Waardenburg Syndrome, Type 4 Clinical CharacteristicsOcular Features: The skin and ocular pigmentary changes and the sensorineural hearing loss in type 4 Waardenburg syndrome resembles that of other types. Patients, however, usually lack synophrys and dystopia canthorum. Systemic Features: Type 4 Waardenburg syndrome is largely similar to other types except that many patients also have Hirschsprung disease. GeneticsBoth autosomal dominant and recessive inheritance have been reported for type 4 Waardenburg syndrome. Both heterozygous and homozygous mutations in the EDNRB (endothelin-B receptor) gene (13q22) occur in patients. The aganglionic megacolon feature may be dose sensitive since homozygotes have been reported to have a 74% chance of developing Hirschsprung disease while only 21% of heterozygotes do so. Types 4A (277580) and 4B (613265) are both caused by mutations in the EDNRB gene, and type 4C (613266) results from a mutation in the SOX10 gene. Waardenburg syndrome WS2E is allelic to type 4C. This is an example of genetic heterogeneity both within the main types and within the subtypes. Pedigree: Autosomal dominantAutosomal recessiveTreatmentTreatment Options: No ocular treatment is necessary but assistive hearing devices can be beneficial. ReferencesArticle Title: Review and update of mutations causing Waardenburg syndrome Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N. Review and update of mutations causing Waardenburg syndrome. Hum Mutat. 2010 Apr;31(4):391-406. Review. PubMed ID: 20127975 Waardenburg syndrome Read AP, Newton VE. Waardenburg syndrome. J Med Genet. 1997 Aug;34(8):656-65. Review. PubMed ID: 9279758 Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease Atti?(c) T, Till M, Pelet A, Amiel J, Edery P, Boutrand L, Munnich A, Lyonnet S. Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease. Hum Mol Genet. 1995 Dec;4(12):2407-9. PubMed ID: 8634719 Read more about Waardenburg Syndrome, Type 4
Review and update of mutations causing Waardenburg syndrome Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N. Review and update of mutations causing Waardenburg syndrome. Hum Mutat. 2010 Apr;31(4):391-406. Review. PubMed ID: 20127975
Waardenburg syndrome Read AP, Newton VE. Waardenburg syndrome. J Med Genet. 1997 Aug;34(8):656-65. Review. PubMed ID: 9279758
Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease Atti?(c) T, Till M, Pelet A, Amiel J, Edery P, Boutrand L, Munnich A, Lyonnet S. Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease. Hum Mol Genet. 1995 Dec;4(12):2407-9. PubMed ID: 8634719
