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Hemochromatosis--the most common deadly genetic disease
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A common genetic disorder that is variable expressed.  The second leading cause of deafness


Waardenburg Syndrome

On this page:

*       Description

*       Types of Waardenburg syndrome

*       Cause

*       Research studies

*       Additional resources


Waardenburg syndrome (WS) is an inherited disorder often characterized by varying degrees of hearing loss and changes in skin and hair pigmentation. The syndrome got its name from a Dutch eye doctor named Petrus Johannes Waardenburg who first noticed that people with differently colored eyes often had a hearing impairment. He went on to study over a thousand individuals in deaf families and found that some of them had certain physical characteristics in common.

One commonly observed characteristic of Waardenburg syndrome is two differently colored eyes. One eye is usually brown and the other blue. Sometimes, one eye has two different colors. Other individuals with Waardenburg syndrome may have unusually brilliant blue eyes.

People with WS may also have distinctive hair coloring, such as a patch of white hair or premature gray hair as early as age 12. Other possible physical features include a wide space between the inner corners of eyes called a broad nasal root. In addition persons with WS may have low frontal hairline and their eyebrows may connect. The levels of hearing loss associated with the syndrome can vary from moderate to profound.

Individuals with Waardenburg syndrome may have some or all of the traits of the syndrome. For example, a person with WS may have a white forelock, a patch of white hair near the forehead, and no hearing impairment. Others may have white patches of skin and severe hearing impairment. The severity of the hearing impairment varies among individuals with WS as do changes in the skin and hair.

On rare occasions, WS has been associated with other conditions that are present at birth, such as intestinal disorders, elevation of the shoulder blade, and disorders of the spine. A facial abnormality, known as cleft lip and/or palate, also has been associated with WS.


Types of Waardenburg syndrome

There are at least four types of Waardenburg syndrome. The most common types of WS identified by scientists are Type 1 and Type 2. The different types of physical characteristics a person has determines the type of WS. Persons who have an unusually wide space between the inner corners of their eyes have WS Type 1. Hearing impairments occur in about 20 percent of individuals with this type of Waardenburg syndrome. Persons who do not have a wide space between the inner corners of their eyes, but who have many other WS characteristics are described as having WS Type 2. About 50 percent of persons with WS Type 2 have a hearing impairment or are deaf.



As a genetic disorder, Waardenburg syndrome is passed down from parent to child much like hair color, blood type, or other physical traits. A child receives genetic material from each parent. Because Waardenburg syndrome is a dominant condition, a child usually inherits the syndrome from just one parent who has the malfunctioning WS gene. Actually, there is a 50/50 chance that a child of an individual with WS will also have the syndrome.


Research studies

Scientists have identified and located four different genes for Waardenburg syndrome: PAX3, MITF, EDNRB, and EDN3. WS type 1 and 3 have been associated with mutations in the PAX3 gene; WS type 2 with the MITF gene; and WS type 4 with the EDNRB and EDN3 genes. While scientists are studying all of these genes, currently, the most information is available on the PAX3 and MITF genes and their role in Waardenburg syndrome.

The PAX3 gene is located on chromosome 2 and controls some aspects of the development of the face and inner ear. The MITF gene is found on chromosome 3. It also controls the development of the ear and hearing. Scientists are now studying these genes to better understand how they operate in controlling the normal growth of the ear and the development of hearing. This information will help scientists understand why persons with WS sometimes develop hearing problems.


Additional resources

Laboratory of Molecular Genetics
Division of Intramural Research, NIDCD
The goal of the Laboratory of Molecular Genetics is to identify, clone, and characterize the genes that contribute to communication disorders. Presently, the laboratory is studying the genes responsible for
hereditary hearing impairment. Check the section on "Selected Publications" for new studies on Waardenburg syndrome.

NIH Pub. No. 91-3260
March 1999




Waardenburg syndrome is inherited as an autosomal dominant trait


The most common types are Type I and Type II.

Type III (Klein-Waardenburg syndrome) and type IV (Waardenburg-Shah syndrome) are more rare.

The multiple types of this syndrome result from mutations occurring in different genes. All types share two dominant features: hearing loss and pigment (coloring) changes in the skin, hair, and eyes. A white patch of hair may appear in an otherwise dark head of hair. Eyes may be very pale light-blue eyes or different colored. Persons with Type I may almost always have wide separation of the inner corners of the eyes. Hearing loss occurs more often in persons with Type II than Type I.

The more rare types of this disease may cause problems with the arms or intestines.

Waardenburg syndrome affects about 1 in every 30,000 people. Almost 90% of patients have an affected parent but the symptoms in the parent can be quite different from those in the child.

Symptoms    Return to top

  • Extremely pale blue eyes or eye colors that don't match (heterochromia), unusually brilliant blue eyes.
  • White patch of hair or early graying of the hair
  • Deafness
  • Possible slight decrease in intellectual functioning
  • Occasional cleft lip
  • Constipation
  • Possible difficulty with completely straightening joints (contracture)
  • Broad nasal bridge

Special diets and medicines to keep the bowel moving are prescribed to type IV patients who have constipation.

Waardenburg syndrome is a group of hereditary conditions characterized by deafness and partial albinism (pale skin, hair, and eye color.






Also known as

Type I, WS1


PAX3 - "paired box 3" (PAX3)



Type IIa, WS2A (originally WS2)


MITF -"microphthalmia-associated transcription factor"



Type IIb, WS2B





Type IIc, WS2C





Type IId, WS2D (very rare)





Type III, WS3


PAX3 - "paired box gene 3"


Klein-Waardenburg syndrome

Type IV, WS4


EDNRB - "endothelin-B receptor"
EDN3 - its
ligand, "endothelin-3"
SOX10 - "
SRY-related HMG-box gene 10"

22q13, 20q13.2-q13.3, 22q13

Waardenberg-Hirschsprung disease, Waardenburg-Shah syndrome

There are several other names used. These include Klein-Waardenburg syndrome, Mende's syndrome II, Van der Hoeve-Halbertsma-Waardenburg syndrome, Ptosis-Epicanthus syndrome, Van der Hoeve-Halbertsma-Gualdi syndrome, Waardenburg type Pierpont[4], Van der Hoeve-Waardenburg-Klein syndrome, Waardenburg's syndrome II, and Vogt’s syndrome

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,



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