces, sufficient in utero, usually becomes insufficient for a normal cerebrospinal fluid (CSF) circulation in the first months following birth. Two hypotheses are discussed: a change in CSF circulation, or bleeding in the dilated fourth ventricle during delivery.

Aase syndrome

MedlinePlus

Aase-Smith syndrome; Hypoplastic anemia - triphalangeal thumbs, Aase-Smith type ... Jones KL, Jones MC, Del Campo M, eds. Smith's Recognizable Patterns of Human Malformation . 7th ed. Philadelphia, ...

α1β1 integrin/Rac1-dependent mesangial invasion of glomerular capillaries in Alport syndrome.

PubMed

Zallocchi, Marisa; Johnson, Brianna M; Meehan, Daniel T; Delimont, Duane; Cosgrove, Dominic

2013-10-01

Alport syndrome, hereditary glomerulonephritis with hearing loss, results from mutations in type IV collagen COL4A3, COL4A4, or COL4A5 genes. The mechanism for delayed glomerular disease onset is unknown. Comparative analysis of Alport mice and CD151 knockout mice revealed progressive accumulation of laminin 211 in the glomerular basement membrane. We show mesangial processes invading the capillary loops of both models as well as in human Alport glomeruli, as the likely source of this laminin. L-NAME salt-induced hypertension accelerated mesangial cell process invasion. Cultured mesangial cells showed reduced migratory potential when treated with either integrin-linked kinase inhibitor or Rac1 inhibitor, or by deletion of integrin α1. Treatment of Alport mice with Rac1 inhibitor or deletion of integrin α1 reduced mesangial cell process invasion of the glomerular capillary tuft. Laminin α2-deficient Alport mice show reduced mesangial process invasion, and cultured laminin α2-null cells showed reduced migratory potential, indicating a functional role for mesangial laminins in progression of Alport glomerular pathogenesis. Collectively, these findings predict a role for biomechanical insult in the induction of integrin α1β1-dependent Rac1-mediated mesangial cell process invasion of the glomerular capillary tuft as an initiation mechanism of Alport glomerular pathology. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

[Blue rubber bleb naevus syndrome].

PubMed

Akutko, Katarzyna; Krzesiek, Elzbieta; Iwańczak, Barbara

2012-10-01

Blue rubber bleb nevus syndrome (Bean syndrome) is a rare disease characterized by the presence of multiple vascular malformation of rubber-like consistence. This disease is of a genetic origin and most often is caused by sporadic mutation, however, exist reports on autosomal dominant type of heritance. Nevi are most frequently met in the skin and alimentary tract but may be present in all organs and tissues. The most frequent symptom of Bean syndrome is anaemia due to ferrum deficiency, which is a result of chronic hemorrhagia from vascular malformations in the alimentary tract. Vascular anomalies on the skin are usually asymptomatic. Other symptoms are less frequent and depend on the localisation of vascular changes and therefore patients with Bean syndrome require meticulous analysis of reported multiple - specialistic medical care.

[Congenital cardiopathy in a patient with Sotos syndrome. Description of a case].

PubMed

Di Marco, G; Levantesi, G; Parisi, G; Chiarelli, A

1989-05-01

The number of cases of Sotos syndrome or cerebral gigantism described in the literature total more than 200. For 6 of these, cardiac malformations were described. The authors report a case of Sotos syndrome in which malformative alterations of the aortic and mitral valves were simultaneously present.

Lethal pallister-killian syndrome: Phenotypic similarity with fryns syndrome

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

Ignacio Rodriquez, J.; Garcia, I.; Alvarez, J.

1994-11-01

The Pallister-Killian syndrome is a sporadic multiple congenital anomaly syndrome characterized by {open_quotes}coarse{close_quotes} face, profound mental retardation, and epilepsy. Chromosomes of peripheral lymphocytes are usually normal, but tissue cultures show varying degrees of mosaicism for isochromosome 12p. In babies who die neonatally of severe malformations, including diaphragmatic hernia, and who also have a {open_quotes}coarse{close_quotes} face, acral hypoplasia, and other internal anomalies, Fryns syndrome is more likely to be suspected than Pallister-Killian syndrome, especially if karyotyping is unavailable or if peripheral lumphocytes have a normal chromosome constitution. An initial diagnosis of Fryns syndrome had to be modified in 3 successive newbornmore » infants since chromosome analysis or in situ hybridization with a chromosome 12 probe on kidney tissue demonstrated the mosaic aneuploidy characteristic of Pallister-Killian syndrome. These 3 patients confirm that a similar pattern of malformations can be present in both conditions at birth. It consists of {open_quotes}coarse{close_quotes} face, acral hypoplasia, diaphragmatic hernia, and other defects. Newborn infants who present this phenotype, but lack a conclusively normal chromosome test, may not have Fryns syndrome. A diagnosis of Fryns syndrome should be made carefully to avoid the risk of inappropriate genetic counseling. 31 refs., 10 figs., 1 tab.« less

Increased pulmonary alveolar-capillary permeability in patients at risk for adult respiratory distress syndrome

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

Tennenberg, S.D.; Jacobs, M.P.; Solomkin, J.S.

1987-04-01

Two methods for predicting adult respiratory distress syndrome (ARDS) were evaluated prospectively in a group of 81 multitrauma and sepsis patients considered at clinical high risk. A popular ARDS risk-scoring method, employing discriminant analysis equations (weighted risk criteria and oxygenation characteristics), yielded a predictive accuracy of 59% and a false-negative rate of 22%. Pulmonary alveolar-capillary permeability (PACP) was determined with a radioaerosol lung-scan technique in 23 of these 81 patients, representing a statistically similar subgroup. Lung scanning achieved a predictive accuracy of 71% (after excluding patients with unilateral pulmonary contusion) and gave no false-negatives. We propose a combination of clinicalmore » risk identification and functional determination of PACP to assess a patient's risk of developing ARDS.« less

The Fourth International Symposium on Genetic Disorders of the Ras/MAPK Pathway

PubMed Central

Stevenson, David A.; Schill, Lisa; Schoyer, Lisa; Andresen, Brage S.; Bakker, Annette; Bayrak-Toydemir, Pinar; Burkitt-Wright, Emma; Chatfield, Kathryn; Elefteriou, Florent; Elgersma, Ype; Fisher, Michael J.; Franz, David; Gelb, Bruce D.; Goriely, Anne; Gripp, Karen W.; Hardan, Antonio Y.; Keppler-Noreuil, Kim M.; Kerr, Bronwyn; Korf, Bruce; Leoni, Chiara; McCormick, Frank; Plotkin, Scott R.; Rauen, Katherine A.; Reilly, Karlyne; Roberts, Amy; Sandler, Abby; Siegel, Dawn; Walsh, Karin; Widemann, Brigitte C.

2016-01-01

The RASopathies are a group of disorders due to variations of genes associated with the Ras/MAPK pathway. Some of the RASopathies include neurofibromatosis type 1 (NF1), Noonan syndrome, Noonan syndrome with multiple lentigines, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, Legius syndrome, and capillary malformation–arteriovenous malformation (CM-AVM) syndrome. In combination, the RASopathies are a frequent group of genetic disorders. This report summarizes the proceedings of the 4th International Symposium on Genetic Disorders of the Ras/MAPK pathway and highlights gaps in the field. PMID:27155140

Arnold Chiari Malformation With Sponastrime (Spondylar and Nasal Changes, With Striations of the Metaphyses) Dysplasia: A Case Report.

PubMed

Jeong, Je Hoon; Lee, A Leum; Cho, Sung Yoon; Jin, Dong Kyu; Im, Soo-Bin

2016-05-01

SPOndylar and NAsal changes, with STRIations of the Metaphyses (SPONASTRIME) dysplasia (SD) is a dwarfing autosomal recessive syndrome, characterized by a variety of clinical and radiographic features, which form the basis for diagnosis. We describe the presentation of an Arnold Chiari malformation in a patient with a clinical diagnosis of SD. The malformation was successfully treated by decompression of the foramen magnum and elevation of the cerebellum, with complete resolution of pain.We report a rare case of Arnold Chiari malformation in a patient presenting with clinical and radiographic features strongly suggestive of SD and be successfully treated.

The cardiofaciocutaneous syndrome

PubMed Central

Roberts, A; Allanson, J; Jadico, S K; Kavamura, M I; Noonan, J; Opitz, J M; Young, T; Neri, G

2006-01-01

The cardiofaciocutaneous (CFC) syndrome is a condition of sporadic occurrence, with patients showing multiple congenital anomalies and mental retardation. It is characterised by failure to thrive, relative macrocephaly, a distinctive face with prominent forehead, bitemporal constriction, absence of eyebrows, hypertelorism, downward‐slanting palpebral fissures often with epicanthic folds, depressed nasal root and a bulbous tip of the nose. The cutaneous involvement consists of dry, hyperkeratotic, scaly skin, sparse and curly hair, and cavernous haemangiomata. Most patients have a congenital heart defect, most commonly pulmonic stenosis and hypertrophic cardiomyopathy. The developmental delay usually is moderate to severe. The syndrome is caused by gain‐of‐function mutations in four different genes BRAF, KRAS, mitogen‐activated protein/extracellular signal‐regulated kinase MEK1 and MEK2, all belonging to the same RAS–extracellular signal‐regulated kinase (ERK) pathway that regulates cell differentiation, proliferation and apoptosis. The CFC syndrome is a member of a family of syndromes that includes the Noonan and Costello syndromes, presenting with phenotypic similarities. Noonan syndrome is caused by mutations in the protein tyrosine phosphatase SHP‐2 gene (PTPN11), with a few people having a mutation in KRAS. Costello syndrome is caused by mutations in HRAS. The protein products of these genes also belong to the RAS–ERK pathway. Thus, the clinical overlap of these three conditions, which often poses a problem of differential diagnosis, is explained by their pathogenetic relatedness. PMID:16825433

Syndrome in question*

PubMed Central

Peruzzo, Juliano; Nazar, Fernanda Luca; Tubone, Mariana Quirino; Escobar, Gabriela Fortes; Cestari, Tania Ferreira

2015-01-01

Waardenburg syndrome is an inherited disease characterized by sensorineural hearing loss, pigmentation changes and minor facial malformations. It has four clinical variants. We report the case of a girl who, like her mother, was affected by this syndrome. The diagnosis was made after detection and treatment of deafness. PMID:26375234

Further delineation of Malan syndrome.

PubMed

Priolo, Manuela; Schanze, Denny; Tatton-Brown, Katrin; Mulder, Paul A; Tenorio, Jair; Kooblall, Kreepa; Acero, Inés Hernández; Alkuraya, Fowzan S; Arias, Pedro; Bernardini, Laura; Bijlsma, Emilia K; Cole, Trevor; Coubes, Christine; Dapia, Irene; Davies, Sally; Di Donato, Nataliya; Elcioglu, Nursel H; Fahrner, Jill A; Foster, Alison; González, Noelia García; Huber, Ilka; Iascone, Maria; Kaiser, Ann-Sophie; Kamath, Arveen; Liebelt, Jan; Lynch, Sally Ann; Maas, Saskia M; Mammì, Corrado; Mathijssen, Inge B; McKee, Shane; Menke, Leonie A; Mirzaa, Ghayda M; Montgomery, Tara; Neubauer, Dorothee; Neumann, Thomas E; Pintomalli, Letizia; Pisanti, Maria Antonietta; Plomp, Astrid S; Price, Sue; Salter, Claire; Santos-Simarro, Fernando; Sarda, Pierre; Segovia, Mabel; Shaw-Smith, Charles; Smithson, Sarah; Suri, Mohnish; Valdez, Rita Maria; Van Haeringen, Arie; Van Hagen, Johanna M; Zollino, Marcela; Lapunzina, Pablo; Thakker, Rajesh V; Zenker, Martin; Hennekam, Raoul C

2018-06-13

Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 previously reported individuals. Results indicate that height is > 2 SDS in infancy and childhood but in only half of affected adults. Cardinal facial characteristics include long, triangular face, macrocephaly, prominent forehead, everted lower lip, and prominent chin. Intellectual disability is universally present, behaviorally anxiety is characteristic. Malan syndrome is caused by deletions or point mutations of NFIX clustered mostly in exon 2. There is no genotype-phenotype correlation except for an increased risk for epilepsy with 19p13.2 microdeletions. Variants arose de novo, except in one family in which mother was mosaic. Variants causing Malan and Marshall-Smith syndrome can be discerned by differences in the site of stop codon formation. We conclude that Malan syndrome has a well recognizable phenotype that usually can be discerned easily from Marshall-Smith syndrome but rarely there is some overlap. Differentiation from Sotos and Weaver syndrome can be made by clinical evaluation only. © 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc.

[Cloverleaf skull and bilateral facial clefts].

PubMed

Alvarez-Manassero, Denisse; Manassero-Morales, Gioconda

2015-01-01

Cloverleaf skull syndrome, or Kleeblattschädel syndrome, is a rare malformation in which the skull has a cloverleaf appearance. It is caused by the premature closure of several sutures, being evident before birth. To present our experience in a case of cloverleaf skull syndrome, and update the information from the literature. A female infant of 5 months of age, diagnosed at birth with cleft lip and palate and hydrocephaly. A peritoneal ventricle valve was implanted at 30 days of life, and an ocular enucleation was performed due to an infectious process. The patient was followed-up in Genetics, where it confirmed a macrocephaly and craniosynostosis type cloverleaf skull. The 46XX cytogenetic study and echocardiography were normal. The brain CT scan showed multiple anomalies associated with hydrocephaly and non-specific malformations. Cloverleaf skull may be present in isolated form or associated with other congenital abnormalities, leading to various craniosynostosis syndromes, such as Crouzon, Pfeiffer or Carpenter. It may also be a component of the amniotic rupture sequence or to different dysplasias, such as campomelic dysplasia, thanatophoric dysplasia type 2, or the asphyxiating thoracic dystrophy of Jeune. The case presented does not fulfil all the characteristics needed to be included within a specific syndrome, and on not having a family history that suggests a hereditary pattern or chromosome abnormalities, it is concluded that it is a case of a congenital anomaly of sporadic presentation. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Acute porphyria in a patient with Arnold Chiari malformation.

PubMed

Shen, Jianbin; O'Keefe, Kevin; Webb, Lisa B; DeGirolamo, Angela

2015-02-20

Acute porphyria and Arnold Chiari malformation are both uncommon genetic disorders without known association. The insidious onset, non-specific clinical manifestations, and precipitating factors often cause diagnosis of acute porphyria to be missed, particularly in patients with comorbidities. A women with Arnold Chiari malformation type II who was treated with oxybutynin and antibiotics, including Bactrim for neurogenic bladder and recurrent urinary tract infection, presented with non-specific abdominal pain, constipation, and diarrhea. After receiving Flagyl for C. difficile colitis, the patient developed psychosis, ascending paralysis, and metabolic derangements. She underwent extensive neurological workup due to her congenital neurological abnormalities, most of which were unremarkable. As a differential diagnosis of Guillain Barré syndrome, acute porphyria was then considered and ultimately proved to be the diagnosis. After hematin administration and intense rehabilitation, the patient slowly recovered from the full-blown acute porphyria attack. This case report, for the first time, documents acute porphyria attack as a result of a sequential combination of 3 common medications. This is the first case report of the concomitant presence of both acute porphyria and Arnold Chiari malformation, 2 genetic disorders with unclear association.

A new overgrowth syndrome is due to mutations in RNF125.

PubMed

Tenorio, Jair; Mansilla, Alicia; Valencia, María; Martínez-Glez, Víctor; Romanelli, Valeria; Arias, Pedro; Castrejón, Nerea; Poletta, Fernando; Guillén-Navarro, Encarna; Gordo, Gema; Mansilla, Elena; García-Santiago, Fé; González-Casado, Isabel; Vallespín, Elena; Palomares, María; Mori, María A; Santos-Simarro, Fernando; García-Miñaur, Sixto; Fernández, Luis; Mena, Rocío; Benito-Sanz, Sara; del Pozo, Ángela; Silla, Juan Carlos; Ibañez, Kristina; López-Granados, Eduardo; Martín-Trujillo, Alex; Montaner, David; Heath, Karen E; Campos-Barros, Ángel; Dopazo, Joaquín; Nevado, Julián; Monk, David; Ruiz-Pérez, Víctor L; Lapunzina, Pablo

2014-12-01

Overgrowth syndromes (OGS) are a group of disorders in which all parameters of growth and physical development are above the mean for age and sex. We evaluated a series of 270 families from the Spanish Overgrowth Syndrome Registry with no known OGS. We identified one de novo deletion and three missense mutations in RNF125 in six patients from four families with overgrowth, macrocephaly, intellectual disability, mild hydrocephaly, hypoglycemia, and inflammatory diseases resembling Sjögren syndrome. RNF125 encodes an E3 ubiquitin ligase and is a novel gene of OGS. Our studies of the RNF125 pathway point to upregulation of RIG-I-IPS1-MDA5 and/or disruption of the PI3K-AKT and interferon signaling pathways as the putative final effectors. © 2014 WILEY PERIODICALS, INC.

New developments in Silver–Russell syndrome and implications for clinical practice

PubMed Central

Ishida, Miho

2016-01-01

Silver–Russell syndrome is a clinically and genetically heterogeneous disorder, characterized by prenatal and postnatal growth restriction, relative macrocephaly, body asymmetry and characteristic facial features. It is one of the imprinting disorders, which results as a consequence of aberrant imprinted gene expressions. Currently, maternal uniparental disomy of chromosome 7 accounts for approximately 10% of Silver–Russell syndrome cases, while ˜50% of patients have hypomethylation at imprinting control region 1 at chromosome 11p15.5 locus, leaving ˜40% of cases with unknown etiologies. This review aims to provide a comprehensive list of molecular defects in Silver–Russell syndrome reported to date and to highlight the importance of multiple-loci/tissue testing and trio (both parents and proband) screening. The epigenetic and phenotypic overlaps with other imprinting disorders will also be discussed. PMID:27066913

Lumbar subdural cerebrospinal fluid collection with acute cauda equina syndrome after posterior fossa decompression for Chiari malformation Type I: case report.

PubMed

Darwish, Houssein A; Oldfield, Edward H

2016-09-01

This report describes the circumstances of a patient with a cauda equina syndrome due to the development of a lumbar subdural CSF collection with ventral displacement of the cauda equina shortly following posterior fossa decompression for Chiari malformation Type I (CM-I). This unusual, but clinically significant, complication was successfully treated with percutaneous drainage of the extraarachnoid CSF collection. Although there are a few cases of intracranial subdural hygroma developing after surgery for CM-I, often attributed to a pinhole opening in the arachnoid, as far as the authors can determine, a spinal subdural hygroma associated with surgery for CM-I has not been recognized.

PHACE syndrome: new views on diagnostic criteria.

PubMed

Poetke, M; Frommeld, T; Berlien, H P

2002-12-01

The association of large facial hemangiomas with posterior fossa malformations and vascular anomalies has been termed the PHACE syndrome. It is characterized by the association of posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and other cardiac defects, and eye abnormalities. Since most articles focus on isolated case reports, an extended retrospective literature review of all reports of large hemangiomas with associated abnormalities of the central nervous system and other malformations was performed to examine the clinical features, and other not as yet reported associated anomalies. Reports were found on 59 patients with PHACE syndrome, to which we added ten cases of our own. The Dandy-Walker syndrome is the most common CNS abnormality reported in association with PHACE syndrome and was seen in 48 (81 %) patients. Arterial malformations were found in 13 (22 %) cases; only 11 patients (19 %) had structural arterial abnormalities without associated Dandy-Walker complex. As published, about one third of patients (31 %) had further ophthalmologic abnormalities, and cardiac anomalies, including coarctation of the aorta. Subglottic hemangiomas were seen in 4 (7 %) patients and ventral developmental defects also in 3 cases. In seven of 59 patients (12 %) with PHACE syndrome, intracranial hemangiomas were present. This study demonstrates that among other CNS abnormalities, special attention should be given to intracranial hemangiomas which seems to be a peculiar phenotype of PHACE syndrome. We therefore suggest that a sixth criterion should be added to the five minimal inclusion criteria for PHACE syndrome. The inclusion criteria would then be: arterial abnormalities or/and intracranial hemangiomas. On the basis of our experience with our patients and with those previously reported, we stress the importance of using contrast-enhanced imaging to detect intracranial lesions.

Anatomic variants in Dandy-Walker complex.

PubMed

Jurcă, Maria Claudia; Kozma, Kinga; Petcheşi, CodruŢa Diana; Bembea, Marius; Pop, Ovidiu Laurean; MuŢiu, Gabriela; Coroi, Mihaela Cristiana; Jurcă, Alexandru Daniel; Dobjanschi, Luciana

2017-01-01

Dandy-Walker complex (DWC) is a malformative association of the central nervous system. DWC includes four different types: Dandy-Walker malformation (vermis agenesis or hypoplasia, cystic dilatation of the fourth ventricle and a large posterior fossa); Dandy-Walker variant (vermis hypoplasia, cystic dilatation of the fourth ventricle, normal posterior fossa); mega cysterna magna (large posterior fossa, normal vermis and fourth ventricle) and posterior fossa arachnoid cyst. We present and discuss four cases with different morphological and clinical forms of the Dandy-Walker complex. In all four cases, diagnosis was reached by incorporation of clinical (macrocephaly, seizures) and imaging [X-ray, computed tomography (CT), magnetic resonance imaging (MRI)] data. Two patients were diagnosed with Dandy-Walker complex, one patient was diagnosed with Dandy-Walker variant in a rare association with neurofibromatosis and one patient was diagnosed with a posterior fossa arachnoid cyst associated with left-sided Claude Bernard-Horner syndrome, congenital heart disease (coarctation of the aorta, mitral stenosis) and gastroesophageal reflux. In all forms of DWC, the clinical, radiological and functional manifestations are variable and require adequate diagnostic and therapeutic measures.

[Papillary oedema revealing Arnold Chiari malformation type 1: about a case].

PubMed

Imane, Mouhoub; Asmae, Maadane; Toufik, Ramdani; Rachid, Sekhsoukh

2016-01-01

Arnold Chiari malformation type 1 is defined as a herniation of the cerebellar tonsils into the foramen magnum of more than 5 mm. Symptoms are most commonly dominated by occipital headache, torticollis and sometimes swallowing disorders. Ophthalmologically abnormal convergences, oculomotor palsy and diplopia are the main clinical signs. We report the case of a 9 year old child, who presented with visual loss evolving since 6 months. Ophthalmologic examination showed visual acuity of 4/10 in both eyes, retained ocular motility and rotational nystagmus. The examination of the anterior segment of the eye showed megalocornea with no evidence of goniodysgenesis, iridodonesis associated with atrophy of the dilator muscle and microcoria with lazy photomotor reflex. Normal intraocular pressure was 14 mmHg. Ocular fundus examination, despite difficulties in performing it, objectified bilateral papilledema (stage II). General physical examination showed torticollis, scoliosis and a tetra-pyramidal syndrome. MRI showed Chiari malformation type I associated with hydrocephalus and syringomyelia. Neurosurgical intervention based on internal CSF drainage with occipitocervical osteo-dural decompression was proposed. The evolution was favorable with regression of clinical signs. Ophthalmologically, there was a regression of papilledema but visual acuity remained stationary. The occurrence of papilledema associated with Chiari malformation type 1 is rare, it has been only reported in 2% of symptomatic patients. Its pathophysiology is still poorly understood. The originality of our study consists in the association of cerebellar malformations with ocular malformations including megalocornea and microcoria which make ophthalmologic examination more difficult to perform.

[Polythelia and renal malformation].

PubMed

Jójárt, G; Seres, E

1992-07-12

The authors found 241 polythelia (5.86) among 4113 schoolchildren (aged 6-14 years). They investigated 236 of the 241 with ultrasound and found 10 renal malformations (4.24%). Among 280 controls with respiratory infection, accident or tonsillectomy they found 9 renal malformations (3.21%). With screening of 1635 neonates they found 66 with accessory nipples (4.05%). Two of the 66 had renal malformations (3.03%), while among the 1957 control neonates 37 had renal malformations (1.89%). In the hospital and ambulancy the authors found 106 polythelia, five of them had renal abnormalities (4.72%). The authors did not found association of polythelia and renal malformation with ultrasound investigation of 408 children with polythelia.

Middle ear abnormalities in Van Maldergem syndrome.

PubMed

Verheij, Emmy; Thomeer, Henricus G X M; Pameijer, Frank A; Topsakal, Vedat

2017-01-01

Van Maldergem syndrome (VMS) is a very rare syndrome that was first described in 1992. The main features of this syndrome comprise intellectual disability, blepharo-naso-facial malformation, and hand anomalies. Almost all nine described patients have been shown to be affected by conductive hearing impairment attributed to microtia, and atresia of the outer ear canal. Here, we present a VMS patient with congenital malformations of the middle ear as the main reason for severe conductive bilateral hearing impairment. To our knowledge, this is the first report to describe middle ear abnormalities in VMS. These malformations were seen on high resolution Computed Tomography scanning and during an exploratory tympanotomy. Due to the severity of the middle ear abnormalities and the risk for facial nerve damage, the patient was not offered an ossicular chain reconstruction but a bone conduction device after this exploratory tympanotomy. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Gorlin-Goltz syndrome and neoplasms: a case study.

PubMed

Lopes, Nilza N F; Caran, Eliana M; Lee, Maria Lucia; Silva, Nasjla Saba; Rocha, André Caroli; Macedo, Carla R D

2010-01-01

Gorlin syndrome is a rare autosomal dominant disorder exhibiting high penetrance and variable expressivity. It is characterized by facial dysmorphism, skeletal anomalies, multiple basal cell carcinomas, odontogenic keratocysts (OKC), palmar and plantar pits, bifid ribs, vertebral anomalies and a variety of other malformations. Various neoplasms, such as medulloblastomas, meningiomas, ovarian and cardiac fibromas are also found in this syndrome. To describe a twelve-year-old patient with Gorlin-Goltz syndrome, with basal cell carcinomas and promyelocytic leukemia developed after receiving craniospinal radiation for a medulloblastoma. Bifid ribs as well as mandibular and maxillar OKC were also diagnosed Conclusion: The patient with Gorlin-Goltz syndrome should receive close follow-up for early detection of malformations nd malignant neoplasias.

A regional survey of malformed frogs in Minnesota (USA) (Minnesota malformed frogs).

PubMed

Vandenlangenberg, Susan M; Canfield, Jeffrey T; Magner, Joseph A

2003-02-01

In late 1995, school children discovered malformed frogs in a south central Minnesota pond. Press coverage resulted in numerous citizen reports of frog malformation across Minnesota in 1996. After some initial site investigation, 3 affected frog sites and 4 nearby reference sites were selected for more detailed evaluation. Field biologists made 89 visits to study sites beginning spring 1997 through fall 1999 to examine the number and type of frog malformations. Over 5,100 Leopard frogs (Rana pipiens) were captured and examined at all study sites. Water elevations and associated littoral inundation were recorded from 1997-2000. Results indicate that malformation occurred at all study sites above historical background levels. Rana pipiens malformation across all sites over three seasons averaged 7.9% and ranged from 0 to 7% at reference sites and 4 to 23% at affected sites. At one northern Minnesota site, mink frog (Rana septentrionalis) malformation was 75% in 1998. A site characteristic common to the most affected sites was an elastic zone of littoral inundation. Climate driven hydrologic variation likely influenced water depth and associated breeding locations.

Urogenital involvement in the Klippel-Trenaunay-Weber syndrome. Treatment options and results.

PubMed

Vicentini, Fabio C; Denes, Francisco T; Gomes, Cristiano M; Danilovic, Alexandre; Silva, Frederico A; Srougi, Miguel

2006-01-01

Klippel-Trenaunay-Weber syndrome (KTWS) is a congenital condition characterized by vascular malformations of the capillary, venous and lymphatic systems associated to soft tissue and bone hypertrophy in the affected areas. This syndrome may involve bladder, kidney, urethra, ureter and genitals. We report the treatment of 7 KTWS patients with urogenital involvement. From 1995 to 2005, 7 patients with KTWS were evaluated and the charts of these patients were reviewed. Patients' median age was 19-years (range 4 to 46-years) and only 1 was female. The clinical presentation included genital deformities in 3 cases, hematuria in 2 and urethrorragia in 2, one of which associated with cryptorchidism and phimosis. Three patients had an association of pelvic and genital malformations, including 2 patients with hematuria due to vesical lesions and 1 patient with left ureterohydronephrosis due to a pelvic mass. Two patients had urethral lesions. Treatment included endoscopic laser coagulation for 1 patient with recurrent hematuria and 1 patient with urethrorrhagia, pelvic radiotherapy for 1 patient with hematuria and circumcision in 2 patients with genital deformities. One patient required placement of a double-J catheter to relieve obstruction. Hematuria and urethrorragia were safely and effectively controlled with laser applications. Circumcision was also effective. The patient treated with radiotherapy developed a contracted bladder and required a continent urinary diversion. Urogenital involvement in patients with KTWS is not rare and must be suspected in the presence of hematuria or significant cutaneous deformity of the external genitalia. Surgical treatment may be warranted in selected cases.

[A phenotypic description of 26 patients with Ritscher-Schinzel syndrome (cranio-cerebello-cardiac dysplasia or 3C syndrome)].

PubMed

Pira-Paredes, S M; Montoya-Villada, J H; Franco-Restrepo, J L; Moncada-Velez, M; Cornejo, J W

2017-06-01

Ritscher-Schinzel syndrome (also known as cranio-cerebello-cardiac dysplasia or 3C syndrome) is a rare genetic syndrome that is mainly characterised by the association of cardiac and craniofacial anomalies together with others affecting the posterior fossa. We report on 26 patients with Ritscher-Schinzel syndrome at a hospital in Medellin, in the Department of Antioquia, Colombia. Males account for 69% of this cohort. The mean age of the cohort was 30 months, and 42% were under the age of one year at the time of diagnosis. All of them presented ocular disorders, and megalocornea was the most frequent ocular manifestation (69%), whereas low-set ears (80.7%) and septal heart defects (68.7%) were the most common facial and cardiac malformations, respectively. The most frequent malformations of the posterior fossa were megacisterna magna (31.8%) and Dandy-Walker malformation (27%). 84% of the cases had delayed neurodevelopment or intellectual disability. Skeletal manifestations were frequent: the group consisting of camptodactyly, single palmar crease, overlapping fingers, vertical talus and nail hypoplasia were found in hands and feet in 96% of the cases. Ritscher-Schinzel syndrome is a heterogeneous syndrome from the genetic and clinical point of view. These results suggest that the skeletal and ocular abnormalities that were observed can facilitate the phenotypic diagnosis. However, it is necessary to conduct further studies that allow us to gain a deeper knowledge of its prevalence and help identify other genes involved in this syndrome.

[Clinical profile of a cohort of Silver-Russell syndrome patients followed at the Hospital Infantil de México Federico Gómez from 1998 to 2012].

PubMed

Galaz-Montoya, Carolina Isabel; García-Delgado, Constanza; Cervantes-Peredo, Alicia; García-Morales, Leticia; Morán-Barroso, Verónica Fabiola

Patients with Silver-Russell syndrome suffer from severe intrauterine and postnatal growth retardation, relative macrocephaly and body asymmetry, among other characteristics. It is caused by several genetic and epigenetic mechanisms in 11p15.5 in 40% of the cases and maternal uniparental disomy of chromosome 7 in 10%. Twenty patients with a diagnosis of Silver-Russell syndrome who were seen at the HIMFG from 1998 to 2012, were evaluated according to international clinical criteria confirming the diagnosis in nine of the subjects. All patients showed intrauterine and postnatal growth retardation and short stature, both considered as major criteria of Silver-Russell syndrome. Relative macrocephaly was present in 78% of the patients and asymmetry in 33%. Other characteristics such as renal tubular acidosis were present > 50% of the cases. The clinical diagnosis of Silver-Russell syndrome is complex. Short stature is the main reason for seeking medical attention and is helpful in the identification of a differential diagnosis. This situation underlines the importance of growth and development evaluation of all patients and particularly in those with short stature to identify those cases that may require molecular studies, with implications in management, prognosis and genetic counseling. Copyright © 2014 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Volumetric analysis of cerebrospinal fluid and brain parenchyma in a patient with hydranencephaly and macrocephaly--case report.

PubMed

Radoš, Milan; Klarica, Marijan; Mučić-Pucić, Branka; Nikić, Ines; Raguž, Marina; Galkowski, Valentina; Mandić, Dora; Orešković, Darko

2014-08-28

The aim of this study was to perform for the first time the intracranial volumetric analysis of cerebrospinal fluid (CSF) and brain parenchyma in the supratentorial and infratentorial space in a 30-year-old female patient with hydranencephaly and macrocephaly. A head scan performed using a 3T magnetic resonance was followed by manual segmentation of the brain parenchyma and CSF on T2 coronal brain sections. The volume of CSF and brain parenchyma was measured separately for the supratentorial and infratentorial space. The total volume of the intracranial space was 3645.5 cm3. In the supratentorial space, the volume of CSF was 3375.2 cm3 and the volume of brain parenchyma was 80.3 cm3. In the infratentorial space, the volume of CSF was 101.3 cm3 and the volume of the brain parenchyma was 88.7 cm3. In the supratentorial space, there was severe malacia of almost all brain parenchyma with no visible remnants of the choroid plexuses. Infratentorial structures of the brainstem and cerebellum were hypoplastic but completely developed. Since our patient had no choroid plexuses in the supratentorial space and no obstruction between dural sinuses and CSF, development of hydrocephalus and macrocephaly cannot be explained by the classic hypothesis of CSF physiology with secretion, unidirectional circulation, and absorption as its basic postulates. However, the origin and turnover of the enormous amount of intracranial CSF volume, at least 10-fold larger than normal, and the mechanisms of macroencephaly development could be elucidated by the new hypothesis of CSF physiology recently published by our research team.

The Arnold-Chiari Malformation and Its Implications for Individuals with Spina Bifida and Hydrocephalus.

ERIC Educational Resources Information Center

Mittler, Joel E.

1986-01-01

The Arnold-Chiari malformation is present in most infants born with myelomeningocele (a form of spina bifida) and hydrocephalus. The syndrome is responsible for structural abnormalities in the brain, and peripheral nervous system. Etiology, symptoms, impact on central nervous system structures, surgical treatment, and implications for education…

Treatment of Previously Treated Facial Capillary Malformations: Results of Single-Center Retrospective Objective 3-Dimensional Analysis of the Efficacy of Large Spot 532 nm Lasers.

PubMed

Kwiek, Bartłomiej; Ambroziak, Marcin; Osipowicz, Katarzyna; Kowalewski, Cezary; Rożalski, Michał

2018-06-01

Current treatment of facial capillary malformations (CM) has limited efficacy. To assess the efficacy of large spot 532 nm lasers for the treatment of previously treated facial CM with the use of 3-dimensional (3D) image analysis. Forty-three white patients aged 6 to 59 were included in this study. Patients had 3D photography performed before and after treatment with a 532 nm Nd:YAG laser with large spot and contact cooling. Objective analysis of percentage improvement based on 3D digital assessment of combined color and area improvement (global clearance effect [GCE]) were performed. The median maximal improvement achieved during the treatment (GCE) was 59.1%. The mean number of laser procedures required to achieve this improvement was 6.2 (range 1-16). Improvement of minimum 25% (GCE25) was achieved by 88.4% of patients, a minimum of 50% (GCE50) by 61.1%, a minimum of 75% (GCE75) by 25.6%, and a minimum of 90% (GCE90) by 4.6%. Patients previously treated with pulsed dye lasers had a significantly less response than those treated with other modalities (GCE 37.3% vs 61.8%, respectively). A large spot 532 nm laser is effective in previously treated patients with facial CM.

Nasopharyngeal teratoma, congenital diaphragmatic hernia and Dandy-Walker malformation - a yet uncharacterized syndrome.

PubMed

Gupta, N; Shastri, S; Singh, P K; Jana, M; Mridha, A; Verma, G; Kabra, M

2016-11-01

An association of congenital diaphragmatic hernia, dandy walker malformation and nasopharyngeal teratoma is very rare. Here, we report a fourth case with this association where chromosomal microarray and whole exome sequencing (WES) was performed to understand the underlying genetic basis. Findings of few variants especially a novel variation in HIRA provided some insights. An association of congenital diaphragmatic hernia, dandy walker malformation and nasopharyngeal teratoma is very rare. Here, we report a fourth case with this association where chromosomal microarray and whole exome sequencing (WES) was performed to understand the underlying genetic basis. Findings of few variants especially a novel variation in HIRA provided some insights. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

IMAGe syndrome: clinical and genetic implications based on investigations in three Japanese patients.

PubMed

Kato, Fumiko; Hamajima, Takashi; Hasegawa, Tomonobu; Amano, Naoko; Horikawa, Reiko; Nishimura, Gen; Nakashima, Shinichi; Fuke, Tomoko; Sano, Shinichirou; Fukami, Maki; Ogata, Tsutomu

2014-05-01

Arboleda et al. have recently shown that IMAGe (intra-uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities) syndrome is caused by gain-of-function mutations of maternally expressed gene CDKN1C on chromosome 11p15.5. However, there is no other report describing clinical findings in patients with molecularly studied IMAGe syndrome. Here, we report clinical and molecular findings in Japanese patients. We studied a 46,XX patient aged 8·5 years (case 1) and two 46,XY patients aged 16·5 and 15·0 years (cases 2 and 3). Clinical studies revealed not only IMAGe syndrome-compatible phenotypes in cases 1-3, but also hitherto undescribed findings including relative macrocephaly and apparently normal pituitary-gonadal endocrine function in cases 1-3, familial glucocorticoid deficiency (FGD)-like adrenal phenotype and the history of oligohydramnios in case 2, and arachnodactyly in case 3. Sequence analysis of CDKN1C, pyrosequencing-based methylation analysis of KvDMR1 and high-density oligonucleotide array comparative genome hybridization analysis for chromosome 11p15.5 were performed, showing an identical de novo and maternally inherited CDKN1C gain-of-function mutation (p.Asp274Asn) in cases 1 and 2, respectively, and no demonstrable abnormality in case 3. The results of cases 1 and 2 with CDKN1C mutation would argue the following: [1] relative macrocephaly is consistent with maternal expression of CDKN1C in most tissues and biparental expression of CDKN1C in the foetal brain; [2] FGD-like phenotype can result from CDKN1C mutation; and [3] genital abnormalities may primarily be ascribed to placental dysfunction. Furthermore, lack of CDKN1C mutation in case 3 implies genetic heterogeneity in IMAGe syndrome. © 2013 John Wiley & Sons Ltd.

