Waardenburg

Waardenburg syndrome is a group of rare genetic disorders characterized by pigmentary abnormalities of the hair, skin, and eyes and often congenital sensorineural hearing loss. The condition is named after the Dutch ophthalmologist Petrus Johannes Waardenburg, who described the syndrome in the early 20th century. It is inherited mainly in an autosomal dominant pattern with variable expression.

There are four main subtypes recognized: WS1, WS2, WS3 (Klein-Waardenburg), and WS4 (Waardenburg-Shah). WS1 is associated with dystopia canthorum, a broad or widened space between the inner corners of the eyes, and is linked to PAX3 mutations. WS2 presents with pigmentary anomalies similar to WS1 but without dystopia canthorum and involves mutations in several genes including MITF, SOX10, EDNRB, and EDN3. WS3 is rarer and includes limb and musculoskeletal abnormalities in addition to the features of WS1, also related to PAX3. WS4 combines Waardenburg features with Hirschsprung disease, reflecting defects in neural crest cell development and involving EDNRB, EDN3, or SOX10.

Clinical features commonly include patchy depigmentation of the skin, white forelock of hair, heterochromia of the irises, and varying degrees of hearing loss. The severity and specific features vary even within families. Diagnosis is based on clinical findings and is supported by genetic testing. Management focuses on monitoring and addressing hearing loss, speech and language development, vision issues, and, when present, intestinal problems in WS4. Genetic counseling is often offered due to the autosomal dominant inheritance pattern.