Waardenburg syndrome

The Waardenburg syndrome is a congenital, inherited disorder in which there is a form of partial leucism. It is characterized by a variable combination of pigmentary disorders of the eyes, the skin and the hair, by deafness and malformations of the face ( facial dysmorphism ). Four different forms of Waardenburg syndrome to be distinguished. By Type IV of the disease is inherited as an autosomal dominant majority.

Epidemiology

The frequency of Waardenburg syndrome is reported to 1:4500 new cases per year (incidence). Waardenburg syndromes account for about 2% percent of cases of congenital deafness.

Types and Causes

After genetic and clinical criteria are four main types of Waardenburg syndrome ( WS) differed ( WS1- WS4 ). The four types can themselves be divided into partial sub-forms:

The Waardenburgsyndrome WS1, WS2 and WS3 are inherited as autosomal dominant, autosomal recessive modes of inheritance for WS4 were exclusively detected.

WS1 and WS3 are caused by mutations in the Pax3 gene. The gene encodes a 479 amino acid among other large protein involved in the regulation of the transcription factor MITF ( microphthalmia -associated transcription factor ) is involved. MITF is involved in the regulation of Melanozytenentwicklung which is disrupted in all known Waardenburg syndromes.

The WSIIa is in front by a mutation directly in the MITF gene. When WSIIB is so far only known DNA locus ( WSIIB: 1p21 - p13.3, WSIIC ) in which there will be mutations. The WSIIC caused by a balanced translocation of chromosome 4 to 8. That is a stretch of DNA that is normally found on chromosome 4, is located on chromosome 8 at WSIIC The very rare WSIID is a mutation in the so-called SNAI2 gene before. Again, it is a transcription factor that is expressed during embryonic development in the Nauralleistenzellen. The WSIIE is based on a genetic mutation in the SOX10 gene.

The WS4 is in contrast to the Waardenburg syndromes 1-3 autosomal recessive. Mutations previously endothelin -3 and endothelin -B receptor genes and the SOX10 gene were detected.

Disease

The deafness in Waardenburg syndrome due to defects in the development of the initial neural crest tissue. The disturbance of the pigment cells, which are also derived from neural tissue affecting mainly the iris, the eyebrows, the part of the skin and the scalp hair, which leads to hypopigmentation. Particularly striking is a different coloration of the eye ( iris heterochromia ), that is, individuals may have, for example, one blue and one brown eye. Dysplasia in the form of eye disorders and malformations of the skull are also part of Waardenburg syndrome. This appears partly in a shift of the crease or a lateral displacement of the inner canthus of both eyes ( dystopia canthorum ).

History

The Waardenburg syndrome in 1951 by the Dutch ophthalmologist and geneticist Petrus Johannes Waardenburg ( 1886-1979 ) first described.