Dumbbell-Shaped Epidural Capillary Hemangioma Presenting as a Lung Mass: Case Report and Review of the Literature.

PubMed

García-Pallero, María A; Torres, Cristina V; García-Navarrete, Eduardo; Gordillo, Carlos; Delgado, Juan; Penanes, Juan R; García-Campos, María T; Sola, R G

2015-07-15

A case report and literature review. We present the fourth case of a spinal epidural capillary hemangioma with a dumbbell-shaped appearance in the magnetic resonance image reported in the literature and the second presented as a lung mass. Hemangiomas are congenital vascular malformations that pathologists frequently consider to be hamartomatous malformations. Hemangiomas of the spine are usually lesions of the vertebral bodies, but they can sit in other locations such as the intramedullary or epidural space. Purely epidural hemangiomas are rare and most of them are of cavernous type. We present a 67-year-old female with a thoracic dumbbell-shaped capillary hemangioma with both foraminal and intrathoracic extensions, whose presentation was pleural effusion associated with mediastinal mass suggestive of pulmonary neoplasia. Surgical treatment consisted of total removal en bloc of the lesion. Microscopic evaluation showed a fibrofatty tissue with a proliferation of vascular structures that were generally of a small size, with areas of myxoid appearance. To date, there have been 8 epidural capillary hemangiomas of the thoracic and lumbar spine reported in the literature, and only 3 of them were dumbbell-shaped with extraforaminal extension. It is important to consider the diagnosis of hemangiomas in the differential diagnosis of epidural lesions with dumbbell-shaped appearance in the magnetic resonance image, especially at the thoracic level. It is a benign and potentially curable disease and the most appropriate surgical treatment is en bloc resection of the entire lesion. They are usually presented as a progressive myelopathy, so early treatment may prevent permanent neurological deficits. 5.

Optic nerve coloboma, Dandy-Walker malformation, microglossia, tongue hamartomata, cleft palate and apneic spells: an existing oral-facial-digital syndrome or a new variant?

PubMed

Toriello, Helga V; Lemire, Edmond G

2002-01-01

We report on a female infant with postaxial polydactyly of the hands, preaxial polydactyly of the right foot, cleft palate, microglossia and tongue hamartomata consistent with an oral-facial-digital syndrome (OFDS). The patient also had optic nerve colobomata, a Dandy-Walker malformation, micrognathia and apneic spells. This combination of clinical features has not been previously reported. This patient either expands the clinical features of one of the existing OFDS or represents a new variant. A review of the literature highlights the difficulties in making a specific diagnosis because of the different classification systems that exist in the literature.

West syndrome in a patient with Schinzel-Giedion syndrome.

PubMed

Miyake, Fuyu; Kuroda, Yukiko; Naruto, Takuya; Ohashi, Ikuko; Takano, Kyoko; Kurosawa, Kenji

2015-06-01

Schinzel-Giedion syndrome is a rare recognizable malformation syndrome defined by characteristic facial features, profound developmental delay, severe growth failure, and multiple congenital anomalies. The causative gene of Schinzel-Giedion syndrome, SETBP1, has been identified, but limited cases have been confirmed by molecular analysis. We present a 9-month-old girl affected by West syndrome with Schinzel-Giedion syndrome. Congenital severe hydronephrosis, typical facial features, and multiple anomalies suggested a clinical diagnosis of Schinzel-Giedion syndrome. Hypsarrhythmia occurred at 7 months of age and was temporarily controlled by adrenocorticotropic hormone (ACTH) therapy during 5 weeks. SETBP1 mutational analysis showed the presence of a recurrent mutation, p.Ile871Thr. The implications in management of Schinzel-Giedion syndrome are discussed. © The Author(s) 2014.

An approach to congenital malformations of the head and neck.

PubMed

Isaacson, Glenn

2007-02-01

It is easy to be overwhelmed when faced with the hundreds of cataloged anomalies of the head and neck region. For any individual defect there may be variation in phenotype, associated anomalies, and cause. To help organize these various disorders, dysmorphologists have grouped them into "syndromes", "sequences" and "associations" based on our level of understanding of their etiologies. Recently, completion of the human genome project has added a new level of complexity to the study of human malformations by providing a flood of new information about the genetic origins of established syndromes. The article describes the dysmorphologist's approach to the child with one or more anomalies and provides a glimpse into the future of human genetics.

Ritscher-Schinzel cranio-cerebello-cardiac (3C) syndrome: report of four new cases and review.

PubMed

Leonardi, M L; Pai, G S; Wilkes, B; Lebel, R R

2001-08-15

Ritscher-Schinzel syndrome, also known as the 3C syndrome, is a rare, autosomal recessive syndrome characterized by craniofacial, cerebellar, and cardiac anomalies. Cardiac manifestations include ventricular septal defect, atrial septal defect, tetralogy of Fallot, double outlet right ventricle, hypoplastic left heart, aortic stenosis, pulmonic stenosis and other valvular anomalies. Central nervous system anomalies include Dandy-Walker malformation, cerebellar vermis hypoplasia and enlargement of the cisterna magna. Craniofacial abnormalities seen are cleft palate, ocular coloboma, prominent occiput, low-set ears, hypertelorism, down-slanting palpebral fissures, depressed nasal bridge and micrognathia. Dandy-Walker malformation, posterior fossa cyst, hydrocephalus and congenital heart defect are common malformations that may occur in isolation or as a part of many syndromes. Accurate genetic diagnosis and counseling require detailed analysis of the external as well as the internal anatomy and knowledge of the relative frequencies of various malformations in syndromes that may have overlapping clinical signs. We have had the opportunity recently to study four cases of the Ritscher-Schinzel syndrome. A review of all reported cases is presented and an attempt made to define the minimum diagnostic criteria for the Ritscher-Schinzel syndrome. Of the nine craniofacial anomalies commonly reported as a part of the Ritscher-Schinzel syndrome, we consider two i.e., cleft palate and ocular coloboma, to be readily and objectively ascertainable. The other seven craniofacial traits, however, are somewhat subjective, require expert interpretation and are sometimes difficult to ascertain in a newborn or stillborn fetus. These are prominent forehead, prominent occiput, hypertelorism, down-slanting palpebral fissures, low-set ears, depressed nasal bridge and micrognathia. At least four of these were present in all cases that had a secure diagnosis of the Ritscher-Schinzel syndrome

Middle and inner ear malformations in two siblings exposed to valproic acid during pregnancy: a case report.

PubMed

Van Houtte, Evelyne; Casselman, Jan; Janssens, Sandra; De Kegel, Alexandra; Maes, Leen; Dhooge, Ingeborg

2014-11-01

Valproic acid (VPA) is a known teratogenic drug. Exposure to VPA during the pregnancy can lead to a distinct facial appearance, a cluster of major and minor anomalies and developmental delay. In this case report, two siblings with fetal valproate syndrome and a mild conductive hearing loss were investigated. Radiologic evaluation showed middle and inner ear malformations in both children. Audiologic, vestibular and motor examination was performed. This is the first case report to describe middle and inner ear malformations in children exposed to VPA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Overgrowth syndromes with vascular anomalies.

PubMed

Blei, Francine

2015-04-01

Overgrowth syndromes with vascular anomalies encompass entities with a vascular anomaly as the predominant feature vs those syndromes with predominant somatic overgrowth and a vascular anomaly as a more minor component. The focus of this article is to categorize these syndromes phenotypically, including updated clinical criteria, radiologic features, evaluation, management issues, pathophysiology, and genetic information. A literature review was conducted in PubMed using key words "overgrowth syndromes and vascular anomalies" as well as specific literature reviews for each entity and supportive genetic information (e.g., somatic mosaicism). Additional searches in OMIM and Gene Reviews were conducted for each syndrome. Disease entities were categorized by predominant clinical features, known genetic information, and putative affected signaling pathway. Overgrowth syndromes with vascular anomalies are a heterogeneous group of disorders, often with variable clinical expression, due to germline or somatic mutations. Overgrowth can be focal (e.g., macrocephaly) or generalized, often asymmetrically (and/or mosaically) distributed. All germ layers may be affected, and the abnormalities may be progressive. Patients with overgrowth syndromes may be at an increased risk for malignancies. Practitioners should be attentive to patients having syndromes with overgrowth and vascular defects. These patients require proactive evaluation, referral to appropriate specialists, and in some cases, early monitoring for potential malignancies. Progress in identifying vascular anomaly-related overgrowth syndromes and their genetic etiology has been robust in the past decade and is contributing to genetically based prenatal diagnosis and new therapies targeting the putative causative genetic mutations. Copyright © 2015 Mosby, Inc. All rights reserved.

Analysis of Maternal Risk Factors Associated With Congenital Vertebral Malformations

PubMed Central

Hesemann, Jennifer; Lauer, Emily; Ziska, Stephen; Noonan, Kenneth; Nemeth, Blaise; Scott-Schwoerer, Jessica; McCarty, Catherine; Rasmussen, Kristen; Goldberg, Jacob M.; Sund, Sarah; Eickhoff, Jens; Raggio, Cathleen L.; Giampietro, Philip F.

2014-01-01

Study Design A retrospective chart review of cases with congenital vertebral malformations (CVM) and controls with normal spine morphology. Objective To determine the relative contribution of maternal environmental factors (MEF) during pregnancy including maternal insulin dependent diabetes mellitus, valproic acid, alcohol, smoking, hyperthermia, twin gestation, assisted reproductive technology, in-vitro fertilization and maternal clomiphene usage to CVM development. Summary of Background Data Congenital vertebral malformations (CVM) represent defects in formation and segmentation of somites occurring with an estimated incidence of between 0.13–0.50 per 1000 live births. CVM may be associated with congenital scoliosis, Klippel-Feil syndrome, hemifacial microsomia and VACTERL syndromes, and represent significant morbidity due to pain and cosmetic disfigurement. Methods A multicenter retrospective chart review of 229 cases with CVM and 267 controls with normal spine morphology between the ages of 1–50 years was performed in order to obtain the odds ratio (OR) of MEF related to CVM among cases vs. controls. CVM due to an underlying syndrome associated with a known gene mutation or chromosome etiology were excluded. An imputation based analysis was performed in which subjects with no documentation of MEF history were treated as no maternal exposure.” Univariate and multivariate analysis was conducted to calculate the OR. Results Of the 229 total cases, 104 cases had single or multiple CVM without additional congenital malformations (CM) (Group 1) and 125 cases had single or multiple CVM and additional CM (Group 2). Nineteen percent of total cases had an identified MEF. The OR (95% CI, P-value) for MEF history for Group 1 was 6.0 (2.4–15.1, P<0.001) in the univariate analysis. The OR for MEF history in Group 2 was 9.1 (95%CI, P-value) (3.8–21.6, P<0.001) in the univariate analysis. The results were confirmed in the multivariate analysis, after adjusting for

Profound microcephaly, primordial dwarfism with developmental brain malformations: a new syndrome.

PubMed

Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Saleem, Sahar N; Ahmed, Mahmoud K H; Issa, Mahmoud; Effat, Laila K; Kayed, Hisham F; Zaki, Maha S; Gaber, Khaled R

2012-08-01

We describe two sibs with a lethal form of profound congenital microcephaly, intrauterine and postnatal growth retardation, subtle skeletal changes, and poorly developed brain. The sibs had striking absent cranial vault with sloping of the forehead, large beaked nose, relatively large ears, and mandibular micro-retrognathia. Brain magnetic resonance imaging (MRI) revealed extremely simplified gyral pattern, large interhemispheric cyst and agenesis of corpus callosum, abnormally shaped hippocampus, and proportionately affected cerebellum and brainstem. In addition, fundus examination showed foveal hypoplasia with optic nerve atrophy. No abnormalities of the internal organs were found. This profound form of microcephaly was identified at 17 weeks gestation by ultrasound and fetal brain MRI helped in characterizing the developmental brain malformations in the second sib. Molecular analysis excluded mutations in potentially related genes such as RNU4ATAC, SLC25A19, and ASPM. These clinical and imaging findings are unlike that of any recognized severe forms of microcephaly which is believed to be a new microcephalic primordial dwarfism (MPD) with developmental brain malformations with most probably autosomal recessive inheritance based on consanguinity and similarly affected male and female sibs. Copyright © 2012 Wiley Periodicals, Inc.

Proteus syndrome*

PubMed Central

Rocha, Ritha de Cássia Capelato; Estrella, Mariani Paulino Soriano; do Amaral, Danielle Mechereffe; Barbosa, Angela Marques; de Abreu, Marilda Aparecida Milanez Morgado

2017-01-01

Proteus syndrome is a rare syndrome characterized by disproportionate overgrowth of limbs, multiple hamartomas, and vascular malformations. The cerebriform connective tissue nevi, also called cerebriform plantar hyperplasia, are present in most patients, and is the main characteristic of the syndrome. If present, even alone, they can be considered as a pathognomonic sign. This article reports a classic case of Proteus syndrome in a 2-year-old male patient who began to show a discrete asymmetry of the right hemibody in relation to the left one after birth, which increased over the months. He also showed cerebriform plantar hyperplasia and Port-wine stains, among other alterations. PMID:29166516

Associated genetic syndromes and extracardiac malformations strongly influence outcomes of fetuses with congenital heart diseases.

PubMed

Bensemlali, Myriam; Bajolle, Fanny; Ladouceur, Magalie; Fermont, Laurent; Lévy, Marilyne; Le Bidois, Jérôme; Salomon, Laurent J; Bonnet, Damien

2016-05-01

Congenital heart disease (CHD) is often associated with extracardiac malformations (ECMs) and genetic syndromes. To determine the effect of cytogenetic anomalies and/or ECMs associated with CHD on parental decision to choose termination of pregnancy (TOP) or compassionate care (CC), as well as on the outcome of children born alive. This 10-year retrospective study included all prenatally diagnosed cases of CHD in a single tertiary referral centre. From January 2002 to December 2011, 2036 consecutive cases of fetal CHD (798 TOPs and 1238 live births, including 59 with postnatal CC) were included. CHD was associated with a known cytogenetic anomaly in 9.8% of cases and a major ECM in 11.7% of cases. The proportion of prenatally identified associated cytogenetic anomalies was significantly lower in the live-birth group than in the TOP plus CC group (4.2% vs 17.5%; P<0.001); this was also true for ECMs (8.1% vs 16.7%; P<0.001). The mortality rate was higher in the group with an associated cytogenetic anomaly or ECM (29.1%) than in cases with isolated CHD; a 2.4-fold increase in the death rate was observed (95% confidence interval 1.34-4.38; P=0.003). These associations remained significant after multivariable analysis, including the severity of the CHD (uni- or biventricular physiology). Prenatal diagnosis of a known cytogenetic anomaly or major ECM strongly influences parental decision to choose TOP or postnatal CC. Genetic syndromes and ECMs are associated with a higher mortality rate, independent of the complexity of the CHD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Spectrum of prenatally detected central nervous system malformations: Neural tube defects continue to be the leading foetal malformation.

PubMed

Siddesh, Anjurani; Gupta, Geetika; Sharan, Ram; Agarwal, Meenal; Phadke, Shubha R

2017-04-01

Prenatal diagnosis of malformations is an important method of prevention and control of congenital anomalies with poor prognosis. Central nervous system (CNS) malformations amongst these are the most common. The information about the prevalence and spectrum of prenatally detected malformations is crucial for genetic counselling and policymaking for population-based preventive programmes. The objective of this study was to study the spectrum of prenatally detected CNS malformations and their association with chromosomal abnormalities and autopsy findings. This retrospective study was conducted in a tertiary care hospital in north India from January 2007 to December 2013. The details of cases with prenatally detected CNS malformations were collected and were related with the foetal chromosomal analysis and autopsy findings. Amongst 6044 prenatal ultrasonographic examinations performed; 768 (12.7%) had structural malformations and 243 (31.6%) had CNS malformations. Neural tube defects (NTDs) accounted for 52.3 per cent of CNS malformations and 16.5 per cent of all malformations. The other major groups of prenatally detected CNS malformations were ventriculomegaly and midline anomalies. Chromosomal abnormalities were detected in 8.2 per cent of the 73 cases studied. Foetal autopsy findings were available for 48 foetuses. Foetal autopsy identified additional findings in eight foetuses and the aetiological diagnosis changed in two of them (4.2%). Amongst prenatally detected malformations, CNS malformations were common. NTD, which largely is a preventable anomaly, continued to be the most common group. Moreover, 60 per cent of malformations were diagnosed after 20 weeks, posing legal issues. Chromosomal analysis and foetal autopsy are essential for genetic counselling based on aetiological diagnosis.

Surgical management of venous malformations.

PubMed

Loose, D A

2007-01-01

Among vascular malformations, the predominantly venous malformations represent the majority of cases. They form a clinical entity and therefore need clear concepts concerning diagnosis and treatment. This paper presents an overview of contemporary classification as well as tactics and techniques of treatment. According to the Hamburg Classification, predominantly venous malformations are categorized into truncular and extratruncular forms, with truncular forms distinguished as obstructions and dilations, and extratruncular forms as limited or infiltrating. The tactics of treatment represent surgical and non-surgical methods or combined techniques. Surgical approaches utilize different tactics and techniques that are adopted based on the pathologic form and type of the malformation: (I) operation to reduce the haemodynamic activity of the malformation; (II) operation to eliminate the malformation; and (III) reconstructive operation. As for (I), a type of a tactic is the operation to derive the venous flow. In (II), the total or partial removal of the venous malformation is demonstrated subdivided into three different techniques. In this way, the infiltrating as well as the limited forms can be treated. An additional technique is dedicated to the treatment of a marginal vein. Approach (III) involves the treatment of venous aneurysms, where a variety of techniques have been successful. Long-term follow-up demonstrates positive results in 91% of the cases. Congenital predominantly venous malformations should be treated according to the principles developed during the past decades in vascular surgery, interventional treatment and multidisciplinary treatment. The days of predominantly conservative treatment should be relegated to the past. Special skills and experiences are necessary to carry out appropriate surgical strategy, and the required operative techniques should be dictated by the location and type of malformation and associated findings.

Increased capillary permeability mediated by a dengue virus-induced lymphokine.

PubMed Central

Khanna, M; Chaturvedi, U C; Sharma, M C; Pandey, V C; Mathur, A

1990-01-01

The mechanism of increased capillary permeability, seen in cases of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), is not known. Dengue type 2 virus (DV) is known to induce production of a lymphokine, the cytotoxic factor (CF), by the T lymphocytes of mouse spleen. The data presented here show that intraperitoneal inoculation of CF in mice results in increased capillary permeability in a dose-dependent manner, as shown by leakage of intravenously injected radiolabelled iodine (125I) or Evans blue dye. Peak leakage occurred 30 min after inoculation of CF and the vascular integrity was restored by 2 hr. The increase in capillary permeability was abrogated by pretreatment of mice with anti-CF antibodies, avil (H1 receptor blocker) or ranitidine (H2 receptor blocker). The findings thus show that a DV-induced lymphokine, the CF, increases the capillary permeability via release of histamine. PMID:2312168

Identification of a PTEN mutation with reduced protein stability, phosphatase activity, and nuclear localization in Hong Kong patients with autistic features, neurodevelopmental delays, and macrocephaly.

PubMed

Wong, Chi Wai; Or, Penelope Mei Yu; Wang, Yubing; Li, Lisha; Li, Jing; Yan, Mingfei; Cao, Ye; Luk, Ho Ming; Tong, Tony Ming For; Leslie, Nick R; Lo, Ivan Fai-Man; Choy, Kwong Wai; Chan, Andrew Man Lok

2018-04-02

PTEN is a tumor suppressor gene inactivated in over 30% of human cancers. It encodes a lipid phosphatase that serves as a gatekeeper of the phosphoinositide 3-kinase signaling pathway. Germline mutation frequently occurs in this gene in patients diagnosed with PTEN Hamartoma Tumor Syndrome (PHTS). PHTS individuals are characterized by macrocephaly, benign growth of multiple tissues and increased tumor risk. In addition, autistic phenotypes are found in 10-20% of individuals carrying the germline PTEN mutation with macrocephaly. In this report, 13 suspected PHTS patients were screened for mutation in the PTEN gene. A missense variant (c. 302T > C) substituting the isoleucine at codon 101 to a threonine, a single nucleotide insertion (c. 327-328insC) causing a frame shift mutation and termination at codon 109, and a nonsense variant (c. 1003C > T) truncated the protein at codon 335 were identified. The I101T mutation significantly reduced PTEN protein expression levels by 2.5- to 4.0-fold. Mechanistically, I101T reduced the protein half-life of PTEN possibly due to enhanced polyubiquitination at Lysine 13. However, the I101T mutant retained almost 30% of the lipid phosphatase activity of the wild-type protein. Finally, the I101T mutant has reduced phosphorylation at a PTEN auto-dephosphorylation site at Threonine 366 and a lowered ratio of nuclear to cytosolic protein level. These partial losses of multiple PTEN biochemical functions may contribute to the tissue overgrowth and autistic features of this PHTS patient. Autism Res 2018. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. The genetics of autism spectrum disorders is highly complex with individual risk influenced by both genetic and environmental factors. Mutation in the human PTEN gene confers a high risk of developing autistic behavior. This report revealed that PTEN mutations occurred in 23% of a selected group of Hong Kong

Quantitative analysis of nailfold capillary morphology in patients with fibromyalgia

PubMed Central

Choi, Dug-Hyun

2015-01-01

Background/Aims Nailfold capillaroscopy (NFC) has been used to examine morphological and functional microcirculation changes in connective tissue diseases. It has been demonstrated that NFC patterns reflect abnormal microvascular dynamics, which may play a role in fibromyalgia (FM) syndrome. The aim of this study was to determine NFC patterns in FM, and their association with clinical features of FM. Methods A total of 67 patients with FM, and 30 age- and sex-matched healthy controls, were included. Nailfold capillary patterns were quantitatively analyzed using computerized NFC. The parameters of interest were as follows: number of capillaries within the central 3 mm, deletion score, apical limb width, capillary width, and capillary dimension. Capillary dimension was determined by calculating the number of capillaries using the Adobe Photoshop version 7.0. Results FM patients had a lower number of capillaries and higher deletion scores on NFC compared to healthy controls (17.3 ± 1.7 vs. 21.8 ± 2.9, p < 0.05; 2.2 ± 0.9 vs. 0.7 ± 0.6, p < 0.05, respectively). Both apical limb width (µm) and capillary width (µm) were significantly decreased in FM patients (1.1 ± 0.2 vs. 3.7 ± 0.6; 5.4 ± 0.5 vs. 7.5 ± 1.4, respectively), indicating that FM patients have abnormally decreased digital capillary diameter and density. Interestingly, there was no difference in capillary dimension between the two groups, suggesting that the length or tortuosity of capillaries in FM patients is increased to compensate for diminished microcirculation. Conclusions FM patients had altered capillary density and diameter in the digits. Diminished microcirculation on NFC may alter capillary density and increase tortuosity. PMID:26161020

Bendectin and human congenital malformations.

PubMed

Shiono, P H; Klebanoff, M A

1989-08-01

The relationship between Bendectin exposure during the first trimester of pregnancy and the occurrence of congenital malformations was prospectively studied in 31,564 newborns registered in the Northern California Kaiser Permanente Birth Defects Study. The odds ratio for any major malformation and Bendectin use was 1.0 (95% confidence interval 0.8-1.4). There were 58 categories of congenital malformations; three of them were statistically associated with Bendectin exposure (microcephaly--odds ratio = 5.3, 95% confidence interval = 1.8-15.6; congenital cataract--odds ratio = 5.3, 95% confidence interval = 1.2-24.3; lung malformations (ICD-8 codes 484.4-484.8)--odds ratio = 4.6, 95% confidence interval = 1.9-10.9). This is exactly the number of associations that would be expected by chance. An independent study (the Collaborative Perinatal Project) was used to determine whether vomiting during pregnancy in the absence of Bendectin use was associated with these three malformations. Two of the three (microcephaly and cataract) had strong positive associations with vomiting in the absence of Bendectin use. We conclude that there is no increase in the overall rate of major malformations after exposure to Bendectin and that the three associations found between Bendectin and individual malformations are unlikely to be causal.

Dandy-Walker malformation and neurocutaneous melanosis in a three-month-old infant

PubMed Central

Mahgoub, Shaza Mohamed; Yassin, Rehab Omer; Osman, Atika Mohamed

2013-01-01

Dandy-Walker Malformation (DWM) is a rare congenital malformation of the brain. It is characterized by cystic enlargement of the fourth ventricle which is communicating with an enlarged posterior fossa, cerebellar dysgenesis, high tentorial insertion and hydrocephalus. Neurocutaneous Melanosis (NCM) is a congenital neurocutaneous syndrome characterized by large or multiple melanocytic nevi and benign or malignant melanocytic tumors of the leptomeninges. We report three months old boy who presented with projectile vomiting associated with a noticeable increase in head size. Several congenital nevi were seen all over his body with evident signs of hydrocephalus. The association of DWM and NCM is a rare complex, and to our knowledge, this is the eleventh case to be reported in the literature. In this article, we discuss the proposed pathogenesis, classification and management of the condition. PMID:27493376

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.

DiGeorge syndrome and unilateral symbrachydactyly.

PubMed

Devriendt, K; De Smet, L; De Boeck, K; Fryns, J P

1997-01-01

We describe a child with DiGeorge syndrome due to a del22(q11) and a symbrachydactyly of the left hand. The underlying cardiovascular malformations in DiGeorge syndrome may lead to an increased susceptibility to vascular disruptions, giving further support to the subclavian-artery-disruption-sequence theory.

[The clinico-neuropsychological aspects of arteriovenous malformations of the hippocampus].

PubMed

Buklina, S B; Filatov, Iu M; Eliava, Sh Sh

1998-01-01

A comprehensive examination was made in 39 patients with arteriovenous malformations (AVM) of hippocampus. Prior to and following surgery, all the patients underwent neuropsychological study after A. R. Luriia (1962). Mnestic disorder was found to be the most common abnormality in patients with AVM at this site. Before surgery, they were detected in 34 of 39 patients, 11 of them having severe memory disorders with the traits of the Korsakoff's syndrome. These patients were found to have mixed posthemorrhagic lesion of the hippocampus, other portions of the temporal lobe and periventricular structures. Twenty nine patients were operated on, 14 of them had progressive mnestic disorder of the modally nonspecific type irrespective the side operated on. There were no postoperative Korsakoff's syndromes. There was no progression in memory defects in patients after surgery on the brain drastically changed after hemorrhage or removal of minor malformations. Before hemorrhage, epileptic paroxysms were observed in 2 of the 39 patients only in the presence of massive AVM obligatorily involving the temporal cortex. Following surgery, there were no new epileptic paroxysms and changes in the emotional status and motivations in the patients. Thus, the hippocampal formation is involved in the primary mechanisms of fixation, retention, reproduction of a memory trace. The participation of many structures of the brain is required to form an emotional status, motivation, and clinical manifestations of epileptic activity.

A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly.

PubMed

Marcadier, Julien L; Mears, Alan J; Woods, Elizabeth A; Fisher, Jamie; Airheart, Cory; Qin, Wen; Beaulieu, Chandree L; Dyment, David A; Innes, A Micheil; Curry, Cynthia J

2016-01-01

PDAC (also termed Matthew Wood) syndrome is a rare, autosomal recessive disorder characterized by pulmonary hypoplasia/aplasia, diaphragmatic defects, bilateral anophthalmia, and cardiac malformations. The disorder is caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. We describe six cases from four families of Hmong ancestry, seen over a 30 years period in California. These include: (i) consanguineous siblings with a combination of bilateral anophthalmia, diaphragmatic abnormalities, truncus arteriosus, and/or pulmonary agenesis/hypoplasia; (ii) a singleton fetus with bilateral anophthalmia, pulmonary agenesis, cardiac malformation, and renal hypoplasia; (iii) a sibling pair with a combination of antenatal contractures, camptodactyly, fused palpebral fissures, pulmonary agenesis, and/or truncus arteriosus; (iv) a fetus with bilateral anophthalmia, bushy eyebrows, pulmonary agenesis, heart malformation, and abnormal hand positioning. The phenotypic spectrum of PDAC syndrome has until now not included contractures or camptodactyly. Sequencing of STRA6 in unrelated members of families three and four identified a novel, shared homozygous splice site alteration (c.113 + 3_4delAA) that is predicted to be pathogenic. We hypothesize this may represent a unique disease allele in the Hmong. We also provide a focused review of all published PDAC syndrome cases with confirmed or inferred STRA6 mutations, illustrating the phenotypic and molecular variability that characterizes this disorder. © 2015 Wiley Periodicals, Inc.

Early postnatal cranial vault reduction and fixation surgery for severe hydrocephalic macrocephaly.

PubMed

Iyer, Rajiv R; Carey, Carolyn M; Rottgers, S Alex; Tetreault, Lisa; Shimony, Nir; Katzenstein, Jennifer; Ruas, Ernesto; Tuite, Gerald F

2018-05-01

OBJECTIVE Infants with severe hydrocephalus and extreme macrocephaly typically undergo CSF diversion early in life, which can result in significant cranial deformity due to CSF overdrainage. In this scenario, overlap of the cranial plates can precede the development of secondary synostosis and/or severe, permanent cranial deformity. As a result, extensive cranial vault remodeling is sometimes undertaken later in life, which is often challenging and has been associated with mortality and a high morbidity rate. The authors have previously described a technique for early postnatal cranial vault reduction and fixation (CVRF), in which the calvarial bones are stabilized using absorbable fixation plates in the neonatal period, in an attempt to facilitate patient positioning, simplify hydrocephalus management, and improve cosmesis. Here, the authors describe their institutional experience managing patients with extreme neonatal hydrocephalus with CSF diversion, with and without CVRF, over the past 12 years. METHODS The authors retrospectively reviewed the charts of infants with extreme hydrocephalus (head circumference > 49 cm) treated at their children's hospital with ventriculoperitoneal shunting, with or without CVRF, between 2005 and 2017. Data collected included age, sex, etiology of hydrocephalus, type of CVRF performed (anterior, posterior, or combined), follow-up duration, orbitofrontal circumference, craniometric measurements, intraoperative blood loss, operative duration, and postoperative complications. Developmental data were collected using the third edition of the Ages and Stages Questionnaire. Photographic imaging was used to demonstrate esthetic outcomes, and family questionnaires were used to evaluate satisfaction with the esthetic outcome. RESULTS Eleven patients with extreme neonatal hydrocephalus underwent CSF shunting; 5 underwent shunting alone and 6 patients underwent shunting and CVRF. For patients who underwent shunting and CVRF, the median age at

Multifocal demyelinating motor neuropathy and hamartoma syndrome associated with a de novo PTEN mutation

PubMed Central

Bansagi, Boglarka; Phan, Vietxuan; Baker, Mark R.; O'Sullivan, Julia; Jennings, Matthew J.; Whittaker, Roger G.; Müller, Juliane S.; Duff, Jennifer; Griffin, Helen; Miller, James A.L.; Gorman, Grainne S.; Lochmüller, Hanns; Chinnery, Patrick F.; Roos, Andreas; Swan, Laura E.

2018-01-01

Objective To describe a patient with a multifocal demyelinating motor neuropathy with onset in childhood and a mutation in phosphatase and tensin homolog (PTEN), a tumor suppressor gene associated with inherited tumor susceptibility conditions, macrocephaly, autism, ataxia, tremor, and epilepsy. Functional implications of this protein have been investigated in Parkinson and Alzheimer diseases. Methods We performed whole-exome sequencing in the patient's genomic DNA validated by Sanger sequencing. Immunoblotting, in vitro enzymatic assay, and label-free shotgun proteomic profiling were performed in the patient's fibroblasts. Results The predominant clinical presentation of the patient was a childhood onset, asymmetric progressive multifocal motor neuropathy. In addition, he presented with macrocephaly, autism spectrum disorder, and skin hamartomas, considered as clinical criteria for PTEN-related hamartoma tumor syndrome. Extensive tumor screening did not detect any malignancies. We detected a novel de novo heterozygous c.269T>C, p.(Phe90Ser) PTEN variant, which was absent in both parents. The pathogenicity of the variant is supported by altered expression of several PTEN-associated proteins involved in tumorigenesis. Moreover, fibroblasts showed a defect in catalytic activity of PTEN against the secondary substrate, phosphatidylinositol 3,4-trisphosphate. In support of our findings, focal hypermyelination leading to peripheral neuropathy has been reported in PTEN-deficient mice. Conclusion We describe a novel phenotype, PTEN-associated multifocal demyelinating motor neuropathy with a skin hamartoma syndrome. A similar mechanism may potentially underlie other forms of Charcot-Marie-Tooth disease with involvement of the phosphatidylinositol pathway. PMID:29720545

Psychosis risk syndrome comorbid with panic attack disorder in a cannabis-abusing patient affected by Arnold-Chiari malformation type I.

PubMed

Del Casale, Antonio; Serata, Daniele; Rapinesi, Chiara; Simonetti, Alessio; Tamorri, Stefano Maria; Comparelli, Anna; De Carolis, Antonella; Savoja, Valeria; Kotzalidis, Georgios D; Sani, Gabriele; Tatarelli, Roberto; Girardi, Paolo

2012-01-01

An 18-year-old man with Arnold-Chiari malformation (ACM) type I developed sudden panic attacks. He also manifested sleep disorder, cannabis abuse, and psychosis-risk syndrome (PRS). Although with average-superior intelligence, he had executive dysfunction. This prompted us to explore the relation between ACM, cannabis abuse, PRS and panic disorder. We report the case and briefly review the literature focusing on ACM and psychiatric disorders. Behavior therapy led to gradual abstinence from cannabis with disappearance of anxiety symptoms. The patient is currently well and maintained on omega-3 polyunsaturated fatty acids. Locus coeruleus compression and cannabis abuse may have triggered the symptoms, and the latter might also be PRS-related. PRS and anxiety symptoms should be explored in ACM patients to allow better prevention of psychosis and anxiety disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

AP1S2 is mutated in X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome).

PubMed

Cacciagli, Pierre; Desvignes, Jean-Pierre; Girard, Nadine; Delepine, Marc; Zelenika, Diana; Lathrop, Mark; Lévy, Nicolas; Ledbetter, David H; Dobyns, William B; Villard, Laurent

2014-03-01

MRXS5 or Pettigrew syndrome was described 20 years ago in a four generation family including nine affected individuals presenting with facial dysmorphism, intellectual disability, Dandy-Walker malformation and inconstant choreoathetosis. Four individuals had iron deposition in the basal ganglia seen on MRI or at autopsy. The mutation causing Pettigrew has remained elusive since the initial description of the condition. We report the identification of a mutation in the X-linked AP1S2 gene in the original Pettigrew syndrome family using X-chromosome exome sequencing. We report additional phenotype details for several of the affected individuals, allowing us to further refine the phenotype corresponding to this X-linked intellectual disability syndrome. The AP1S2 c.426+1 G>T mutation segregates with the disease in the Pettigrew syndrome family and results in loss of 46 amino acids in the clathrin adaptor complex small chain domain that spans most of the AP1S2 protein sequence. The mutation reported here in AP1S2 is the first mutation that is not predicted to cause a premature termination of the coding sequence or absence of the AP1S2 protein. Although most of the families affected by a mutation in AP1S2 were initially described as having different disorders assigned to at least three different OMIM numbers (MIM 300629, 300630 and 304340), our analysis of the phenotype shows that they are all the same syndrome with recognition complicated by highly variable expressivity that is seen within as well as between families and is probably not explained by differences in mutation severity.

AP1S2 is mutated in X-linked Dandy–Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome)

PubMed Central

Cacciagli, Pierre; Desvignes, Jean-Pierre; Girard, Nadine; Delepine, Marc; Zelenika, Diana; Lathrop, Mark; Lévy, Nicolas; Ledbetter, David H; Dobyns, William B; Villard, Laurent

2014-01-01

MRXS5 or Pettigrew syndrome was described 20 years ago in a four generation family including nine affected individuals presenting with facial dysmorphism, intellectual disability, Dandy–Walker malformation and inconstant choreoathetosis. Four individuals had iron deposition in the basal ganglia seen on MRI or at autopsy. The mutation causing Pettigrew has remained elusive since the initial description of the condition. We report the identification of a mutation in the X-linked AP1S2 gene in the original Pettigrew syndrome family using X-chromosome exome sequencing. We report additional phenotype details for several of the affected individuals, allowing us to further refine the phenotype corresponding to this X-linked intellectual disability syndrome. The AP1S2 c.426+1 G>T mutation segregates with the disease in the Pettigrew syndrome family and results in loss of 46 amino acids in the clathrin adaptor complex small chain domain that spans most of the AP1S2 protein sequence. The mutation reported here in AP1S2 is the first mutation that is not predicted to cause a premature termination of the coding sequence or absence of the AP1S2 protein. Although most of the families affected by a mutation in AP1S2 were initially described as having different disorders assigned to at least three different OMIM numbers (MIM 300629, 300630 and 304340), our analysis of the phenotype shows that they are all the same syndrome with recognition complicated by highly variable expressivity that is seen within as well as between families and is probably not explained by differences in mutation severity. PMID:23756445

Symbrachydactyly in Turner's syndrome.

