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Waardenburg syndrome type 2
An autosomal dominant subtype of Waardenburg syndrome (WS) characterized by varying degrees of deafness and pigmentation anomalies of eyes, hair and skin, but without dystopia canthorum.
ORPHA:895Classification level: Subtype of disorder
The prevalence of WS2 is unknown; the worldwide prevalence of WS is estimated at around 1/40,000. WS2 is one of the most common types of Waardenburg syndrome.
Clinical manifestations for WS2 resemble those of Waardenburg syndrome type 1 (WS1; see this term). Sensorineural hearing loss (77%) and heterochromia iridum (47%) are the two most important clinical features for WS. In addition, individuals with WS2 lack dystopia canthorum and are usually more frequently affected by hearing loss and heterochromia iridum. In some cases (mutation in SOX10 gene), patients may present associated signs of Kallmann syndrome (anosmia, hypogonadism; see this term) and/or neurological defects (neurological Waardenburg syndrome).
WS2 is genetically very heterogeneous and still much of the etiology of WS2 remains elusive. Mutations have been found in MITF (3p14-p13; subtype designated as WS2A), SNAI2 (8q11.21; WS2D), and SOX10 (22q13.1; WS2E) genes. Furthermore WS2 loci have been mapped to chromosome 1p21-p13.3 (subtype designated as WS2B) and to chromosome 8p23 (designated as WS2C). Digenic inheritance of MITF mutation in combination a TYR mutation (and/or the TYRR402Qhypomorphic allele) has been reported in two families with WS2 and ocular albinism.
Diagnosis is determined by the presence of major and minor characteristic clinical features according to the Waardenburg Consortium criteria, as well as by genetic testing.
Differential diagnosis includes Waardenburg syndrome type 1 and 4, piebaldism, Tietz syndrome, oculocutaneous albinism (see these terms) and other forms of congenital non-progressive sensorineural hearing loss.
In the majority of cases, WS2 is transmitted as an autosomal dominant disorder with a large variable inter- and intrafamilial expressivity. Some affected patients present with a de novo mutation.
Management and treatment
Hearing aids to counter hearing loss and effective therapy to improve language, communication, and cognitive skill are recommended. Pigmentation defects do not require medical care but cosmetic products are available. Rarely, in case of extended depigmentation, care is taken to protect the skinand eyesfrom the sun.
With hearing aids, prognosis is good for most affected individuals with WS2.