title: Abnormal facial appearance, body asymmetry, limb deformities, and internal malformations.
abstract: We describe a newborn girl with multiple congenital anomalies and abnormal phenotype comprising underdeveloped corpus callosum with ventriculomegaly, chorioretinal atrophy, pulmonary arterial hypertension, annular pancreas, horseshoe kidney, asymmetric limb and chest anomalies, spinal segmentation defects, hypertrichosis, and unusual face with large anterior fontanel, high anterior hairline, broad forehead, mildly underdeveloped midface, hypertelorism, depressed nasal bridge, short and upturned nose, large mouth, retrognathia, and large and malformed ears. Work-up included cytogenetic studies of lymphocytes and skin fibroblasts, subtelomere Multiplex Ligation-dependent Probe Amplification (MLPA), whole-genome oligo-array, and molecular analysis of SETBP1 and NSDHL: no abnormalities were found. Mucopolysaccharide urinary excretion was elevated. Results of metabolic studies for sterol and peroxisomal abnormalities in fibroblasts were normal. Additional electronic microscopy studies in skin fibroblasts did not show evidence for storage in fibroblasts or lysosomal changes. Nosologic considerations allowed exclusion of Schinzel-Giedion and Urioste syndrome. This condition seems not to have been described before; a segregating Mendelian mutation is assumed.
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands. g.oudesluijs@erasmusmc.nl
authors.forename: Grétel
authors.initials: G
authors.lastname: Oudesluijs
authors.forename: Marleen E H
authors.initials: ME
authors.lastname: Simon
authors.forename: Rianne H J
authors.initials: RH
authors.lastname: Burggraaf
authors.forename: Hans R
authors.initials: HR
authors.lastname: Waterham
authors.forename: Raoul C M
authors.initials: RC
authors.lastname: Hennekam
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003337:Corpus Callosum / Q000254:growth & development / Q000473:pathology*; D019465:Craniofacial Abnormalities / Q000175:diagnosis; D003456:Cryptorchidism / Q000175:diagnosis; D003937:Diagnosis, Differential; D058490:Disorder of Sex Development, 46,XY / Q000175:diagnosis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000652:urine; D006228:Hand Deformities, Congenital / Q000175:diagnosis; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000175:diagnosis; D017880:Limb Deformities, Congenital / Q000473:pathology*; D008214:Lymphocytes / Q000166:cytology; D009095:Mullerian Ducts / Q000002:abnormalities; D009154:Mutation; D009264:Nails, Malformed / Q000175:diagnosis; D010641:Phenotype; D017689:Polydactyly / Q000175:diagnosis
chemical_list: D006025:Glycosaminoglycans