title: Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature.
abstract: Shah-Waardenburg syndrome is a rare congenital disorder with variable clinical expression, characterised by aganglionosis of the rectosigmoïd (Hirschsprung disease), and abnormal melanocyte migration, resulting in pigmentary abnormalities and sensorineural deafness (Waardenburg syndrome). Mutations in the EDN, EDNRB and SOX10 genes can be found in patients with this syndrome. SOX10 mutations are specifically associated with a more severe phenotype called PCWH: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease. Neuronal expression of SOX10 occurs in neural crest cells during early embryonic development and in glial cells of the peripheral and central nervous systems during late embryonic development and in adults. We present a 4-year-old girl with the PCWH phenotype associated with a de novo nonsense mutation (S384X) in SOX10. Main clinical features were mental retardation, peripheral neuropathy, deafness, Hirschsprung disease, distal arthrogryposis, white hairlock, and growth retardation. She presented with hypotonia, developmental delay, reduced peripheral nerve conduction velocities, and radiologically assessed central hypomyelination. Subsequently, the formation of abnormal myelin within the central and peripheral nervous system was functionally and radiologically assessed. Children presenting with features of Waardenburg syndrome and neurological dysfunction should be tested for mutations in the SOX10 gene to enable diagnosis and counselling.
authors.affiliation: Department of Medical Genetics, University Medical Centre Groningen, Groningen University, Box 30.001, 9700 RB Groningen, The Netherlands. j.b.g.m.verheij@medgen.umcg.nl
authors.forename: Johanna B G M
authors.initials: JB
authors.lastname: Verheij
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Sival
authors.forename: Johannes H
authors.initials: JH
authors.lastname: van der Hoeven
authors.forename: Yvonne J
authors.initials: YJ
authors.lastname: Vos
authors.forename: Linda C
authors.initials: LC
authors.lastname: Meiners
authors.forename: Oebele F
authors.initials: OF
authors.lastname: Brouwer
authors.forename: Anthonie J
authors.initials: AJ
authors.lastname: van Essen
mesh_terms: D001921:Brain / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D003711:Demyelinating Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D005260:Female; D006128:Growth / Q000502:physiology; D006609:High Mobility Group Proteins / Q000235:genetics*; D006627:Hirschsprung Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D009123:Muscle Hypotonia / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009431:Neural Conduction / Q000502:physiology; D009460:Neurologic Examination; D011859:Radiography; D055757:SOXE Transcription Factors; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D014849:Waardenburg Syndrome / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D014157:Transcription Factors