Waardenburg Syndrome

The clinical symptoms of Waardenburg Syndrome (WS) include:

  1. Dystopia canthorum (lateral displacement of the inner canthus of each eye)
  2. Pigmentary abnormalities of hair, iris, and skin (often white forelock and heterochromia iridis)
  3. Sensorineural deafness

Some symptoms may be absent.

WS is subdivided in two types (I and II) on the basis of dystopia canthorum.
The combination of WS type I characteristics with upper limb abnormalities has been called Klein-Waardenburg syndrome or WS type III.
The combination of recessively inherited WS type II characteristics with Hirschsprung disease has been called Waardenburg-Shah syndrome or WS type IV.

Clinical classification of waardenburg syndrome
Type Clinical Features
Type I Dystopia canthorum
Type II No dystopia canthorum
Type III (Klein-Waardenburg syndrome) Type I and upper limb abnormalaties
Type IV (Waardenburg-Shah syndrome) Type II and Hirschsprung disease
MOLECULAR classification of waardenburg syndrome
Type Locus Gene (OMIM) Genomic Location Inheritance Key Reference (Pubmed)
Type I WS1 PAX3 2q36.1 Autosomal Dominant Tassebehji et al., 1992
Type II WS2A MITF 3p13 Autosomal Dominant Tassabehji et al., 1994
Type II WS2B - 1p21-p13.3 Autosomal Dominant Hughes et al., 1994
Type II WS2C - 8p23 Autosomal Dominant Selicorni et al., 2002
Type II WS2D SNAI2 8q11 Autosomal Recessive Sánchez-Martin et al., 2002
Type II WS2E SOX10 22q13.1 Autosomal Dominant Bondurand et al., 2007
Type III WS3 PAX3 2q36.1 Autosomal Dominant or Recessive Zlotogora et al., 1995
Type IV WS4A EDNRB 13q22.3 Autosomal Dominant or Recessive Attié et al., 1995
Type IV WS4B EDN3 20q13.32 Autosomal Dominant or Recessive Edery et al., 1996
Type IV WS4C SOX10 22q13.1 Autosomal Dominant Pingault et al., 1998


Note that mutations in PAX3 cause WS Type I and Type III and mutations in SOX10 cause WS Type II and Type IV.