PubMed

De Smet, L; Fryns, J P

1995-01-01

In the report we describe the occurrence of symbrachydactyly of the right hand in an adult female with Turner syndrome and classical 45,X karyotype. Symbrachydactyly is a unilateral and sporadic hand malformation. The pathogenesis may be part of an arterial vascular disruption sequence, possibly secondary to fetal oedema which is an important and frequent symptom in the prenatal development of Turner syndrome foetusses.

Noonan syndrome

PubMed Central

Roberts, Amy E; Allanson, Judith E; Tartaglia, Marco; Gelb, Bruce D

2014-01-01

Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS–MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype–phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments. PMID:23312968

Stress failure of pulmonary capillaries: role in lung and heart disease

NASA Technical Reports Server (NTRS)

West, J. B.; Mathieu-Costello, O.

1992-01-01

Pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently it has been shown that the wall stresses become very large when the capillary pressure is raised, and in anaesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mm Hg and above. The changes include breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. The strength of the thin part of the capillary wall can be attributed to the type IV collagen in the extracellular matrix. Stress failure of pulmonary capillaries results in a high-permeability form of oedema, or even frank haemorrhage, and is apparently the mechanism of neurogenic pulmonary oedema and high-altitude pulmonary oedema. It also explains the exercise-induced pulmonary haemorrhage that occurs in all racehorses. Several features of mitral stenosis are consistent with stress failure. Overinflation of the lung also leads to stress failure, a common cause of increased capillary permeability in the intensive care environment. Stress failure also occurs if the type IV collagen of the capillary wall is weakened by autoantibodies as in Goodpasture's syndrome. Neutrophil elastase degrades type IV collagen and this may be the starting point of the breakdown of alveolar walls that is characteristic of emphysema. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in lung and heart disease.

Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature.

PubMed

Kawame, H; Sugio, Y; Fuyama, Y; Hayashi, Y; Suzuki, H; Kurosawa, K; Maekawa, K

1999-01-01

We report a male infant with multiple congenital anomalies and mosaic variegated aneuploidy; a rare cytogenetic abnormality characterized by mosaicism for several different aneuploidies involving many different chromosomes. He had prenatal-onset growth retardation, microcephaly, dysmorphic face, seizures, hypotonia, feeding difficulty, and developmental delay. In addition, he developed bilateral Wilms tumors. Neuroradiological examination revealed Dandy-Walker malformation and hypoplasia of the cerebral hemisphere and pons. Cytogenetic analysis revealed various multiple numerical aneuploidies in blood lymphocytes, fibroblasts, and bone marrow cells, together with premature centromere division (PCD). Peripheral blood chromosome analysis from his parents also showed PCD, but no aneuploid cells. The clinical phenotype and multiple aneuploidies of the patient may be a consequence of the homozygous PCD trait inherited from his parents. Comparison with previously reported cases of multiple aneuploidy suggests that mosaic variegated aneuploidy with PCD may be a clinically recognizable syndrome with major phenotypes being mental retardation, microcephaly, structural brain anomalies (including Dandy-Walker malformation), and possible cancer predisposition.

The short arm deletion syndrome of chromosome 4 (4p- syndrome).

PubMed

Zellweger, H; Bardach, J; Bordwell, J; Williams, K

1975-01-01

Partial deletion of the short arm of chromosome 4 (4p-) represents another (rare) cause of cleft lip and cleft palate. Further characteristic manifestations of the syndrome (also called Wolf or Wolf-Hirschhorn syndrome) are growth failure, microcephaly, prominent glabella, hypertelorism, beaked nose, poorly differentiated and low set ears, cardiac and renal malformation and hypospadias. Life expectancy is often shortened. The 4p- syndrome has many features in common with another deletion syndrome, the cri-du-chat syndrome, and also with the Smith-Lemli-Opitz syndrome. The latter is a hereditary condition with normal karyotype. The cri-du-chat syndrome is characterized by a peculiar high-pitched, mewing cry and can be differentiated from the Wolf syndrome by the different staining characteristics (banding) of chromosomes 4 and 5.

Loss-of-function variants in NFIA provide further support that NFIA is a critical gene in 1p32-p31 deletion syndrome: A four patient series.

PubMed

Revah-Politi, Anya; Ganapathi, Mythily; Bier, Louise; Cho, Megan T; Goldstein, David B; Hemati, Parisa; Iglesias, Alejandro; Juusola, Jane; Pappas, John; Petrovski, Slavé; Wilson, Ashley L; Aggarwal, Vimla S; Anyane-Yeboa, Kwame

2017-12-01

The association between 1p32-p31 contiguous gene deletions and a distinct phenotype that includes anomalies of the corpus callosum, ventriculomegaly, developmental delay, seizures, and dysmorphic features has been long recognized and described. Recently, the observation of overlapping phenotypes in patients with chromosome translocations that disrupt NFIA (Nuclear factor I/A), a gene within this deleted region, and NFIA intragenic deletions has led to the hypothesis that NFIA is a critical gene within this region. The wide application and increasing accessibility of whole exome sequencing (WES) has helped identify new cases to support this hypothesis. Here, we describe four patients with loss-of-function variants in the NFIA gene identified through WES. The clinical presentation of these patients significantly overlaps with the phenotype described in previously reported cases of 1p32-p31 deletion syndrome, NFIA gene disruptions and intragenic NFIA deletions. Our cohort includes a mother and daughter as well as an unrelated individual who share the same nonsense variant (c.205C>T, p.Arg69Ter; NM_001145512.1). We also report a patient with a frameshift NFIA variant (c.159_160dupCC, p.Gln54ProfsTer49). We have compared published cases of 1p32-p31 microdeletion syndrome, translocations resulting in NFIA gene disruption, intragenic deletions, and loss-of-function mutations (including our four patients) to reveal that abnormalities of the corpus callosum, ventriculomegaly/hydrocephalus, macrocephaly, Chiari I malformation, dysmorphic features, developmental delay, hypotonia, and urinary tract defects are common findings. The consistent overlap in clinical presentation provides further evidence of the critical role of NFIA haploinsufficiency in the development of the 1p32-p31 microdeletion syndrome phenotype. © 2017 Wiley Periodicals, Inc.

RAS signalling in energy metabolism and rare human diseases.

PubMed

Dard, L; Bellance, N; Lacombe, D; Rossignol, R

2018-05-08

The RAS pathway is a highly conserved cascade of protein-protein interactions and phosphorylation that is at the heart of signalling networks that govern proliferation, differentiation and cell survival. Recent findings indicate that the RAS pathway plays a role in the regulation of energy metabolism via the control of mitochondrial form and function but little is known on the participation of this effect in RAS-related rare human genetic diseases. Germline mutations that hyperactivate the RAS pathway have been discovered and linked to human developmental disorders that are known as RASopathies. Individuals with RASopathies, which are estimated to affect approximately 1/1000 human birth, share many overlapping characteristics, including cardiac malformations, short stature, neurocognitive impairment, craniofacial dysmorphy, cutaneous, musculoskeletal, and ocular abnormalities, hypotonia and a predisposition to developing cancer. Since the identification of the first RASopathy, type 1 neurofibromatosis (NF1), which is caused by the inactivation of neurofibromin 1, several other syndromes have been associated with mutations in the core components of the RAS-MAPK pathway. These syndromes include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), which was formerly called LEOPARD syndrome, Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), Legius syndrome (LS) and capillary malformation-arteriovenous malformation syndrome (CM-AVM). Here, we review current knowledge about the bioenergetics of the RASopathies and discuss the molecular control of energy homeostasis and mitochondrial physiology by the RAS pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional Connectivity and Genetic Profile of a “Double-Cortex”-Like Malformation

PubMed Central

Sprugnoli, Giulia; Vatti, Giampaolo; Rossi, Simone; Cerase, Alfonso; Renieri, Alessandra; Mencarelli, Maria A.; Zara, Federico; Rossi, Alessandro; Santarnecchi, Emiliano

2018-01-01

Laminar heterotopia is a rare condition consisting in an extra layer of gray matter under properly migrated cortex; it configures an atypical presentation of periventricular nodular heterotopia (PNH) or a double cortex (DC) syndrome. We conducted an original functional MRI (fMRI) analysis in a drug-resistant epilepsy patient with “double-cortex”-like malformation to reveal her functional connectivity (FC) as well as a wide genetic analysis to identify possible genetic substrates. Heterotopias were segmented into region of interests (ROIs), whose voxel-wise FC was compared to that of (i) its normally migrated counterpart, (ii) its contralateral homologous, and (iii) those of 30 age-matched healthy controls. Extensive genetic analysis was conducted to screen cortical malformations-associated genes. Compared to healthy controls, both laminar heterotopias and the overlying cortex showed significant reduction of FC with the contralateral hemisphere. Two heterozygous variants of uncertain clinical significance were found, involving autosomal recessive disease-causing genes, FAT4 and COL18A1. This first FC analysis of a unique case of “double-cortex”-like malformation revealed a hemispheric connectivity segregation both in the laminar cortex as in the correctly migrated one, with a new pattern of genes’ mutations. Our study suggests the altered FC could have an electrophysiological and functional impact on large-scale brain networks, and the involvement of not yet identified genes in “double-cortex”-like malformation with a possible role of rare variants in recessive genes as pathogenic cofactors. PMID:29946244

Brainstem and cerebellar cavernous malformations.

PubMed

Atwal, Gursant S; Sarris, Christina E; Spetzler, Robert F

2017-01-01

Cavernous malformations are vascular lesions that occur throughout the central nervous system, most commonly in the supratentorial location, with brainstem and cerebellar cavernous malformations occurring more rarely. Cavernous malformations are associated with developmental venous anomalies that occur sporadically or in familial form. Patients with a cavernous malformation can present with headaches, seizures, sensorimotor disturbances, or focal neurologic deficits based on the anatomic location of the lesion. Patients with infratentorial lesions present more commonly with a focal neurologic deficit. Cavernous malformations are increasingly discovered incidentally due to the increasing use of magnetic resonance imaging. Understanding the natural history of these lesions is essential to their management. Observation and surgical resection are both reasonable options in the treatment of patients with these lesions. The clinical presentation of the patient, the location of the lesion, and the surgical risk assessment all play critical roles in management decision-making. © 2017 Elsevier B.V. All rights reserved.

Congenital heart defects and extracardiac malformations.

PubMed

Rosa, Rosana Cardoso M; Rosa, Rafael Fabiano M; Zen, Paulo Ricardo G; Paskulin, Giorgio Adriano

2013-06-01

To review the association between congenital heart defects and extracardiac malformations. Scientific articles were searched in the Medline, Lilacs, and SciELO databases, using the descriptors "congenital heart disease," "congenital heart defects," "congenital cardiac malformations," "extracardiac defects," and "extracardiac malformations." All case series that specifically explored the association between congenital heart defects and extracardiac malformations were included. Congenital heart diseases are responsible for about 40% of birth defects, being one of the most common and severe malformations. Extracardiac malformations are observed in 7 to 50% of the patients with congenital heart disease, bringing a greater risk of comorbidity and mortality and increasing the risks related to heart surgery. Different studies have attempted to assess the presence of extracardiac abnormalities in patients with congenital heart disease. Among the changes described, those of the urinary tract are more often reported. However, no study has evaluated all patients in the same way. Extracardiac abnormalities are frequent among patients with congenital heart disease, and patients with these alterations may present an increased risk of morbimortality. Therefore, some authors have been discussing the importance and cost-effectiveness of screening these children for other malformations by complementary exams.

Pathogenesis, Epidemiology, Diagnosis and Clinical Aspects of Smith-Lemli-Opitz Syndrome

PubMed Central

Bianconi, Simona E.; Cross, Joanna L.; Wassif, Christopher A.; Porter, Forbes D.

2015-01-01

Introduction Smith-Lemli-Opitz Syndrome (SLOS) is a malformation syndrome inherited in an autosomal recessive fashion. It is due to a metabolic defect in the conversion of 7-dehydrocholesterol to cholesterol, which leads to an accumulation of 7-dehydrocholesterol and frequently a deficiency of cholesterol. The syndrome is characterized by typical dysmorphic facial features, multiple malformations, and intellectual disability. Areas covered In this paper we provide an overview of the clinical phenotype and discuss how the manifestations of the syndrome vary depending on the age of the patients. We then explore the underlying biochemical defect and pathophysiological alterations that may contribute to the many disease manifestations. Subsequently we explore the epidemiology and succinctly discuss population genetics as they relate to SLOS. The next section presents the diagnostic possibilities. Thereafter, the treatment and management as is standard of care are presented. Expert opinion Even though the knowledge of the underlying molecular mutations and the biochemical alterations is being rapidly accumulated, there is currently no efficacious therapy addressing neurological dysfunction. We discuss the difficulty of treating this disorder, which manifests as a combination of a malformation syndrome and an inborn error of metabolism. A very important factor in developing new therapies is the need to rigorously establish efficacy in controlled trials. PMID:25734025

De novo interstitial deletion of 3q22.3-q25.2 encompassing FOXL2, ATR, ZIC1, and ZIC4 in a patient with blepharophimosis/ptosis/epicanthus inversus syndrome, Dandy-Walker malformation, and global developmental delay.

PubMed

Lim, Byung Chan; Park, Woong Yang; Seo, Eul-Ju; Kim, Ki Joong; Hwang, Yong Seung; Chae, Jong Hee

2011-05-01

We report a case carrying a de novo interstitial deletion of chromosome 3q22-q25. The clinical phenotype of this case included blepharophimosis/ptosis/epicanthus inversus syndrome, Dandy-Walker malformation, and global developmental delay. Contiguous heterozygous deletion of FOXL2, ATR, ZIC1, and ZIC4 was postulated as the causative mechanism of the clinical phenotype. The association of blepharophimosis, ptosis, and epicanthus inversus syndrome with developmental delay or mental retardation may be an indication for the use of brain imaging and chromosomal analysis capable of detecting chromosomal rearrangements encompassing several candidate genes.

Familial renal-hepatic-pancreatic dysplasia and Dandy-Walker cyst: a distinct syndrome?

PubMed

Hunter, A G; Jimenez, C; Tawagi, F G

1991-11-01

Ivemark et al. first described sibs with renal-hepatic-pancreatic dysplasia (RHPD) (Ivemark BI, Oldfelt V, Zetterström R (1959): Acta Pediatr Scand 48: 1-11). Subsequent reports of affected individuals have described additional malformations and syndromes associated with RHPD. In this paper we describe 2 sibs with RHPD in association with Dandy-Walker cyst (DW). Through an examination of the pattern of associated malformations seen in RHPD we argue that RHPD-DW is a distinct monogenetic syndrome, and not an association.

Otologic manifestations of Larsen syndrome.

PubMed

Marques, Letícia Helena de Sousa; Martins, Daniela Vieira; Juares, Gabriel Liria; Lorenzetti, Fábio Tadeu Moura; Monsanto, Rafael da Costa

2017-10-01

To describe and discuss otologic manifestations of Larsen syndrome, based on a case report and a systematic review of the literature. We performed a PubMED database search, and we selected studies reporting otolaryngologic manifestations secondary to Larsen syndrome. The selected articles were read in full, and three researchers independently extracted data from the studies. In parallel, we report the case of a 14-year-old patient who had hearing loss secondary to Larsen syndrome. Fifteen studies met our selection criteria. Seven studies reported hearing loss in patients with Larsen syndrome (4 had conductive hearing loss and 3 had mixed hearing loss). The conductive hearing loss may be secondary to ossicular malformations and/or middle ear effusions. Other causes for conductive hearing loss are mesenchymal remnants in the middle ear, Eustachian tube dysfunction, and cleft palate. Surgical management of the hearing loss is possible in selected cases, although the surgical and anesthetic risks should be considered. Hearing aids seem to be safe and effective treatment options for the hearing loss secondary to Larsen syndrome. Although rare, patients with Larsen syndrome may have hearing loss. The most frequent type of deficit is conductive, either secondary to malformation of the ossicles or middle ear effusion. Possible surgical correction of these abnormalities should be weighed against the anesthetic risks of these patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Neurobehavioral development in Joubert syndrome.

PubMed

Gitten, J; Dede, D; Fennell, E; Quisling, R; Maria, B L

1998-08-01

Research on children with Joubert syndrome has focused on brain structural abnormalities and associated clinical symptoms. The degree of developmental delay has not been objectively reported. We investigated the neurobehavioral development of children with Joubert syndrome through neurobehavioral assessment in the largest sample to date. Thirty-two parents of children with Joubert syndrome completed the Child Development Inventory and magnetic resonance imaging (MRI) data was gathered on 17 of these children. Results indicate that 94% were severely impaired according to the Child Development Inventory, with age being positively correlated with degree of neurobehavioral impairment. The average developmental age of our sample was 19 months (63% below chronological age). Severity of illness as measured by the General Development scale of the Child Development Inventory and severity of illness as measured by MRI (overall severity rating) did not yield consistent data regarding severity of the midbrain and cerebellar malformations. Similarly, markers of abnormal cerebral development such as cortical atrophy and delayed myelination were independent of severity of illness ratings on the Child Development Inventory. The degree of developmental delay in Joubert syndrome and the severity of gross central nervous system malformations appear independent.

Kabuki syndrome: expanding the phenotype to include microphthalmia and anophthalmia.

PubMed

McVeigh, Terri P; Banka, Siddharth; Reardon, William

2015-10-01

Kabuki syndrome is a rare genetic malformation syndrome that is characterized by distinct facies, structural defects and intellectual disability. Kabuki syndrome may be caused by mutations in one of two histone methyltransferase genes: KMT2D and KDM6A. We describe a male child of nonconsanguineous Irish parents presenting with multiple malformations, including bilateral extreme microphthalmia; cleft palate; congenital diaphragmatic hernia; duplex kidney; as well as facial features of Kabuki syndrome, including interrupted eyebrows and lower lid ectropion. A de-novo germline mutation in KMT2D was identified. Whole-exome sequencing failed to reveal mutations in any of the known microphthalmia/anopthalmia genes. We also identified four other patients with Kabuki syndrome and microphthalmia. We postulate that Kabuki syndrome may produce this type of ocular phenotype as a result of extensive interaction between KMT2D, WAR complex proteins and PAXIP1. Children presenting with microphthalmia/anophthalmia should be examined closely for other signs of Kabuki syndrome, especially at an age where the facial gestalt might be less readily appreciable.

Cerebellar and Brainstem Malformations.

PubMed

Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

2016-08-01

The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa. A wide spectrum of cerebellar and brainstem malformations has been shown. Familiarity with the spectrum of cerebellar and brainstem malformations and their well-defined diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and correct genetic counseling. This article discusses cerebellar and brainstem malformations, with emphasis on neuroimaging findings (including diagnostic criteria), neurologic presentation, systemic involvement, prognosis, and recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Pediatric neuroanesthesia. Arteriovenous malformations.

PubMed

Newfield, P; Hamid, R K

2001-06-01

Intracranial arteriovenous malformations can occur singly, multiply, and in conjunction with aneurysms and denovo, family, or in conjunction with connective-tissue disorders. Intracranial hemorrhage is the most common presentation, occurring in 20% to 50% of cases. In children, seizures are the second most common presentation occurring in 15% to 20% of cases. The modalities available treatment of arteriovenous malformations are microsurgery, embolization, and stereotactic radiosurgery with heavy particles, alpha knife, or linear accelerator. Induction, maintenance, and emergence from anesthesia are designed to prevent rupture of arteriovenous malformation and aneurysm and to improve intracranial compliance in the presence of an intracranial hematoma, during both diagnostic (CT, MR scanning) and therapeutic procedures.

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations

PubMed Central

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M.; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders. PMID:24782720

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations.

PubMed

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders.

CT of the ear in Pendred syndrome.

PubMed

Goldfeld, Moshe; Glaser, Benjamin; Nassir, Elias; Gomori, John Moshe; Hazani, Elitsur; Bishara, Nassir

2005-05-01

To prospectively determine the structural anomalies of the inner ear by using thin-section computed tomography (CT) in an extended family with Pendred syndrome. Ethics committee approved the study, and informed consent was obtained from every patient or from parents of patients under legal age. Twelve patients (three females and nine males aged 7-47 years) with Pendred syndrome (all from the same ethnic isolate and with the same mutation in the PDS gene) were evaluated for inner-ear malformation at thin-section CT. Both ears were evaluated. Presence or absence of interscalar septum between upper and middle turns of the cochlea was evaluated, and vestibule and vestibular aqueduct were examined for enlargement. Modiolus was determined to be present or absent (modiolar deficiency). CT scans were evaluated in consensus by two radiologists (M.G., J.M.G.). All patients had inner ear malformation on both sides. Modiolus was absent and vestibule was enlarged on both sides in all 12 patients. Interscalar septum was absent in 18 (75%) of 24 ears. In eight patients, interscalar septum was absent in both ears, whereas in two patients, it was absent on only one side. Aqueduct was enlarged in 20 (80%) of 24 ears. In nine patients, both ears had enlarged aqueducts, while in two patients, only one side was abnormal. Inner ear malformation is an invariable finding in Pendred syndrome. Modiolus deficiency and vestibular enlargement were the most consistent anomalies in this population with Pendred syndrome. (c) RSNA, 2005.

[Fetal malformations and chromosome abnormalities diagnosed at the Center of Prenatal Diagnosis of the University of Aquila in the 1995-1998 triennium].

PubMed

Carta, G; Iovenitti, P; D'Alfonso, A; Mascaretti, G; Moscarini, M

1999-10-01

Over the past few years numerous techniques have been developed, allowing an evaluation of fetal physiopathology that was unthinkable until recently. The authors describe 20 cases of fetal malformations and chromosomal abnormalities diagnosed by scan and amniocentesis at the Centre for Diagnosis and Obstetric Prophylaxis at L'Aquila University. Between January 1995 and April 1998 a total of 1180 amniocentesis and 4000 obstetric scans were performed in a group of 1650 pregnant women. Of the patients examined using ultrasound scan, 8 presented manifest fetal pathologies, of which 5 were associated with chromosome abnormalities: 1) left ventricular hypoplasia, common atrium, tricuspid dysplasia; 2) omphalocele; 3) Morgagni-Stewart-Morel syndrome; 4) plurilobate cystic hygroma; 5) duodenal atresia; 6) Dandy-Walker syndrome; 7) cystic hygroma and hydrops; 8) cystic hygroma, hydrops, cardiopathy and Dandy-Walker syndrome. Among the pregnant women undergoing amniocentesis without a prior diagnosis of fetal malformation, 12 presented pathological fetal karyotypes: 2 cases of Turner's syndrome; 2 cases of Edward's syndrome; 2 cases of Klinefelter's syndrome, of deletion of a stretch of chromosome 8; 1 case of Down's syndrome; 2 cases of supernumerary marker chromosome; 1 twin pregnancy with Klinefelter's syndrome in one twin and paracentric inversion of chromosome 13 in the other; 1 twin pregnancy with a small supernumerary marker chromosome in both twins. Ultrasonography often enables the diagnosis of congenital abnormalities not associated with chromosome pathologies. However, karyotype studies play an essential role in pregnancies with a high genetic risk.

Headache in children with Chiari I malformation.

PubMed

Toldo, Irene; Tangari, Marta; Mardari, Rodica; Perissinotto, Egle; Sartori, Stefano; Gatta, Michela; Calderone, Milena; Battistella, Pier Antonio

2014-05-01

Headache is the most common symptom of Chiari 1 malformation, a condition characterized by the herniation of cerebellar tonsils through the foramen magnum. However, the headache pattern of cases with Chiari 1 malformations is not well defined in the literature, especially in children. The aim of this retrospective chart review was to evaluate the frequency and the characteristics of headache in children with Chiari 1 malformation at initial evaluation and during follow up. Forty-five cases with tonsillar ectopia were selected among 9947 cases under 18 years of age who underwent neuroimaging between 2002 and 2010. A semistructured clinical interview (mean follow-up: 5.2 years) was conducted. Headache was classified according to the second edition of the International Classification of Headache Disorders. Possible associations between clinical picture, in particular headache pattern, but also other signs and symptoms attributable to Chiari 1 malformation, and the extent of tonsillar ectopia were found for 3 different groups: those with borderline (<5 mm, N = 12), mild (5-9 mm, N = 27), and severe tonsillar ectopia (≥10 mm, N = 6), respectively. Twenty-four out of 33 (73%) cases with Chiari 1 malformation complained of headache, and 9/33 (27%) of those patients (5 with mild and 4 with severe tonsillar ectopia) reported headache attributed to Chiari 1 malformation. In our studied pediatric population, the most common symptom for cases diagnosed with Chiari 1 malformation was headache, and headache attributed to Chiari 1 malformation was the most common headache pattern in patients with Chiari 1 malformation. The presence of headache attributed to Chiari 1 malformation along with 3 other signs or symptoms of Chiari 1 malformation were highly predictive of severe tonsillar ectopia. © 2014 American Headache Society.

Malformations among 289,365 Births Attributed to Mutations with Autosomal Dominant and Recessive and X-Linked Inheritance.

PubMed

Toufaily, M Hassan; Westgate, Marie-Noel; Nasri, Hanah; Holmes, Lewis B

2018-01-01

The number of malformations attributed to mutations with autosomal or X-linked patterns of inheritance has increased steadily since the cataloging began in the 1960s. These diagnoses have been based primarily on the pattern of phenotypic features among close relatives. A malformations surveillance program conducted in consecutive pregnancies can identify both known and "new" hereditary disorders. The Active Malformations Surveillance Program was carried out among 289,365 births over 41 years (1972-2012) at Brigham and Women's Hospital in Boston. The findings recorded by examining pediatricians and all consultants were reviewed by study clinicians to establish the most likely diagnoses. The findings in laboratory testing in the newborn period were reviewed, as well. One hundred ninety-six (0.06%) infants among 289,365 births had a malformation or malformation syndrome that was attributed to Mendelian inheritance. A total of 133 (68%) of the hereditary malformations were attributed to autosomal dominant inheritance, with 94 (71%) attributed to apparent spontaneous mutations. Forty-six (23%) were attributed to mutations with autosomal recessive inheritance, 17 associated with consanguinity. Seventeen (9%) were attributed to X-linked inheritance. Fifteen novel familial phenotypes were identified. The family histories showed that most (53 to 71%) of the affected infants were born, as a surprise, to healthy, unaffected parents. It is important for clinicians to discuss with surprised healthy parents how they can have an infant with an hereditary condition. Future studies, using DNA samples from consecutive populations of infants with malformations and whole genome sequencing, will identify many more mutations in loci associated with mendelizing phenotypes. Birth Defects Research 110:92-97, 2018.© 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Multifocal demyelinating motor neuropathy and hamartoma syndrome associated with a de novo PTEN mutation.

PubMed

Bansagi, Boglarka; Phan, Vietxuan; Baker, Mark R; O'Sullivan, Julia; Jennings, Matthew J; Whittaker, Roger G; Müller, Juliane S; Duff, Jennifer; Griffin, Helen; Miller, James A L; Gorman, Grainne S; Lochmüller, Hanns; Chinnery, Patrick F; Roos, Andreas; Swan, Laura E; Horvath, Rita

2018-05-22

To describe a patient with a multifocal demyelinating motor neuropathy with onset in childhood and a mutation in phosphatase and tensin homolog ( PTEN ), a tumor suppressor gene associated with inherited tumor susceptibility conditions, macrocephaly, autism, ataxia, tremor, and epilepsy. Functional implications of this protein have been investigated in Parkinson and Alzheimer diseases. We performed whole-exome sequencing in the patient's genomic DNA validated by Sanger sequencing. Immunoblotting, in vitro enzymatic assay, and label-free shotgun proteomic profiling were performed in the patient's fibroblasts. The predominant clinical presentation of the patient was a childhood onset, asymmetric progressive multifocal motor neuropathy. In addition, he presented with macrocephaly, autism spectrum disorder, and skin hamartomas, considered as clinical criteria for PTEN-related hamartoma tumor syndrome. Extensive tumor screening did not detect any malignancies. We detected a novel de novo heterozygous c.269T>C, p.(Phe90Ser) PTEN variant, which was absent in both parents. The pathogenicity of the variant is supported by altered expression of several PTEN-associated proteins involved in tumorigenesis. Moreover, fibroblasts showed a defect in catalytic activity of PTEN against the secondary substrate, phosphatidylinositol 3,4-trisphosphate. In support of our findings, focal hypermyelination leading to peripheral neuropathy has been reported in PTEN-deficient mice. We describe a novel phenotype, PTEN-associated multifocal demyelinating motor neuropathy with a skin hamartoma syndrome. A similar mechanism may potentially underlie other forms of Charcot-Marie-Tooth disease with involvement of the phosphatidylinositol pathway. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Sotos syndrome

PubMed Central

Baujat, Geneviève; Cormier-Daire, Valérie

2007-01-01

Sotos syndrome is an overgrowth condition characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty, and associated with variable minor features. The exact prevalence remains unknown but hundreds of cases have been reported. The diagnosis is usually suspected after birth because of excessive height and occipitofrontal circumference (OFC), advanced bone age, neonatal complications including hypotonia and feeding difficulties, and facial gestalt. Other inconstant clinical abnormalities include scoliosis, cardiac and genitourinary anomalies, seizures and brisk deep tendon reflexes. Variable delays in cognitive and motor development are also observed. The syndrome may also be associated with an increased risk of tumors. Mutations and deletions of the NSD1 gene (located at chromosome 5q35 and coding for a histone methyltransferase implicated in transcriptional regulation) are responsible for more than 75% of cases. FISH analysis, MLPA or multiplex quantitative PCR allow the detection of total/partial NSD1 deletions, and direct sequencing allows detection of NSD1 mutations. The large majority of NSD1 abnormalities occur de novo and there are very few familial cases. Although most cases are sporadic, several reports of autosomal dominant inheritance have been described. Germline mosaicism has never been reported and the recurrence risk for normal parents is very low (<1%). The main differential diagnoses are Weaver syndrome, Beckwith-Wiedeman syndrome, Fragile X syndrome, Simpson-Golabi-Behmel syndrome and 22qter deletion syndrome. Management is multidisciplinary. During the neonatal period, therapies are mostly symptomatic, including phototherapy in case of jaundice, treatment of the feeding difficulties and gastroesophageal reflux, and detection and treatment of hypoglycemia. General pediatric follow-up is important during the first years of life to allow detection

Genetics Home Reference: ophthalmo-acromelic syndrome

MedlinePlus

... The eyes are often absent or severely underdeveloped (anophthalmia), or they may be abnormally small ( microphthalmia ). Usually ... limbs, and eyes. These changes likely underlie the anophthalmia and skeletal malformations of ophthalmo-acromelic syndrome . It ...

Extensive comedonal and cystic acne in Patau syndrome.

PubMed

Torrelo, Antonio; Fernandez-Crehuet, Pablo; Del Prado, Elena; Martes, Pilar; Hernández-Martín, Angela; De Diego, Verónica; Carapeto, Francisco

2010-01-01

Patau syndrome is a chromosomal disorder associated with multiple malformations caused by inheritance of an extra chromosome (trisomy 13). Some skin defects have been reported in patients with Patau syndrome, such as scalp defects, glabellar stains, deep palmar creases, rocker-bottom feet, convex soles, hyperconvextity of the nails, and multiple hemangiomas. To our knowledge, widespread comedonal and cystic acne have not been previously reported in Patau syndrome.

Capillary Structures for Exploration Life Support (Capillary Structures)

NASA Image and Video Library

2017-07-10

iss052e013146 (July 10, 2017) --- Astronaut Jack Fischer is photographed during setup of hardware for the Capillary Structures for Exploration Life Support (Capillary Structures) two sorbent demonstrations. The Capillary Structures for Exploration Life Support (Capillary Structures) investigation studies a new method using structures of specific shapes to manage fluid and gas mixtures. The investigation studies water recycling and carbon dioxide removal, benefiting future efforts to design lightweight, more reliable life support systems for future space missions.

Somatic KRAS mutation in an infant with linear nevus sebaceous syndrome associated with lymphatic malformations: A case report and literature review.

PubMed

Lihua, Jiang; Feng, Gao; Shanshan, Mao; Jialu, Xu; Kewen, Jiang

2017-11-01

Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous syndrome, characterized by nevus sebaceous,central nervous system (CNS), ocular and skeletal abnormalities. The present study describes KRAS somatic mosaic mutation in a case of LNSS with lymphatic malformations (LMs). A 4-month-old female with a clinical diagnosis of LNSS presented with infantile spasms, mental retardation, skull dysplasia, ocular abnormalities, congenital atrial septal defect, and LMs. Cervical ultrasonography revealed a 4.6 × 4.6 × 2.2cm no echo packet with clear boundary in the subcutaneous tissues of the right neck. The neck MRI indicated a cyst in the subcutaneous tissues of the right neck. Whole-exome sequencing revealed a low-level heterozygous mutation of the KRAS gene (c.35C > T; p.G12D, 19%) in the skin lesion sample. This mutation was not present in the blood samples of the patient and her parents. The patient received sclerotherapy with paicibanil (OK-432) injection for the cyst. Following 1 year of treatment, the patient exhibited fewer seizures. The mental and motor development was significantly improved. The patient can currently walk with assistance and speak simple words. LNSS is a rare, congenital neurocutaneous syndrome consisting of a spectrum of abnormalities involving the skin, central nervous system, eyes, LMs and other systems. LNSS can be caused by postzygotic somatic mutation in the RAS family of genes. Multidisciplinary evaluation and treatment is needed. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3.

PubMed

Lezirovitz, Karina; Maestrelli, Sylvia Regina Pedrosa; Cotrim, Nelson Henderson; Otto, Paulo A; Pearson, Peter L; Mingroni-Netto, Regina Celia

2008-07-01

Split-hand/foot malformation (SHFM) associated with aplasia of long bones, SHFLD syndrome or Tibial hemimelia-ectrodactyly syndrome is a rare condition with autosomal dominant inheritance, reduced penetrance and an incidence estimated to be about 1 in 1,000,000 liveborns. To date, three chromosomal regions have been reported as strong candidates for harboring SHFLD syndrome genes: 1q42.2-q43, 6q14.1 and 2q14.2. We characterized the phenotype of nine affected individuals from a large family with the aim of mapping the causative gene. Among the nine affected patients, four had only SHFM of the hands and no tibial defects, three had both defects and two had only unilateral tibial hemimelia. In keeping with previous publications of this and other families, there was clear evidence of both variable expression and incomplete penetrance, the latter bearing hallmarks of anticipation. Segregation analysis and multipoint Lod scores calculations (maximum Lod score of 5.03 using the LINKMAP software) using all potentially informative family members, both affected and unaffected, identified the chromosomal region 17p13.1-17p13.3 as the best and only candidate for harboring a novel mutated gene responsible for the syndrome in this family. The candidate gene CRK located within this region was sequenced but no pathogenic mutation was detected.

[Klippel-Feil syndrome with tracheoesophageal fistula, bifid thumb and cerebral angiolipoma.

PubMed

Urdaneta Carruyo, Eliéxer; Rojas Zerpa, Gustavo; Urdaneta Contreras, Adriana; Maldonado Alviarez, Malvy; Brito Rodríguez, Miguel

2016-12-01

The Klippel-Feil syndrome is a congenital malformation of the skull flap involving complex cervical vertebrae and organs, characterized by a classic triad: short neck, limitation of movement of the head due to cervical spine fusion and low hairline in occipital region. It results from an error in the axial skeleton segmentation of the embryo; its incidence is estimated at 1/40,000-42,000 births and predominates in females. The aim of this paper is to describe the clinical picture of a patient with Klippel-Feil syndrome and multiple malformations, including tracheoesophageal fistula, bifid thumb and intracranial lipomas/angiolipomas,that have not been previously described in the syndrome, so it is considered an exceptional finding. Sociedad Argentina de Pediatría.

Baraitser and Winter syndrome with growth hormone deficiency.

PubMed

Chentli, Farida; Zellagui, Hadjer

2014-01-01

Baraitser-Winter syndrome (BWS), first reported in 1988, is apparently due to genetic abnormalities that are still not well-defined, although many gene abnormalities are already discovered and de novo missense changes in the cytoplasmic actin-encoding genes (called ACTB and ACTG1) have been recently discovered. The syndrome combines facial and cerebral malformations. Facial malformations totally or partially present in the same patient are: Iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, and prominent epicanthic folds. The various brain malformations are probably responsible for growth and mental retardation. To the best of our knowledge, the syndrome is very rare as few cases have been reported so far. Our aim was to describe a child with a phenotype that looks like BWS with proved partial growth hormone (GH) deficiency which was not reported before. A girl aged 7-year-old of consanguineous parents was referred for short stature and mental retardation. Clinical examination showed dwarfism and a delay in her mental development. Other clinical features included: Strabismus, epicanthic folds, broad nasal bridge, and brain anomalies such as lissencephaly, bilateral hygroma, and cerebral atrophy. Hormonal assessment showed partial GH deficiency without other endocrine disorders. Our case looks exactly like BWS. However, apart from facial and cerebral abnormalities, there is a partial GH deficiency which can explain the harmonious short stature. This case seems worth to be reported as it adds GH deficiency to the very rare syndrome.

[Congenital portosystemic shunt. The Abernethy malformation].

