A case report of reversible generalized seizures in a patient with Waardenburg syndrome associated with a novel nonsense mutation in the penultimate exon of SOX10

• Published in: BMC pediatrics Vol. 18; no. 1; p. 171
• Main Authors: Suzuki, Noriomi, Mutai, Hideki, Miya, Fuyuki, Tsunoda, Tatsuhiko, Terashima, Hiroshi, Morimoto, Noriko, Matsunaga, Tatsuo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 23.05.2018; BioMed Central; BMC
• Subjects: Age; Case Report; Case reports; Case studies; Congenital diseases; Delayed myelination; Deoxyribonucleic acid; DNA; Exons; Families & family life; Gene mutations; Genes; Hearing loss; Humans; Infant; Klein-Waardenburg syndrome; Male; Medical imaging; Mutation; NMR; Nonsense mutation; Nuclear magnetic resonance; Seizure attack; Seizures (Medicine); Seizures - etiology; SOX10; SOXE Transcription Factors - genetics; Waardenburg syndrome; Waardenburg Syndrome - complications; Waardenburg Syndrome - diagnosis; Waardenburg Syndrome - genetics; United States > US; Seizure attack; Delayed myelination; Nonsense mutation; Waardenburg syndrome; SOX10
• ISSN: 1471-2431; 1471-2431
• DOI: 10.1186/s12887-018-1139-2

Waardenburg syndrome type 1 (WS1) can be distinguished from Waardenburg syndrome type 2 (WS2) by the presence of dystopia canthorum. About 96% of WS1 are due to PAX3 mutations, and SOX10 mutations have been reported in 15% of WS2. This report describes a patient with WS1 who harbored a novel SOX10 nonsense mutation (c.652G > T, p.G218*) in exon 3 which is the penultimate exon. The patient had mild prodromal neurological symptoms that were followed by severe attacks of generalized seizures associated with delayed myelination of the brain. The immature myelination recovered later and the neurological symptoms could be improved. This is the first truncating mutation in exon 3 of SOX10 that is associated with neurological symptoms in Waardenburg syndrome. Previous studies reported that the neurological symptoms that associate with WS are congenital and irreversible. These findings suggest that the reversible neurological phenotype may be associated with the nonsense mutation in exon 3 of SOX10. When patients of WS show mild prodromal neurological symptoms, the clinician should be aware of the possibility that severe attacks of generalized seizures may follow, which may be associated with the truncating mutation in exon 3 of SOX10.