Waardenburg Syndrome, Type 2d

A number sign (#) is used with this entry because Waardenburg syndrome type IID (WS2D) is caused by homozygous deletion of the SNAI2 gene (602150) on chromosome 8q11.

Description

Waardenburg syndrome type 2 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the inner canthus of each eye, which is seen in some other forms of WS (review by Read and Newton, 1997). WS type 2D is caused by mutation in the SNAI2 gene (602150). Waardenburg syndrome type 2 is genetically heterogeneous (see WS2A; 193510).

For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS3 (148820), and WS4 (277580).

Clinical Features

Sanchez-Martin et al. (2002) reported 2 unrelated patients with WS2D. One was a 15-year-old girl of Bangladeshi origin with profound bilateral sensorineural hearing loss and heterochromia iridis, but no other dysmorphic features or pigmentary changes. The other patient was a 3-year-old Dutch boy with hearing loss and unilateral heterochromia.

Molecular Genetics

The identification of Slug, a zinc finger transcription factor expressed in migratory neural crest cells, as the gene responsible for pigmentary disturbances in mice (see Perez-Losada et al., 2002) prompted Sanchez-Martin et al. (2002) to analyze the role of its human homolog, SNAI2, in neural crest defects. In 2 of 38 unrelated patients with WS2 and no mutation in the MITF gene (156845), Sanchez-Martin et al. (2002) detected homozygous deletions of the SNAI2 gene (602150.0001). The parents of both patients were nonconsanguineous and unaffected,and one of the patients had 4 unaffected sibs.