PubMed

Avila, L F; Luis, A L; Encinas, J L; Hernández, F; Olivares, P; Fernández Cuadrado, J; Hierro, L; Jara, P; López Santamaría, M; Tovar, J A

2006-10-01

Congenital portosystemic shunt (CEPS) is a rare condition that was first reported by John Abernethy in 1793. Two types of CEPS are described: type I (side to end anastomosis) or congenital absence of the portal vein, and type II (side to side anastomosis) with portal vein supply partially conserved. Type I CEPS is usually seen in girls and associates multiple malformations as polysplenia, malrotation, and cardiac anomalies. Type II is even rarer with no sex preference and no malformations associated. Hepatic encephalopathy is a common complication of both types in adulthood. Liver transplantation is the only effective treatment for symptomatic type I CEPS. A therapeutic approach for type II could be surgical closure of the shunt. To analyse our experience in diagnosis and management of portosystemic shunts. We report 4 cases of CEPS (3 type I and 1 type II) diagnosed between January-1997 and March-2005 in our department. We present 4 patients with ages at diagnosis ranging from 0 to 28 months, 3 type I CEPS (2 boys and 1 girl) and 1 boy type II. The type I girl was prenatally diagnosed at 12 weeks of gestation. Initial clinical signs in type 1 boys were splenomegaly and hypersplenism, both with normal pondo-statural growth. No polysplenia or cardiac anomalies were assessed. One of them presented mild developmental delay, dismorphic features and facial telangiectasias. He had normal coagulation tests with chronic hepatic dysfunction (high transaminases) and regenerative nodular lesions were seen by imaging techniques. The other type I patient had hypoprothrombinemia, tendency to capillary bleeding (haematomas and epistaxis) with preserved liver function. Both patients have developed mild portal hypertension and present steatosis signs at liver biopsy. The type I girl presents a 21 trisomy and associates a cardiac anomaly (interauricular communication). Her hepatic function test are normal but liver calcifications can be seen by ultrasound. Type II child associates

Synchronous Hepatoblastoma, Neuroblastoma, and Cutaneous Capillary Hemangiomas: A Case Report.

PubMed

Ozawa, Michael G; Cooney, Tabitha; Rangaswami, Arun; Hazard, Florette K

2016-01-01

Multiple synchronous tumors presenting in infancy raise concern for inherited or sporadic cancer predisposition syndromes, which include Beckwith-Wiedemann syndrome, familial adenomatous polyposis syndrome, and Li-Fraumeni syndrome. We report a case of a 7-month-old previously healthy male born following an in vitro fertilization-assisted twin pregnancy who presented with new-onset refractory shock, severe acidosis, and rapid decline over several hours. An autopsy revealed a ruptured liver involved by hepatoblastoma, an adrenal gland involved by neuroblastoma, and multiple cutaneous capillary hemangiomas. Standard genetic testing demonstrated that both twins were Gaucher disease (GD) carriers without evidence of other known cancer predisposition syndromes. This report describes a unique association of multiple synchronous tumors, which underscores the utility and importance of the pediatric autopsy. Moreover, given that the reported child was a GD carrier, the possibility the tumors were the result of a GD-mediated cancer-associated phenotype or an unrecognized sporadic clinical syndrome remains an unanswered, but intriguing, question worthy of further investigation.

Intestinal atresia, encephalocele, and cardiac malformations in infants with 47,XXX: Expansion of the phenotypic spectrum and a review of the literature.

PubMed

Bağci, Soyhan; Müller, Andreas; Franz, Axel; Heydweiller, Andreas; Berg, Christoph; Nöthen, Markus M; Bartmann, Peter; Reutter, Heiko

2010-01-01

Identification of the 47,XXX karyotype often occurs adventitiously during prenatal fetal karyotyping in cases of advanced maternal age. Although most females with 47,XXX appear healthy at birth, various types of congenital malformations have been reported, of which urinary tract anomalies are the most frequent. We report on 2 newborns with 47,XXX and congenital cardiac defects, one of whom had duodenal atresia and the other an occipital encephalocele. This expands the spectrum of malformations reported in association with the triple-X syndrome. We also present a review of the literature on non-urinary tract malformations in females with 47,XXX. We conclude that prenatal identification of the 47,XXX karyotype is an indication for detailed fetal ultrasonography which should include examination of multiple organ systems. Such prenatal screening for possible associated congenital malformations should help to ensure optimal perinatal clinical management of 47,XXX cases. 2010 S. Karger AG, Basel.

Management of the Amniotic Band Syndrome with Cleft Palate: Literature Review and Report of a Case

PubMed Central

Cortez-Ortega, Carolina; Flores-Velázquez, Joselín; Ruiz-Rodríguez, Socorro; Noyola-Frías, Miguel Ángel; Santos-Díaz, Miguel Ángel

2017-01-01

Amniotic Band Syndrome (ABS) is a group of congenital malformations that includes the majority of typical constriction rings and limb and digital amputations, together with major craniofacial, thoracic, and abdominal malformations. The syndrome is caused by early rupture of the amniotic sac. Some of the main oral manifestations include micrognathia, hyperdontia, and cleft lip with or without cleft palate, which is present in 14.6% of patients with this syndrome. The purpose of this report was to describe the clinical characteristics and the oral treatment provided to a 6-month-old male patient affected with ABS with cleft lip and palate. PMID:28246561

Pathogenesis of arteriovenous malformations in the absence of endoglin.

PubMed

Mahmoud, Marwa; Allinson, Kathleen R; Zhai, Zhenhua; Oakenfull, Rachael; Ghandi, Pranita; Adams, Ralf H; Fruttiger, Marcus; Arthur, Helen M

2010-04-30

Arteriovenous malformations (AVMs) result in anomalous direct blood flow between arteries and veins, bypassing the normal capillary bed. Depending on size and location, AVMs may lead to severe clinical effects including systemic cyanosis (pulmonary AVMs), hemorrhagic stroke (cerebral AVMs) and high output cardiac failure (hepatic AVMs). The factors leading to AVM formation are poorly understood, but patients with the familial disease hereditary hemorrhagic telangiectasia (HHT) develop AVMs at high frequency. As most HHT patients have mutations in ENG (endoglin) or ACVRL1 (activin receptor-like kinase 1), a better understanding of the role of these genes in vascular development is likely to reveal the etiology of AVM formation. Using a mouse with a conditional mutation in the Eng gene, we investigated the sequence of abnormal cellular events occurring during development of an AVM. In the absence of endoglin, subcutaneous Matrigel implants in adult mice were populated by reduced numbers of new blood vessels compared with controls, and resulted in local venous enlargement (venomegaly). To investigate abnormal vascular responses in more detail, we turned to the more readily accessible vasculature of the neonatal retina. Endoglin-deficient retinas exhibited delayed remodeling of the capillary plexus, increased proliferation of endothelial cells and localized AVMs. Muscularization of the resulting arteriovenous shunts appeared to be a secondary response to increased blood flow. AVMs develop when an angiogenic stimulus is combined with endoglin depletion. Moreover, AVM formation appears to result from the combination of delayed vascular remodeling and an inappropriate endothelial cell proliferation response in the absence of endoglin.

Longevity and Patau syndrome: what determines survival?

PubMed

Peroos, Sherina; Forsythe, Elizabeth; Pugh, Jennifer Harriet; Arthur-Farraj, Peter; Hodes, Deborah

2012-12-06

The authors report of an 8-year-old girl with non-mosaic Patau syndrome. The median life expectancy of Patau syndrome is 7-10 days, and 90% die in the first year of life. Survival is often attributed to mosaicism and the severity of associated malformations. We delineate the developing phenotype and review the literature discussing potential contributory factors to longevity.

Ultrasound features in trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) in a consecutive series of 47 cases.

PubMed

Kroes, I; Janssens, S; Defoort, P

2014-01-01

To determine and list the variety of the predominant appeal signs leading to referral and their accompanying features found during specialized ultrasound evaluation in foetuses with trisomy 13 and trisomy 18. In a period of thirty years, 1110 cases of foetal malformations were detected during specialized echographic evaluation. 47 Of these cases were foetuses with trisomy 13 or trisomy 18. We evaluated the predominant signs leading to referral, the difference and overlap in presenting signs between both syndromes and when the data were available, we also compared the echographic signs with the foetal pathology. In foetuses with trisomy 13 the most common malformations were craniofacial defects, cerebral malformations and genitourinary tract anomalies. The most common malformations associated with trisomy 18 were limb abnormalities and intrauterine growth restriction. Most malformations were predominant in trisomy 18, except for genitourinary tract anomalies. In most cases the sonographic signs correlated with the pathology findings. Trisomy 13 as well as trisomy 18 are characterized by a number of various malformations in the foetus. Most of the ultrasound features were predominant in foetuses with trisomy 18. Mostly the foetal pathology correlated with the sonographic evaluation.

Ultrasound features in trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) in a consecutive series of 47 cases

PubMed Central

Kroes, I.; Janssens, S.; Defoort, P.

2014-01-01

Objective: To determine and list the variety of the predominant appeal signs leading to referral and their accompanying features found during specialized ultrasound evaluation in foetuses with trisomy 13 and trisomy 18. Materials and Methods: In a period of thirty years, 1110 cases of foetal malformations were detected during specialized echographic evaluation. 47 Of these cases were foetuses with trisomy 13 or trisomy 18. We evaluated the predominant signs leading to referral, the difference and overlap in presenting signs between both syndromes and when the data were available, we also compared the echographic signs with the foetal pathology. Results: In foetuses with trisomy 13 the most common malformations were craniofacial defects, cerebral malformations and genitourinary tract anomalies. The most common malformations associated with trisomy 18 were limb abnormalities and intrauterine growth restriction. Most malformations were predominant in trisomy 18, except for genitourinary tract anomalies. In most cases the sonographic signs correlated with the pathology findings. Conclusion: Trisomy 13 as well as trisomy 18 are characterized by a number of various malformations in the foetus. Most of the ultrasound features were predominant in foetuses with trisomy 18. Mostly the foetal pathology correlated with the sonographic evaluation. PMID:25593701

Dandy-Walker malformation and Wisconsin syndrome: novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions.

PubMed

Ferraris, Alessandro; Bernardini, Laura; Sabolic Avramovska, Vesna; Zanni, Ginevra; Loddo, Sara; Sukarova-Angelovska, Elena; Parisi, Valentina; Capalbo, Anna; Tumini, Stefano; Travaglini, Lorena; Mancini, Francesca; Duma, Filip; Barresi, Sabina; Novelli, Antonio; Mercuri, Eugenio; Tarani, Luigi; Bertini, Enrico; Dallapiccola, Bruno; Valente, Enza Maria

2013-05-16

The Dandy-Walker malformation (DWM) is one of the commonest congenital cerebellar defects, and can be associated with multiple congenital anomalies and chromosomal syndromes. The occurrence of overlapping 3q deletions including the ZIC1 and ZIC4 genes in few patients, along with data from mouse models, have implicated both genes in the pathogenesis of DWM. Using a SNP-array approach, we recently identified three novel patients carrying heterozygous 3q deletions encompassing ZIC1 and ZIC4. Magnetic resonance imaging showed that only two had a typical DWM, while the third did not present any defect of the DWM spectrum. SNP-array analysis in further eleven children diagnosed with DWM failed to identify deletions of ZIC1-ZIC4. The clinical phenotype of the three 3q deleted patients included multiple congenital anomalies and peculiar facial appearance, related to the localization and extension of each deletion. In particular, phenotypes resulted from the variable combination of three recognizable patterns: DWM (with incomplete penetrance); blepharophimosis, ptosis, and epicanthus inversus syndrome; and Wisconsin syndrome (WS), recently mapped to 3q. Our data indicate that the 3q deletion is a rare defect associated with DWM, and suggest that the hemizygosity of ZIC1-ZIC4 genes is neither necessary nor sufficient per se to cause this condition. Furthermore, based on a detailed comparison of clinical features and molecular data from 3q deleted patients, we propose clinical diagnostic criteria and refine the critical region for WS.

[Differential diagnosis of Dandy-Walker syndrome different presentations].

PubMed

Tobías-González, Pablo; Gil Mira, Mar; Valero de Bernabé, Javier; Zapardiel, Ignacio

2012-08-01

Dandy-Walker syndrome is a set of abnormalities of the posterior fossa including three modalities: classic Dandy-Walker malformation, Dandy-Walker variant and mega-cisterna magna. Our objective is clarify the differential diagnosis among these entities. Descriptive and retrospective study of Dandy-Walker cases diagnosed at our Department during the last five years plus a review of the related Medical literature. Three cases of Dandy-Walker modalities are reported: one case of classic Dandy-Walker malformation, one case of Dandy-Walker variant, and one case of false Dandy-Walker. In the first two cases the patients underwent legal abortion, whereas in the last one a healthy male newborn was delivered in the week 38 of gestation. Malformations in the posterior fossa, including Dandy-Walker syndrome, are still a challenge in prenatal diagnosis. Technical developments in imaging, such as in three-dimensional sonography and magnetic resonance, allow higher resolution and multiplanar images for an easier diagnose. There is a high rate of false positive, particularly before the 18th week of gestation. It is advisable not to establish a final diagnose before that week.

Two-dimensional capillary electrophoresis: capillary isoelectric focusing and capillary zone electrophoresis with laser-induced fluorescence detection

PubMed Central

Dickerson, Jane A.; Ramsay, Lauren M.; Dada, Oluwatosin O.; Cermak, Nathan

2011-01-01

Capillary isoelectric focusing and capillary zone electrophoresis are coupled with laser-induced fluorescence detection to create an ultrasensitive two-dimensional separation method for proteins. In this method, two capillaries are joined through a buffer filled interface. Separate power supplies control the potential at the injection end of the first capillary and at the interface; the detector is held at ground potential. Proteins are labeled with the fluorogenic reagent Chromeo P503, which preserves the isoelectric point of the labeled protein. The labeled proteins were mixed with ampholytes and injected into the first dimension capillary. A focusing step was performed with the injection end of the capillary at high pH and the interface at low pH. To mobilize components, the interface was filled with a high pH buffer, which was compatible with the second dimension separation. A fraction was transferred to the second dimension capillary for separation. The process of fraction transfer and second dimension separation was repeated two dozen times. The separation produced a spot capacity of 125. PMID:20603830

Neuro-ophthalmology of type 1 Chiari malformation

PubMed Central

Shaikh, Aasef G.; Ghasia, Fatema F.

2016-01-01

Chiari malformation is a congenital deformity leading to herniation of cerebellar tonsils. Headache is a typical symptom of this condition, but patients with Chiari malformation often present with double vision and vertigo. Examination of eye movements in such patients often reveals nystagmus and strabismus. Eye movement deficits in the context of typical symptomatic presentation are critical clinical markers for the diagnosis of Chiari malformation. We will review eye movement deficits that seen in patients with type 1 Chiari malformation. We will then discuss the underlying pathophysiology and therapeutic options for such deficits. PMID:26843890

A developmental classification of malformations of the brainstem.

PubMed

Barkovich, A James; Millen, Kathleen J; Dobyns, William B

2007-12-01

With advances in imaging and genetics, malformations of the brainstem are being more commonly identified. We describe and classify brainstem anomalies in 138 patients ascertained over a period of 10 years Magnetic resonance imaging studies and, where available, clinical records of the patients were retrospectively reviewed. Malformations were segregated according to magnetic resonance findings and classified when possible by embryological mechanisms The most common location for anomalies was the pons, which was involved in 114 patients. The midbrain was involved in 45 patients, whereas the medulla was involved in 14. In 53 patients, more than 1 region was affected (all 3 regions in 6 patients, midbrain and pons in 39, and medulla and pons in 8). The malformations were divided into four groups: (1) malformations with abnormal brainstem segmentation, (2) malformations with segmental hypoplasia, (3) postsegmentation malformations, and (4) malformations associated with abnormal cortical organization The malformations of the brainstem identified in this study were diverse and complex. This proposed classification organizes them into groupings based on known genetics and embryological events. Use of this system will help clinicians and scientists to better understand these disorders and, ultimately, to better counsel families of affected patients.

Rare malformation of glans penis: arteriovenous malformation.

PubMed

Akin, Y; Sarac, M; Yucel, S

2013-01-01

Pediatric glans penis malformations, especially arteriovenous malformations (AVM), are very rare. Herein, we report two rare cases. A 14-year-old boy attended our outpatient clinic with chief complaints of purple swelling and rapidly growing lesion on the glans penis. The lesion was excised surgically after physical and radiological evaluations. Pathology reported AVM and the patient is being followed up. The second case is a 2-year-old boy who was admitted with a big lesion involving glans penis and genital area that has been present since birth. In physical and radiological evaluations, lesion on the glans penis was pulsatile. Parents of the patient did not want any surgery and patient has been in follow-up. Diagnosis of the vascular lesions on glans penis is very easy by physical and radiological examinations today. Long-term follow-up is very important for AVM. Clinicians must make a careful effort to document new glans lesions in the pediatric population and decrease anxiety in the parents of affected children.

[Lymphatic malformations in the head and neck area].

PubMed

Wiegand, S; Werner, J A

2016-02-01

Lymphatic malformations are congenital malformations of the lymphatic system. They are mainly located in the head and neck area, and grow proportional to the patients' body growth. Depending on the morphology, it can be distinguished between macrocystic, microcystic and mixed lymphatic malformations. Due to their infiltrative growth, microcystic lymphatic malformations are particularly difficult to treat. Therapeutic approaches include conventional surgical resection, laser therapy, sclerotherapy and systemic drug therapies.

Novel cAMP binding protein-BP (CREBBP) mutation in a girl with Rubinstein-Taybi syndrome, GH deficiency, Arnold Chiari malformation and pituitary hypoplasia

PubMed Central

2013-01-01

Background Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disorder (prevalence 1:125,000) characterised by broad thumbs and halluces, facial dysmorphism, psychomotor development delay, skeletal defects, abnormalities in the posterior fossa and short stature. The known genetic causes are point mutations or deletions of the cAMP-response element binding protein-BP (CREBBP) (50-60% of the cases) and of the homologous gene E1A-binding protein (EP300) (5%). Case presentation We describe, for the first time in literature, a RTS Caucasian girl, 14-year-old, with growth hormone (GH) deficiency, pituitary hypoplasia, Arnold Chiari malformation type 1, double syringomyelic cavity and a novel CREBBP mutation (c.3546insCC). Conclusion We hypothesize that CREBBP mutation we have identified in this patient could be responsible also for RTS atypical features as GH deficiency and pituitary hypoplasia. PMID:23432975

A FETAL RAT TESTIS ENDOCRINE AND GENOMIC "SIGNATURE"ACCURATELY PREDICTS THE PHTHALATE SYNDROME OF MALFORMATIONS.

EPA Science Inventory

ABSTRACT BODY: Phthalate esters (PE) vary greatly in their potency to induce malformations during sexual differentiation in the male rat. Since in vitro assay batteries are currently unable to generate useful information on the potential of chemicals within this class to disrupt ...

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.

[Neonatal tumours and congenital malformations].

PubMed

Berbel Tornero, O; Ortega García, J A; Ferrís i Tortajada, J; García Castell, J; Donat i Colomer, J; Soldin, O P; Fuster Soler, J L

2008-06-01

The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data

Atypical cerebellar slump syndrome and external hydrocephalus following craniocervical decompression for Chiari I malformation: case report.

PubMed

Thakar, Sumit; Dadlani, Ravi; Tawari, Manish; Hegde, Alangar S

2014-01-01

Symptomatic cerebellar slump (CS) and external hydrocephalus (EH) are amongst the rarer complications of foramen magnum decompression (FMD) for Chiari I malformation (CM). CS typically presents with delayed onset headache related to dural traction or with neurological deficit offsetting the benefit of FMD. EH, consisting of ventriculomegaly along with subdural fluid collection(s) (SFCs), has been related to cerebrospinal fluid egress from a tiny breach in an otherwise intact arachnoid. We describe the case of a 21-year-old man with CM and syringomyelia who presented with impaired gag, spastic quadriparesis, and raised intracranial pressure 1 week following an uneventful FMD during which the arachnoid had been widely fenestrated. Magnetic resonance imaging (MRI) showed an infratentorial SFC, dilated aqueduct and triventriculomegaly, features of CS, and a residual but resolving syrinx. His symptoms resolved following a high pressure ventriculo-peritoneal shunt. At a 6-month follow-up visit, he was asymptomatic and demonstrated partial resolution of the syrinx, with no recurrence of the SFC. The unusual features in the clinical course of this patient were an atypical CS syndrome presenting with concomitantly resolving syringomyelia, and the development of EH after a wide arachnoidal fenestration. This is the first case in indexed literature describing such a combination of unusual postoperative complications of a FMD. A hypothesis is presented to explain the clinico-radiological findings of the case.

Atypical Cerebellar Slump Syndrome and External Hydrocephalus following Craniocervical Decompression for Chiari I Malformation: Case Report

PubMed Central

THAKAR, Sumit; DADLANI, Ravi; TAWARI, Manish; HEGDE, Alangar S

2014-01-01

Symptomatic cerebellar slump (CS) and external hydrocephalus (EH) are amongst the rarer complications of foramen magnum decompression (FMD) for Chiari I malformation (CM). CS typically presents with delayed onset headache related to dural traction or with neurological deficit offsetting the benefit of FMD. EH, consisting of ventriculomegaly along with subdural fluid collection(s) (SFCs), has been related to cerebrospinal fluid egress from a tiny breach in an otherwise intact arachnoid. We describe the case of a 21-year-old man with CM and syringomyelia who presented with impaired gag, spastic quadriparesis, and raised intracranial pressure 1 week following an uneventful FMD during which the arachnoid had been widely fenestrated. Magnetic resonance imaging (MRI) showed an infratentorial SFC, dilated aqueduct and triventriculomegaly, features of CS, and a residual but resolving syrinx. His symptoms resolved following a high pressure ventriculo-peritoneal shunt. At a 6-month follow-up visit, he was asymptomatic and demonstrated partial resolution of the syrinx, with no recurrence of the SFC. The unusual features in the clinical course of this patient were an atypical CS syndrome presenting with concomitantly resolving syringomyelia, and the development of EH after a wide arachnoidal fenestration. This is the first case in indexed literature describing such a combination of unusual postoperative complications of a FMD. A hypothesis is presented to explain the clinico-radiological findings of the case. PMID:24257499

Vascular Ehlers–Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci

PubMed Central

Park, Min A.; Shin, So Youn; Kim, Young Jin; Park, Myung Jae; Lee, Seung Hyeun

2017-01-01

Abstract Rationale: Vascular Ehlers–Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. Patient concerns: We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. Diagnoses: Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. Interventions: The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. Outcomes: Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. Lessons: To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the

The role of nailfold capillary dropout on mortality in systemic sclerosis.

PubMed

Tieu, Joanna; Hakendorf, Paul; Woodman, Richard J; Patterson, Karen; Walker, Jenny; Roberts-Thomson, Peter

2018-05-01

Semi-quantitative wide-field nailfold capillaroscopy (NFC) is a simple technique with proven utility in the early diagnosis of systemic sclerosis (SSc). Its role in prognosis, however, remains uncertain. To investigate the possible utility of NFC in predicting survival. Patients with SSc listed on the South Australian Scleroderma Register (SASR) with prior NFC performed at Flinders Medical Centre from 1991 to 2015 were included in this study. Baseline demographic data, diagnosis, scleroderma antibody status and mortality status were also collected for each patient. The cohort consisted of 99 patients with limited cutaneous SSc, 30 patients with diffuse cutaneous SSc and 23 with an overlap scleroderma syndrome. Fifty-six patients died during the period of study (censured end June 2015). Patients with diffuse scleroderma had significantly greater capillary dropout compared with limited and overlap scleroderma (P < 0.001). In univariate analysis, both capillary dropout scores (log-rank χ 2 = 8.75, P = 0.003) and antibody status (log-rank χ 2 = 13.94, P = 0.003) were associated with mortality. ANOVA showed a significant association between antibody status and capillary dropout (P < 0.001). In Cox regression, adjustment for capillary dropout attenuated the impact of autoantibody group on survival. Nailfold capillary dropout was significantly associated with mortality and the severity of dropout attenuates survival dictated by antibody status. Together these observations support the hypothesis that capillary dropout is on the causal pathway between induction of scleroderma associated autoantibodies and mortality. © 2018 Royal Australasian College of Physicians.

Longevity and Patau syndrome: what determines survival?

PubMed Central

Peroos, Sherina; Forsythe, Elizabeth; Pugh, Jennifer Harriet; Arthur-Farraj, Peter; Hodes, Deborah

2012-01-01

The authors report of an 8-year-old girl with non-mosaic Patau syndrome. The median life expectancy of Patau syndrome is 7–10 days, and 90% die in the first year of life. Survival is often attributed to mosaicism and the severity of associated malformations. We delineate the developing phenotype and review the literature discussing potential contributory factors to longevity. PMID:23220825

Hydrocephalus in Dandy-Walker malformation.

PubMed

Spennato, Pietro; Mirone, Giuseppe; Nastro, Anna; Buonocore, Maria Consiglio; Ruggiero, Claudio; Trischitta, Vincenzo; Aliberti, Ferdinando; Cinalli, Giuseppe

2011-10-01

Even if the first description of Dandy-Walker dates back 1887, difficulty in the establishment of correct diagnosis, especially concerning differential diagnosis with other types of posterior fossa CSF collection, still persists. Further confusion is added by the inclusion, in some classification, of different malformations with different prognosis and therapeutic strategy under the same label of "Dandy-Walker". An extensive literature review concerning embryologic, etiologic, pathogenetic, clinical and neuroradiological aspects has been performed. Therapeutic options, prognosis and intellectual outcome are also reviewed. The correct interpretation of the modern neuroradiologic techniques, including CSF flow MR imaging, may help in identifying a "real" Dandy-Walker malformation. Among therapeutical strategies, single shunting (ventriculo-peritoneal or cyst-peritoneal shunts) appears effective in the control of both ventricle and cyst size. Endoscopic third ventriculostomy may be considered an acceptable alternative, especially in older children, with the aim to reduce the shunt-related problems. Prognosis and intellectual outcome mostly depend on the presence of associated malformations, the degree of vermian malformation and the adequate control of hydrocephalus.

Study of placenta of children born with congenital malformations.

PubMed

Stoll, Claude; Alembik, Yves; Dott, Béatrice; Roth, Marie-Paule

2003-01-01

The malformations in this study were observed in a series of 279,642 consecutive births of known outcome registered in our Registry of congenital anomalies. For each case, more than 50 factors included in the registration forms were studied. One of the factors studied was the placenta. For each malformed child, a control was chosen. Cases with maternal known factors impairing placenta function, i.e. vasculopathy and diabetes, were excluded. In each category of malformations studied, the malformed children were divided into isolated and non-isolated (multiple malformed) cases. The weight of placenta of isolated cases was not lower than the weight of placenta of the controls. In contrast, the weight of placenta of the cases with non-isolated malformations was lower than the weight of placenta of the controls and of the isolated cases, for all categories of malformations but gastroschisis and omphalocele. The mean weights at birth of the cases with multiple malformations were also lower than those of the controls. The human placenta discounts a principal functional part, the maternal blood in the intervillous space. Congenital malformations may interact with this function.

[Hydrocephalus in childhood : causes and imaging patterns].

PubMed

Pomschar, A; Koerte, I; Peraud, A; Heinen, F; Herber-Jonat, S; Reiser, M; Ertl-Wagner, B

2012-09-01

Causes and imaging patterns of hydrocephalus differ depending on the age of the patient. Traditionally, hydrocephalus was classified into non-communicating and communicating hydrocephalus but more recent classifications also take the site of occlusion and the etiology into account. For the diagnostic work-up computed tomography (CT), sonography and magnetic resonance imaging (MRI) are available and MRI is the method of choice for children and adolescents as it allows determination of the cause and location of a possible obstruction. In the first 12-18 months sonography allows evaluation of the lateral ventricles and the third ventricle and CT is usually only chosen in children in emergency situations and/or if no other modality is available. We retrospectively evaluated a population of 785 children and adolescents (426 males aged 0-17 years) referred for MRI between April 2009 and March 2012 due to headaches, somnolence, concentration difficulties or developmental delay. Among these 80 (49 male) met the MRI criteria for hydrocephalus, 75 (46 male) had non-communicating hydrocephalus and 5 (3 male) communicating hydrocephalus. Of the patients 24 (15 male) had posthemorrhagic aqueductal stenosis, 16 (8 male) intracranial tumors, 9 (6 male) Chiari II malformations, 5 (4 male) other congenital malformations including malformations of the Dandy Walker spectrum, 9 (3 male) idiopathic aqueductal stenosis, 7 (5 male) arachnoidal cysts and 10 (8 male) other disorders, such as post-infections, macrocephaly cutis marmorata telangiectatica congenita (M-CMTC) syndrome, mesencephalic arteriovenous malformation (AVM), Langerhans cell histiocystosis. It is important to take the age of the patient and the imaging pattern into account and to exclude tumors when reporting MR images of children with hydrocephalus.

Brain Malformations

MedlinePlus

Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

Capillary descent.

PubMed

Delannoy, Joachim; de Maleprade, Hélène; Clanet, Christophe; Quéré, David

2018-05-31

A superhydrophobic capillary tube immersed in water and brought in contact with the bath surface will be invaded by air, owing to its aerophilicity. We discuss this phenomenon where the ingredients of classical capillary rise are inverted, which leads to noticeable dynamical features. (1) The main regime of air invasion is linear in time, due to the viscous resistance of water. (2) Menisci in tubes with millimetre-size radii strongly oscillate before reaching their equilibrium depth, a consequence of inertia. On the whole, capillary descent provides a broad variety of dynamics where capillary effects, viscous friction and liquid inertia all play a role.

Comprehensive review of the duplication 3q syndrome and report of a patient with Currarino syndrome and de novo duplication 3q26.32-q27.2.

PubMed

Dworschak, G C; Crétolle, C; Hilger, A; Engels, H; Korsch, E; Reutter, H; Ludwig, M

2017-05-01

Partial duplications of the long arm of chromosome 3, dup(3q), are a rare but well-described condition, sharing features of Cornelia de Lange syndrome. Around two thirds of cases are derived from unbalanced translocations, whereas pure dup(3q) have rarely been reported. Here, we provide an extensive review of the literature on dup(3q). This search revealed several patients with caudal malformations and anomalies, suggesting that caudal malformations or anomalies represent an inherent phenotypic feature of dup(3q). In this context, we report a patient with a pure de novo duplication 3q26.32-q27.2. The patient had the clinical diagnosis of Currarino syndrome (CS) (characterized by the triad of sacral anomalies, anorectal malformations and a presacral mass) and additional features, frequently detected in patients with a dup(3q). Mutations within the MNX1 gene were found to be causative in CS but no MNX1 mutation could be detected in our patient. Our comprehensive search for candidate genes located in the critical region of the duplication 3q syndrome, 3q26.3-q27, revealed a so far neglected phenotypic overlap of dup(3q) and the Pierpont syndrome, associated with a mutation of the TBL1XR1 gene on 3q26.32. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A tumor profile in Patau syndrome (trisomy 13).

PubMed

Satgé, Daniel; Nishi, Motoi; Sirvent, Nicolas; Vekemans, Michel; Chenard, Marie-Pierre; Barnes, Ann

2017-08-01

Individuals with trisomic conditions like Down syndrome and Edwards syndrome are prone to certain types of malignancy. However, for Patau syndrome (constitutional trisomy 13), which occurs in 1/10,000-1/20,000 live births, the tumor profile has not been well characterized. An awareness of susceptibility to malignancies can improve care of affected individuals, as well as further our understanding of the contribution of trisomy to carcinogenesis. Therefore, we conducted an extensive review of the literature; we found 17 malignancies reported in individuals with Patau syndrome. These comprised eight embryonic tumors, three leukemias, two malignant germ cell tumors, two carcinomas, a malignant brain tumor, and a sarcoma. Benign tumors were mainly extragonadal teratomas. The small number of reported malignant tumors suggests that there is not an increased risk of cancer in the context of trisomy 13. The tumor profile in Patau syndrome differs from that observed in Edwards syndrome (trisomy 18) and Down syndrome (trisomy 21), suggesting that the supernumerary chromosome 13 could promote particular tumor formations as it does particular malformations. No general and direct relationships of tumor occurrence with organ weight, congenital malformations, histological changes, or presence of tumor suppressor genes on chromosome 13 were observed. However, some tumors were found in tissues whose growth and development are controlled by genes mapping to chromosome 13. Recent reports of successful outcomes following surgical treatment and adapted chemotherapy indicate that treatment of cancer is possible in Patau syndrome. © 2017 Wiley Periodicals, Inc.

Discrete subvalvular aortic stenosis in the Beckwith-Wiedemann syndrome.

PubMed

Shirani, J; Natarajan, K; Varga, P; Vitullo, D A

1993-07-01

Various congenital cardiac malformations have been described in patients with Beckwith-Wiedemann (BW) syndrome, including reversible obstructive subaortic stenosis in one patient. We herein present a case of a 2.5-year-old black boy with BW syndrome and discrete subvalvular aortic stenosis of the membraneous type. Such association of these two entities has previously not been documented.

Radiological characteristics of the knee joint in nail patella syndrome.

PubMed

Tigchelaar, S; Rooy, J de; Hannink, G; Koëter, S; van Kampen, A; Bongers, E

2016-04-01

Nail patella syndrome (NPS) is a skeletal dysplasia with patellofemoral dysfunction as a key symptom. We present the first in-depth radiological evaluation of the knee in a large series of NPS patients and describe the typical malformations. Conventional radiological examination of 95 skeletally mature patients with NPS was performed. Patellar morphology was classified according to the Wiberg classification as modified by Baumgartl and Ficat criteria, and trochlear shape was classified according to the Dejour classification. Patellar aplasia was present in 4/90 (4%), and patellar hypoplasia in 77/90 (86%) of patients. The prevailing patellar shapes were type III, type IV and Hunter's cap. No patellar shape genotype-phenotype association could be found. The malformations of the distal femur comprised shortening of the lateral femoral condyle in 46 out of 84 patients (55%), with a prominent anterior surface of the lateral femoral condyle in 47 out of 84 patients (56%) and a flat anterior surface of the medial femoral condyle in 78 out of 85 patients (92%). The trochlea was type A1 according to the Dejour classification in 79 out of 85 patients (93%). An easily recognisable characteristic quartet of malformations consisting of patellar aplasiaor hypoplasia and the malformations of the distal femur was found in 22 out of 81 patients (27%), with the majority displaying at least three malformations. The distinct malformations of the knee in nail patella syndrome are easily recognisable on conventional radiographs and lead to the correct interpretation of the aberrant morphology which is essential in the treatment of these patellofemoral disorders. ©2016 The British Editorial Society of Bone & Joint Surgery.

Drag reducing polymers improve coronary flow reserve through modulation of capillary resistance.

PubMed

Pacella, John J; Kameneva, Marina V; Villanueva, Flordeliza S

2009-01-01

We have shown that drag-reducing polymers (DRP) reduce microvascular resistance and improve myocardial perfusion during coronary stenosis. We used myocardial contrast echocardiography (MCE) and mathematical modeling to define the DRP microvascular effects. A non-flow-limiting left anterior descending (LAD) stenosis was created in 8 dogs. Intramyocardial blood volume, RBC velocity and flow in the LAD and circumflex (CX) beds were obtained from MCE at baseline, and in hyperemia, stenosis, hyperemia + stenosis, and hyperemia + stenosis + DRP. Microvascular resistances were calculated from a lumped-parameter model. During stenosis + hyperemia, LAD bed microvascular resistance increased (p<0.015), and capillary volume (p<0.002) and red cell velocity (p<0.0004) decreased relative to baseline. With DRP, during stenosis and hyperemia, LAD bed microvascular resistance decreased (p<0.04); there was an increase in capillary volume (p<0.007), RBC velocity (p<0.006), and flow (p<0.05). Decreased model-computed capillary resistance accounted for the reduction in LAD bed resistance after DRP. We conclude that DRP improve flow reserve during coronary stenosis by modulating capillary resistance. Primary modification of the rheological properties of blood to affect capillary resistance is a novel approach for the treatment of acute coronary syndromes.

Nailfold capillaroscopic changes in Kindler syndrome.

PubMed

Dobrev, Hristo P; Vutova, Nina I

2015-11-01

Kindler syndrome (KS), the fourth major type of hereditary epidermolysis bullosa (HEB), is a rare, autosomal recessive disorder characterized by skin fragility and blistering at birth followed by development of marked photosensitivity and progressive poikilodermatous skin changes in later years. We reported here the case of a 54-year-old woman, who fulfills the diagnostic criteria of KS type of HEB, putting accent on the nailfold capillaroscopic changes. Using videocapillaroscopy we observed pronounced alterations in finger nail capillaries including reduction in capillary density, features of neoangiogenesis (architectural derangement, elongated loops, extremely tortuous, bushy or branching capillaries, thin, branching and interconnected capillaries), enlarged and giant capillaries. We consider the changes observed as an adaptive mechanism that compensate the loss of capillaries due to chronic periungual trauma. Further studies with larger number of patients are needed to confirm the significance of capillaroscopy findings for patients with HEB.

Outcomes of Infantile-Onset Glaucoma Associated With Port Wine Birthmarks and Other Periocular Cutaneous Vascular Malformation.

PubMed

Reyes-Capó, Daniela; Cavuoto, Kara M; Chang, Ta C

2018-01-01

The incidence of infantile-onset secondary glaucoma associated with periocular cutaneous vascular malformations is high and the outcomes of these glaucomatous eyes have anecdotally been poor. The purpose of this study was to determine the anatomic and visual outcomes of affected eyes. Retrospective case series. Consecutive patients with early-onset (younger than 36 months of age) glaucoma associated with cutaneous vascular malformations from 1995‒2015 were included. Seventeen eyes of 13 patients with Sturge-Weber syndrome (SW, n = 10), Klippel-Trenaunay-Weber syndrome (KTW, n = 1), cutis marmorata telangiectatica congenita (CMTC, n = 1), and phakomatosis pigmentovascularis (PPV, n = 1) were included. Three SW and 1 KTW patient had bilateral glaucoma. At presentation, mean age was 6.5 ± 9.1 months and mean intraocular pressure was 27.2 ± 6.13 mm Hg. The average number of surgical procedures per eye increased from 1.0 ± 0.5 (range, 0‒2) at less than 5 years' follow-up (9 eyes) to 3.5 ± 2.3 (range, 1‒7) with at least 5 years' follow-up (8 eyes). Visual acuity was better than or equal to 20/70 in 2 of 6 eyes (33%) with less than 5 years' follow-up and in 3 of 7 eyes (43%) with at least 5 years' follow-up. Additionally, a higher number of baseline risk factors correlated with poorer visual outcome. After a mean follow-up of 6.6 years, visual outcome in infantile-onset secondary glaucoma associated with cutaneous periocular vascular malformation is guarded. Increased numbers of baseline risk factors and procedures are associated with poorer vision. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Gorlin-Goltz syndrome: A rare case report.

