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
TypeClinical Features
Type IDystopia canthorum
Type IINo dystopia canthorum
Type III (Klein-Waardenburg syndrome)Type I and upper limb abnormalities
Type IV (Waardenburg-Shah syndrome)Type II and Hirschsprung disease
MOLECULAR classification of Waardenburg syndrome
TypeLocus (OMIM)Gene (OMIM)InheritanceKey Locus References (PubMed)Key Gene References (PubMed)
Evidence (ClinGen)
Type IWS1PAX3Autosomal DominantFoy et al., 1990Tassabehji et al., 1992Definitive
Type IIWS2AMITFAutosomal DominantHughes et al., 1994Tassabehji et al., 1994Definitive
Type IIWS2BunknownAutosomal DominantHughes et al., 1994; Lalwani et al., 1994n/an/a
Type IIWS2CunknownunknownSelicorni et al., 2002n/an/a
Type IIWS2DSNAI2Autosomal RecessiveSánchez-Martin et al., 2002Sánchez-Martin et al., 2002Limited
Type IIWS2ESOX10Autosomal DominantBondurand et al., 2007Bondurand et al., 2007not reviewed
Type IIWS2FKITLGAutosomal RecessiveOgawa et al., 2017Ogawa et al., 2017not reviewed
Type IIIWS3PAX3Autosomal DominantZlotogora et al., 1995Zlotogora et al., 1995Definitive
Type IIIWS3PAX3Autosomal RecessiveZlotogora et al., 1995Zlotogora et al., 1995not reviewed
Type IVWS4AEDNRBAutosomal DominantVan Camp et al., 1995Attié et al., 1995Limited
Type IVWS4AEDNRBAutosomal RecessiveVan Camp et al., 1995Attié et al., 1995Moderate
Type IVWS4BEDN3Autosomal DominantEdery et al., 1996Edery et al., 1996Limited
Type IVWS4BEDN3Autosomal RecessiveEdery et al., 1996Edery et al., 1996Moderate
Type IVWS4CSOX10Autosomal DominantPingault et al., 1998Pingault et al., 1998Definitive

n/a = not applicable

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