An auditory pigmentary syndrome characterized by
hypopigmentation of the skin, iris, hair and stria vascularis of the
cochlea. Most patients present with two different colored eyes, white
forelock and eyelashes, and premature graying of the hair. Moderate
acrocephaly, lack of osseous fusion of the short tubular bones, oligodactyly
of the feet, short stature, pericardial cysts, rectal prolapse, and deformed
ears are reported. Other features include hypoplastic maxilla, asymmetry of
hands, deformity of the first phalanx of the head, absence of the first
digit of the foot, and bifid distal phalanges of the second and third toes.
Hypopigmentation of the hair (white forelock), high nasal root,
hypoplasia of the nasal alae, short and retropositioned maxilla, short
philtrum, and a dysplastic ear in a 14-year-old girl with sensorineural
Petrus Johannes Waardenburg Syndrome (Dutch
ophthalmologist, 1886-1979); WS I.
All forms of WS together, estimates are that about 1:40,000 individuals of the
general population are affected by this disorder, which may be responsible for up to 3% of patients
with congenital deafness. In Kenya, the estimated frequency is reported at 1:20,000 persons. It
is also reported at 1:212,000 individuals in the general population of the Netherlands.
(see also Clinical Aspects) Autosomal dominant inheritance
characterizes Waardenburg Syndrome Type 1 (WS 1), which has been mapped to 2q35. If dystopia canthorum
(lateral displacement of the inner canthi of the eyes) is absent, the syndrome is called
WS Type 2. WS 3 is a severe form of this disorder in which both, heterozygosity and homozygosity
of mutations in the PAX3 gene (paired box gene 3) have been reported.
Almost all cases are at least due in part to mutations of the
PAX3 gene (paired box gene 3), which is involved in the formation of the caudal neural
crest derivatives and the migration of myoblasts into the extremities. Children with this
syndrome have a normal life expectancy.
Two major or one major plus two minor features must be
present for the diagnosis. Major features: congenital sensory hearing loss and pigmentary
disturbance of the iris with different-colored eyes or segmental
heterochromia; hair hypopigmentation; affected first-degree relative. Minor features:
congenital leukoderma, medial eyebrow flare, high nasal root, nasal alae
hypoplasia, premature graying of scalp.
Four different types of Waardenburg Syndrome have been defined:
Waardenburg Syndrome Type 1 (WS 1): It was in 1947, when the Dutch ophthalmologist and geneticist
Petrus Johannes Waardenburg first presented a patient with sensorineural hearing loss, dystopia
canthorum (lateral displacement of the inner canthi of the eyes), hypertrichosis of the medial
aspect of the eyebrows, broad nasal bridge, and pigment anomalies of skin (albinism), iris (heterochromia
iridis) retina, and hair (white forelock or poliosis) to the Swiss Society of Genetics. After he found several
more patients with ...