Waardenburg syndrome (WS) is a genetic disorder characterised by congenital hearing loss, dystopia canthorum (increased distance between the inner canthi), and abnormalities in pigmentation of the hair, skin, and eyes. There are four different types of Waardenburg Syndrome: types 1 and 2 are the most common types, whereas types 3 and 4 are relatively rare. Waardenburg syndrome type 4 (WS4; Waardenburg-Shah syndrome) is distinguished from the other types of WS by its association with Hirschsprung disease, which is a neurocristopathy clinically recognized by aganglionosis of the distal gastrointestinal tract.
WS4 is genetically heterogeneous and has several subtypes. Mutations in the EDNRB (Endothelin Receptor, Type B ) gene, located on chromosome 13q22.3, is known to cause WS4A. Other subtypes of WS4 are caused by mutations in the EDN3 gene or SOX10 gene.
Abdulrazzaq (1989) reported a full term baby boy with Waardenburg's syndrome with long segment Hirschsprung's disease who was born to a non-consanguineous Omani family. At birth the baby was noted to have a white forelock and a hypopigmented area on the forehead. On the second day of life, he developed abdominal distension. Two male siblingswho died during the neonatal period had long segment Hirschsprung's disease, with one them having in addition, a white forelock.
[Abdulrazzaq YM. Waardenburg's syndrome with long segment Hirschsprung's disease in an Omani family. Emirates Med J. 1989; 7:26-9.]
In two girls born to consanguineous Tunisian parents, Attie et al. (1995) described features of both Waardenburg syndrome and Hirschsprung disease. Neither affected sister had dystopia canthorum. However, both had deafness, white forelock, and heterochromia iridis, as well as Hirschsprung disease.
One year later, Bonnet et al. (1996) reported a Tunisian infant of consanguineous parents with pigmentary disorders, congenital deafness and long-segment Hirschsprung disease. Her elder sister had the same disorders but with short-segment aganglionosis. Their father, mother and two brothers are healthy without history of deafness, constipation or pigmentary disorder. Bonnet et al. (1996) confirmed that this Waardenburg-Hirschsprung association seems to be a distinct clinical entity with a possible autosomal recessive mode of inheritance. Linkage analyses performed in this family support the view that neither the RET locus (candidate for familial dominant Hirschsprung disease) nor the HuP2 locus (candidate for Waardenburg syndrome type I) are involved in the disease phenotype. They also suggested that Waardenburg-Hirschsprung complex is a distinct genetic entity and at least one additional locus altering cranial neural crest cell development is responsible for pleiotropic features observed in this association.
[See: Oman > Abdulrazzaq, 1989].