Dermatologic Manifestations of Waardenburg Syndrome

Updated: Jan 27, 2020
  • Author: Lyubomir A Dourmishev, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
  • Print


Waardenburg syndrome is a rare disease characterized by deafness in association with pigmentary anomalies and defects of neural crest-derived tissues.

Hammerschlag, in 1907, and Urbantschitsch, in 1910, both mentioned heterochromia iridium and partial albinism as occurring as complications of deafmutism. In 1916, van der Hoeve described a dystopia canthi medialis lateroversa in a pair of monozygotic twin girls with deafmutism. In 1951, Waardenburg [1] defined the syndrome with the following 6 main features:

  • Lateral displacement of the medial canthi combined with dystopia of the lacrimal puncta and blepharophimosis

  • Prominent broad nasal root

  • Hypertrichosis of the medial part of the eyebrows

  • White forelock

  • Heterochromia iridis

  • Deafmutism

In 1947, Klein reported a case of a 10-year-old girl with deafmutism, partial albinism of the skin and hair, hypochromia iridis, blepharophimosis with hypertelorism and absence of the nasofrontal angle, hypertrichosis of the eyebrows, and multiple associated abnormalities (myo-osteo-articulare dysplasia).



Waardenburg syndrome is a rare disease with an autosomal dominant mode of inheritance. Several hypotheses, including the following, have been advanced to explain all the clinical features of the syndrome:

  • The deficient neural crest theory, suggesting a developmental abnormality of the neural crest as a cause of the disease: The association of Waardenburg syndrome and congenital aganglionic megacolon supports this hypothesis.

  • Waardenburg syndrome as a part of the first arch syndrome

  • A relationship of Waardenburg syndrome with status dysraphicus

  • The intrauterine necrosis theory

None of these possibilities explains all the features of Waardenburg syndrome. Inherited causes account for approximately 50% of individuals seen for childhood (prelingual) hearing loss, of which 70% are due to mutations in numerous single genes that impair auditory function alone (nonsyndromic). The remainder are associated with other developmental anomalies termed syndromic deafness.

Genes responsible for syndromic forms of hearing loss in Waardenburg syndrome include PAX3 on band 2q37, observed in types I and III, and MITF mapped on 3p12-p 14.1 for type II. [2, 3, 4] Waardenburg syndrome is autosomal dominant for most persons with types I, II, or III. Waardenburg syndrome type IV is autosomal recessive with variable penetrance and is due to SOX10 or endothelin-B receptor (EDNRB) gene mutations, which appear to correlate with the intestinal and/or neurological symptoms manifested in patients. [5, 6, 7, 8, 9, 10, 11]

Sznajer et al [12] described a novel SOX10 splice site mutation (c.698-2A > C) that resulted in severe type 4 Waardenburg syndrome without Hirschsprung disease. The child presented with vivid blue eye, mental retardation, synophrys, deafness, bilateral complete semicircular canals, and peripheral neuropathy.



Waardenburg syndrome is a rare disease with an autosomal dominant mode of inheritance.




The frequency of Waardenburg syndrome is estimated to be 1 case per 212,000 persons in the general population of the Netherlands, but owing to a low penetrance of about 20%, the frequency of the entire syndrome (with or without deafness) is probably approximately 1 case per 42,000 persons. In Kenya, the estimated frequency is 1 case per 20,000 persons. The syndrome has been observed in 0.9-2.8% of persons with deafmutism. [13]


Waardenburg syndrome affects people of all races worldwide.


The disease affects both sexes equally. No sex differences among persons with congenital deafmutism have been found.


As an inheritable disease, Waardenburg syndrome can be recognized immediately or soon after birth. Some dermatologic features (eg, poliosis) change with age.



Children with Waardenburg syndrome have a normal life expectancy. Morbidity is related to deafness and to defects of neural crest-derived tissues, including mental retardation, seizures, psychiatric disorders, skeletal anomalies, and eye disorders (including cataracts).