PubMed

Pol, Chetan A; Ghige, Suvarna K; Kalaskar, Ritesh R; Gosavi, Suchitra R

2013-10-01

Gorlin-Goltz syndrome is an uncommon autosomal dominant inherited disorder characterized by numerous basal cell carcinomas, odontogenic keratocysts (OKCs) and musculoskeletal malformations. A rare case of this syndrome observed in a 13-year-old male patient is presented in which multiple OKCs were causing disfigurement of the lower jaw as well as displacement and malocclusion of the teeth. Early diagnosis and treatment of this syndrome is important to reduce the severity of complications including cutaneous and cerebral malignancy and oromaxillofacial deformation and destruction due to jaw cysts.

Dandy-Walker malformation and Wisconsin syndrome: novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions

PubMed Central

2013-01-01

Background The Dandy-Walker malformation (DWM) is one of the commonest congenital cerebellar defects, and can be associated with multiple congenital anomalies and chromosomal syndromes. The occurrence of overlapping 3q deletions including the ZIC1 and ZIC4 genes in few patients, along with data from mouse models, have implicated both genes in the pathogenesis of DWM. Methods and results Using a SNP-array approach, we recently identified three novel patients carrying heterozygous 3q deletions encompassing ZIC1 and ZIC4. Magnetic resonance imaging showed that only two had a typical DWM, while the third did not present any defect of the DWM spectrum. SNP-array analysis in further eleven children diagnosed with DWM failed to identify deletions of ZIC1-ZIC4. The clinical phenotype of the three 3q deleted patients included multiple congenital anomalies and peculiar facial appearance, related to the localization and extension of each deletion. In particular, phenotypes resulted from the variable combination of three recognizable patterns: DWM (with incomplete penetrance); blepharophimosis, ptosis, and epicanthus inversus syndrome; and Wisconsin syndrome (WS), recently mapped to 3q. Conclusions Our data indicate that the 3q deletion is a rare defect associated with DWM, and suggest that the hemizygosity of ZIC1-ZIC4 genes is neither necessary nor sufficient per se to cause this condition. Furthermore, based on a detailed comparison of clinical features and molecular data from 3q deleted patients, we propose clinical diagnostic criteria and refine the critical region for WS. PMID:23679990

The neurologic findings in Taybi-Linder syndrome (MOPD I/III): case report and review of the literature.

PubMed

Pierce, Melinda J; Morse, Richard P

2012-03-01

Taybi-Linder syndrome, also known as microcephalic osteodysplastic primordial dwarfism types I and III, is a rare disorder with presumed autosomal recessive inheritance. It is characterized by intrauterine growth retardation, distinctive bone dysplasia, and central nervous system malformations. We present two siblings with Taybi-Linder syndrome, with an emphasis on the neurological profile in this disease, which includes brain malformations, intractable epilepsy, sensory deficits, profound cognitive deficits, and neuroendocrine dysfunction. We also present distinctive correlative neuroimaging (MRI) and electroencephalographic (EEG) findings. Increased knowledge of the neurological profile of Taybi-Linder syndrome may be helpful for clinicians and genetic counselors managing these patients. Copyright © 2012 Wiley Periodicals, Inc.

[PELVIS/SACRAL syndrome with livedoid haemangioma and amniotic band].

PubMed

Bourrat, E; Lemarchand-Venencie, F; Jacquemont, M-L; El Ghoneimi, A; Wassef, M; Leger, J; Morel, P

2008-12-01

PELVIS or SACRAL syndrome denotes the association of local haemangioma and malformation in the pelvic region. In this paper, we report a case noteworthy on account of the initially livedoid appearance of the haemangioma as well as associated amniotic banding of an upper limb. A newborn male infant underwent left colostomy on the day of birth due to anal imperforation and anomalies of the external genital organs with sexual ambiguity. Examination of the skin and appendages revealed poorly delineated hypopigmentation in the sacrolumbar region and a fibrous groove around the right arm characteristic of amniotic band syndrome. Sacrolumbar and pelvic MRI scans revealed deviation towards the left of the last three sacral vertebrae with no medullary anomalies. Retrograde cystography showed a recto-uretral fistula. Progression of the infant's condition was marked by the appearance during the first month of a flat, violaceous, angiomatous, livedoid lesion in the middle of the buttocks and the perineum and a linear lesion on the rear aspect of the right lower limb. The skin biopsy of this lesion revealed a single capillary lobule at the dermal-hypodermal junction of non-specific appearance but with marked Glut1 expression by endothelial cells highly evocative of infantile haemangioma. Segmented haemangiomas are commonly associated with extracutaneous abnormalities. By analogy with PHACE syndrome, defined as association of segmented facial haemangioma with cerebral, ocular and cardio-aortic abnormalities, PELVIS/SACRAL syndrome denotes the association of segmented haemangioma of the loins (sacrolumbar region, buttocks or perineum=napkin haemangioma) with spinal dysraphia affecting the sacrolumbar spine, the terminal medullary cone, the genitourinary organs and the anal region to different degrees. Diagnosis of haemangioma associated with PELVIS/SACRAL syndrome may be delayed or complicated due to the macular, telangiectasic or livedoid appearance commonly seen. To our

Cerebellar hematoma in a patient with Marfan syndrome.

PubMed

Passalacqua, Marcello; Grasso, Giovanni; Alafaci, Concetta; Collufio, Domenicantonio; Morabito, Antonio; Salpietro, Francesco M; Tomasello, Francesco

2003-08-01

Marfan syndrome is a connective tissue disorder affecting many structures, including the skeleton, lungs, eyes, heart and blood vessels. It is an autosomal dominant inherited disorder due to a mutation of a gene encoding fibrillin-1, which affects connective tissue. Few case reports have associated Marfan syndrome with vascular malformations of the brain and spinal cord. In this regard, association with intracranial aneurysm has been vaguely proposed. We report here a patient with Marfan syndrome who was admitted because of a sudden loss of consciousness. The patient underwent computed tomography (CT) examination, which disclosed a right intracerebellar hematoma. Cerebral angiogram did not demonstrate aneurysm or arteriovenous malformation (AVM), or evidence of any other vascular lesions or neoplasms in the posterior fossa. Conservative treatment was undertaken. The clinical course was uneventful and after 6 weeks the patient was discharged free of symptoms. Although patients with Marfan syndrome are at high risk of vascular abnormalities, a clear association with cerebral aneurysm has not yet been established. Our experience and the contrasting reports available in the medical literature strongly warrant further studies in order to better clarify this controversial association.

Hypochondroplasia due to FGFR3 gene mutation (N540K) and mosaic form of Down syndrome in the same patient.

PubMed

Dumic, Katja; Barisic, Ingeborg; Potocki, Kristina; Sansovic, Ivona

2011-05-01

The simultaneous presence of Down syndrome and achondroplasia has rarely been reported in the literature, and our search revealed only six patients with such an association. We are reporting the first case of a patient with Down syndrome and hypochondroplasia. In this patient, Down syndrome was clinically recognised and confirmed by the cytogenetic finding of mosaic karyotype (47,XX,+21/46,XX) shortly after birth. She was subsequently diagnosed with hypochondroplasia at the age of 6 years when disproportional short stature, stocky habitus and macrocephaly were observed. These phenotypic findings were later confirmed by the presence of fibroblast growth factor receptor 3 (FGFR3) gene mutation N540K. The overlapping common clinical features of Down syndrome and hypochondroplasia resulted in delayed diagnosis of hypochondroplasia in our patient and the associated deleterious effect on her linear growth. Her final height is 126.5 cm, which is -3.76 standard deviations (SD) lower than the median height in patients with Down syndrome, and is under the lower borderline of the adult height range for women with hypochondroplasia.

Malformations associated with congenital diaphragmatic hernia: Impact on survival.

PubMed

Bojanić, Katarina; Pritišanac, Ena; Luetić, Tomislav; Vuković, Jurica; Sprung, Juraj; Weingarten, Toby N; Schroeder, Darrell R; Grizelj, Ruža

2015-11-01

Congenital diaphragmatic hernia (CDH) is associated with high mortality. Survival is influenced by the extent of pulmonary hypoplasia and additional congenital defects. The purpose of this study was to assess the association of congenital anomalies and admission capillary carbon dioxide levels (PcCO2), as a measure of extent of pulmonary hypoplasia, on survival in neonates with CDH. This is a retrospective review of neonates with CDH admitted to a tertiary neonatal intensive care unit between 1990 and 2014. Logistic regression was used to assess whether hospital survival was associated with admission PcCO2 or associated anomalies (isolated CDH, CDH with cardiovascular anomalies, and CDH with noncardiac anomalies). The probabilities of survival (POS) score, based on birth weight and 5-min Apgar as defined by the Congenital Diaphragmatic Hernia Study Group were included as a covariate. Of 97 patients, 55 had additional malformations (cardiovascular n=12, noncardiac anomalies n=43). POS was lower in CDH with other anomalies compared to isolated CDH. Survival rate was 61.9%, 53.5% and 41.7% in isolated CDH, CDH with noncardiac anomalies and CDH with cardiovascular anomalies, respectively. After adjusting for POS score the likelihood of survival in CDH groups with additional anomalies was similar to isolated CDH (OR 0.95, 95% CI 0.22-4.15, and 1.10, 0.39-3.08, for CDH with and without cardiovascular anomalies, respectively). After adjusting for POS score, lower PcCO2 levels (OR=1.25 per 5mmHg decrease, P=0.003) were associated with better survival. Neonates with CDH have a high prevalence of congenital malformations. However, after adjusting for POS score the presence of additional anomalies was not associated with survival. The POS score and admission PcCO2 were important prognosticating factors for survival. Copyright © 2015 Elsevier Inc. All rights reserved.

Congenital malformations of the skull and meninges.

PubMed

Kanev, Paul M

2007-02-01

The surgery and management of children who have congenital malformations of the skull and meninges require multidisciplinary care and long-term follow-up by multiple specialists in birth defects. The high definition of three-dimensional CT and MRI allows precise surgery planning of reconstruction and management of associated malformations. The reconstruction of meningoencephaloceles and craniosynostosis are challenging procedures that transform the child's appearance. The embryology, clinical presentation, and surgical management of these malformations are reviewed.

Molecular and Functional Characterization of Three Different Postzygotic Mutations in PIK3CA-Related Overgrowth Spectrum (PROS) Patients: Effects on PI3K/AKT/mTOR Signaling and Sensitivity to PIK3 Inhibitors

PubMed Central

Forte, Giovanna; Bagnulo, Rosanna; Stella, Alessandro; Lastella, Patrizia; Cutrone, Mario; Benedicenti, Francesco; Susca, Francesco C.; Patruno, Margherita; Varvara, Dora; Germani, Aldo; Chessa, Luciana; Laforgia, Nicola; Tenconi, Romano; Simone, Cristiano; Resta, Nicoletta

2015-01-01

Background PIK3CA-related overgrowth spectrum (PROS) include a group of disorders that affect only the terminal portion of a limb, such as type I macrodactyly, and conditions like fibroadipose overgrowth (FAO), megalencephaly-capillary malformation (MCAP) syndrome, congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies (CLOVES) syndrome and Hemihyperplasia Multiple Lipomatosis (HHML). Heterozygous postzygotic PIK3CA mutations are frequently identified in these syndromes, while timing and tissue specificity of the mutational event are likely responsible for the extreme phenotypic variability observed. Methods We carried out a combination of Sanger sequencing and targeted deep sequencing of genes involved in the PI3K/AKT/mTOR pathway in three patients (1 MCAP and 2 FAO) to identify causative mutations, and performed immunoblot analyses to assay the phosphorylation status of AKT and P70S6K in affected dermal fibroblasts. In addition, we evaluated their ability to grow in the absence of serum and their response to the PI3K inhibitors wortmannin and LY294002 in vitro. Results and Conclusion Our data indicate that patients’ cells showed constitutive activation of the PI3K/Akt pathway. Of note, PI3K pharmacological blockade resulted in a significant reduction of the proliferation rate in culture, suggesting that inhibition of PI3K might prove beneficial in future therapies for PROS patients. PMID:25915946

Dlx5 Homeodomain: DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome

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

Proudfoot, Andrew; Axelrod, Herbert L.; Geralt, Michael

The Dlx5 homeodomain is a transcription factor related to the Drosophila Distal-less gene that is associated with breast and lung cancer, lymphoma, Rett syndrome and osteoporosis in humans. Mutations in the DLX5 gene have been linked to deficiencies in craniofacial and limb development in higher eukaryotes, including Split Hand and Foot Malformation-1 (SHFM-1) in humans. Our characterization of a Dlx5 homeodomain–(CGACTAATTAGTCG) 2 complex by NMR spectroscopy paved the way for determination of its crystal structure at 1.85 Å resolution that enabled rationalization of the effects of disease-related mutations on the protein function. A remarkably subtle mutation, Q186H, is linked tomore » SHFM-1; this change likely affects affinity of DNA binding by disrupting water-mediated interactions with the DNA major groove. A more subtle effect is implicated for the Q178P mutation, which is not in direct contact with the DNA. Our data indicate that these mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and likely destabilize the formation of functional complexes.« less

Dlx5 Homeodomain: DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome

DOE PAGES

Proudfoot, Andrew; Axelrod, Herbert L.; Geralt, Michael; ...

2016-01-29

The Dlx5 homeodomain is a transcription factor related to the Drosophila Distal-less gene that is associated with breast and lung cancer, lymphoma, Rett syndrome and osteoporosis in humans. Mutations in the DLX5 gene have been linked to deficiencies in craniofacial and limb development in higher eukaryotes, including Split Hand and Foot Malformation-1 (SHFM-1) in humans. Our characterization of a Dlx5 homeodomain–(CGACTAATTAGTCG) 2 complex by NMR spectroscopy paved the way for determination of its crystal structure at 1.85 Å resolution that enabled rationalization of the effects of disease-related mutations on the protein function. A remarkably subtle mutation, Q186H, is linked tomore » SHFM-1; this change likely affects affinity of DNA binding by disrupting water-mediated interactions with the DNA major groove. A more subtle effect is implicated for the Q178P mutation, which is not in direct contact with the DNA. Our data indicate that these mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and likely destabilize the formation of functional complexes.« less

A locus for cerebral cavernous malformations maps to chromosome 7q in two families

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

Marchuk, D.A.; Gallione, C.J.; Morrison, L.A.

1995-07-20

Cavernous malformations (angiomas) affecting the central nervous system and retina can be inherited in autosomal dominant pattern (OMIM 116860). These vascular lesions may remain clinically silent or lead to a number of neurological symptoms including seizure, intracranial hemorrhage, focal neurological deficit, and migraine. We have mapped a gene for this disorder in two families, one of Italian-American origin and one of Mexican-American origin, to markers on proximal 7q, with a combined maximum lod score of 3.92 ({theta} of zero) with marker D7S479. Haplotype analysis of these families places the locus between markers D7S502 proximally and D7S515 distally, an interval ofmore » approximately 41 cM. The location distinguishes this disorder from an autosomal dominant vascular malformation syndrome where lesions are primarily cutaneous and that maps to 9p21. 16 refs., 3 figs., 1 tab.« less

Chiari I Malformation in Nephropathic Cystinosis

PubMed Central

Rao, Kavya I; Hesselink, John; Trauner, Doris A

2015-01-01

Objective To determine the relative incidence of Chiari I malformations in children with cystinosis compared with those in the general population. Study design Magnetic resonance imaging (MRI) scans were performed on 53 patients with nephropathic cystinosis and 120 controls, age range 3-18 years. Results Ten of 53 (18.9%) cystinosis patients had Chiari I or tonsillar ectopia, and only 2 of 120 controls (1.6%) had a similar finding. At least 2 of the patients had symptoms or signs thought to be related to the malformation, and one had surgical decompression. Two had an associated cervical syrinx. Conclusions Children with cystinosis have a 12-fold higher prevalence of Chiari I malformations than the general pediatric population. Chiari I malformations should be high on the differential diagnosis when individuals with cystinosis develop neurologic signs and symptoms, and MRI scans should be performed on children with cystinosis who present with new-onset headache, ataxia, incontinence, or other unexplained neurologic symptoms. PMID:26265281

Gorlin-Goltz syndrome: A rare case report

PubMed Central

Pol, Chetan A; Ghige, Suvarna K; Kalaskar, Ritesh R; Gosavi, Suchitra R

2013-01-01

Gorlin-Goltz syndrome is an uncommon autosomal dominant inherited disorder characterized by numerous basal cell carcinomas, odontogenic keratocysts (OKCs) and musculoskeletal malformations. A rare case of this syndrome observed in a 13-year-old male patient is presented in which multiple OKCs were causing disfigurement of the lower jaw as well as displacement and malocclusion of the teeth. Early diagnosis and treatment of this syndrome is important to reduce the severity of complications including cutaneous and cerebral malignancy and oromaxillofacial deformation and destruction due to jaw cysts. PMID:24403808

Refined localization of the Prieto-syndrome locus

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

Martinez, F.; Prieto, F.; Gal, A.

PRS designates the locus for a syndromal form of X-linked mental retardation (Prieto syndrome) characterized by minor facial anomalies, ear malformation, abnormal growth of teeth, clinodactyly, sacral dimple, patellar luxation, malformation of lower limbs, abnormalities of the fundus of the eye, and subcortical cerebral atrophy. Linkage analysis localized the disease locus between DXS84 (Xp21.1) and DXS255. Here we present additional linkage data that provide further support and refinement of this localization. Individual III-18 gave birth to a male, currently aged 2 7/12 years, who clearly shows delayed psychomotor development. He began to walk at 23 months and his speech ismore » delayed. In addition, he shows the characteristic facial anomalies, {open_quotes}dysplastic{close_quotes} ears, sacral dimple, and clinodactyly, as do all other affected males in this family. 7 refs., 1 tab.« less

Acquired Uterine Arteriovenous Malformation and Retained Placenta Increta.

PubMed

Roach, Michelle K; Thomassee, May S

2015-09-01

Uterine arteriovenous malformations are rare and have been reported to occur after uterine trauma (eg, surgery, gestational trophoblastic disease, malignancy). A 33-year-old woman, gravida 3 para 3, presented 4 weeks post-cesarean delivery with episodic profuse vaginal bleeding. Pelvic ultrasonography and magnetic resonance imaging revealed a left uterine arteriovenous malformation. After consideration of all treatment options, total laparoscopic hysterectomy was performed. Acquired uterine arteriovenous malformations and placental ingrowth into the myometrium are increasingly reported after surgical uterine procedures. This case of a postpartum patient with both uterine arteriovenous malformation and retained placenta increta suggests a correlation between the two complications.

Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies.

PubMed

Sadick, Maliha; Müller-Wille, René; Wildgruber, Moritz; Wohlgemuth, Walter A

2018-06-06

 Vascular anomalies are a diagnostic and therapeutic challenge. They require dedicated interdisciplinary management. Optimal patient care relies on integral medical evaluation and a classification system established by experts in the field, to provide a better understanding of these complex vascular entities.  A dedicated classification system according to the International Society for the Study of Vascular Anomalies (ISSVA) and the German Interdisciplinary Society of Vascular Anomalies (DiGGefA) is presented. The vast spectrum of diagnostic modalities, ranging from ultrasound with color Doppler, conventional X-ray, CT with 4 D imaging and MRI as well as catheter angiography for appropriate assessment is discussed.  Congenital vascular anomalies are comprised of vascular tumors, based on endothelial cell proliferation and vascular malformations with underlying mesenchymal and angiogenetic disorder. Vascular tumors tend to regress with patient's age, vascular malformations increase in size and are subdivided into capillary, venous, lymphatic, arterio-venous and combined malformations, depending on their dominant vasculature. According to their appearance, venous malformations are the most common representative of vascular anomalies (70 %), followed by lymphatic malformations (12 %), arterio-venous malformations (8 %), combined malformation syndromes (6 %) and capillary malformations (4 %).  The aim is to provide an overview of the current classification system and diagnostic characterization of vascular anomalies in order to facilitate interdisciplinary management of vascular anomalies.   · Vascular anomalies are comprised of vascular tumors and vascular malformations, both considered to be rare diseases.. · Appropriate treatment depends on correct classification and diagnosis of vascular anomalies, which is based on established national and international classification systems, recommendations and guidelines.. · In the classification

Genetic modifiers of Velo- cardio- facial syndrome/DiGeorge syndrome

PubMed Central

Aggarwal, Vimla S.; Morrow, Bernice E.

2009-01-01

Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), the most common micro-deletion disorder in humans, is characterized by craniofacial, parathyroid and thymic defects as well as cardiac outflow tract malformations. Most patients have a similar hemizygous 3 million base pair deletion on 22q11.2. Studies in mouse have shown that Tbx1, a T- box containing transcription factor present on the deleted region, is likely responsible for the etiology of the syndrome. Furthermore, mutations in TBX1 have been found in rare non-deleted patients. Despite having the same sized deletion, most VCFS/DGS patients exhibit significant clinical variability. Stochastic, environmental and genetic factors likely modify the phenotype of patients with the disorder. Here, we review mouse genetics studies which may help identify genetic modifiers for VCFS/DGS. PMID:18636633

Otologic manifestations of Fanconi anemia and other inherited bone marrow failure syndromes.

PubMed

Kalejaiye, Adedoyin; Giri, Neelam; Brewer, Carmen C; Zalewski, Christopher K; King, Kelly A; Adams, Charleen D; Rosenberg, Philip S; Kim, H Jeffrey; Alter, Blanche P

2016-12-01

The inherited bone marrow failure syndromes (IBMFSs) are diverse disorders with syndrome-specific features; their otologic and audiologic manifestations have not been well described. Our objective was to characterize these in patients with Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS), and to determine the association between physical findings and hearing loss. Patients with an IBMFS underwent comprehensive clinical and laboratory evaluations and testing for syndrome-specific gene mutations. Hearing loss was measured by pure tone audiometry and otologic abnormalities by otomicroscopy. Patients included 33 with FA, 37 with DC, 32 with DBA, and nine with SDS. Hearing loss was most frequent in patients with FA (45%) and DBA (14%). The most common type of hearing loss in FA was conductive (65%). Absent or hypoplastic radius, noted in 21% of the patients with FA, was associated with hearing loss in all cases. Otomicroscopy was abnormal in 66% of patients with FA. Characteristic ear abnormalities included small tympanic membrane (66%), malformed malleus (57%), aberrant tympanic bony island (48%), narrow external auditory canal (EAC) (32%), and abnormal course of chorda tympani (34%). Ear malformations were almost always associated with hearing loss. Hearing loss was rare in patients with DC and SDS. FA is the major IBMFS with associated hearing loss, which is most commonly conductive. Radial hypoplasia or aplasia and characteristic congenital ear malformations are associated with hearing loss in patients with FA. Recognition of these syndrome-specific abnormalities should lead to earlier management of hearing loss. © 2016 Wiley Periodicals, Inc.

Choledochal malformations: the Scottish experience.

PubMed

Yeung, Baldwin Po Man; Broadis, Emily; Maguire, Kirsty; Bradnock, Timothy J; Munro, Fraser D; Driver, Chris P; Haddock, Graham

2012-06-01

Excisional surgery for choledochal malformations in Scotland is currently performed in three specialist pediatric surgical centers using open or laparoscopic-assisted techniques. We reviewed the outcome of children who had excisional surgery in Scotland between 1992 and 2010. Case notes for all patients undergoing excisional surgery in any of the three specialist pediatric surgical centers in Scotland between 1992 and 2010 were retrospectively reviewed. A total of 25 patients were identified, with a female preponderance of 4:1. Of these, three patients (12%) were diagnosed by antenatal ultrasound scan. The commonest presenting symptoms were anorexia (56%), abdominal pain (52%), and jaundice (52%). Only 20% had the classical triad of abdominal pain, jaundice, and a palpable mass. Using the King's College Hospital classification, 14 patients had type 1 malformations, 8 had type 4 malformations, and 3 had type 2 malformations. Median age at operation was 2 years (range 35 days to 13.5 years). Two centers performed open excision while the third center used primarily a laparoscopic-assisted technique. Median follow-up was 2.1 years (range 30 days to 11.9 years). Three patients (12%) required repeat laparotomy. The wound infection rate was 8% (n=2). The recurrent cholangitis rate was 8% (n=2). There was one late death due to adhesive small bowel obstruction, 4 years after surgery. To date, no patient has developed biliary tree stones or liver failure. Choledochal malformation excisional surgery, either open or laparoscopic assisted, can be safely performed in appropriately equipped, pediatric surgical centers in Scotland by experienced pediatric surgeons. Copyright © 2012 by Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Upper limb malformations in DiGeorge syndrome

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

Cormier-Daire, V.; Iserin, L.; Sidi, D.

1995-03-13

We report on upper limb anomalies in two children with a complete DiGeorge sequence: conotruncal defects, hypocalcemia, thymic aplasia, and facial anomalies. One child had preaxial polydactyly, and the other had club hands with hypoplastic first metacarpal. In both patients, molecular analysis documented a 22q11 deletion. To our knowledge, limb anomalies have rarely been reported in DiGeorge syndrome, and they illustrate the variable clinical expression of chromosome 22q11 deletions. 13 refs., 2 figs.

Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome

PubMed Central

Baas, Annette F; Gabbett, Michael; Rimac, Milan; Kansikas, Minttu; Raphael, Martine; Nievelstein, Rutger AJ; Nicholls, Wayne; Offerhaus, Johan; Bodmer, Danielle; Wernstedt, Annekatrin; Krabichler, Birgit; Strasser, Ulrich; Nyström, Minna; Zschocke, Johannes; Robertson, Stephen P; van Haelst, Mieke M; Wimmer, Katharina

2013-01-01

Constitutional mismatch repair deficiency (CMMR-D) syndrome is a rare inherited childhood cancer predisposition caused by biallelic germline mutations in one of the four mismatch repair (MMR)-genes, MLH1, MSH2, MSH6 or PMS2. Owing to a wide tumor spectrum, the lack of specific clinical features and the overlap with other cancer predisposing syndromes, diagnosis of CMMR-D is often delayed in pediatric cancer patients. Here, we report of three new CMMR-D patients all of whom developed more than one malignancy. The common finding in these three patients is agenesis of the corpus callosum (ACC). Gray matter heterotopia is present in two patients. One of the 57 previously reported CMMR-D patients with brain tumors (therefore all likely had cerebral imaging) also had ACC. With the present report the prevalence of cerebral malformations is at least 4/60 (6.6%). This number is well above the population birth prevalence of 0.09–0.36 live births with these cerebral malformations, suggesting that ACC and heterotopia are features of CMMR-D. Therefore, the presence of cerebral malformations in pediatric cancer patients should alert to the possible diagnosis of CMMR-D. ACC and gray matter heterotopia are the first congenital malformations described to occur at higher frequency in CMMR-D patients than in the general population. Further systematic evaluations of CMMR-D patients are needed to identify possible other malformations associated with this syndrome. PMID:22692065

Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome.

PubMed

Baas, Annette F; Gabbett, Michael; Rimac, Milan; Kansikas, Minttu; Raphael, Martine; Nievelstein, Rutger Aj; Nicholls, Wayne; Offerhaus, Johan; Bodmer, Danielle; Wernstedt, Annekatrin; Krabichler, Birgit; Strasser, Ulrich; Nyström, Minna; Zschocke, Johannes; Robertson, Stephen P; van Haelst, Mieke M; Wimmer, Katharina

2013-01-01

Constitutional mismatch repair deficiency (CMMR-D) syndrome is a rare inherited childhood cancer predisposition caused by biallelic germline mutations in one of the four mismatch repair (MMR)-genes, MLH1, MSH2, MSH6 or PMS2. Owing to a wide tumor spectrum, the lack of specific clinical features and the overlap with other cancer predisposing syndromes, diagnosis of CMMR-D is often delayed in pediatric cancer patients. Here, we report of three new CMMR-D patients all of whom developed more than one malignancy. The common finding in these three patients is agenesis of the corpus callosum (ACC). Gray matter heterotopia is present in two patients. One of the 57 previously reported CMMR-D patients with brain tumors (therefore all likely had cerebral imaging) also had ACC. With the present report the prevalence of cerebral malformations is at least 4/60 (6.6%). This number is well above the population birth prevalence of 0.09-0.36 live births with these cerebral malformations, suggesting that ACC and heterotopia are features of CMMR-D. Therefore, the presence of cerebral malformations in pediatric cancer patients should alert to the possible diagnosis of CMMR-D. ACC and gray matter heterotopia are the first congenital malformations described to occur at higher frequency in CMMR-D patients than in the general population. Further systematic evaluations of CMMR-D patients are needed to identify possible other malformations associated with this syndrome.

Generalized overgrowth syndromes with prenatal onset.

PubMed

Yachelevich, Naomi

2015-04-01

Children with generalized overgrowth syndromes are large at birth, or have excessive postnatal growth. Many of these syndromes are associated with an increase in neoplasia. Consideration of the possibility of overgrowth syndrome in a pediatric patient who presents with increased growth parameters, variable malformations and neurodevelopmental phenotype, and distinctive features, is important for medical management, reproductive counseling, and tumor surveillance for some of the disorders. This review describes the clinical features and surveillance recommendations for the common generalized overgrowth syndromes the pediatrician may encounter. It also provides a glimpse into advances of recent years in understanding the molecular mechanisms responsible for the disrupted growth regulation in these disorders. Copyright © 2015 Mosby, Inc. All rights reserved.

Adult onset of the Dandy-Walker syndrome.

PubMed

Lipton, H L; Preziosi, T J; Moses, H

1978-10-01

Two patients with the Dandy-Walker malformation first developed neurologic symptoms in adult life. In both patients there was normal motor and intellectual development during childhood, but as adults they had gradual evolution of brain stem and cerebellar signs and obstructive hydrocephalus. Following resection of the fourth ventricular cyst, both patients recovered. A review of the literature disclosed seven additional patients in whom the Dandy-Walker syndrome was first diagnosed in adult life. These cases illustrate that this congenital brain malformation may not only first become symptomatic later in life, but that it is possible for patients to remain asymptomatic.

Cephalometric oropharynx and oral cavity analysis in Chiari malformation Type I: a retrospective case-control study.

PubMed

Urbizu, Aintzane; Ferré, Alex; Poca, Maria-Antonia; Rovira, Alex; Sahuquillo, Juan; Martin, Bryn A; Macaya, Alfons

2017-02-01

OBJECTIVE Traditionally, Chiari malformation Type I has been related to downward herniation of the cerebellar tonsils as a consequence of an underdeveloped posterior cranial fossa. Although the common symptoms of Chiari malformation Type I are occipital headaches, cervical pain, dizziness, paresthesia, and sensory loss, patients often report symptoms related to pharyngeal dysfunction such as choking, regurgitation, dysphagia, aspiration, chronic cough, and sleep disorders. In addition, tracheal intubation is often difficult in these patients. The purpose of this study was to analyze the morphological features of the oropharynx and oral cavity in patients with Chiari malformation Type I to help identify underlying anatomical anomalies leading to these debilitating symptoms. METHODS Seventy-six adult patients with symptomatic Chiari malformation Type I with cerebellar tonsillar descent greater than 5 mm below the foramen magnum and a small posterior cranial fossa and 49 sex-matched controls were selected to perform a retrospective case-control MRI-based morphometric study in a tertiary hospital. Eleven linear and areal parameters of the oropharyngeal cavity on midsagittal T1-weighted MRI were measured and the average values between patients and control cohorts were compared. Correlations between variables showing or approaching statistical significance in these structures and posterior cranial fossa measurements related with the occipital bone were sought. RESULTS Significant differences were detected for several oropharynx and oral cavity measures in the patient cohort, primarily involving the length and thickness of the soft palate (p = 9.5E-05 and p = 3.0E-03, respectively). A statistically significant (p < 0.01) moderate correlation between some of these variables and posterior cranial fossa parameters was observed. CONCLUSIONS The existence of structural oropharyngeal and oral cavity anomalies in patients with Chiari malformation Type I was confirmed, which may

Multiple capillary biochemical analyzer

DOEpatents

Dovichi, N.J.; Zhang, J.Z.

1995-08-08

A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber. One sideways dimension of the chamber is equal to the diameter of the capillaries and one end to end dimension varies from, at the top of the chamber, slightly greater than the sum of the diameters of the capillaries to, at the bottom of the chamber, slightly smaller than the sum of the diameters of the capillaries. The optical system utilizes optic fibers to deliver light to individual photodetectors, one for each capillary tube. A filter or wavelength division demultiplexer may be used for isolating fluorescence at particular bands. 21 figs.

Multiple capillary biochemical analyzer

DOEpatents

Dovichi, Norman J.; Zhang, Jian Z.

1995-01-01

A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber. One sideways dimension of the chamber is equal to the diameter of the capillaries and one end to end dimension varies from, at the top of the chamber, slightly greater than the sum of the diameters of the capillaries to, at the bottom of the chamber, slightly smaller than the sum of the diameters of the capillaries. The optical system utilizes optic fibres to deliver light to individual photodetectors, one for each capillary tube. A filter or wavelength division demultiplexer may be used for isolating fluorescence at particular bands.

Dandy-Walker Malformation Presenting with Affective Symptoms.

PubMed

Batmaz, Mert; Balçik, Zeynep Ezgi; Özer, Ürün; Hamurişçi Yalçin, Burcu; Özen, Şakir

2017-09-01

Dandy-Walker malformation is defined by enlarged posterior fossa, cystic dilatation of the fourth ventricle, and cerebellar hypoplasia. Although developmental delay and mental retardation are common in Dandy-Walker malformation cases, other comorbid psychiatric conditions have been rarely reported. There are limited numbers of case reports about comorbidity of bipolar disorder with Dandy-Walker malformation in the literature. Herein, a Dandy-Walker malformation case presenting affective symptoms is reported, and psychiatric symptoms which might be seen in this rare malformation are discussed along with diagnosis, treatment, and follow-up processes. A 27-year-old male patient, hospitalized for compulsory treatment, had been diagnosed with Dandy-Walker malformation in childhood. First complaints were attention deficiency, behavioral problems, learning difficulties; and manic and depressive episodes have occurred during follow-ups. He recently complained of decreased need for sleep, irritability, and increased speed of thought, and psychiatric examination was consistent with manic episode. Cranial computed tomography (CT) revealed bilateral ventriculomegaly, enlarged third and fourth ventricles with posterior fossa cyst, and cerebellar hypoplasia. His treatment included 30 mg/day aripiprazole, 1000 mg/day valproic acid, 200 mg/day quetiapine, 4 mg/day biperiden, and 100 mg/month paliperidone palmitate. Beside its traditional role in the regulation of coordination and motor functions, cerebellum is increasingly emphasized for its involvement in the mood regulation. Thus, as seen in Dandy-Walker malformation, cerebellar anomalies are suggested to play a role in the pathophysiology of mood disorders. Further studies are needed to better understand the relationship between mood disorders and cerebellum. Moreover, treatment options should be considered carefully in terms of resistance to treatment and potential side effects, for psychiatric disorders occurring in these

Computed tomography of congenital brain malformations

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

Sarwar, M.

1984-01-01

This book is illustrated showing each condition. This book is designed to correlate the pathology of CNS malformations with their CT scan appearance, mainly on the axial images. The author has drawn upon his personal experience and the information gleaned from the literature dealing with the description of the CT scan findings of these malformations. The emphasis is on simplicity of description. Since a large degree of morphological variation exists in each entity, numerous illustrations (wherever applicable) are shown to depict those variations. When appropriate, deficiency of the CT scan in the evaluation of these CNS malformations also is indicated.more » A description of CNS embryology is included as well.« less

Management of lymphatic malformations in children.

PubMed

Bagrodia, Naina; Defnet, Ann M; Kandel, Jessica J

2015-06-01

To review the literature on lymphatic malformations and to provide current opinion about the management of these lesions. Current treatment options include nonoperative management, surgery, sclerotherapy, radiofrequency ablation, and laser therapy. New therapies are emerging, including sildenafil, propranolol, sirolimus, and vascularized lymph node transfer. The primary focus of management centers on the patient's quality of life. Multimodal treatment of lymphatic malformations continues to expand as new information about the biology and genetics of these lesions is discovered, in addition to knowledge gained from clinical practice. A patient-centered approach should guide timing and modality of treatment. Continued study of lymphatic malformations will increase and solidify a treatment algorithm for these complicated lesions.

Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

PubMed Central

Lo Muzio, Lorenzo

2008-01-01

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic

Update on the management of anorectal malformations.

PubMed

Bischoff, Andrea; Levitt, Marc A; Peña, Alberto

2013-09-01

Thirty-three years ago, on 10 August 1980, in Mexico City, the first patient with an anorectal malformation was operated on using the posterior sagittal approach. At that time it was not obvious that we were actually opening a "Pandora's box" that continues to give many positive surprises, a few disappointments, and the constant hope that each day we can learn more about how to improve the quality of life of children born with all different types of anorectal malformations. In November 2012, patient number 3000 in our database was operated in the city of Cochabamba, Bolivia; during one of our International Courses of Anorectal Malformations and Colorectal Problems in Children. The goal of this article is to give a brief update on the current management of patients with anorectal malformation, based on the multiple lessons learned during this period.

Klippel-Feil syndrome and associated ear anomalies.

