Waardenburg syndrome (WS) is clinically heterogeneous and can be subdivided into four major types (WS1-WS4), where WS4 or Shah-Waardenburg is when WS2 is accompanied by Hirschsprung’s disease.

A recent study published in the International Journal of Pediatric Otorhinolaryngology aimed to determine the pathogenic variant of WS4.

This study recruited a two-generation Iranian pedigree affected by WS4, with three affected members having considerable phenotypic heterogeneity. The proband was a 15-year-old boy, with severe to profound sensorineural hearing impairment, heterochromia iridis, hypoplastic blue eyes and Hirschprung’s disease. The other two participants presented with characteristic symptoms of WS2 and complained of chronic constipation with normal anorectal reflex.

The results of sequencing of all exons and exon-intron boundaries of SOX10, EDN3/EDNRB revealed a heterozygous variant c.422T > C in exon-3 of SOX10, which was confirmed by a series of evidence to be pathogenic. The variant led to p.L141P at the protein level.

From the findings, it was inferred that SOX10 mutations is associated with distinctive phenotypic profile, and symptoms including chronic constipation. It was stated that the results could further improve diagnosis and counseling of patients with WS and its associated constipation.