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Waardenburg syndrome

Waardenburg syndrome (also Waardenburg Shah Syndrome, Waardenburg-

Klein syndrome, Mende's syndrome II, Van der Hoeve-Halbertsma-
Waardenburg syndrome, Ptosis-Epicanthus syndrome, Van der Hoeve-
Halbertsma-Gualdi syndrome, Waardenburg type Pierpont,[5] Van der
Hoeve-Waardenburg-Klein syndrome, Waardenburg's syndrome II and Vogts
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.

Eponyms and classification

Waardenburg syndrome is named after Dutch ophthalmologist Petrus Johannes
Waardenburg (18861979), who described the syndrome in detail in 1951.[1][2] The
condition he described is now categorized as WS1. Swiss ophthalmologist David
Klein also made contributions towards the understanding of the syndrome.[3]

WS2 was identified in 1971, to describe cases where "dystopia canthorum" did not
present.[4] WS2 is now split into subtypes, based upon the gene responsible.

Other types have been identified, but they are less common.

Signs and symptoms

There are five major and five minor diagnostic criteria for Waardenburg syndrome.


sensorineural hearing loss

iris pigmentary abnormality (two eyes different color or iris bicolor or

characteristic brilliant blue iris)

hair hypopigmentation (white forelock or white hairs at other sites on the


dystopia canthorum (lateral displacement of inner canthi)

firstdegree relative previously diagnosed with Waardenburg syndrome


skin hypopigmentation (congenital leukoderma/white skin patches)

medial eyebrow flare (synophrys)

broad nasal root

hypoplasia alae nasi

premature graying of the hair (before age 30).

The overall incidence is ~1/42,000 to 1/50,000 people. Types I and II are the most
common types of the syndrome, whereas types III and IV are rare. Type 4 is also
known as WaardenburgShah syndrome (association of Waardenburg syndrome
with Hirschsprung disease).

Type 4 is rare with only 48 cases reported up to 2002.[5]

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


Subtypes of the syndrome are traceable to different genetic variations:

Type OMIM Gene Locus Also known as

Type I, WS1 193500 PAX3 2q35 -
Type IIa, WS2A (originally 3p14.1-
193510 MITF -
WS2) 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 2q35 Klein-Waardenburg
Type IVa, WS4A 277580 13q22
Type IVb, WS4B 613265 EDN3 20q13
Type IVc, WS4C 613266 SOX10 22q13


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

A forelock of white hair (poliosis), or premature graying of the hair;

Appearance of wide-set eyes due to a prominent, broad nasal root (dystopia

canthorum)particularly associated with type I) also known as telecanthus;

Moderate to profound hearing loss (higher frequency associated with type


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.

Type IV may include neurologic manifestations.

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 and palate. Sometimes this is concurrent with Hirschsprung disease.

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.

Waardenburg syndrome is usually inherited in an autosomal dominant


Types II and IV Waardenburg syndrome may sometimes have an autosomal
recessive pattern of inheritance.

There is currently 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, Hirschsprung disease)
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 or back of its head, sometimes
down the back of the neck (known as a blaze) or a solid white head (from nose to
shoulders; ferrets with this are known as a panda marked ferret) 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 by private, reputable breeders, although it may still be neutered and sold
as a pet. However, largely as a result of mass-breeding due to the "exotic"
markings it gives (when compared to a standard sable/pole cat marked or albino
ferret), 75% of US ferrets with a blaze or white head sold from pet stores are deaf

In Popular Culture
In the season 6 episode of Bones (TV Series), 'The Signs in the Silence', the team
must solve a case in which the suspected killer has Waardenburg syndrome.

Enzo Macleod, protagonist of Peter May's series The Enzo Files, has Waardenburg
syndrome. His eyes are different colors and he has a white streak in his hair. See
pp. 17-18 of "Extraordinary People" (2006) by Peter Mays.
Other Contributors

Waardenburg-Klein syndrome is named after Petrus Johannes Waardenburg

(18861979), a Dutch ophthalmologist and geneticist, and David Klein, a
Swiss human geneticist and ophthalmologist.

Mende's syndrome II is named after Irmgard Mende (1938-), a German-

American physician.

Van der Hoeve-Halbertsma-Waardenburg Syndrome is named after Jan Van

der Hoeve (1878-1952), a Dutch ophthalmologist, Nicolaas Adolf
Halbertsma (1889-1968), Dutch physician and Petrus Johannes Waardenburg

Van der Hoeve-Halbertsma-Gualdi syndrome is named for Jan Van der

Hoeve (1878-1952), Nicolaas Adolf Halbertsma (1889-1968) and Vincenzo
Gualdi (1891-1976),an Italian physician.

Vogts syndrome is named for Cecile Vogt (1875-1962), a French-German


See also

ChediakHigashi syndrome

List of cutaneous conditions


1. ^ a b Waardenburg PJ (September 1951). "A new syndrome combining

developmental anomalies of the eyelids, eyebrows and noseroot with
pigmentary anomalies of the iris and head hair and with congenital deafness;
Dystopia canthi medialis et punctorum lacrimalium lateroversa, hyperplasia
supercilii medialis et radicis nasi, heterochromia iridum totaliis sive
partialis, albinismus circumscriptus (leucismus, polioss) et surditas
congenita (surdimutitas)". Am. J. Hum. Genet. 3 (3): 195253.
PMC 1716407. PMID 14902764.
2. ^ doctor/1012 at Who Named It?

3. ^ Klein-Waardenburg syndrome at Who Named It?

4. ^ Arias S (1971). "Genetic heterogeneity in the Waardenburg

syndrome". Birth Defects Orig. Artic. Ser. 07 (4): 87101. PMID 5006208.

5. ^ Egbalian F (2008). "Waardenburg Shah syndrome; A case report and

review of the literature". Iran J Ped 18 (1): 717.

6. ^ Erika Matulich, Ph.D,

External links

GeneReviews/NCBI/NIH/UW entry on Waardenburg Syndrome Type I

OMIM Genetic disorder catalog Waardenburg syndrome