Waardenburg Syndrome

Excerpt

Waardenburg syndrome (WS) is a group of genetic conditions inherited in an autosomal dominant fashion. It is named after Dutch ophthalmologist and geneticist Petrus Johannes Waardenburg, who described it in 1951. During embryogenesis, there is an abnormal distribution of melanocytes, which results in patchy areas of depigmentation. It is a rare disease, caused by loss of pigmentary cells in eyes, skin, stria vascularis of the cochlea, and hair. It is characterized by a broad nasal root, lateral displacement of medial canthi with the dystopia of lacrimal puncta, pigmentary abnormalities of the iris, hypertrichosis of the medial part of the eyebrows, white forelock, and deaf-mutism.

Several different gene mutations (insertion, deletion, frameshifts, missense, and nonsense mutations) can cause Waardenburg syndrome. There are four clinical variants, type 1 and type 2 are the most common types. Type 1 is due to the mutations in the PAX3 gene, which clinically manifests as congenital deafness (sensorineural), dystopia canthorum (lateral displacement of medial corner of eyes), neural tube defects, cleft palate, and lip with patchy depigmentation of hair and skin. These symptoms are associated with pigmentary abnormalities of the eyes. Type II WS is due to mutations in the MITF gene.

The inner canthi of both eyes are normal but have some other features similar to type-1. Type-III WS is an extreme presentation of type I with the abnormality of upper limbs. Type IV WS is due to mutations in the genes for one of its receptors, EDNRB or endothelin-3, usually autosomal recessive. As it is a genetic disease, there is no definitive treatment for Waardenburg syndrome, but supportive treatment with cochlear implants and surgery in case of association with Hirschsprung syndrome can be done. Genetic counseling is necessary.