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Waardenburg syndrome is a group of genetic auditory–pigmentary syndromes characterized by congenital sensorineural hearing loss and abnormal pigmentation of the eyes, hair, and skin due to defective neural crest cell migration.

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Waardenburg's Syndrome - CRASH! Medical Review Series

Genetics & Pathogenesis

• Inheritance: Mostly autosomal dominant (Type IV can be autosomal recessive).
• Pathophysiology: Abnormal development/migration of melanocytes (neural crest derivatives).
• Common genes involved:
  • PAX3 (Types I & III)
  • MITF, SNAI2 (Type II)
  • EDNRB, EDN3, SOX10 (Type IV)

Clinical Spectrum

• Sensorineural hearing loss (congenital, unilateral or bilateral)
• Pigmentary abnormalities
  • Heterochromia iridis (complete or segmental)
  • Hypoplastic or brilliant blue irides
  • White forelock / premature greying
  • Patchy skin depigmentation
• Craniofacial features
  • Broad nasal root
  • Medial eyebrow flare (synophrys)
  • Dystopia canthorum (lateral displacement of medial canthi) – characteristic of Type I

![Iris color of Waardenburg syndrome type 2 patients. A II-2, complete heterochromia iridis. B II-7, a blue segment in his right iris. C II-9, blue segments in both irises. D II-11, brown and blue segments in her right iris and a blue segment in her left iris. E II-13, F III-8 and G I-1, brilliant blue irises

Zardadi, S., Rayat, S., Hassani Doabsari, M. et al. Waardenburg syndrome type 2A in a large Iranian family with a novel MITF gene mutation. BMC Med Genomics 14, 230 (2021). https://doi.org/10.1186/s12920-021-01074-y](attachment:5f69a846-e05f-4803-86c6-f94c04fc3569:12920_2021_1074_Fig2_HTML.webp)

Iris color of Waardenburg syndrome type 2 patients. A II-2, complete heterochromia iridis. B II-7, a blue segment in his right iris. C II-9, blue segments in both irises. D II-11, brown and blue segments in her right iris and a blue segment in her left iris. E II-13, F III-8 and G I-1, brilliant blue irises

Zardadi, S., Rayat, S., Hassani Doabsari, M. et al. Waardenburg syndrome type 2A in a large Iranian family with a novel MITF gene mutation. BMC Med Genomics 14, 230 (2021). https://doi.org/10.1186/s12920-021-01074-y

Types of Waardenburg Syndrome

Diagnostic Criteria ()

Type I classic type:

Diagnosis requires

• 2 major, or