aganglionic megacolon

Waardenburg Syndrome, Type 4

Clinical Characteristics
Ocular 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.

Genetics

Both 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 dominant
Autosomal recessive
Treatment
Treatment Options: 

No ocular treatment is necessary but assistive hearing devices can be beneficial.

References
Article Title: 

Waardenburg syndrome

Read AP, Newton VE. Waardenburg syndrome. J Med Genet. 1997 Aug;34(8):656-65. Review.

PubMed ID: 
9279758
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