Waardenburg Syndrome, Type 2

Clinical Characteristics
Ocular Features: 

This type of Waardenburg syndrome is distinguished from type 1 and 3 (193500) by the fact that it is caused by mutations in a different gene and in the absence of dystopia canthorum.  It has been claimed that hearing loss is more common and severe in type 2 (77%) as is heterochromia of the iris (47%) while skin and hair hypopigmentation are less common.

Families with WS2A may have the full spectrum of eye findings seen in X-linked ocular albinism I (300500) including decreased acuity, photophobia, nystagmus, translucent irides, hypermetropia, and albinotic fundi with foveal hypoplasia.  Indeed, such families have been considered to have 'albinism, ocular, with sensorineural deafness' (103470).  Such families might be considered to have an autosomal dominant form of ocular albinism.

Systemic Features: 

Congenital sensorineural hearing loss is an important and common feature.  Also characteristic are the white forelock, poliosis, and hypopigmented skin patches.


Waardenburg syndrome is an excellent example of genetic heterogeneity as types 1 and 3 (193500, 148820), 2 (193510), and 4 (277580) are all caused by mutations in different genes. 

Type 2 described here is a genetically heterogeneous autosomal dominant disorder.  WS2A is caused by a mutation in MITF (microphthalmia-associated transcription factor) (3p14.1-p12.3).  This is the same disorder described as 'Albinism, ocular, with sensorineural deafness' in OMIM (103470)  (WS2-OA).

A locus at 1p21-p13.3 is associated with WS2B (600193) and WS2C (606662) maps to 8p23.  In addition, homozygous SNAI2 mutations at 8q11 have been found in several patients with WS2D (608890) suggesting autosomal recessive inheritance but the normal parents were not studied.  Recent evidence suggests that SOX10 mutations can also play a role via MITF promoter modulation (WS2E) (611584).

Type 4 is also the result of mutations in at last three genes.

A child has been reported who was doubly heterozygous for mutations involving both MITF and PAX3.  Hypopigmentation in the scalp hair, eyebrows and eyelashes was more severe than usually seen in patients with single mutations.  In addition the face showed marked patchy pigmentation.  One parent contributed the MITF mutation and the other added the mutation in PAX3.

Autosomal dominant
Treatment Options: 

No ocular treatment is necessary but assistive hearing devices can be helpful.

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