Waardenburg Syndrome Type 3

A very rare subtype of Waardenburg syndrome (WS) that is characterized by limb anomalies in association with congenital hearing loss, minor defects in structures arising from neural crest, resulting in pigmentation anomalies of eyes, hair, and skin.

Epidemiology

Incidence is unknown, but WS3 is the rarest form of all Waardenburg syndrome types.

Clinical description

WS3 is characterized by the association of limb anomalies (predominantly involving upper limbs, with hypoplasia of the musculoskeletal system, flexion contractures, fusion of the carpal bones, syndactylia) with features of Waardenburg syndrome (see this term), which include congenital sensorineural hearing loss, hypopigmentation abnormalities of irides, hair and skin and minor facial dysmorphism in combination with dystopia canthorum.

Etiology

WS3 is caused by heterozygous or homozygous mutations in the PAX3 (2q36.1) gene.

Diagnostic methods

Diagnosis is made through criteria of the association of WS1 manifestations with limb anomalies. PAX3 gene analysis confirms diagnosis resulting in an abnormality of melanocytes of skin, ears and hair.

Antenatal diagnosis

Antenatal diagnosis is possible for affected parents.

Genetic counseling

The defects are more severe in homozygous than heterozygous forms. Genetic counseling is recommended.

Management and treatment

Hearing aids to counter hearing loss, effective therapy to improve language, communication, and cognitive skill and limbs physiotherapy are recommended. Associated manifestations are treated as appropriate (e.g. skin and eyes protection from the sun).

Prognosis

Due to the very few number of cases described so far, information on prognosis and quality of life is limited. Disease progression is variable, with symptoms being more severe in homozygous than in heterozygous forms.