Waardenburg syndrome with Hirschsprung disease

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:

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