PubMed

Yildirim, Nadir; Arslanoğlu, Atilla; Mahiroğullari, Mahir; Sahan, Murat; Ozkan, Hüseyin

2008-01-01

Klippel-Feil syndrome (KFS) is a congenital segmentation anomaly of the cervical vertebrae that manifests as short neck, low hair line, and limited neck mobility. Various systemic malformations may also accompany the syndrome including wide variety of otopathologies affecting all 3 compartments of the ear (external, middle, and inner ear) as well as internal acoustic canal and vestibular aqueduct. We aimed to investigate these involvements and their clinical correlates in a group of patients with KFS. We present 20 KFS cases, of which 12 (% 60) displayed most of the reported ear abnormalities such as microtia, external ear canal stenosis, chronic ear inflammations and their sequels, anomalies of the tympanic cavity and ossicles, inner ear dysplasies, deformed internal acoustic canal, and wide vestibular aqueduct, which are demonstrated using the methods of otoscopy, audiologic testing, and temporal bone computed tomography. This series represents one of the highest reported rate of ear involvement in KFS. We found no correlation between the identified ear pathologies and the skeletal and extraskeletal malformations. The genetic nature of the syndrome was supported by the existence of affected family members in 4 (20%) of the cases.

Cerebro-fronto-facial syndrome type 3 with polymicrogyria: a clinical presentation of Baraitser-Winter syndrome.

PubMed

Eker, Hatice Koçak; Derinkuyu, Betül Emine; Ünal, Sevim; Masliah-Planchon, Julien; Drunat, Séverine; Verloes, Alain

2014-01-01

Baraitser-Winter syndrome (BRWS) is a rare condition affecting the development of the brain and the face. The most common characteristics are unusual facial appearance including hypertelorism and ptosis, ocular colobomas, hearing loss, impaired neuronal migration and intellectual disability. BRWS is caused by mutations in the ACTB and ACTG1 genes. Cerebro-fronto-facial syndrome (CFFS) is a clinically heterogeneous condition with distinct facial dysmorphism, and brain abnormalities. Three subtypes are identified. We report a female infant with striking facial features and brain anomalies (included polymicrogyria) that fit into the spectrum of the CFFS type 3 (CFFS3). She also had minor anomalies on her hands and feet, heart and kidney malformations, and recurrent infections. DNA investigations revealed c.586C>T mutation (p.Arg196Cys) in ACTB. This mutation places this patient in the spectrum of BRWS. The same mutation has been detected in a polymicrogyric patient reported previously in literature. We expand the malformation spectrum of BRWS/CFFS3, and present preliminary findings for phenotype-genotype correlation in this spectrum. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Mutations in zebrafish pitx2 model congenital malformations in Axenfeld-Rieger syndrome but do not disrupt left-right placement of visceral organs.

PubMed

Ji, Yongchang; Buel, Sharleen M; Amack, Jeffrey D

2016-08-01

Pitx2 is a conserved homeodomain transcription factor that has multiple functions during embryonic development. Mutations in human PITX2 cause autosomal dominant Axenfeld-Rieger syndrome (ARS), characterized by congenital eye and tooth malformations. Pitx2(-/-) knockout mouse models recapitulate aspects of ARS, but are embryonic lethal. To date, ARS treatments remain limited to managing individual symptoms due to an incomplete understanding of PITX2 function. In addition to regulating eye and tooth development, Pitx2 is a target of a conserved Nodal (TGFβ) signaling pathway that mediates left-right (LR) asymmetry of visceral organs. Based on its highly conserved asymmetric expression domain, the Nodal-Pitx2 axis has long been considered a common denominator of LR development in vertebrate embryos. However, functions of Pitx2 during asymmetric organ morphogenesis are not well understood. To gain new insight into Pitx2 function we used genome editing to create mutations in the zebrafish pitx2 gene. Mutations in the pitx2 homeodomain caused phenotypes reminiscent of ARS, including aberrant development of the cornea and anterior chamber of the eye and reduced or absent teeth. Intriguingly, LR asymmetric looping of the heart and gut was normal in pitx2 mutants. These results suggest conserved roles for Pitx2 in eye and tooth development and indicate Pitx2 is not required for asymmetric looping of zebrafish visceral organs. This work establishes zebrafish pitx2 mutants as a new animal model for investigating mechanisms underlying congenital malformations in ARS and high-throughput drug screening for ARS therapeutics. Additionally, pitx2 mutants present a unique opportunity to identify new genes involved in vertebrate LR patterning. We show Nodal signaling-independent of Pitx2-controls asymmetric expression of the fatty acid elongase elovl6 in zebrafish, pointing to a potential novel pathway during LR organogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Capillaries for use in a multiplexed capillary electrophoresis system

DOEpatents

Yeung, Edward S.; Chang, Huan-Tsang; Fung, Eliza N.

1997-12-09

The invention provides a side-entry optical excitation geometry for use in a multiplexed capillary electrophoresis system. A charge-injection device is optically coupled to capillaries in the array such that the interior of a capillary is imaged onto only one pixel. In Sanger-type 4-label DNA sequencing reactions, nucleotide identification ("base calling") is improved by using two long-pass filters to split fluorescence emission into two emission channels. A binary poly(ethyleneoxide) matrix is used in the electrophoretic separations.

Capillaries for use in a multiplexed capillary electrophoresis system

DOEpatents

Yeung, E.S.; Chang, H.T.; Fung, E.N.

1997-12-09

The invention provides a side-entry optical excitation geometry for use in a multiplexed capillary electrophoresis system. A charge-injection device is optically coupled to capillaries in the array such that the interior of a capillary is imaged onto only one pixel. In Sanger-type 4-label DNA sequencing reactions, nucleotide identification (``base calling``) is improved by using two long-pass filters to split fluorescence emission into two emission channels. A binary poly(ethyleneoxide) matrix is used in the electrophoretic separations. 19 figs.

Question mark ears, temporo-mandibular joint malformation and hypotonia: auriculo-condylar syndrome or a distinct entity?

PubMed

Priolo, M; Lerone, M; Rosaia, L; Calcagno, E P; Sadeghi, A K; Ghezzi, F; Ravazzolo, R; Silengo, M

2000-10-01

We report a boy with prominent, peculiarly malformed ears, abnormality of the ramus of the mandible and hypotonia. An isolated peculiar bilateral ear deformity named 'question mark ear' has been delineated in plastic reconstruction surgery reviews [Cosman et al., 1970 Plast Reconstr Surg 46:454-457; Cosman (1984) Plast Reconstr Surg 73:572-576; Takato et al. (1989) Ann Plast Surg 22:69-73; Brodovsky (1997) Plast Reconstr Surg 100:1254-1257; Park (1998) Plast Reconstr Surg 101:1620-1623; Al-Quattan (1998) Plast Reconstr Surg 102:439-441] and a similar deformity of the ear and changes in the temporo-mandibular joint and condyle has been described by Jampol et al. [(1998) Am J Med Genet 75:449-452] and by Guion-Almeida et al. [(1999) Am J Med Genet 86:130-133]. The present case may be the third description of this malformation complex with additional clinical features characterized by hypotonia and mild developmental delay, or possibly a new distinct entity.

HAEMORRHAGIC SYNDROME IN THE CLINICAL PICTURE OF RADIATION SICKNESS IN DOGS AFFECTED BY POLONIUM (in Russian)

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

Mikhailovich, S.M.

Subcutaneous introduction of polonium to dogs brings about development of radiation sickness with appearance of haemorrhagic syndrome, which is characterized by disturbed process of blood coagulation, thrombocytopenia, decreased prothrombin value of the blood, increased permeability of capillaries. The clinical picture of the usually developed affection corresponds to the well known symptomatology, described in literature. Indicators of the haemorrhagic syndrome (blood coagulation, prothrombin value, permeabillty and stability of capillaries) appear in animals earlier than the clinical manifestations of this syndrome. (tr-auth)

Congenital malformations of human dermatoglyphs

PubMed Central

David, T. J.

1973-01-01

A classification for congenital malformations of dermatoglyphs is presented, dividing them into ridge aplasia, ridge hypoplasia, ridge dissociation, ridges-off-the-end, and a combination of the last two. The medical and genetic significance of these are considered in the light both of previous published cases and of new material. Malformations of dermatoglyphs are important as physical signs in paediatric diagnosis. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7 PMID:4693462

Cantú Syndrome Resulting from Activating Mutation in the KCNJ8 Gene

PubMed Central

Cooper, Paige E.; Reutter, Heiko; Woelfle, Joachim; Engels, Hartmut; Grange, Dorothy K.; van Haaften, Gijs; van Bon, Bregje W.; Hoischen, Alexander; Nichols, Colin G.

2014-01-01

ATP-sensitive potassium (KATP) channels, composed of inward-rectifying potassium channel subunits (Kir6.1 and Kir6.2, encoded by KCNJ8 and KCNJ11, respectively) and regulatory sulfonylurea receptor (SUR1 and SUR2, encoded by ABCC8 and ABCC9, respectively), couple metabolism to excitability in multiple tissues. Mutations in ABCC9 cause Cantú syndrome, a distinct multi-organ disease, potentially via enhanced KATP channel activity. We screened KCNJ8 in an ABCC9 mutation-negative patient who also exhibited clinical hallmarks of Cantú syndrome (hypertrichosis, macrosomia, macrocephaly, coarse facial appearance, cardiomegaly, and skeletal abnormalities). We identified a de novo missense mutation encoding Kir6.1[p.Cys176Ser] in the patient. Kir6.1[p.Cys176Ser] channels exhibited markedly higher activity than wild-type channels, as a result of reduced ATP sensitivity, whether co-expressed with SUR1 or SUR2A subunits. Our results identify a novel causal gene in Cantú syndrome, but also demonstrate that the cardinal features of the disease result from gain of KATP channel function, not from Kir6-independent SUR2 function. PMID:24700710

Capillary reference half-cell

DOEpatents

Hall, Stephen H.

1996-01-01

The present invention is a reference half-cell electrode wherein intermingling of test fluid with reference fluid does not affect the performance of the reference half-cell over a long time. This intermingling reference half-cell may be used as a single or double junction submersible or surface reference electrode. The intermingling reference half-cell relies on a capillary tube having a first end open to reference fluid and a second end open to test fluid wherein the small diameter of the capillary tube limits free motion of fluid within the capillary to diffusion. The electrode is placed near the first end of the capillary in contact with the reference fluid. The method of operation of the present invention begins with filling the capillary tube with a reference solution. After closing the first end of the capillary, the capillary tube may be fully submerged or partially submerged with the second open end inserted into test fluid. Since the electrode is placed near the first end of the capillary, and since the test fluid may intermingle with the reference fluid through the second open end only by diffusion, this intermingling capillary reference half-cell provides a stable voltage potential for long time periods.

Capillary reference half-cell

DOEpatents

Hall, S.H.

1996-02-13

The present invention is a reference half-cell electrode wherein intermingling of test fluid with reference fluid does not affect the performance of the reference half-cell over a long time. This intermingling reference half-cell may be used as a single or double junction submersible or surface reference electrode. The intermingling reference half-cell relies on a capillary tube having a first end open to reference fluid and a second end open to test fluid wherein the small diameter of the capillary tube limits free motion of fluid within the capillary to diffusion. The electrode is placed near the first end of the capillary in contact with the reference fluid. The method of operation of the present invention begins with filling the capillary tube with a reference solution. After closing the first end of the capillary, the capillary tube may be fully submerged or partially submerged with the second open end inserted into test fluid. Since the electrode is placed near the first end of the capillary, and since the test fluid may intermingle with the reference fluid through the second open end only by diffusion, this intermingling capillary reference half-cell provides a stable voltage potential for long time periods. 11 figs.

DOORS syndrome: phenotype, genotype and comparison with Coffin-Siris syndrome.

PubMed

Campeau, Philippe M; Hennekam, Raoul C

2014-09-01

DOORS syndrome (Deafness, Onychodystrophy, Osteodystrophy, mental Retardation, Seizures) is characterized mainly by sensorineural deafness, shortened terminal phalanges with small nails of hands and feet, intellectual deficiency, and seizures. Half of the patients with all clinical features have mutations in TBC1D24. We review here the manifestations of patients clinically diagnosed with DOORS syndrome. In this cohort of 32 families (36 patients) we detected 13 individuals from 10 families with TBC1D24 mutations. Subsequent whole exome sequencing in the cohort showed the same de novoSMARCB1 mutation (c.1130G>A), known to cause Coffin-Siris syndrome, in two patients. Distinguishing features include retinal anomalies, Dandy-Walker malformation, scoliosis, rocker bottom feet, respiratory difficulties and absence of seizures, and 2-oxoglutaric aciduria in the patients with the SMARCB1 mutation. We briefly discuss the heterogeneity of the DOORS syndrome phenotype and the differential diagnosis of this condition. © 2014 Wiley Periodicals, Inc.

Implant rehabilitation for a patient with Hallerman-Streiff syndrome: a case report.

PubMed

Abadi, Behruz J; Van Sickels, Joseph E; McConnell, Thomas A; Kluemper, G Thomas

2009-01-01

Hallermann-Streiff syndrome is a rare genetic disorder characterized by craniofacial malformations, sparse hair, eye abnormalities, dental defects, degenerative skin changes, and short stature. The syndrome has many implications for dental treatment. Patients typically present with multiple missing and poorly formed teeth. The purpose of this case report is to discuss the overall management of a patient with Hallermann-Streiff syndrome by oral maxillofacial surgery, orthodontic treatment, and prosthodontic reconstruction.

Sirolimus for the Treatment of a Massive Capillary-Lymphatico-Venous Malformation: A Case Report.

PubMed

Vlahovic, Aleksandar M; Vlahovic, Natasa S; Haxhija, Emir Q

2015-08-01

Management of patients with complex vascular anomalies (VAs) is often associated with significant morbidity and mortality because of the lack of effective treatment modalities that may lead to significant improvement of the disease and/or healing. Recently, reports of treatment of patients with complex VAs with sirolimus revealed encouraging results. Sirolimus inhibits the mammalian target of rapamycin, which acts as a master switch of numerous cellular processes. We report a successful use of sirolimus for the treatment of a patient with a complex CLVM of the trunk and the right lower extremity believed to be untreatable. Our patient had 44 hospitalizations during the 10-year period, with various unsuccessful treatments and continuous deterioration of his clinical condition, ending up in a wheelchair. His condition reversed to normal everyday activities 9 months after initiation of sirolimus therapy. We conclude that sirolimus is a very promising therapeutic option for children with complex VAs of capillary-lymphatico-venous type. Copyright © 2015 by the American Academy of Pediatrics.

Effect of Capillary Tube’s Shape on Capillary Rising Regime for Viscos Fluids

NASA Astrophysics Data System (ADS)

Soroush, F.; Moosavi, A.

2018-05-01

When properties of the displacing fluid are considered, the rising profile of the penetrating fluid in a capillary tube deviates from its classical Lucas-Washburn profile. Also, shape of capillary tube can affect the rising profile in different aspects. In this article, effect of capillary tube’s shape on the vertical capillary motion in presence of gravity is investigated by considering the properties of the displacing fluid. According to the fact that the differential equation of the capillary rising for a non-simple wall type is very difficult to solve analytically, a finite element simulation model is used for this study. After validation of the simulation model with an experiment that has been done with a simple capillary tube, shape of the capillary tube’s wall is changed in order to understand its effects on the capillary rising and different motion regimes that may appear according to different geometries. The main focus of this article is on the sinusoidal wall shapes and comparing them with a simple wall.

Heterotaxy syndrome with severe pulmonary hypertension in an adult.

PubMed

Brandenburg, Vincent M; Krueger, Stefan; Haage, Patrick; Mertens, Peter; Riehl, Jochen

2002-05-01

Heterotaxy syndrome is a rare clinical entity in adults, characterized by situs ambiguus, congenital heart defects, and splenic malformations. We report the case of an adult with heterotaxy syndrome (including situs ambiguus, bilateral superior vena cava, hypoplastic right-sided spleen and portosystemic shunts) presenting with dyspnea due to severe pulmonary hypertension. Vasodilatory therapy was initiated, leading to marked reduction of clinical symptoms. This case exhibits 2 particular and partially novel features: primary diagnosis of heterotaxy syndrome may be delayed until adulthood, and heterotaxy syndrome may be associated with pulmonary hypertension, possibly on the basis of longstanding portosystemic shunts.

Moyamoya Vasculopathy in PHACE Syndrome: Six New Cases and Review of the Literature.

PubMed

Tortora, Domenico; Severino, Mariasavina; Accogli, Andrea; Martinetti, Carola; Vercellino, Nadia; Capra, Valeria; Rossi, Andrea; Pavanello, Marco

2017-12-01

PHACE syndrome (Posterior fossa malformations, large cervicofacial infantile Hemangiomas, Arterial anomalies, aortic coarctation and Cardiac abnormalities, and Eye abnormalities) is a neurocutaneous disorder including posterior fossa malformations, hemangiomas, arterial lesions, cardiac defects, and eye abnormalities. PHACE arteriopathies may be progressive and recently have been categorized based on the risk of acute ischemic stroke, increasing attention to the potentially devastating consequences of cerebrovascular complications in this syndrome. In contrast, the natural history of arteriopathy in PHACE syndrome remains poorly understood. At the moment, there are no established surgical guidelines for high-risk vasculopathies, including quasi-moyamoya, in this syndrome. We described the clinicoradiologic features of a small series of 6 patients with PHACE syndrome and quasi-moyamoya (5 female, age range 4 months to 12 years), focusing on the clinical course and surgical outcome of 3 children who were treated with encephaloduroarteriosynangiosis and encephalomyosynangiosis. In addition, we reviewed the radiologic, clinical, and surgical aspects of moyamoya vasculopathy in PHACE syndrome, providing information on 15 additional published cases. Although the natural history of arteriopathy in PHACE syndrome is poorly understood, patients with high-risk vasculopathies, such as quasi-moyamoya disease, may benefit of revascularization by using encephaloduroarteriosynangiosis and encephalomyosynangiosis. Copyright © 2017 Elsevier Inc. All rights reserved.

The Smith-Lemli-Opitz syndrome

PubMed Central

Kelley, R.; Hennekam, R.

2000-01-01

The Smith-Lemli-Opitz syndrome (SLOS) is one of the archetypical multiple congenital malformation syndromes. The recent discovery of the biochemical cause of SLOS and the subsequent redefinition of SLOS as an inborn error of cholesterol metabolism have led to important new treatment possibilities for affected patients. Moreover, the recent recognition of the important role of cholesterol in vertebrate embryogenesis, especially with regard to the hedgehog embryonic signalling pathway and its effects on the expression of homeobox genes, has provided an explanation for the abnormal morphogenesis in the syndrome. The well known role of cholesterol in the formation of steroid hormones has also provided a possible explanation for the abnormal behavioural characteristics of SLOS.


Keywords: Smith-Lemli-Opitz syndrome; cholesterol metabolism; 7-dehydrocholesterol reductase; clinical history; management PMID:10807690

Slide tracheoplasty outcomes in children with congenital pulmonary malformations.

PubMed

DeMarcantonio, Michael A; Hart, Catherine K; Yang, Christina J; Tabangin, Meredith; Rutter, Michael J; Bryant, Roosevelt; Manning, Peter B; de Alarcón, Alessandro

2017-06-01

Evaluate and compare surgical outcomes of slide tracheoplasty for the treatment of congenital tracheal stenosis in children with and without pulmonary malformations. Retrospective chart review at a tertiary care pediatric medical center. We identified patients with tracheal stenosis who underwent slide tracheoplasty from 2001 to 2014, and a subset of these patients who were diagnosed with congenital pulmonary malformations. Hospital course and preoperative and postoperative complications were recorded. One hundred thirty patients (18 with pulmonary malformations, 112 with normal pulmonary anatomy) were included. Pulmonary malformations included unilateral pulmonary agenesis (61%) and hypoplasia (39%). Children with pulmonary malformations had a greater median age compared to their normal lung anatomy counterparts. Preoperatively, patients with pulmonary malformations more frequently required preoperative mechanical ventilation (55.6% vs. 21.3%, P = .007), extracorporeal membrane oxygenation (ECMO) (11% vs. 0.9%, P = .05), and tracheostomy (22.2% vs. 3.6%, P = .01). Postoperatively, patients with pulmonary malformations more frequently required mechanical ventilation >48 hours (78% vs. 37%, P =.005) and ECMO use (11% vs. 0.9%, P = .05). Pulmonary malformation patients and children with normal anatomy did not differ in terms of postoperative tracheostomy (16.7% vs. 4.4%, P > .05), dehiscence (6% vs. 0%, P > .05%), restenosis (11% vs. 6%, P > .05) or postoperative figure 8 deformity (6% vs. 3%, P > .05). Mortality, however, was significantly increased (22.2% vs. 3.6%, P = .01) in children with pulmonary malformations. Although slide tracheoplasty can be successfully performed in patients with abnormal pulmonary anatomy, surgeons and families should anticipate a more difficult postoperative course, with possible associated prolonged mechanical ventilation, ECMO use, and higher mortality than in children with tracheal stenosis alone. 4. Laryngoscope, 127:1283-1287, 2017

Ellis-van Creveld syndrome in adulthood: extending the clinical spectrum

PubMed Central

Pérez-Andreu, Joaquín; Ray, Victor Glenn; Arribas, José María; Sánchez, Sergio Juan

2015-01-01

Ellis-van Creveld (EvC) syndrome is a rare autosomal recessive malformation disorder. Cardiac defects are observed in about 50% of EvC cases. Surgical data is lacking on the prognosis and life expectancy of EvC patients. Herein, we report the case of a 38-year-old man with EvC syndrome who underwent two surgical corrections for cardiac anomalies. This report supplements the available information on the clinical course of EvC syndrome in older patients. PMID:26106249

Focal cortical malformations in children with early infantile epilepsy and PCDH19 mutations: case report.

PubMed

Kurian, Mary; Korff, Christian M; Ranza, Emmanuelle; Bernasconi, Andrea; Lübbig, Anja; Nangia, Srishti; Ramelli, Gian Paolo; Wohlrab, Gabriele; Nordli, Douglas R; Bast, Thomas

2018-01-01

In this case report we assess the occurrence of cortical malformations in children with early infantile epilepsy associated with variants of the gene protocadherin 19 (PCDH19). We describe the clinical course, and electrographic, imaging, genetic, and neuropathological features in a cohort of female children with pharmacoresistant epilepsy. All five children (mean age 10y) had an early onset of epilepsy during infancy and a predominance of fever sensitive seizures occurring in clusters. Cognitive impairment was noted in four out of five patients. Radiological evidence of cortical malformations was present in all cases and, in two patients, validated by histology. Sanger sequencing and Multiplex Ligation-dependent Probe Amplification analysis of PCDH19 revealed pathogenic variants in four patients. In one patient, array comparative genomic hybridization showed a microdeletion encompassing PCDH19. We propose molecular testing and analysis of PCDH19 in patients with pharmacoresistant epilepsy, with onset in early infancy, seizures in clusters, and fever sensitivity. Structural lesions are to be searched in patients with PCDH19 pathogenic variants. Further, PCDH19 analysis should be considered in epilepsy surgery evaluation even in the presence of cerebral structural lesions. Focal cortical malformations and monogenic epilepsy syndromes may coexist. Structural lesions are to be searched for in patients with protocadherin 19 (PCDH19) pathogenic variants with refractory focal seizures. © 2017 Mac Keith Press.

Chronic cerebral herniation in shunted Dandy-Walker malformation.

PubMed

Naidich, T P; Radkowski, M A; McLone, D G; Leestma, J

1986-02-01

A review of serial computed tomography (CT) scans of 25 patients with the Dandy-Walker malformation revealed six patients with chronic downward transincisural herniation of the cerebrum after shunt decompression of the posterior fossa cyst or malfunction of a lateral ventricular drainage catheter, or both. Chronic cerebral herniation was detected postmortem in a seventh patient with the Dandy-Walker malformation. The CT findings and autopsy appearance of this previously undescribed feature of shunted Dandy-Walker malformation are illustrated.

Head and neck vascular malformations: time-resolved MR projection angiography.

PubMed

Ziyeh, S; Schumacher, M; Strecker, R; Rössler, J; Hochmuth, A; Klisch, J

2003-10-01

Extracranial vascular anomalies can be divided into haemangiomas and vascular malformations. The latter can be subdivided on the basis of the predominant type of vascular channels. Separation of high- and low-flow vascular malformations is of clinical importance. We report preliminary observations on time-resolved magnetic resonance projection angiography (MRPA) of vascular malformations of the head and neck. We examined eight patients with vascular anomalies of the head and neck. On MRPA the time between the early arterial phase and enhancement of the malformation could be used to distinguish high- and low-flow lesions. High-flow arteriovenous malformations showed early, intense enhancement. Venous malformations were either not visible on MRPA or showed late enhancement of veins. One patient was examined after embolisation of an arteriovenous fistula of the mandible. Normal MRPA was taken to indicate absence of a residual lesion.

A case of pancreatic AV malformation in an elderly man.

PubMed

Gupta, Vipin; Kedia, Saurabh; Sonika, Ujjwal; Madhusudhan, Kumble Seetharama; Pal, Sujoy; Garg, Pramod

2018-06-01

A 60-year-old man presented with recurrent abdominal pain and weight loss for 6 months. Abdominal imaging showed a large vascular lesion in the head and neck of pancreas suggestive of arteriovenous malformation (AV malformation). Endoscopic ultrasound was done which showed features of AV malformation with no evidence of pancreatic malignancy. Surgery was planned for definitive treatment of malformation. Digital subtraction angiography with angioembolization was done prior to surgery to reduce vascularity of the lesion. He recovered after a pylorus preserving pancreaticoduodenectomy. Histopathology of the resected specimen confirmed the pancreatic AV malformation. There has been no recurrence at 2 years of follow-up.

[Association between Williams syndrome and adrenal insufficiency].

PubMed

Rchachi, Meryem; Larwanou, Maazou Mahamane; El Ouahabi, Hanan; Ajdi, Farida

2017-01-01

Williams syndrome is a developmental disorder including dysmorphia, cardiovascular malformations and a specific neuropsychological profile together with other associated disorders. We report the case of a 17-year old girl, born of a non-inbred marriage, with Williams syndrome discovered during an assessment of degree of failure to thrive. Its association with primary adrenal insufficiency makes it unique. Diagnosis is confirmed by cytogenetic and molecular analysis. Its management consists of the implementation of treatment for adrenal insufficiency associated with a clinico-biological monitoring.

Chromosome 6p25 deletion syndrome: report of a case with optic disc coloboma and review of published ophthalmic findings.

PubMed

Beby, Francis; Des Portes, Vincent; Till, Marianne; Mottolese, Carmine; Denis, Philippe

2012-12-01

The 6p25 deletion syndrome is a rare disorder characterized by Dandy-Walker malformation, congenital heart defects, developmental delay, dysmorphic facial features, and malformations of the anterior segment of the eye with a risk for glaucoma. Here we report a child harboring a cryptic de novo 6p25 deletion, bilateral optic disc coloboma and characteristic anterior segment anomalies. We review reported ophthalmic findings in patients with this syndrome. Retrospective case review of a 4-day-old male with Dandy-Walker malformation and cardiac defects who was referred with a suspected diagnosis of iris coloboma. The ophthalmic examination showed bilateral corectopia associated with posterior embryotoxon. Fundus examination revealed bilateral optic disc excavation, which was diagnosed as colobomatous because of its configuration and stability over time. Because of the association of posterior embryotoxon with Dandy-Walker malformation, a terminal 6p deletion syndrome was clinically suspected. Array comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies revealed a 3.2 Mb deletion at 6p25.2p25.3 including the FOXC1 gene. Neither unaffected parent carried this deletion. Optic disc colobomas may be found in patients carrying a 6p25 deletion. This has the potential to confound assessment of affected children for glaucoma and intracranial hypertension.

[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.

Continuous glucose monitoring in acute coronary syndrome.

PubMed

Rodríguez-Quintanilla, Karina Alejandra; Lavalle-González, Fernando Javier; Mancillas-Adame, Leonardo Guadalupe; Zapata-Garrido, Alfonso Javier; Villarreal-Pérez, Jesús Zacarías; Tamez-Pérez, Héctor Eloy

2013-01-01

Diabetes mellitus is an independent risk factor for cardiovascular disease. To compare the efficacy of devices for continuous glucose monitoring and capillary glucose monitoring in hospitalized patients with acute coronary syndrome using the following parameters: time to achieve normoglycemia, period of time in normoglycemia, and episodes of hypoglycemia. We performed a pilot, non-randomized, unblinded clinical trial that included 16 patients with acute coronary artery syndrome, a capillary or venous blood glucose ≥ 140 mg/dl, and treatment with a continuous infusion of fast acting human insulin. These patients were randomized into 2 groups: a conventional group, in which capillary measurement and recording as well as insulin adjustment were made every 4h, and an intervention group, in which measurement and recording as well as insulin adjustment were made every hour with a subcutaneous continuous monitoring system. Student's t-test was applied for mean differences and the X(2) test for qualitative variables. We observed a statistically significant difference in the mean time for achieving normoglycemia, favoring the conventional group with a P = 0.02. Continuous monitoring systems are as useful as capillary monitoring for achieving normoglycemia. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Dandy-Walker Malformation Presenting with Affective Symptoms

PubMed Central

BATMAZ, Mert; BALÇIK, Zeynep Ezgi; ÖZER, Ürün; HAMURİŞÇİ YALÇIN, Burcu; ÖZEN, Şakir

2017-01-01

Dandy-Walker malformation is defined by enlarged posterior fossa, cystic dilatation of the fourth ventricle, and cerebellar hypoplasia. Although developmental delay and mental retardation are common in Dandy-Walker malformation cases, other comorbid psychiatric conditions have been rarely reported. There are limited numbers of case reports about comorbidity of bipolar disorder with Dandy-Walker malformation in the literature. Herein, a Dandy-Walker malformation case presenting affective symptoms is reported, and psychiatric symptoms which might be seen in this rare malformation are discussed along with diagnosis, treatment, and follow-up processes. A 27-year-old male patient, hospitalized for compulsory treatment, had been diagnosed with Dandy-Walker malformation in childhood. First complaints were attention deficiency, behavioral problems, learning difficulties; and manic and depressive episodes have occurred during follow-ups. He recently complained of decreased need for sleep, irritability, and increased speed of thought, and psychiatric examination was consistent with manic episode. Cranial computed tomography (CT) revealed bilateral ventriculomegaly, enlarged third and fourth ventricles with posterior fossa cyst, and cerebellar hypoplasia. His treatment included 30 mg/day aripiprazole, 1000 mg/day valproic acid, 200 mg/day quetiapine, 4 mg/day biperiden, and 100 mg/month paliperidone palmitate. Beside its traditional role in the regulation of coordination and motor functions, cerebellum is increasingly emphasized for its involvement in the mood regulation. Thus, as seen in Dandy-Walker malformation, cerebellar anomalies are suggested to play a role in the pathophysiology of mood disorders. Further studies are needed to better understand the relationship between mood disorders and cerebellum. Moreover, treatment options should be considered carefully in terms of resistance to treatment and potential side effects, for psychiatric disorders occurring in these

Capillary Structures for Exploration Life Support (Capillary Structures)

NASA Image and Video Library

2017-07-10

iss052e013081 (7/10/2017) --- The Capillary Structures for Exploration Life Support (Capillary Structures) investigation studies a new method using structures of specific shapes to manage fluid and gas mixtures. The investigation studies water recycling and carbon dioxide removal, benefiting future efforts to design lightweight, more reliable life support systems for future space missions.

[Toe transplantation in congenital malformations of the hand].

PubMed

Foucher, G

1997-11-01

Toe transfer is a well established procedure for thumb and finger reconstruction after mutilation. The indications in congenital malformations are a mater of controversy. Out of a personal series of 209 patients, 42 were children presenting a congenital malformation. Thirty six, with 46 transfers were available for review. There is only one failure at the beginning of our experience. The main indication was absence of pinch either due to absence of thumb (like in congenital band syndrome or some extreme cases of ulnar club hand or cleft hand) or absence of long finger (like in symbrachydactyly monodactylous type) or lack of both thumb and finger (like in peromelic type of symbrachydactyly). In this last type, we have been disappointed by the functional result of the distal implantation of two second toes taken from both feet; we have proposed a "stub" operation consisting in a second toe transfer on the anterior aspect of the radial epiphysis to take advantage of the mobility of the wrist and the availability of plenty tendon transfer (in this proximal situation). When planing to "built" an absent pincer, an early age is mandatory for operation (mean 12 months), to ensure a good cortical integration. A less frequent indication is a partial toe transfer with a vascularized epiphysis to provide growth and mobility in some cases of thumb hypoplasia (like in symbrachydactyly or Blauth and Manske type III b). Results are difficult to assess due to the early operation but if the mobility has been disappointing (mean 32 degrees), sensibility (mean 2PD 5 mm) and growth were excellent.

Abernethy malformation: a case report

PubMed Central

2012-01-01

Background Abernethy malformation is a very rare congenital vascular malformation defined by diversion of portal blood away from liver. It is commonly associated with multiple congenital anomalies. We present a case of Abernethy malformation, without associated congenital anomalies from India. Case presentation A 5-year-old female child presented with short history of jaundice. A provisional diagnosis of acute viral hepatitis was made in view of clinical presentation and local endemicity of viral hepatitis A. Persistence of jaundice on follow up after 4 weeks led to detailed investigations. Ultrasound and doppler study of abdomen revealed drainage of portal vein into inferior vena cava. CT angiography was performed which confirmed the diagnosis of Type 1 b Abernethy malformation without associated major anomalies. We discuss the common clinical presentations, associated anomalies, diagnostic workup and treatment options of this disorder. Conclusion The treatment of the patients with congenital porto-systemic shunts depends on the site of the shunt, associated congenital anomalies and the extent of liver damage but the prognosis depends on the complications irrespective of anatomical type. However, the extent of associated abnormalities should not deter paediatricians to refer patients for treatment. Whenever possible closure of the shunt should be advised for cure or to prevent complications. Only symptomatic type I patients with absence of possibility to close the shunt may require liver transplant. Long-term follow-up is indicated for all patients. PMID:22642663

Field guide to malformations of frogs and toads: with radiographic interpretations

USGS Publications Warehouse

Meteyer, Carol U.

2000-01-01

In 1995, students found numerous malformed frogs on a field trip to a Minnesota pond. Since that time, reports of malformed frogs have increased dramatically. Malformed frogs have now been reported in 44 states in 38 species of frogs, and 19 species of toads. Estimates as high as 60% of the newly metamorphosed frog populations have had malformations at some ponds (NARCAM, ’99). The wide geographic distribution of malformed frogs and the variety of malformations are a concern to resource managers, research scientists and public health officials. The potential for malformations to serve as a signal of ecosystem disruption, and the affect this potential disruption might have on other organisms that share those ecosystems, has not been resolved. Malformations represent an error that occurred early in development. The event that caused the developmental error is temporally distant from the malformation we see in the fully developed animal. Knowledge of normal developmental principles is necessary to design thoughtful investigations that will define the events involved in abnormal development in wild frog populations.Development begins at the time an egg is fertilized and progresses by chemical communication between cells and cell layers. This communication is programmed through gene expression. Malformations represent primary errors in development, errors in chemical communication or translation of genetic information. Deformations arise later in development and usually result from the influence of mechanical factors (such as amputation) that alter shape or anatomy of a structure that has developed normally. The occurrence and the type of malformations are influenced by the type of error or insult as well as the timing of the error (the developmental stage at which the error occurred). The appearance of the malformation can therefore provide clues that suggest when the error may have occurred. If the malformation is an incomplete organ, such as an incomplete limb, the

Congenital heart defects in newborns with apparently isolated single gastrointestinal malformation: A retrospective study.

PubMed

Schierz, Ingrid Anne Mandy; Pinello, Giuseppa; Giuffrè, Mario; La Placa, Simona; Piro, Ettore; Corsello, Giovanni

2016-12-01

Congenital gastrointestinal system malformations/abdominal wall defects (GISM) may appear as isolated defects (single or complex), or in association with multiple malformations. The high incidence of association of GISM and congenital heart defects (CHD) in patients with syndromes and malformative sequences is known, but less expected is the association of apparently isolated single GISM and CHD. The aim of this study was to investigate the frequency of CHD in newborns with isolated GISM, and the possibility to modify the diagnostic-therapeutic approach just before the onset of cardiac symptoms or complications. Anamnestic, clinical, and imaging data of newborns requiring abdominal surgery for GISM, between 2009 and 2014, were compared with a control group of healthy newborns. Distribution of GISM and cardiovascular abnormalities were analyzed, and risk factors for adverse outcomes were identified. Seventy-one newborns with isolated GISM were included in this study. More frequent GISM were intestinal rotation and fixation disorders. CHD were observed in 15.5% of patients, augmenting their risk for morbidity. Risk factors for morbidity related to sepsis were identified in central venous catheter, intestinal stoma, and H2-inhibitor-drugs. Moreover, 28.2% of newborns presented only functional cardiac disorders but an unexpectedly higher mortality. The high incidence of congenital heart disease in infants with apparently isolated GISM confirms the need to perform an echocardiographic study before surgery to improve perioperative management and prevent complications such as sepsis and endocarditis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

CONGENITAL HEART MALFORMATIONS IN NEWBORN BABIES WITH LOW BIRTH WEIGHT.

PubMed

Luca, Alina-Costina; Holoc, Andreea-Simona; Iordache, C

2015-01-01

Congenital heart malformations represent a public health problem, holding a significant percentage of the total of heart diseases. Beside the elevated frequency of the malformations, we also notice their occurrence in newborn babies with low birth weight, increasing, thus, the risk of complications and late therapeutic approach. The goal of the study was to highlight the general and particular aspects of cardiovascular malformations epidemiology in newborn babies with low weight at birth, the correlation of the malformations with implied genetic and environmental factors, assessing the complications and their procedures on the therapeutic management. Our study was performed on a group of 271 patients, hospitalized in the Department of Pediatric Cardiology of "Sf. Maria" Emergency Clinical Hospital for Children of Iasi, during January 2011-December 2013. The patients were assessed based on anamnesis, clinical, biological and imagistic exam. The study lot was divided according to the type of the structural defect: 95% of the patients were diagnosed with non-cyanogenic congenital heart malformations and 5% with cyanogenic congenital heart malformations. Regarding the patient's origin background, we notice an elevated frequency of the rural environment (71%). The incidence of the malformations was high in premature low birth weight (48%), followed by premature very low birth weight (22%). In evolution, congenital heart malformations often get more complicated heart failure, arterial hypertension and respiratory infections being most often met. Mortality was maximum in the first year of life, a third of the cases being associated with chromosomal malformations. Congenital heart malformations in newborn patients with low weight at birth represented an elevated percentage of 44.13% of the total of the cases hospitalized for cardiovascular diseases from the Department of Pediatric Cardiology of Iasi. Many cases were associated with other congenital malformations or

In utero oxcarbazepine and a withdrawal syndrome, anomalies, and hyponatremia.

