http://www.nidcd.nih.gov/health/hearing/waard.asp
Waardenburg Syndrome
On this page:
Description
Types of Waardenburg syndrome
Cause
Research studies
Additional resources
Description
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.
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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.
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Cause
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.
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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.
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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
http://www.nlm.nih.gov/medlineplus/ency/article/001428.htm
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.
Type |
OMIM |
Gene |
Locus |
Also known as |
Type I, WS1 |
193500 |
PAX3 - "paired box 3" (PAX3) |
2q35 |
- |
Type IIa, WS2A (originally WS2) |
193510 |
MITF -"microphthalmia-associated transcription factor" |
3p14.1-p12.3 |
- |
Type IIb, WS2B |
600193 |
WS2B |
1p21-p13.3 |
- |
Type IIc, WS2C |
606662 |
WS2C |
8p23 |
- |
Type IId, WS2D (very rare) |
608890 |
SNAI2 |
8q11 |
- |
Type III, WS3 |
148820 |
PAX3 - "paired box gene 3" |
2q35 |
Klein-Waardenburg syndrome |
Type IV, WS4 |
277580 |
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,