Waardenburg syndrome

Waardenburg syndrome

Waardenburg syndrome (WS) can cause hearing loss, vertigo and disequilibrium. It is a rare genetic condition and inherited mainly in an autosomal dominant way. The incidence is 1/42 000 people. Both males and females are equally effected. It occurs in all races. Mutations in the EDN3, EDNRB, MITF, PAX3, SNAI2 and SOX10 genes are implicated in WS.

The syndrome was named after the Dutch eye specialist Petrus Johannes Waardenburg (1886–1979), who described what is now known as type 1 WS in 1951. Other names are also associated with different types of the syndrome.

Waardenburg syndrome
Different colour eyes (Heterchromia) in Waardenburg syndrome

Types of Waardenburg syndrome

There are 4 types of WS. Type 1 and type 2 are the most common and type 4 is extremely rare. Type 2 and 4 can also be inherited in an autosomal recessive way. The types are:

• Type 1 WS: Characterised by wide spaced eyes and congenital hearing loss. Hearing loss however is less common than in type 2.
• Type 2 WS: Characterised by heterochromia and hearing loss.
• Type 3 WS leads to abnormalities of the arms, progressive hearing loss and skin pigmentation issues.
• Type 4 WS is associated with Hirschprungs disease (intestinal abnormalities).

The clinical findings

The clinical findings may vary from patient to patient and between subtypes. These include:
• Hearing loss
• Heterochromia (eyes with different colours), very pale eyes or brillantly blue eyes
• Poliosos (forelock of white hair) or premature greying
• Wide set eyes (telecanthus) and a broad nasal bridge (especially seen with type1)
• Low hairline and eyebrows that meet in the middle
• Areas of white skin pigmentation
• Cleft lip and palate (with type 1)
• Abnormality with the arms (with type 3)
• Neurological signs (with type 4)
• Normal cognition
• Patients have a normal life expectancy

Waardenburg syndrome and hearing loss

The prevalence of sensorineural hearing loss in WS is 71%. It accounts to between 2%-5% of all congenital hearing loss. About 1 out of 30 children in a deaf school has WS. Hearing loss can be moderate to profound and is most common in type 2. A review reported that 69% of patients with type 1 WS and 87% with type 2 WS had a sensorineural hearing loss. Bilateral hearing loss is more common than unilateral hearing loss. Asymetric hearing loss can occur and hearing loss may be progressive. With imaging it appears that temporal bone abnormalities may occur in up to 50% of cases. The most common inner ear malformations are enlarged vestibular aqueduct (EVA) and semi-circular canal malformations.

Waardenburg syndrome and vestibular function

Vestibular abnormalities seem to be more common than was previously anticipated. Vestibular abnormalities are found in up to 77% of patients with WS. In type 1 and type 2 patients with vestibular abnormalities may have normal hearing. According to Black and co-workers, patients present primarily with a picture suggestive of secondary endolymphatic hydrops. The clinical picture is that of spontaneous episodes of dizziness, vertigo, nausea, tinnitus, aural fullness, aural pressure/discomfort, and hypersensitivity to noise. Vestibular tests that may be of benefit in evaluating the vestibular system include videonystagmography (VNG), electrocochleography (ECOG), rotation tests and computerised dynamic posturopraphy (CDP).

The cause of hearing loss and vestibular dysfunction

One of the results of the abnormal genes in WS is the formation of defective melanocytes. Melanocytes are cells containing the pigment melanin. Besides being important in the development of the eyes, skin and hair colour, the melanocytes are also implicated in the functioning of the inner ear (cochlea, vestibular apparatus and endolymphatic sac) as it pertains to hearing and vestibular function.

Treatment of Waardenburg syndrome

There is currently no cure for WS. Patients with hearing loss may be helped with hearing aids or cochlear implantation (CI). Those with secondary endolymphatic hydrops are managed in the standard way with treatment that includes lifestyle and diet modification, medication or surgery. Patients with vestibular loss may benefit from vestibular rehabilitation. Patients with WS are therefore managed by a team of professionals to address all the associated difficulties with this syndrome.