PubMed

Rolnitsky, Asaph; Merlob, Paul; Klinger, Gil

2013-06-01

Oxcarbazepine is an antiepileptic agent that has been used during pregnancy, although its safety during pregnancy has not been sufficiently established. This article presents an infant born with renal and cardiac malformations who developed a withdrawal syndrome and hyponatremia following in utero exposure to oxcarbazepine. The infant was born at 35 weeks' gestation by urgent cesarean section to a mother in status epilepticus who had been treated with oxcarbazepine throughout her pregnancy. Evaluation for congenital anomalies identified mild aortic stenosis, a bicuspid aortic valve, patent foramen ovale, patent ductus arteriosus, and severe left hydronephrosis due to left ureteropelvic junction stenosis. On the third day of life the infant developed clinical signs of a withdrawal syndrome, which peaked on day 7 and resolved by day 12. Transient hyponatremia resolved by day 8 of life. Follow-up showed normal development at 15 months. The association of a withdrawal syndrome with oxcarbazepine exposure has not been previously reported. The hyponatremia is consistent with adult reports. The possible association of oxcarbazepine with renal and cardiac malformations requires further confirmation. Copyright © 2013 Elsevier Inc. All rights reserved.

Dandy-Walker malformation: a rare association with hypoparathyroidism.

PubMed

Coban, Dilek; Akin, Mustafa Ali; Kurtoglu, Selim; Oktem, Suat; Yikilmaz, Ali

2010-12-01

Dandy-Walker malformation is characterized by cystic dilatation of the fourth ventricle and an enlarged posterior cranial fossa with upward displacement of the tentorium, lateral sinuses, and torcular, with agenesis or hypoplasia of the cerebellar vermis. Dandy-Walker malformation occurs in approximately the 4th week of gestation and is associated with various abnormalities involving the cardiac, skeletal, genitourinary, and gastrointestinal systems. The parathyroid gland also forms in the 3rd and 4th gestational weeks. Reported here is the case of a male infant with Dandy-Walker malformation with ventricular and atrial septal defect, unilateral renal agenesis, and hypoparathyroidism. To our knowledge, this rare association with neural crest events during the development of Dandy-Walker malformation has not been reported previously. Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

Lethal acrodysgenital dwarfism: a severe lethal condition resembling Smith-Lemli-Opitz syndrome.

PubMed Central

Merrer, M L; Briard, M L; Girard, S; Mulliez, N; Moraine, C; Imbert, M C

1988-01-01

We report eight cases of a lethal association of failure to thrive, facial dysmorphism, ambiguous genitalia, syndactyly, postaxial polydactyly, and internal developmental anomalies (Hirschsprung's disease, cardiac and renal malformation). This syndrome is likely to be autosomal recessive and resembles Smith-Lemli-Opitz (SLO) syndrome. However, the lethality, the common occurrence of polydactyly, and the sexual ambiguity distinguishes this condition from SLO syndrome. A review of published reports supports the separate classification of this syndrome for which we propose the name lethal acrodysgenital dwarfism. Images PMID:2831368

Abnormal brain magnetic resonance imaging in two patients with Smith-Magenis syndrome.

PubMed

Maya, Idit; Vinkler, Chana; Konen, Osnat; Kornreich, Liora; Steinberg, Tamar; Yeshaya, Josepha; Latarowski, Victoria; Shohat, Mordechai; Lev, Dorit; Baris, Hagit N

2014-08-01

Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion in chromosome 17p11.2. Seventy percent of SMS patients have a common deletion interval spanning 3.5 megabases (Mb). Clinical features of SMS include characteristic mild dysmorphic features, ocular anomalies, short stature, brachydactyly, and hypotonia. SMS patients have a unique neurobehavioral phenotype that includes intellectual disability, self-injurious behavior and severe sleep disturbance. Little has been reported in the medical literature about anatomical brain anomalies in patients with SMS. Here we describe two patients with SMS caused by the common deletion in 17p11.2 diagnosed using chromosomal microarray (CMA). Both patients had a typical clinical presentation and abnormal brain magnetic resonance imaging (MRI) findings. One patient had subependymal periventricular gray matter heterotopia, and the second had a thin corpus callosum, a thin brain stem and hypoplasia of the cerebellar vermis. This report discusses the possible abnormal MRI images in SMS and reviews the literature on brain malformations in SMS. Finally, although structural brain malformations in SMS patients are not a common feature, we suggest baseline routine brain imaging in patients with SMS in particular, and in patients with chromosomal microdeletion/microduplication syndromes in general. Structural brain malformations in these patients may affect the decision-making process regarding their management. © 2014 Wiley Periodicals, Inc.

Vascular anomalies of the head and neck: a review of genetics.

PubMed

Yadav, Prashant; De Castro, Dawn K; Waner, Milton; Meyer, Lutz; Fay, Aaron

2013-01-01

Vascular anomalies comprise malformations, hemangiomas, and rare tumors. The commonality among these lesions is their origin in vascular endothelia. Most occur sporadically, but occasional inheritance is observed and thus allows genetic research and insight into etiology. This review highlights those vascular anomalies in which genetic inheritance has been demonstrated. A comprehensive literature search was performed on PubMed. Fifty-five full-length articles were reviewed. Five categories of vascular anomalies with patterned inheritance were identified: arteriovenous malformation (AVM), capillary malformation (CM), lymphatic malformation (LM), venous malformation (VM), and infantile hemangioma (IH). Capillary and arteriovenous malformation subtypes are associated with a RASA-1 gene mutation and show autosomal dominant inheritance. VEGFR3 mutations have been associated with generalized forms of LM and lymphedema. Mutations in TIE2/TEK genes cause inherited forms of venous malformations also with autosomal dominant inheritance. Familial clustering and atopic disease are associated with infantile hemangioma, and gene expression varies with the developmental stage of these lesions. Most vascular anomalies occur sporadically, but several genes and genetic disorders have been associated with them. Specific forms of capillary malformation appear to be most convincingly associated with genomic errors. Further research promises new insights into the development of this diverse group of disorders.

Horseshoe kidney with growth retardation: Don't forget Turner syndrome.

PubMed

Arslansoyu-Çamlar, Seçil; Soylu, Alper; Abacı, Ayhan; Türkmen, Mehmet Atilla; Ülgenalp, Ayfer; Kavukçu, Salih

2016-01-01

Horseshoe kidney is the most frequent renal fusion anomaly that is usually asymptomatic and isolated malformation. However it can be seen with various syndromes and chromosomal anomalies. It was reported that 15-35% of Turner syndrome cases (TS) also display horseshoe kidney condition. TS is a chromosomal anomaly that had been characterized by delayed puberty, short body height and gonadal dysgenesis. In this report a five-year-old girl with horseshoe kidney, which has growth retardation during follow-up as only symptom of Turner syndrome.

Anaesthetic management of a child with massive extracranial arteriovenous malformation

PubMed Central

Shamim, Faisal; Ullah, Hameed; Rehman, Azhar

2012-01-01

Vascular tumors affect the head and neck commonly but arteriovenous malformations are rare. Vascular malformations are often present at birth and grow with the patient, usually only becoming significant later in childhood. Embolization has been the mainstay of treatment in massive and complex arteriovenous malformations. We present a case of massive extracranial arteriovenous malformation in a 7-year-old boy causing significant workload on right heart and respiratory distress. The management of angioembolization under general anaesthesia and anaesthetic concerns are presented. PMID:22345959

cis-Regulatory Mutations Are a Genetic Cause of Human Limb Malformations

PubMed Central

VanderMeer, Julia E.; Ahituv, Nadav

2011-01-01

The underlying mutations that cause human limb malformations are often difficult to determine, particularly for limb malformations that occur as isolated traits. Evidence from a variety of studies shows that cis-regulatory mutations, specifically in enhancers, can lead to some of these isolated limb malformations. Here, we provide a review of human limb malformations that have been shown to be caused by enhancer mutations and propose that cis-regulatory mutations will continue to be identified as the cause of additional human malformations as our understanding of regulatory sequences improves. PMID:21509892

Noonan syndrome.

PubMed

Bhambhani, Vikas; Muenke, Maximilian

2014-01-01

Noonan syndrome is a common genetic disorder that causes multiple congenital abnormalities and a large number of potential health conditions. Most affected individuals have characteristic facial features that evolve with age; a broad, webbed neck; increased bleeding tendency; and a high incidence of congenital heart disease, failure to thrive, short stature, feeding difficulties, sternal deformity, renal malformation, pubertal delay, cryptorchidism, developmental or behavioral problems, vision problems, hearing loss, and lymphedema. Familial recurrence is consistent with an autosomal dominant mode of inheritance, but most cases are due to de novo mutations. Diagnosis can be made on the basis of clinical features, but may be missed in mildly affected patients. Molecular genetic testing can confirm diagnosis in 70% of cases and has important implications for genetic counseling and management. Most patients with Noonan syndrome are intellectually normal as adults, but some may require multidisciplinary evaluation and regular follow-up care. Age-based Noonan syndrome-specific growth charts and treatment guidelines are available.

Automated Parallel Capillary Electrophoretic System

DOEpatents

Li, Qingbo; Kane, Thomas E.; Liu, Changsheng; Sonnenschein, Bernard; Sharer, Michael V.; Kernan, John R.

2000-02-22

An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a gel delivery module containing a gel syringe/a stepper motor or a high pressure chamber with a pump to quickly and uniformly deliver gel through the capillary tubes. The system further includes a multi-wavelength beam generator to generate a laser beam which produces a beam with a wide range of wavelengths. An off-line capillary reconditioner thoroughly cleans a capillary cartridge to enable simultaneous execution of electrophoresis with another capillary cartridge. The streamlined nature of the off-line capillary reconditioner offers the advantage of increased system throughput with a minimal increase in system cost.

PHACES syndrome associated with carcinoid endobronchial tumor.

PubMed

Mama, Nadia; H'mida, Dorra; Lahmar, Imen; Yacoubi, Mohamed Tahar; Tlili-Graiess, Kalthoum

2014-05-01

PHACES syndrome consists of the constellation of manifestations including posterior fossa anomalies of the brain (most commonly Dandy-Walker malformations), hemangiomas of the face and scalp, arterial abnormalities, cardiac defects, eye anomalies and sternal defects. We present a case with a possible PHACES syndrome including sternal cleft and supraumbilical raphé, precordial skin tag, persistent left superior vena cava and subtle narrowing of the aorta with an endobronchial carcinoid tumor. All these anomalies were discovered on chest multi-detector CT. This is a unique case of PHACES syndrome associated with carcinoid tumor. Review of the literature revealed 3 cases of PHACES syndrome with glial tumor. The authors tried to find the relationship between PHACES syndrome and carcinoid tumors or gliomas, which all derive from the neural crest cells.

Updates and Future Horizons on the Understanding, Diagnosis, and Treatment of Sturge-Weber Syndrome Brain Involvement

ERIC Educational Resources Information Center

Lo, Warren; Marchuk, Douglas A.; Ball, Karen L.; Juhasz, Csaba; Jordan, Lori C.; Ewen, Joshua B.; Comi, Anne

2012-01-01

Aim: To review recent developments in the understanding, diagnosis, and treatment of Sturge-Weber syndrome (SWS). Method: Members of the Brain Vascular Malformation Consortium Sturge-Weber Syndrome National Workgroup contributed their expertise to review the literature and present promising directions for research. Results: The increasing number…

[Absent or hypoplastic thymus: A marker for 22q11.2 microdeletion syndrome in case of polyhydramnios].

PubMed

Lamouroux, A; Mousty, E; Prodhomme, O; Bigi, N; Le Gac, M-P; Letouzey, V; De Tayrac, R; Mares, P

2016-04-01

In prenatal diagnosis of 22q11.2 microdeletion syndrome, without cardiac malformation or multiple associated congenital anomalies, we study the presence of polyhydramnios and its association with thymic dysgenesis. This was a multicenter retrospective observational study. It was performed in two multidisciplinary centers for prenatal diagnosis in the south of France between January 1, 2010 and June 30, 2013. Inclusion criteria were prenatal diagnosis of 22q11.2 deletion syndrome. We excluded from the study any fetus with cardiac malformation or multiple associated congenital anomalies. During the inclusion period, eleven antenatal diagnoses of 22q11.2 microdeletion syndrome have been made. Six cases were excluded: 5 fetuses with cardiac malformation and one with multiple associated congenital anomalies. Therefore, five cases of isolated polyhydramnios were included. All 5 fetuses had a thymic dysgenesis: 3 had a thymic agenesis and 1 thymic hypoplasia diagnosed by sonography and 1 had a thymic agenesis diagnosed by retrospective reading of fetal MRI. When faced with a polyhydramnios, the presence of a thymic dysgenesis should be search for by ultrasound screening and would alert to the possibility of a 22q11.2 microdeletion syndrome. The confirmation of this is diagnosis by amniocentesis would enable improved antenatal support for parents and would enable early implementation of the multidisciplinary neonatal care that is required to avoid serious complications of this syndrome. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Hydrocephalus due to multiple ependymal malformations is caused by mutations in the MPDZ gene.

PubMed

Saugier-Veber, Pascale; Marguet, Florent; Lecoquierre, François; Adle-Biassette, Homa; Guimiot, Fabien; Cipriani, Sara; Patrier, Sophie; Brasseur-Daudruy, Marie; Goldenberg, Alice; Layet, Valérie; Capri, Yline; Gérard, Marion; Frébourg, Thierry; Laquerrière, Annie

2017-05-01

Congenital hydrocephalus is considered as either acquired due to haemorrhage, infection or neoplasia or as of developmental nature and is divided into two subgroups, communicating and obstructive. Congenital hydrocephalus is either syndromic or non-syndromic, and in the latter no cause is found in more than half of the patients. In patients with isolated hydrocephalus, L1CAM mutations represent the most common aetiology. More recently, a founder mutation has also been reported in the MPDZ gene in foetuses presenting massive hydrocephalus, but the neuropathology remains unknown. We describe here three novel homozygous null mutations in the MPDZ gene in foetuses whose post-mortem examination has revealed a homogeneous phenotype characterized by multiple ependymal malformations along the aqueduct of Sylvius, the third and fourth ventricles as well as the central canal of the medulla, consisting in multifocal rosettes with immature cell accumulation in the vicinity of ependymal lining early detached from the ventricular zone. MPDZ also named MUPP1 is an essential component of tight junctions which are expressed from early brain development in the choroid plexuses and ependyma. Alterations in the formation of tight junctions within the ependyma very likely account for the lesions observed and highlight for the first time that primary multifocal ependymal malformations of the ventricular system is genetically determined in humans. Therefore, MPDZ sequencing should be performed when neuropathological examination reveals multifocal ependymal rosette formation within the aqueduct of Sylvius, of the third and fourth ventricles and of the central canal of the medulla.

Multigenerational pedigree with STAR syndrome: A novel FAM58A variant and expansion of the phenotype.

PubMed

Boczek, Nicole J; Kruisselbrink, Teresa; Cousin, Margot A; Blackburn, Patrick R; Klee, Eric W; Gavrilova, Ralitza H; Lanpher, Brendan C

2017-05-01

STAR syndrome is a rare X-linked dominant disorder characterized by toe Syndactyly, Telecanthus, Anogenital malformations, and Renal malformations, and is caused by loss-of-function variants in FAM58A. Our proband presented with the hallmark features of STAR syndrome, as well as some additional less typical features including tethered cord and hearing loss. The proband's mother and maternal half-sister had similar clinical histories, but had variability in phenotypic severity. Clinical whole exome sequencing revealed a novel pathogenic nonsense variant, c.651G>A (p.Trp217X; NM_152274), in FAM58A in the proband, mother, and maternal half-sister. This pedigree represents the 11-13th patients described with STAR syndrome and the third instance of familial inheritance. To our knowledge, this is the first occurrence of a nonsense variant in FAM58A described in individuals with STAR syndrome and the phenotype in this pedigree suggests that tethered cord and hearing loss are features of STAR syndrome. © 2017 Wiley Periodicals, Inc.

Onyx(®) in endovascular treatment of cerebral arteriovenous malformations - a review.

PubMed

Szajner, Maciej; Roman, Tomasz; Markowicz, Justyna; Szczerbo-Trojanowska, Małgorzata

2013-07-01

Arteriovenous malformation (AVM) is an abnormal connection between arteries and veins, bypassing the capillary system. In most cases, the disorder may be asymptomatic. The objective of endovascular AVM treatment is set individually for each case upon consultations with a neurosurgeon and a neurologist. The endpoint of the treatment should consist in prevention of AVM bleeding in a management procedure characterized by a significantly lower risk of complications as compared to the natural history of AVM. Endovascular interventions within AVM may include curative exclusion of AVM from circulation, embolization adjuvant to resection or radiation therapy, targeted closure of a previously identified bleeding site as well as palliative embolization. Onyx was first described in the 1990s. It is a non-adhesive and radiolucent compound. Onyx-based closure of the lumen of the targeted vessel is obtained by means of precipitation. The process is enhanced peripherally to the main flux of the injected mixture. This facilitates angiographic monitoring of embolization at any stage. The degree of lumen closure is associated with the location of the vessel. Supratentorial and cortical locations are most advantageous. Dense and plexiform structure of AVM nidus as well as a low number of supplying vessels and a single superficial drainage vein are usually advantageous for Onyx administration. Unfavorable factors include nidus drainage into multiple compartments as well as multiarterial supply of the AVM, particularly from meningeal arteries, en-passant arteries or perforating feeders. Onyx appears to be a safe and efficient material for embolization of cerebral AVMs, also in cases of intracranial bleeding associated with AVM. Curative embolization of small cerebral AVMs is an efficient and safe alternative to neurosurgical and radiosurgical methods. Careful angiographic assessment of individual arteriovenous malformations should be performed before each Onyx administration.

Clinical relevance of cytogenetics to pediatric practice. Postnatal findings of Patau syndrome - Review of 5 cases.

PubMed

Plaiasu, Vasilica; Ochiana, Diana; Motei, Gabriela; Anca, Ioana; Georgescu, Adrian

2010-07-01

Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing. In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department. For each child cytogenetic analysis was performed to determine the genetic variant; also, the patients were investigated for other associated malformations (cardiac, cerebral, renal, ocular anomalies). All 5 cases presented multiple malformations, including some but not all signs of the classical clinical triad suggestive of Patau syndrome. The cytogenetic investigation confirmed for each case the suspected diagnosis and also indicated the specific genetic variant, this being a valuable information for the genetic counselling of the families. The application of genetic analysis can increase diagnosis and prognosis accuracy and have an impact on clinical management.

Posterior axial corneal malformation and uveoretinal angiodysgenesis--a neurocristopathy?

PubMed

Mooy, C M; Clark, B J; Lee, W R

1990-01-01

This clinicopathological report describes an unusual combination of axial corneal malformation and angiodysgenesis in the uvea, retina and optic nerve in three eyes. In each specimen there was hypocellularity in the posterior axial stroma, with corresponding loss of the corneal endothelium. The vascular malformation consisted of numerous telangiectatic endothelium-lined tubes with inconspicuous or absent media. One globe was obtained from a stillborn fetus (36 weeks) in which renal agenesis and a sireniform malformation (mermaid fetus) occurred in conjunction with a Fallot's tetralogy, pulmonary hypoplasia and atresia of the trachea and duodenum. Eyes with almost identical malformations were obtained from a 39-week female neonate who died after 5 h as a consequence of renal agenesis and pulmonary hypoplasia. This combination of ocular tissue malformations can be explained by embryological studies, which have shown that the corneal stroma and endothelium and the ocular periendothelial vascular tissues are derived from the neural crest.

The Chiari 3 Malformation and a Systemic Review of the Literature.

PubMed

Young, Richard M; Shafa, Justin S; Myseros, John S

2015-01-01

Chiari type 3 is a rare hindbrain malformation that has been reported in the literature primarily as case reports and case series. Radiological, pathophysiological and surgical definitions of the malformation are inconsistent in the literature and subsequently can be confusing, and outcomes have also been uniformly poor. The definition of this rare malformation will be clarified through a case presentation. A retrospective review of prior publications in the PubMed and MEDLINE databases was performed looking for reports of 'Chiari 3 +/- malformation' and 'occipital encephalocele'. Relevant papers were reviewed and compiled into table format with associated descriptions of a Chiari type 3 malformation. A case illustration is presented with radiological and intraoperative imaging to reinforce and clarify the definition. Upon review of the prior publications in the detail of the descriptions and imaging associated with each article, there is a wide range of variability in the description of what is considered a Chiari 3 malformation. Occipital, occipitocervical and high cervical defects have all been described as Chiari 3 malformation. Our case illustration presents a patient with an occipitocervical encephalocele with neural elements, which is the classic and accepted definition of the Chiari 3 malformation. Chiari type 3 is a rare congenital malformation, and prior publications describing this developmental disorder have not demonstrated a consensus in its definition. In addition, outcomes have traditionally been reported as poor. This case illustration of a Chiari type 3 enforces the definition of an occipitocervical encephalocele with hindbrain herniation, and with proper management not all Chiari 3 malformation patients have bad outcomes. © 2015 S. Karger AG, Basel.

Genetic Syndromes Associated with Congenital Cardiac Defects and Ophthalmologic Changes - Systematization for Diagnosis in the Clinical Practice.

PubMed

Oliveira, Priscila H A; Souza, Beatriz S; Pacheco, Eimi N; Menegazzo, Michele S; Corrêa, Ivan S; Zen, Paulo R G; Rosa, Rafael F M; Cesa, Claudia C; Pellanda, Lucia C; Vilela, Manuel A P

2018-01-01

Numerous genetic syndromes associated with heart disease and ocular manifestations have been described. However, a compilation and a summarization of these syndromes for better consultation and comparison have not been performed yet. The objective of this work is to systematize available evidence in the literature on different syndromes that may cause congenital heart diseases associated with ocular changes, focusing on the types of anatomical and functional changes. A systematic search was performed on Medline electronic databases (PubMed, Embase, Cochrane, Lilacs) of articles published until January 2016. Eligibility criteria were case reports or review articles that evaluated the association of ophthalmic and cardiac abnormalities in genetic syndrome patients younger than 18 years. The most frequent genetic syndromes were: Down Syndrome, Velo-cardio-facial / DiGeorge Syndrome, Charge Syndrome and Noonan Syndrome. The most associated cardiac malformations with ocular findings were interatrial communication (77.4%), interventricular communication (51.6%), patent ductus arteriosus (35.4%), pulmonary artery stenosis (25.8%) and tetralogy of Fallot (22.5%). Due to their clinical variability, congenital cardiac malformations may progress asymptomatically to heart defects associated with high morbidity and mortality. For this reason, the identification of extra-cardiac characteristics that may somehow contribute to the diagnosis of the disease or reveal its severity is of great relevance.

Recurrent Hyperammonemia After Abernethy Malformation Type 2 Closure: a Case Report.

PubMed

Li, Hui; Ma, Zhi; Xie, Ying; Tian, Feng

The Abernethy malformation is a rare congenital malformation defined by the presence of an extrahepatic portosystemic shunt. Although most patients are asymptomatic, clinical encephalopathy is present in 15% of cases. We present a patient with type 2 Abernethy malformation, hyperammonemia, and encephalopathy. Shunt closure was performed successfully using interventional angiography; however, hyperammonemia recurred 3 months later. The diagnosis of Abernethy malformation can be made easily, but the ideal patient management strategy has not yet been established. This is the first reported patient with recurrence of hyperammonemia after interventional treatment; we discuss the therapeutic options for Abernethy malformation.

Phenotypic heterogeneity in lung capillary and extra-alveolar endothelial cells. Increased extra-alveolar endothelial permeability is sufficient to decrease compliance.

PubMed

Lowe, Kevin; Alvarez, Diego; King, Judy; Stevens, Troy

2007-11-01

In acute respiratory distress syndrome, pulmonary vascular permeability increases, causing intravascular fluid and protein to move into the lung's interstitium. The classic model describing the formation of pulmonary edema suggests that fluid crossing the capillary endothelium is drawn by negative interstitial pressure into the potential space surrounding extra-alveolar vessels and, as interstitial pressure builds, is forced into the alveolar air space. However, the validity of this model is challenged by animal models of acute lung injury in which extra-alveolar vessels are more permeable than capillaries under a variety of conditions. In the current study, we sought to determine whether extravascular fluid accumulation can be produced because of increased permeability of either the capillary or extra-alveolar endothelium, and whether different pathophysiology results from such site-specific increases in permeability. We perfused isolated lungs with either the plant alkaloid thapsigargin, which increases extra-alveolar endothelial permeability, or with 4alpha-phorbol 12, 13-didecanoate, which increases capillary endothelial permeability. Both treatments produced equal increases in whole lung vascular permeability, but caused fluid accumulations in separate anatomical compartments. Light microscopy of isolated lungs showed that thapsigargin caused fluid cuffing of large vessels, while 4alpha-phorbol 12, 13-didecanoate caused alveolar flooding. Dynamic compliance was reduced in lungs with cuffing of large vessels, but not in lungs with alveolar flooding. Phenotypic differences between vascular segments resulted in site-specific increases in permeability, which have different pathophysiological outcomes. Our findings suggest that insults leading to acute respiratory distress syndrome may increase permeability in extra-alveolar or capillary vascular segments, resulting in different pathophysiological sequela.

[Larsen syndrome: two reports of cases with spinal cord compromise].

PubMed

Martín Fernández-Mayoralas, D; Fernández-Jaén, A; Muñoz-Jareño, N; Calleja-Pérez, B; San Antonio-Arce, V; Martínez-Boniche, H

Larsen syndrome is characterised by untreatable congenital dislocation of multiple body joints, along with marked foot deformities. These patients have a flattened face with a short nose, a broad depressed nasal bridge and a prominent forehead. In this clinical note our aim is to report two cases that coursed with spinal cord compromise. Case 1: an 18-month-old female with congenital dislocation of knees and hips. The patient had a flat face, sunken root of nose, and carp mouth. Magnetic resonance imaging of the spine showed severe cervical kyphosis secondary to malformation and hypoplasia of the cervical vertebral bodies and important compression of the spinal cord. Clinically, there were also signs of upper motor neuron syndrome, which was especially prominent in the lower limbs. Case 2: a 14-year-old male with a characteristic face and dislocation of the head of the radius. The patient presented amyotrophy of the muscles in the right hand and clinical signs of lower motor neuron syndrome due to neuronal damage secondary to spinal malformations. Larsen syndrome is an infrequent osteochondrodysplasia. Alteration of the spine is common and may give rise to spinal cord compression with varying clinical repercussions which require surgical treatment in the early years of the patient's life.

A novel mutation of the glomulin gene in an Italian family with autosomal dominant cutaneous glomuvenous malformations.

PubMed

Borroni, Riccardo G; Narula, Nupoor; Diegoli, Marta; Grasso, Maurizia; Concardi, Monica; Rosso, Renato; Cerica, Alessandra; Brazzelli, Valeria; Arbustini, Eloisa

2011-12-01

Glomuvenous malformations (GVM) are hamartomas characterized histologically by glomus cells, which should be distinguished from glomus tumors. Familial GVM are rare, often present as multiple lesions, and exhibit familial aggregation, with autosomal dominant transmission. GVM are caused by mutations of the glomulin (GLMN) gene on chromosome 1p21-p22. Their development is thought to follow the 'two-hit' hypothesis, with a somatic mutation required in addition to the inherited germline mutation. We describe a novel GLMN mutation in an Italian family with GVM in which some members present with the less commonly observed phenotype of solitary lesions. A second somatic 'hit' mutation in GLMN was not discovered in our family. We further provide histological, immunohistochemical and electron microscopic data exhibiting the classic features of GVM. The diagnosis of GVM is critical because of distinction from venous malformations and blue rubber bleb nevus syndrome, which may demonstrate clinical similarities but require different treatment. © 2011 John Wiley & Sons A/S.

Microfluidic Investigation Reveals Distinct Roles for Actin Cytoskeleton and Myosin II Activity in Capillary Leukocyte Trafficking

PubMed Central

Gabriele, Sylvain; Benoliel, Anne-Marie; Bongrand, Pierre; Théodoly, Olivier

2009-01-01

Circulating leukocyte sequestration in pulmonary capillaries is arguably the initiating event of lung injury in acute respiratory distress syndrome. We present a microfluidic investigation of the roles of actin organization and myosin II activity during the different stages of leukocyte trafficking through narrow capillaries (entry, transit and shape relaxation) using specific drugs (latrunculin A, jasplakinolide, and blebbistatin). The deformation rate during entry reveals that cell stiffness depends strongly on F-actin organization and hardly on myosin II activity, supporting a microfilament role in leukocyte sequestration. In the transit stage, cell friction is influenced by stiffness, demonstrating that the actin network is not completely broken after a forced entry into a capillary. Conversely, membrane unfolding was independent of leukocyte stiffness. The surface area of sequestered leukocytes increased by up to 160% in the absence of myosin II activity, showing the major role of molecular motors in microvilli wrinkling and zipping. Finally, cell shape relaxation was largely independent of both actin organization and myosin II activity, whereas a deformed state was required for normal trafficking through capillary segments. PMID:19450501

The Hungarian congenital malformation monitoring system.

PubMed

Czeizel, A

1978-01-01

The Hungarian Congenital Malformation Monitor has been operating since 1973 in order to detect the temporal and regional clusters of 12 indicator congenital malformations as early as possible. This Monitor takes part in the International Clearinghouse for Birth Defects Monitoring System. Three continuously increasing trends were detected in 1973--1976. They may be connected with the more complete notifications, although the increase of limb reduction deformities are only partly explained by this factor. Transitional (quarterly) significant clusters were observed in the case of anencephaly (1974, IV), spina bifida (1974, II; and 1975, III; 1976, III), cleft lip +/- cleft palate (1974, III). The possibility of three technical biases (changes in diagnosis, notification and evaluation of the given congenital malformation) has to be excluded before accepting the fact of a real epidemic. Subsequently, a case-control epidemiological study by personal interviews and with matched controls has to be performed.

FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation

PubMed Central

Aldinger, Kimberly A; Lehmann, Ordan J; Hudgins, Louanne; Chizhikov, Victor V; Bassuk, Alexander G; Ades, Lesley C; Krantz, Ian D; Dobyns, William B; Millen, Kathleen J

2010-01-01

Dandy-Walker malformation (DWM), the most common human cerebellar malformation, has only one characterized associated locus1,2. Here we characterize a second DWM-linked locus on 6p25.3, showing that deletions or duplications encompassing FOXC1 are associated with cerebellar and posterior fossa malformations including cerebellar vermis hypoplasia (CVH), mega-cisterna magna (MCM) and DWM. Foxc1-null mice have embryonic abnormalities of the rhombic lip due to loss of mesenchyme-secreted signaling molecules with subsequent loss of Atoh1 expression in vermis. Foxc1 homozygous hypomorphs have CVH with medial fusion and foliation defects. Human FOXC1 heterozygous mutations are known to affect eye development, causing a spectrum of glaucoma-associated anomalies (Axenfeld-Rieger syndrome, ARS; MIM no. 601631). We report the first brain imaging data from humans with FOXC1 mutations and show that these individuals also have CVH. We conclude that alteration of FOXC1 function alone causes CVH and contributes to MCM and DWM. Our results highlight a previously unrecognized role for mesenchyme-neuroepithelium interactions in the mid-hindbrain during early embryogenesis. PMID:19668217

Ultrasound-guided high-intensity focused ultrasound ablation for treating uterine arteriovenous malformation.

PubMed

Yan, X; Zhao, C; Tian, C; Wen, S; He, X; Zhou, Y

2017-08-01

To explore HIFU treatment for uterine arteriovenous malformation. A case report. Gynaecological department in a university teaching hospital of China. A patient with uterine arteriovenous malformation. The diagnosis of uterine arteriovenous malformation was made through MRI. Ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation was performed. HIFU is effective in treating uterine arteriovenous malformation. The patient had reduction of the lesion volume and obvious symptom relief, without significant adverse effects. HIFU can be used as a new treatment option for uterine arteriovenous malformation. Ultrasound-guided high-intensity focused ultrasound ablation is effective in treating uterine arteriovenous malformation. © 2017 Royal College of Obstetricians and Gynaecologists.

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations

PubMed Central

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Dejene, Sara Z; Fischer, Michael A; Friedman, Alexander M; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2016-01-01

Objective To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk for overall major congenital, cardiac, and central nervous system (CNS) malformations. Methods We used a cohort of completed pregnancies linked to liveborn infants derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. Results The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor–exposed was 5.9% versus 3.3% in the unexposed (unadjusted relative risk (RR), 1.82; 95% confidence interval (CI) 1.61 to 2.06), of cardiac malformations was 3.4% versus 1.2% (RR 2.95; 95% CI 2.50 to 3.47), and of CNS malformations was 0.27% versus 0.18% (RR 1.46; 95% CI 0.81 to 2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk for any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75 to 1.06) for overall malformations, 0.95 (95% CI 0.75 to 1.21) for cardiac malformations, and 0.54 (95% CI 0.26 to 1.11) for CNS malformations. Conclusions After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations. PMID:27926639

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations.

PubMed

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Dejene, Sara Z; Fischer, Michael A; Friedman, Alexander M; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2017-01-01

To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk of overall major congenital, cardiac, and central nervous system malformations. We used a cohort of completed pregnancies linked to liveborn neonates derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score-based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor-exposed pregnancies was 5.9% compared with 3.3% in the unexposed (unadjusted relative risk, 1.82; 95% confidence interval [CI] 1.61-2.06), of cardiac malformations was 3.4% compared with 1.2% (relative risk 2.95, 95% CI 2.50-3.47), and of central nervous system malformations was 0.27% compared with 0.18% (relative risk 1.46, 95% CI 0.81-2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk of any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75-1.06) for overall malformations, 0.95 (95% CI 0.75-1.21) for cardiac malformations, and 0.54 (95% CI 0.26-1.11) for CNS malformations. After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations.

Skeletal and cranio-facial signs in Gorlin syndrome from ancient Egypt to the modern age: sphenoid asymmetry in a patient with a novel PTCH1 mutation.

PubMed

Ponti, Giovanni; Ruini, Cristel; Pastorino, Lorenza; Loschi, Pietro; Pecchi, Annarita; Malagoli, Marcella; Mandel, Victor Desmond; Boano, Rosa; Conti, Andrea; Pellacani, Giovanni; Tomasi, Aldo

2014-05-01

Gorlin syndrome is an autosomal dominant disorder linked to PTCH1 mutation, identified by a collection of clinical and radiologic signs. We describe the case of a family in which father and son fulfilled clear cut diagnostic criteria for Gorlin syndrome including multiple basal cell carcinomas, keratocystic odontogenic tumors, atypical skeletal anomalies and a novel PTCH1 germline mutation (c.1041delAA). Craniofacial and other skeletal anomalies displayed at 3D and helical CT scan were: macrocephaly, positional plagiocephaly, skull base and sphenoid asymmetry, bifidity of multiple ribs and giant multilocular odontogenic jaw cysts. Extensive multilamellar calcifications were found in falx cerebri, tentorium, falx cerebelli and in the atlanto-occipital ligament. The inclusion of bifid ribs as a novel major criteri may be useful for the recognition and characterization of misdiagnosed cases.

Dandy-Walker syndrome together with occipital encephalocele.

PubMed

Cakmak, A; Zeyrek, D; Cekin, A; Karazeybek, H

2008-08-01

Dandy-Walker malformation is an anomaly characterized by dysgenesis of the foramina of Magendie and Lushka in the upper 4(th) ventricle, hypoplasia of the cerebellar vermis and agenesis of the corpus callosum. Encephalocele is diagnosed from the calvarium defect, cerebrospinal fluid (CSF) and herniation of the meninges. It is the rarest neural tube defect. A 7 x 9 cm encephalocele was found on physical examination of a 6-day old baby boy patient. From cranial magnetic resonance, it was seen that the posterior fossa was enlarged with cysts and there was agenesis of the vermis. A connection was established between the ventricle and the development of cysts on the posterior fossa. These findings were evaluated as significant from the aspect of Dandy-Walker malformation. The extension of the bone defect in the left occipital area towards the posterior, and the cranio-caudal diameter reaching 9 cm was seen to be in accordance with encephalocele. It is rare for Dandy-Walker syndrome to occur together with occipital encephalocele. The authors present a case of Dandy-Walker syndrome together with occipital encephalocele.

An open-label study to evaluate sildenafil for the treatment of lymphatic malformations.

PubMed

Danial, Christina; Tichy, Andrea L; Tariq, Umar; Swetman, Glenda L; Khuu, Phuong; Leung, Thomas H; Benjamin, Latanya; Teng, Joyce; Vasanawala, Shreyas S; Lane, Alfred T

2014-06-01

Lymphatic malformations can be challenging to treat. Mainstay interventions including surgery and sclerotherapy are invasive and can result in local recurrence and complications. We sought to assess the effect of 20 weeks of oral sildenafil on reducing lymphatic malformation volume and symptoms in children. Seven children (4 boys, 3 girls; ages 13-85 months) with lymphatic malformations were given oral sildenafil for 20 weeks in this open-label study. The volume of the lymphatic malformation was calculated blindly using magnetic resonance imaging performed before and after 20 weeks of sildenafil. Lymphatic malformations were assessed clinically on weeks 4, 12, 20, and 32. Both the physician and parents evaluated the lymphatic malformation in comparison with baseline. Four subjects had a lymphatic malformation volume decrease (1.0%-31.7%). In 2 subjects, despite a lymphatic malformation volume increase (1.1%-3.7%), clinical improvement was noted while on sildenafil. One subject had a 29.6% increase in lymphatic malformation volume and no therapeutic response. Lymphatic malformations of all 6 subjects who experienced a therapeutic response on sildenafil softened and became easily compressible. Adverse events were minimal. A randomized controlled trial will be necessary to verify the effects of sildenafil on lymphatic malformations. Sildenafil can reduce lymphatic malformation volume and symptoms in some children. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Progesterone receptors identified in vascular malformations of the head and neck.

