Waardenburg's Syndrome is a rare disorder that results from an autosomal dominant mutation as a deletion in Pax-3. Some of the characteristics of this syndrome may include pigment abnormalities, deafness, and defects in the neural crest derivative tissue. In 1951, Waardenburg defined the main features of the syndrome:

• Prominent broad nasal root
• Connection of the medial part of the eyebrows (unibrow)
• White forelock
• Two differently-colored eyes (one usually brown and the other bright blue)
• Deafmutism
  

There are four types of Waardenburg's Syndrome: types 1, 2, 3, and 4. Type 1 is characterized by displacement of the folds in the eyelid; hearing loss occurs in 20% of those suffering from this first type. The incidence is about 1/40,000. Although type 2 is more frequent than type 1, type 2 has a higher frequency of deafness; hearing loss/deafness occurs in 50% of those suffering from this second type. Waardenburg's Syndrome type 3, or Klein-Waardenburg Syndrome, is extremely rare. In addition to the characteristics of type 1, musculoskeletal abnormalities are observed in type 3 as well. Type 4 is also known as Waardenburg-Shah syndrome.

WS is inherited, and the chance of the carrier passing on the gene to their offspring is 50%. The gene that is thought to cause WS is the PAX3 gene. Scientists discovered this gene in mice (splotching color of the coat). Both sexes are affected equally by WS, and it does not affect life expectancy in any way. No effective treatment exists for WS.

Some of the many characteristics of Waardenburg's Syndrome are summarized below according to the different parts of the body:

Eyes

• Two differently colored eyes (one brown the other blue)
• One eye may have two different colors
• Unusually brilliant blue eyes
• Wide space between the inner corners of eyes (broad nasal root)

Hair

• Patch of white hair
• Premature gray hair as early as 12
• Low frontal hairline
• Eyebrows may connect
• Distinctive hair coloring
  

Other conditions present at birth

• White patches of skin
• Moderate to profound hearing loss
• Intestinal disorders
• Elevation of the shoulder blade
• Disorders of the spine
• Facial abnormalities (cleft lip, cleft palate)
  
  

Four genes- PAX3, MITF, EDNRB, and EDN3- are involved in the effects of the Waardenburg Syndrome. PAX3 controls some aspects of development of the face and the inner ear and is located on chromosome 2. MITF is found on chromosome 3, controls the development of the ear and hearing, and is involved in WS Type 2. EDNRB and EDN3 are involved in WS Type 4.

Auditory-Pigmentary syndrome is included under Waardenburg's Syndrome. This syndrome is unlike albinism because it involves the physical absence of melanocytes, while albinism is characterized by an enzyme defect that affects the amount of melanin. The absence of melanocytes causes deafness but does not have an effect on the eye. This syndrome is caused by a failure of neural crest differentiation or a failure of melanocyte precursors to migrate correctly or to differentiate and survive in their end location.

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