LAUSR

Waardenburg Syndrome (WS) is named after the ophthalmologist who first described the association between deafness, depigmentation, and dysmorphology.[1] It is the most common cause of syndromic hearing loss with variable degrees of pigmentation defects and ocular changes like heterochromia iridis, iris hypopigmentation, medial eyebrow flare (synophrys), and dystopia canthorum.[2] Four subtypes of WS have been defined, with type I and II being the most common.[1] Type I WS (WS1) is inherited as an autosomal dominant (AD) disease.[3] Dystopia canthorum is the distinguishing and constant feature in this subtype. Iris heterochromia and strabismus are other ocular features. Other main features are broad, high nasal root, medial hypertrichosis, synophrys, hypoplasia of the alae nasi, patent metopic suture, piebaldism, and congenital non‐progressive sensorineural hearing loss. These features show marked inter‐ and intra‐familial variability.[3] Some authors also report progressive post‐lingual hearing loss associated with WS.[4] Nearly all patients with WS1 have Paired Box 3 (PAX3) mutation.[3] Type 2 WS (WS2) has identical auditory and pigmentary features to WS1 but lacks dystopia canthorum. It is inherited as AD, and 15% have microphthalmia‐associated transcription factor (MITF) mutation.[3] Type 3 WS (WS3) or Klein–Waardenburg syndrome is a variant of WS1 with musculoskeletal abnormalities like limb muscles hypoplasia and joint contracture. Usually a PAX3 heterozygote, it is inherited as AD.[3] Type 4 WS (WS4) or Shah–Waardenburg syndrome is associated with Hirschsprung’s Disease (HD). It is primarily autosomal‐recessive (AR) and associated with endothelin 3 (EDN3) or endothelin receptor type B (EDNRB) mutations.[3] Various other genes have also been implicated in the pathogenesis of this disorder, namely, sex‐determining region Y—Box 10 (SOX10) for WS2 and WS4 and snail family transcriptional repressor 2 (SNAI2) for WS2.[1] EDNRB mutation has been detected in WS1 also.[1]