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 abnormalities |
| Type IV (Waardenburg-Shah syndrome) | Type II and Hirschsprung disease |
MOLECULAR classification of Waardenburg syndrome
| Type | Locus (OMIM) | Gene (OMIM) | Inheritance | Key Locus References (PubMed) | Key Gene References (PubMed) | |
|---|
| Type I | WS1 | PAX3 | Autosomal Dominant | Foy et al., 1990 | Tassabehji et al., 1992 | Definitive |
| Type II | WS2A | MITF | Autosomal Dominant | Hughes et al., 1994 | Tassabehji et al., 1994 | Definitive |
| Type II | WS2B | unknown | Autosomal Dominant | Hughes et al., 1994; Lalwani et al., 1994 | n/a | n/a |
| Type II | WS2C | unknown | unknown | Selicorni et al., 2002 | n/a | n/a |
| Type II | WS2D | SNAI2 | Autosomal Recessive | Sánchez-Martin et al., 2002 | Sánchez-Martin et al., 2002 | Limited |
| Type II | WS2E | SOX10 | Autosomal Dominant | Bondurand et al., 2007 | Bondurand et al., 2007 | not reviewed |
| Type II | WS2F | KITLG | Autosomal Recessive | Ogawa et al., 2017 | Ogawa et al., 2017 | not reviewed |
| Type III | WS3 | PAX3 | Autosomal Dominant | Zlotogora et al., 1995 | Zlotogora et al., 1995 | Definitive |
| Type III | WS3 | PAX3 | Autosomal Recessive | Zlotogora et al., 1995 | Zlotogora et al., 1995 | not reviewed |
| Type IV | WS4A | EDNRB | Autosomal Dominant | Van Camp et al., 1995 | Attié et al., 1995 | Limited |
| Type IV | WS4A | EDNRB | Autosomal Recessive | Van Camp et al., 1995 | Attié et al., 1995 | Moderate |
| Type IV | WS4B | EDN3 | Autosomal Dominant | Edery et al., 1996 | Edery et al., 1996 | Limited |
| Type IV | WS4B | EDN3 | Autosomal Recessive | Edery et al., 1996 | Edery et al., 1996 | Moderate |
| Type IV | WS4C | SOX10 | Autosomal Dominant | Pingault et al., 1998 | Pingault et al., 1998 | Definitive |
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.
