The clinical symptoms of Waardenburg Syndrome (WS) include:
- Dystopia canthorum (lateral displacement of the inner canthus of each eye)
- Pigmentary abnormalities of hair, iris, and skin (often white forelock and heterochromia iridis)
- 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.