PubMed

Duyka, Landon J; Fan, Chun Y; Coviello-Malle, Jean M; Buckmiller, Lisa; Suen, James Y

2009-10-01

To identify hormone receptors within vascular malformations (arteriovenous malformations [AVMs], venous malformations [VMs], and lymphatic malformations [LMs]) of the head and neck. Immunohistochemical staining for estrogen receptor (ER) and progesterone receptor (PR) was performed on archival vascular malformation tissue collected from both pediatric and adult patients. Tertiary referral center from 2006 to 2008. Twelve AVM, 10 VM, and eight LM specimens were stained for both ER and PR. Ten breast carcinoma specimens were used as controls, with the carcinoma cells serving as positive controls, and the endothelium and smooth muscle cells of the blood vessels serving as negative controls. Five normal supraglottic mucosal samples served as head and neck controls. The Fisher exact test was used for statistical analysis. Ten of the 12 (83%) AVM specimens stained diffusely positive for PR within the nuclei of the endothelium and smooth muscle of the malformed vessels (P < 0.0001). Five of the 10 (50%) VM specimens stained positive for PR (2 [20%] focal, 3 [30%] diffuse) within the nuclei of the endothelium and smooth muscle of the malformed vessels (P = 0.0325). Four of the eight (50%) LM specimens stained focally positive for PR within the nuclei of the endothelium of the malformed vessels (P = 0.0229). None of the vascular malformation specimens stained positive for ER. Our data suggest that PR, but not ER, is expressed in AVMs, VMs, and LMs of the head and neck.

7D.09: REDUCED VIT D AND ELEVATED URICEMIA INDUCE CAPILLARY RAREFACTION BEFORE MACROVASCULAR DAMAGE IN PATIENTS WITH METABOLIC SYNDROME AT THE VERY EARLY STAGES OF HYPERTENSION.

PubMed

Nazzaro, P; Schirosi, G; De Benedittis, L; Mezzapesa, D; Federico, F

2015-06-01

Reduced (L) Vit D (D) and high (H) uric acid (U) levels have been associate with increased cardiovascular risk. Aim of the study was to highlight their association with the subclinical vascular damage in untreated recently diagnosed very mild hypertensives with a similar number of metabolic syndrome factors (nATPIII). By medical visit and identification of the metabolic syndrome factors, 238 very mild hypertensives (136 ± 15/84 ± 9 mmHg), 62 controls with normal (N) D and U, 96 with LD, 40 with HU and 40 with both the conditions (LDHU) with similar metabolic assessment, underwent measures of carotid-femoral pulse wave velocity (PWV), ankle-brachial index (ABI), carotid intima-media thickness (IMT), as indices of functional and structural arterial damage, and videocapillaroscopy of the middle and distal phalangeal skin of the 2nd, 3rd and 4th finger of the non-dominant hand during baseline (CAP) and venous congestion (CVC) obtaining capillary recruitment (REC) as indices of functional and structural microcirculatory damage. Patients showed a similar hypertensive state during the medical visit and ABPM but different capillary indices.(m ± s:d.*:p<.05, **:p < .01, ***:p < .001 vs NDNU; °:p < .05, °°:p < .01, °°°:p < .001 vs LDNU;^p < .05, ^^:p < .01, ^^^:p < .001 vs NDHU).(Figure is included in full-text article.)Pearson analysis showed the association between Vit D and CVC (.440*) and REC (.335***) in LDNU and with CVC (631***) and REC (.666*) in LDHU as well as between U and CAP (-.470*) in NDHU and (-606*) in LDHU. The results suggest that, in very mild hypertensives with metabolic syndrome, reduced Vit D is associate to structural microvascular damage before the onset of structural or functional macrovascular impairment. Hyperuricemia show a lower microcirculatory damage but this is amplified in patients with both the disorders (LDHU).

Giant canine with dentine anomalies in oculo-facio-cardio-dental syndrome.

PubMed

Larhant, Matthieu; Sourice, Sophie; Grimaud, Fanny; Cordoba, Luis; Leveau, Sophie; Huet, Pascal; Corre, Pierre; Khonsari, Roman Hossein

2014-06-01

Radiculomegaly affecting incisors, canines or premolars is a rare radiological finding (Maden et al., 2010) but is pathognomomic of a rare x-linked dominant syndrome called oculo-facio-cardio-dental syndrome (OFCDS). As this syndrome includes cardiac malformations and can lead to blindness due to congenital glaucoma, oral and maxillofacial surgeons should be aware of the somatic anomalies potentially associated with radiculomegaly. We report a typical case of OFCDS and provide the first description of the microscopic dental anomalies associated with this syndrome. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations

PubMed Central

Huybrechts, Krista F.; Hernández-Díaz, Sonia; Patorno, Elisabetta; Desai, Rishi J.; Mogun, Helen; Dejene, Sara Z.; Cohen, Jacqueline M.; Panchaud, Alice; Cohen, Lee; Bateman, Brian T.

2017-01-01

IMPORTANCE The frequency of antipsychotic (AP) use during pregnancy has approximately doubled during the last decade. However, little is known about their safety for the developing fetus, and concerns have been raised about a potential association with congenital malformations. OBJECTIVE To examine the risk for congenital malformations overall and cardiac malformations associated with first-trimester exposure to APs. DESIGN, SETTING, AND PARTICIPANTS This nationwide sample of 1 360 101 pregnant women enrolled in Medicaid with a live-born infant constituted the pregnancy cohort nested in the Medicaid Analytic Extract database, which included data from January 1, 2000, to December 31, 2010. Participants were enrolled in Medicaid from 3 months before their last menstrual period through at least 1 month after delivery. Relative risks (RRs) were estimated using generalized linear models with fine stratification on the propensity score to control for the underlying psychiatric disorders and other potential confounders. Data were analyzed during 2015. EXPOSURES Use of APs during the first trimester, the etiologically relevant period for organogenesis. MAIN OUTCOMES AND MEASURES Major congenital malformations overall and cardiac malformations identified during the first 90 days after delivery. RESULTS Of the 1 341 715 pregnancies that met inclusion criteria (mean [SD] age of women, 24.02 [5.77] years), 9258 (0.69%) filled at least 1 prescription for an atypical AP and 733 (0.05%) filled at least 1 prescription for a typical AP during the first trimester. Overall, 32.7 (95% CI, 32.4–33.0) per 1000 births not exposed to APs were diagnosed with congenital malformations compared with 44.5 (95% CI, 40.5–48.9) per 1000 births exposed to atypical and 38.2 (95% CI, 26.6–54.7) per 1000 births exposed to typical APs. Unadjusted analyses suggested an increased risk for malformations overall for atypical APs (RR, 1.36; 95% CI, 1.24–1.50) but not for typical APs (RR, 1.17; 95

Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations.

PubMed

Huybrechts, Krista F; Hernández-Díaz, Sonia; Patorno, Elisabetta; Desai, Rishi J; Mogun, Helen; Dejene, Sara Z; Cohen, Jacqueline M; Panchaud, Alice; Cohen, Lee; Bateman, Brian T

2016-09-01

The frequency of antipsychotic (AP) use during pregnancy has approximately doubled during the last decade. However, little is known about their safety for the developing fetus, and concerns have been raised about a potential association with congenital malformations. To examine the risk for congenital malformations overall and cardiac malformations associated with first-trimester exposure to APs. This nationwide sample of 1 360 101 pregnant women enrolled in Medicaid with a live-born infant constituted the pregnancy cohort nested in the Medicaid Analytic Extract database, which included data from January 1, 2000, to December 31, 2010. Participants were enrolled in Medicaid from 3 months before their last menstrual period through at least 1 month after delivery. Relative risks (RRs) were estimated using generalized linear models with fine stratification on the propensity score to control for the underlying psychiatric disorders and other potential confounders. Data were analyzed during 2015. Use of APs during the first trimester, the etiologically relevant period for organogenesis. Major congenital malformations overall and cardiac malformations identified during the first 90 days after delivery. Of the 1 341 715 pregnancies that met inclusion criteria (mean [SD] age of women, 24.02 [5.77] years), 9258 (0.69%) filled at least 1 prescription for an atypical AP and 733 (0.05%) filled at least 1 prescription for a typical AP during the first trimester. Overall, 32.7 (95% CI, 32.4-33.0) per 1000 births not exposed to APs were diagnosed with congenital malformations compared with 44.5 (95% CI, 40.5-48.9) per 1000 births exposed to atypical and 38.2 (95% CI, 26.6-54.7) per 1000 births exposed to typical APs. Unadjusted analyses suggested an increased risk for malformations overall for atypical APs (RR, 1.36; 95% CI, 1.24-1.50) but not for typical APs (RR, 1.17; 95% CI, 0.81-1.68). After confounding adjustment, the RR was reduced to 1.05 (95% CI, 0.96-1.16) for

Prenatal diagnosis of Joubert syndrome

PubMed Central

Zhu, Lingling; Xie, Limei

2017-01-01

Abstract Introduction: Joubert syndrome (JS) is a rare autosomal recessive inherited disease belonging to ciliopathy with the causative mutation of genes. Except for X-linked inheritance, the high recurrence rate of a family is about 25%. After birth, it may cause a series of neurological symptoms, even with retina, kidney, liver, and other organ abnormalities, which is defined as Joubert syndrome and related disorders (JSRD). Molecular genetics research contributes to disease prediction and genetic counseling. Prenatal diagnosis is rare. Magnetic resonance imaging (MRI) is usually the first-choice diagnostic modality with typical brain images characterized by the molar tooth sign. We describe a case of JS prenatally and Dandy-Walker malformation for the differential diagnosis based on ultrasonograms. We also review the etiology, imaging features, clinical symptoms, and diagnosis of JSRD. Case presentation: A 22-year-old woman was pregnant at 27 1/7 weeks’ gestation with fetal cerebellar vermis hypoplasia. Fetal ultrasonography and MRI confirmed a diagnosis of JS at our center. The couple finally opted to terminate the fetus, which had a normal appearance and growth parameters. The couple also had an AHI1 gene mutation on chromosome 6. Conclusions: Currently, a diagnosis of JS is commonly made after birth. Fewer cases of prenatal diagnosis by ultrasonography have been made, and they are more liable to be misdirected because of some nonspecial features that also manifest in Dandy-Walker malformation, cranio-cerebello-cardiac syndrome, and so on. PMID:29390414

Capillary discharge source

DOEpatents

Bender, III, Howard Albert

2003-11-25

Debris generation from an EUV electric discharge plasma source device can be significantly reduced or essentially eliminated by encasing the electrodes with dielectric or electrically insulating material so that the electrodes are shielded from the plasma, and additionally by providing a path for the radiation to exit wherein the electrodes are not exposed to the area where the radiation is collected. The device includes: (a) a body, which is made of an electrically insulating material, that defines a capillary bore that has a proximal end and a distal end and that defines at least one radiation exit; (b) a first electrode that defines a first channel that has a first inlet end that is connected to a source of gas and a first outlet end that is in communication with the capillary bore, wherein the first electrode is positioned at the distal end of the capillary bore; (c) a second electrode that defines a second channel that has a second inlet end that is in communication with the capillary bore and an outlet end, wherein the second electrode is positioned at the proximal end of the capillary bore; and (d) a source of electric potential that is connected across the first and second electrodes, wherein radiation generated within the capillary bore is emitted through the at least one radiation exit and wherein the first electrode and second electrode are shielded from the emitted radiation.

A large pulmonary arteriovenous malformation causing cerebrovascular accidents.

PubMed

Sladden, David; Casha, Aaron; Azzopardi, Conrad; Manche', Alexander

2015-04-16

The incidence of pulmonary arteriovenous malformations (PAVMs) is 2.5 in 100,000. 80% are associated with Osler-Weber-Rendu syndrome or hereditary haemorrhagic telangiectasia. We report the case of a 70-year-old man with a 6 cm spherical mass incidentally found on chest X-ray. There was a localised systolic bruit over the right lower zone posteriorly; however, he was asymptomatic. He had suffered a stroke, affecting his right hand and his speech, from which he recovered. He experienced regular transient ischaemic attacks, on an average of every 2 months. He underwent a right lower lobectomy and on ligating the right lower lobe pulmonary artery the saturations of oxygen rose from 92% to 97%, demonstrating a significant right to left extracardiac shunt. Postoperative recovery was excellent and 1 year later the patient reports no further neurological symptoms. 40% of such lesions exhibit symptoms, however, only one-third are neurological. Treatment should be by percutaneous embolisation. 2015 BMJ Publishing Group Ltd.

Malformations of the craniocervical junction (chiari type I and syringomyelia: classification, diagnosis and treatment)

PubMed Central

2009-01-01

Chiari disease (or malformation) is in general a congenital condition characterized by an anatomic defect of the base of the skull, in which the cerebellum and brain stem herniate through the foramen magnum into the cervical spinal canal. The onset of Chiari syndrome symptoms usually occurs in the second or third decade (age 25 to 45 years). Symptoms may vary between periods of exacerbation and remission. The diagnosis of Chiari type I malformation in patients with or without symptoms is established with neuroimaging techniques. The most effective therapy for patients with Chiari type I malformation/syringomyelia is surgical decompression of the foramen magnum, however there are non-surgical therapy to relieve neurophatic pain: either pharmacological and non-pharmacological. Pharmacological therapy use drugs that act on different components of pain. Non-pharmacological therapies are primarly based on spinal or peripheral electrical stimulation. It is important to determine the needs of the patients in terms of health-care, social, educational, occupational, and relationship issues, in addition to those derived from information aspects, particularly at onset of symptoms. Currently, there is no consensus among the specialists regarding the etiology of the disease or how to approach, monitor, follow-up, and treat the condition. It is necessary that the physicians involved in the care of people with this condition comprehensively approach the management and follow-up of the patients, and that they organize interdisciplinary teams including all the professionals that can help to increase the quality of life of patients. PMID:20018097

Vascular Ehlers-Danlos syndrome with cryptorchidism, recurrent pneumothorax, and pulmonary capillary hemangiomatosis-like foci: A case report.

PubMed

Park, Min A; Shin, So Youn; Kim, Young Jin; Park, Myung Jae; Lee, Seung Hyeun

2017-11-01

Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the importance of comprehensive physical examination and history-taking, and the clinical

Orbital exenteration after transarterial embolization in a patient with Wyburn-Mason syndrome: pathological findings.

PubMed

Matsuo, Toshihiko; Yanai, Hiroyuki; Sugiu, Kenji; Tominaga, Susumu; Kimata, Yoshihiro

2008-01-01

We present the pathological findings at orbital exenteration in a patient with Wyburn-Mason syndrome who underwent transarterial embolization. A 31-year-old man with a 10-year history of gradual exacerbation of left exophthalmos and left cheek swelling was found to have facial and orbital arteriovenous malformations on the left side. There was no vascular malformation in the brain. The feeding arteries derived from the left internal maxillary artery, facial artery, and ophthalmic artery. He underwent several courses of transarterial embolization of the feeding arteries from the left internal maxillary artery and then from the facial artery, resulting in no reduction of the arteriovenous malformation. He finally elected to undergo ophthalmic artery embolization in the expectation of a reduction and with the understanding that he would lose sight in his left eye. Two years later, he requested lid-sparing orbital exenteration and reconstruction with cutaneous flap transfer and prosthesis for cosmetic reasons. Pathologically, orbital vascular channels of varying sizes were filled with embolizing glue and had degenerating vascular wall cells surrounded by inflammatory cell infiltration. The central retinal artery in the optic nerve was also filled with the embolizing glue, and the retina lost the ganglion cell layer and inner nuclear layer but maintained the outer nuclear layer and outer segments. Marked anastomoses and hence incomplete embolization among the feeding arteries of facial and orbital vascular malformations in Wyburn-Mason syndrome do not respond well to attempts at feeding vessel embolization, which result in unsuccessful closure of the malformation.

Type I Chiari malformation presenting central sleep apnea.

PubMed

Kitamura, Takuro; Miyazaki, Soichiro; Kadotani, Hiroshi; Kanemura, Takashi; Okawa, Masako; Tanaka, Toshihiko; Komada, Ichiro; Hatano, Taketo; Suzuki, Hideaki

2014-04-01

Sleep apnea is a rare but a well-known clinical feature of type I Chiari malformation. It may be obstructive or central in nature. Sleep apnea in patients with type I Chiari malformation rarely presents without accompanying neurological signs or symptoms. We here report a case of a 10-year-old girl who presented with central sleep apnea without any other neurological signs but was ultimately diagnosed with type I Chiari malformation. The patient initially showed mild improvement in symptoms after administration of an acetazolamide. Finally, posterior fossa decompression dramatically improved her respiratory status during sleep, both clinically and on polysomnography. This case suggests that type I Chiari malformation should be considered in the differential diagnoses of central apneas in children, even if there are no other neurological signs and symptoms. Furthermore, sagittal craniocervical magnetic resonance imaging may be necessary for a definitive diagnosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Congenital malformations in offspring of women with a history of malignancy.

PubMed

Sabeti Rad, Zahra; Friberg, Britt; Henic, Emir; Rylander, Lars; Ståhl, Olof; Källén, Bengt; Lingman, Göran

2017-02-15

Survival after malignancy has increased and the question of risks, including risk for congenital malformations for the offspring of these women has become important. Data on congenital malformations in such offspring are limited. We compared congenital malformation in offspring, born 1994 to 2011 of women with a history of malignancy (at least 1 year before delivery) with all other offspring. Adjustment for confounders was mainly made by Mantel-Haenszel methodology. Data were obtained by linkage between Swedish national health registers. We identified 71,954 (4.1%) infants with congenital malformation, of which 47,081 (2.7%) were relatively severe (roughly corresponding to major malformation). Among 7284 infants to women with a history of malignancy 204 relatively severe malformations were found (2.8%; odds ratio [OR] = 1.04; 95% confidence interval [CI], 0.91-1.20). After in vitro fertilization, the risk of a relatively severe malformation was significantly increased in women without a history of malignancy (OR = 1.31; 95% CI, 1.24-1.38) and still more in women with such a history (risk ratio = 1.85; 95% CI, 1.08-2.97). However, there were no significant differences neither, for any malformations (OR = 1.04; 95% CI, 0.92-1.16) nor for relatively severe malformations (OR = 1.04; 95% CI, 0.91-1.20), when comparing offspring only after maternal history of malignancy. No general increase in malformation rate was found in infants born to women with a history of malignancy. A previously known increased risk after in vitro fertilization was verified and it is possible that this risk is further augmented among infants born of women with a history of malignancy. Birth Defects Research 109:224-233, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Controversies in Poland Syndrome: Alternative Diagnoses in Patients With Congenital Pectoral Muscle Deficiency.

PubMed

Baas, Martijn; Burger, Elise B; Sneiders, Dimitri; Galjaard, Robert-Jan H; Hovius, Steven E R; van Nieuwenhoven, Christianne A

2018-02-01

Poland syndrome was first described as a deficiency of the pectoral muscle with ipsilateral symbrachydactyly. Currently, numerous case reports describe variations of Poland syndrome in which pectoral muscle deficiency is often used as the only defining criterion. However, more syndromes can present with pectoral muscle deficiency. The aim of this review is to illustrate the diversity of the phenotypic spectrum of Poland syndrome and to create more awareness for alternative diagnoses in pectoral muscle deficiency. A systematic literature search was performed. Articles containing phenotypical descriptions of Poland syndrome were included. Data extraction included number of patients, sex, familial occurrence, and the definition of Poland syndrome used. In addition, hand deformities, thoracic deformities, and other deformities in each patient were recorded. Alternative syndrome diagnoses were identified in patients with a combination of hand, thorax, and other deformities. One hundred-and-thirty-six articles were included, describing 627 patients. Ten different definitions of Poland syndrome were utilized. In 58% of the cases, an upper extremity deformity was found and 43% of the cases had an associated deformity. Classic Poland syndrome was seen in 29%. Fifty-seven percent of the patients with a pectoral malformation, a hand malformation, and another deformity had at least 1feature that matched an alternative syndrome. Pectoral muscle hypoplasia is not distinctive for Poland syndrome alone but is also present in syndromes with other associated anomalies with a recognized genetic cause. Therefore, in patients with an atypical phenotype, we recommend considering other diagnoses and/or syndromes before diagnosing a patient with Poland syndrome. This can prevent diagnostic and prognostic errors. Differentiating Poland syndrome from the alternative diagnoses has serious consequences for the patient and their family in terms of inheritance and possible related anomalies

Quantification of shape and cell polarity reveals a novel mechanism underlying malformations resulting from related FGF mutations during facial morphogenesis

PubMed Central

Li, Xin; Young, Nathan M.; Tropp, Stephen; Hu, Diane; Xu, Yanhua; Hallgrímsson, Benedikt; Marcucio, Ralph S.

2013-01-01

Fibroblast growth factor (FGF) signaling mutations are a frequent contributor to craniofacial malformations including midfacial anomalies and craniosynostosis. FGF signaling has been shown to control cellular mechanisms that contribute to facial morphogenesis and growth such as proliferation, survival, migration and differentiation. We hypothesized that FGF signaling not only controls the magnitude of growth during facial morphogenesis but also regulates the direction of growth via cell polarity. To test this idea, we infected migrating neural crest cells of chicken embryos with  replication-competent avian sarcoma virus expressing either FgfR2C278F, a receptor mutation found in Crouzon syndrome or the ligand Fgf8. Treated embryos exhibited craniofacial malformations resembling facial dysmorphologies in craniosynostosis syndrome. Consistent with our hypothesis, ectopic activation of FGF signaling resulted in decreased cell proliferation, increased expression of the Sprouty class of FGF signaling inhibitors, and repressed phosphorylation of ERK/MAPK. Furthermore, quantification of cell polarity in facial mesenchymal cells showed that while orientation of the Golgi body matches the direction of facial prominence outgrowth in normal cells, in FGF-treated embryos this direction is randomized, consistent with aberrant growth that we observed. Together, these data demonstrate that FGF signaling regulates cell proliferation and cell polarity and that these cell processes contribute to facial morphogenesis. PMID:23906837

Behavior of 10 patients with FG Syndrome (Opitz-Kaveggia Syndrome) and the p.R961W Mutation in the MED12 Gene

PubMed Central

Graham, John M; Visootsak, Jeannie; Dykens, Elisabeth; Huddleston, Lillie; Clark, Robin D; Jones, Kenneth L; Moeschler, John B; Opitz, John M; Morford, Jackie; Simensen, Richard; Rogers, R. Curtis; Schwartz, Charles E; Friez, Michael J; Stevenson, Roger E

2011-01-01

Opitz and Kaveggia [1974] reported on a family of five affected males with distinctive facial appearance, mental retardation, macrocephaly, imperforate anus and hypotonia. Risheg et al. [2007] identified an identical mutation (p.R961W) in MED12 in six families with Opitz-Kaveggia syndrome, including a surviving affected man from the family reported in 1974. The previously defined behavior phenotype of hyperactivity, affability, and excessive talkativeness is very frequent in young boys with this mutation, along with socially oriented, attention-seeking behaviors. We present case studies of two older males with FG syndrome and the p.R961W mutation to illustrate how their behavior changes with age. We also characterize the behavior of eight additional individuals with FG syndrome and this recurrent mutation in MED12 using the Vineland Adaptive Behavior Scales 2nd ed., the Reiss Profile of Fundamental Goals and Motivation Sensitivities, and the Achenbach Child Behavior Checklist. Males with this MED12 mutation had deficits in communication skills compared to their socialization and daily living skills. In addition, they were at increased risk for maladaptive behavior, with a propensity towards aggression, anxiety, and inattention. Based on the behavior phenotype in 10 males with this recurrent MED12 mutation, we offer specific recommendations and interventional strategies. Our findings reinforce the importance of testing for the p.R961W MED12 mutation in males who are suspected of having developmental and behavioral problems with a clinical phenotype that is consistent with FG syndrome. PMID:18973276

AB119. Computer-aided facial recognition of Chinese individuals with 22q11.2 deletion-algorithm training using NIH atlas of human malformation syndromes from diverse population

PubMed Central

Mok, Gary Tsz Kin; Chung, Brian Hon-Yin

2017-01-01

Background 22q11.2 deletion syndrome (22q11.2DS) is a common genetic disorder with an estimated frequency of 1/4,000. It is a multi-systemic disorder with high phenotypic variability. Our previous work showed substantial under-diagnosis of 22q11.2DS as 1 in 10 adult patients with conotruncal defects were found to have 22q11.2DS. The National Institute of Health (NIH) has created an atlas of human malformation syndrome from diverse populations to provide an easy tool to assist clinician in diagnosing the syndromic across various populations. In this study, we seek to determine whether training the computer-aided facial recognition technology using images from ethnicity-matched patients from the NIH Atlas can improve the detection performance of this technology. Methods Clinical photographs of 16 Chinese subjects with molecularly confirmed 22q11.2DS, from the NIH atlas and its related publication were used for training the facial recognition technology. The system automatically localizes hundreds of facial fiducial points and takes measurements. The final classification is based on these measurements, as well as an estimated probability of subjects having 22q11.2DS based on the entire facial image. Clinical photographs of 7 patients with molecularly confirmed 22q11.2DS were obtained with informed consent and used for testing the performance in recognizing facial profiles of the Chinese subjects before and after training. Results All 7 test cases were improved in ranking and scoring after the software training. In 4 cases, 22q11.2DS did not appear as one possible syndrome match before the training; however, it appeared within the first 10 syndrome matches after training. Conclusions The present pilot data shows that this technology can be trained to recognize patients with 22q11.2DS. It also highlights the need to collect clinical photographs of patients from diverse populations to be used as resources for training the software which can lead to improvement of the

Poland syndrome: description of an atypical variant.

PubMed

Ferraro, G A; Perrotta, A; Rossano, F; D'Andrea, F

2005-01-01

Poland syndrome comprises a unilateral absence of the large pectoral muscle, ipsilateral symbrachydactyly, and occasionally other malformations of the anterior chest wall and breast. The condition is more frequent among males, and usually occurs on the right hemithorax in the unilateral form. The syndrome is believed to be caused by a genetic disorder that reduces the embryonal circulation in the interior chest artery: the stronger the interaction, the more severe the pathology. This article analyzes an unusual pathologic case in which the 17-year-old patient lacked the large pectoral muscle on the left side, but showed no arterial alteration. This case raises questions as to the true pathogenesis of this syndrome.

A Very Rare Cause of Anal Atresia: Currarino Syndrome

PubMed Central

Buyukbese Sarsu, Sevgi; Parmaksiz, Mehmet Ergun; Cabalar, Esra; Karapur, Ali; Kaya, Cihat

2016-01-01

Currarino syndrome (triad) is an extremely rare condition characterized by presacral mass, anorectal malformation, and sacral bone deformation. The complete form of this syndrome displays all three irregularities. Herein, we report a male case who was admitted to our hospital with symptoms of urinary system infection and persistent constipation 2 years after colostomy operation performed with the indication of rectovestibular fistula and anal atresia, diagnosed as Currarino syndrome based on imaging modalities. In a patient who was admitted because of the presence of anal atresia, in order to preclude potential complications, probable concomitancy of this syndrome should not be forgotten. Early diagnosis is important for the prevention of meningitis, urinary tract infections, and malignant change. PMID:27081429

Congenital Malformations in River Buffalo (Bubalus bubalis)

PubMed Central

Albarella, Sara; Ciotola, Francesca; D’Anza, Emanuele; Coletta, Angelo; Zicarelli, Luigi; Peretti, Vincenzo

2017-01-01

Simple Summary Congenital malformations (due to genetic causes) represent a hidden danger for animal production, above all when genetic selection is undertaken for production improvements. These malformations are responsible for economic losses either because they reduce the productivity of the farm, or because their spread in the population would decrease the total productivity of that species/breed. River buffalo is a species of increasing interest all over the world for its production abilities, as proved by the buffalo genome project and the genetic selection plans that are currently performed in different countries. The aim of this review is to provide a general view of different models of congenital malformations in buffalo and their world distribution. This would be useful either for those who performed buffalo genetic selection or for researchers in genetic diseases, which would be an advantage to their studies with respect to the knowledge of gene mutations and interactions in this species. Abstract The world buffalo population is about 168 million, and it is still growing, in India, China, Brazil, and Italy. In these countries, buffalo genetic breeding programs have been performed for many decades. The occurrence of congenital malformations has caused a slowing of the genetic progress and economic loss for the breeders, due to the death of animals, or damage to their reproductive ability or failing of milk production. Moreover, they cause animal welfare reduction because they can imply foetal dystocia and because the affected animals have a reduced fitness with little chances of survival. This review depicts, in the river buffalo (Bubalus bubalis) world population, the present status of the congenital malformations, due to genetic causes, to identify their frequency and distribution in order to develop genetic breeding plans able to improve the productive and reproductive performance, and avoid the spreading of detrimental gene variants. Congenital

MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert Syndrome related disorder with liver involvement.

PubMed

Brancati, Francesco; Iannicelli, Miriam; Travaglini, Lorena; Mazzotta, Annalisa; Bertini, Enrico; Boltshauser, Eugen; D'Arrigo, Stefano; Emma, Francesco; Fazzi, Elisa; Gallizzi, Romina; Gentile, Mattia; Loncarevic, Damir; Mejaski-Bosnjak, Vlatka; Pantaleoni, Chiara; Rigoli, Luciana; Salpietro, Carmelo D; Signorini, Sabrina; Stringini, Gilda Rita; Verloes, Alain; Zabloka, Dominika; Dallapiccola, Bruno; Gleeson, Joseph G; Valente, Enza Maria

2009-02-01

The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the "molar tooth sign", a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14 COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs. (c) 2008 Wiley-Liss, Inc.

MKS3/TMEM67 Mutations Are a Major Cause of COACH Syndrome, a Joubert Syndrome Related Disorder with Liver Involvement

PubMed Central

Brancati, Francesco; Iannicelli, Miriam; Travaglini, Lorena; Mazzotta, Annalisa; Bertini, Enrico; Boltshauser, Eugen; D’Arrigo, Stefano; Emma, Francesco; Fazzi, Elisa; Gallizzi, Romina; Gentile, Mattia; Loncarevic, Damir; Mejaski-Bosnjak, Vlatka; Pantaleoni, Chiara; Rigoli, Luciana; Salpietro, Carmelo D.; Signorini, Sabrina; Stringini, Gilda Rita; Verloes, Alain; Zabloka, Dominika; Dallapiccola, Bruno; Gleeson, Joseph G.; Valente, Enza Maria

2008-01-01

The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the “molar tooth sign”, a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14 COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs. PMID:19058225

Notch-1 Signalling Is Activated in Brain Arteriovenous Malformations in Humans

ERIC Educational Resources Information Center

ZhuGe, Qichuan; Zhong, Ming; Zheng, WeiMing; Yang, Guo-Yuan; Mao, XiaoOu; Xie, Lin; Chen, Gourong; Chen, Yongmei; Lawton, Michael T.; Young, William L.; Greenberg, David A.; Jin, Kunlin

2009-01-01

A role for the Notch signalling pathway in the formation of arteriovenous malformations during development has been suggested. However, whether Notch signalling is involved in brain arteriovenous malformations in humans remains unclear. Here, we performed immunohistochemistry on surgically resected brain arteriovenous malformations and found that,…

SOX2 anophthalmia syndrome and dental anomalies.

PubMed

Chacon-Camacho, Oscar Francisco; Fuerte-Flores, Bertha Irene; Ricardez-Marcial, Edgar F; Zenteno, Juan Carlos

2015-11-01

SOX2 anophthalmia syndrome is an uncommon autosomal dominant syndrome caused by mutations in the SOX2 gene and clinically characterized by severe eye malformations (anophthalmia/microphthalmia) and extraocular anomalies mainly involving brain, esophagus, and genitalia. In this work, a patient with the SOX2 anophthalmia syndrome and exhibiting a novel dental anomaly is described. SOX2 genotyping in this patient revealed an apparently de novo c.70del20 deletion, a commonly reported SOX2 mutation. A review of the phenotypic variation observed in patients carrying the recurrent SOX2 c.70del20 mutation is presented. Although dental anomalies are uncommonly reported in the SOX2 anophthalmia syndrome, we suggest that a dental examination should be performed in patients with SOX2 mutations. © 2015 Wiley Periodicals, Inc.

Pigmentary changes and atopic dermatitis in a patient with Seckel syndrome.

PubMed

Brackeen, Amy; Babb-Tarbox, Michelle; Smith, Jennifer

2007-01-01

Seckel syndrome is a very rare form of primordial dwarfism characterized by antenatal and postnatal growth delay, proportionate extreme short stature, a prominent beak-like nose, hypoplasia of the malar area, small chin, microcephaly, deformed ears lacking lobules, skeletal malformations, mental retardation, and developmental delay. This syndrome has been described with associated disorders of orthopedic, neurologic, hematologic, cardiac, and ocular systems; however, only a few reports mention dermatologic involvement. We describe a 5-year-old girl with classic Seckel syndrome who presented with moderately severe atopic dermatitis and diffuse hypopigmented macules and papules.

Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (L-CHAD) deficiency in a patient with the Bannayan-Riley-Ruvalcaba syndrome.

PubMed

Fryburg, J S; Pelegano, J P; Bennett, M J; Bebin, E M

1994-08-01

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is an autosomal dominant condition of macrocephaly in combination with lipomas/hemangiomas, hypotonia, developmental delay, and a lipid myopathy. The etiology of the lipid storage myopathy has been unclear. We describe a black boy with findings of BRRS who also has a defect in long-chain fatty acid oxidation expressed in cultured skin fibroblasts as a deficiency of long-chain-L-3-hydroxyacyl-CoA dehydrogenase (L-CHAD). He also has an abnormal brain MRI and increased size of both lower limbs. We present this child because of his unusual combination of findings, and postulate that L-CHAD deficiency may be the cause of the lipid myopathy in BRRS.

Onyx® in endovascular treatment of cerebral arteriovenous malformations – a review

PubMed Central

Szajner, Maciej; Roman, Tomasz; Markowicz, Justyna; Szczerbo-Trojanowska, Małgorzata

2013-01-01

Summary Arteriovenous malformation (AVM) is an abnormal connection between arteries and veins, bypassing the capillary system. In most cases, the disorder may be asymptomatic. The objective of endovascular AVM treatment is set individually for each case upon consultations with a neurosurgeon and a neurologist. The endpoint of the treatment should consist in prevention of AVM bleeding in a management procedure characterized by a significantly lower risk of complications as compared to the natural history of AVM. Endovascular interventions within AVM may include curative exclusion of AVM from circulation, embolization adjuvant to resection or radiation therapy, targeted closure of a previously identified bleeding site as well as palliative embolization. Onyx was first described in the 1990s. It is a non-adhesive and radiolucent compound. Onyx-based closure of the lumen of the targeted vessel is obtained by means of precipitation. The process is enhanced peripherally to the main flux of the injected mixture. This facilitates angiographic monitoring of embolization at any stage. The degree of lumen closure is associated with the location of the vessel. Supratentorial and cortical locations are most advantageous. Dense and plexiform structure of AVM nidus as well as a low number of supplying vessels and a single superficial drainage vein are usually advantageous for Onyx administration. Unfavorable factors include nidus drainage into multiple compartments as well as multiarterial supply of the AVM, particularly from meningeal arteries, en-passant arteries or perforating feeders. Onyx appears to be a safe and efficient material for embolization of cerebral AVMs, also in cases of intracranial bleeding associated with AVM. Curative embolization of small cerebral AVMs is an efficient and safe alternative to neurosurgical and radiosurgical methods. Careful angiographic assessment of individual arteriovenous malformations should be performed before each Onyx administration

Noise suppressing capillary separation system

DOEpatents

Yeung, Edward S.; Xue, Yongjun

1996-07-30

A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans.

Genetic Syndromes Associated with Congenital Cardiac Defects and Ophthalmologic Changes - Systematization for Diagnosis in the Clinical Practice

PubMed Central

Oliveira, Priscila H. A.; Souza, Beatriz S.; Pacheco, Eimi N.; Menegazzo, Michele S.; Corrêa, Ivan S.; Zen, Paulo R. G.; Rosa, Rafael F. M.; Cesa, Claudia C.; Pellanda, Lucia C.; Vilela, Manuel A. P.

2018-01-01

Background Numerous genetic syndromes associated with heart disease and ocular manifestations have been described. However, a compilation and a summarization of these syndromes for better consultation and comparison have not been performed yet. Objective The objective of this work is to systematize available evidence in the literature on different syndromes that may cause congenital heart diseases associated with ocular changes, focusing on the types of anatomical and functional changes. Method A systematic search was performed on Medline electronic databases (PubMed, Embase, Cochrane, Lilacs) of articles published until January 2016. Eligibility criteria were case reports or review articles that evaluated the association of ophthalmic and cardiac abnormalities in genetic syndrome patients younger than 18 years. Results The most frequent genetic syndromes were: Down Syndrome, Velo-cardio-facial / DiGeorge Syndrome, Charge Syndrome and Noonan Syndrome. The most associated cardiac malformations with ocular findings were interatrial communication (77.4%), interventricular communication (51.6%), patent ductus arteriosus (35.4%), pulmonary artery stenosis (25.8%) and tetralogy of Fallot (22.5%). Conclusion Due to their clinical variability, congenital cardiac malformations may progress asymptomatically to heart defects associated with high morbidity and mortality. For this reason, the identification of extra-cardiac characteristics that may somehow contribute to the diagnosis of the disease or reveal its severity is of great relevance. PMID:29538527