Article: Waardenburg syndrome

Waardenburg syndrome is a rare genetic disorder most often characterized by varying degrees of deafness, minor defects in structures arising from the neural crest, and pigmentation anomalies. It is named after Dutch ophthalmologist Petrus Johannes Waardenburg (1886-1979), who first defined it in 1951. Other names for the syndrome include Van der Hoeve / Halbertsma / Gualdi syndrome, Ptosis-Epicanthus syndrom, and Mende syndrome. Several subtypes of the disorder are known.

Subtypes of Waardenburg syndrome

Subtypes of the syndrome are traceable to different genetic variations:

• Type I: associated with mutations in the paired box 3 (PAX3) gene.
• Type IIa: associated with mutations in the microphthalmia-associated transcription factor (MITF) gene
• Type IIb: associated with a locus designated WS2B
• Type IIc: associated with a locus designated WS2C
• Type IId: associated with a deletion in the SNAI2 gene. Very rare.
• Type III: associated with mutations in the paired box gene 3 (PAX3) gene
• Type IV: Waardenberg-Hirschsprung disease, or Waardenburg-Shah syndrome, is associated with mutations in the endothelin-B receptor gene (EDNRB), the gene for its ligand, endothelin-3 (EDN3), or in the SRY-related HMG-box gene 10 (SOX10) gene. This subtype may include neurologic manifestations.

Incidence

Types I and II are the most common types of the syndrome, whereas types III and IV are rare. Overall, the syndrome affects perhaps 1 in 15,000 people. About 1 in 30 students in schools for the deaf have Waardenburg syndrome. All races and both sexes are affected equally. The highly variable presentation of the syndrome makes it difficult to arrive at precise figures for its prevalence.

Symptoms

Symptoms vary from one type of the syndrome to another and from one patient to another, but they include:

• Very pale or brilliantly blue eyes, eyes of two different colors (complete heterochromia), or eyes with one iris having two different colours (sectoral heterochromia);
• A forelock of white hair, or premature graying of the hair;
• Wide-set eyes due to a prominent, broad nasal root (dystopia canthorum—particularly associated with type I);
• Moderate to profound hearing impairment (higher frequency associated with type II); and
• A low hairline and eyebrows that touch in the middle.

Patches of white pigmentation on the skin have been observed in some people. Sometimes, abnormalities of the arms, associated with type III, have been observed.

Waardenburg syndrome has also been associated with a variety of other congenital disorders, such as intestinal and spinal defects, elevation of the scapula, and cleft lip/palate.

Inheritance

This condition is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. A small percentage of cases result from new mutations in the gene; these cases occur in people with no history of the disorder in their family.

Some cases of type II and type IV Waardenburg syndrome appear to have an autosomal recessive pattern of inheritance, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.

Treatment

There is no treatment or cure for Waardenburg syndrome. The symptom most likely to be of practical importance is deafness, and this is treated as any other irreversible deafness would be. In marked cases there may be cosmetic issues. Other abnormalities (neurological, structural) associated with the syndrome are treated symptomatically.

In animals

Waardenburg syndrome is known to occur in ferrets. The affected animal will usually have a small white stripe along the top of its head and a somewhat, although barely noticeably, flatter skull than normal ferrets. As a ferret's sense of hearing is poor to begin with it is not easily noticeable except for when the affected animal does not react to loud noises that non-affected ones will respond to. As the disorder is easily spread to offspring, the affected animal will not be used for breeding, although it may still be neutered and sold as a pet.

Additional information and links

• eMedicine - Waardenburg syndrome
• MedlinePlus - Waardenburg syndrome
• OMIM Genetic disorder catalog - Waardenburg syndrome