Dermatologic Manifestations of Waardenburg Syndrome

Updated: Jun 21, 2022
  • Author: Lyubomir A Dourmishev, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Practice Essentials

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).


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).


Waardenburg syndrome types 1 and 3 are most commonly associated with point mutations in PAX3, and type 2 is associated with MITF point mutations. Multiplex ligation-dependent probe amplification can be used to detect changes in targeted genes. [2]

Also see Workup.


No effective treatment is available for persons with Waardenburg syndrome. Early diagnosis and improvement of the hearing defect are important for the psychological development of children with this disease and help to reduce the sense of isolation.

Lack of resources in some societies may add to the physical and psychological obstacles faced by persons with Waardenburg syndrome. Tolerance and understanding of persons with Waardenburg syndrome help support their integration into society.

Surgical care

No effective surgical care is available except cochlear implantation in children with Waardenburg syndrome, which can improve the speech perception ability. [3]  Bilateral cochlear implantation has advantages compared with unilateral. [4]


Consultations with a geneticist are important since Waardenburg syndrome type I is an autosomal dominant disease and some affected persons have relatives with the same disease. However, even if prenatal test determines the presence of gene pathology, it still cannot predict the severity of its clinical expression.



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. [5, 6, 7] 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. [8, 9, 10, 11, 12, 13, 14]

Sznajer et al [15] 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.




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. [16]

Race-, sex-, and age-related information

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.