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At a glance

It is a rare genetic disorder characterized by a congenital defect involving skin pigmentation. The clinical features include a white forelock, vitiligo, partial or total heterochromic irides, pale blue eyes, hyperplastic broad high nasal root, lateral displacement of the medial canthi and lacrimal points, hyperplasia of the median portion of the eyebrows, and a unilateral deafness that is present in 15 to 20% of affected persons. The congenital deafness represents the most serious complication of this medical condition. Other clinical features include bone fragility as seen in osteogenesis imperfecta and Lobstein’s disease. Certain other structural abnormalities include short stature, hyperflexibility of joints, dental anomalies, laryngomalacia, and congenital heart defects.

Synonyms

Klein-Waardenburg Syndrome; Mende’s Syndrome II; van der Hoeve-Halbertsma-Waardenburg Syndrome; van der Hoeve-Waardenburg-Klein Syndrome; Vogt’s Syndrome; Waardenburg Syndrome II; Eddowe’s Syndrome; Adair-Dighton Syndrome.

History

This medical condition was originally described in 1913 by Jan van der Hoeve (1878-1952), a Dutch ophthalmologist, Nicolaas Adolf Halbertsma (1889-1966), a Dutch physician, and Vincenzo Gualdi (1891-1976), an Italian physician, who reported in identical deaf mute twins a lateral position of the lacrimal points and shortened eyelid slit. In August 1947, David Klein (1908-1993), a Swiss human geneticist and ophthalmologist, presented to the Swiss Society of Genetics the case of a 10-year-old deaf mute child affected with partial albinism of the hair and the body, blue hypoplastic rides, blepharophimosis, and malformation of arms. Petrus Johannes Waardenburg (1886-1979), a Dutch ophthalmologist and geneticist, gave an account of a deaf adult with similar facial features in December 1948 and he published a detailed review in 1951. Waardenburg described the syndrome as a distinct entity and found the anomalies in 12 of 840 deaf mutes.

Incidence

The incidence in the general population is established between 1/42,000 and 1/50,000 people. It affects males and females equally. It is present in all ethnic portion of the population.

Genetic inheritance

It is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. It is most often associated with a father-son transmission.

Pathophysiology

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.

Diagnosis

The diagnosis is based on the presence of specific criteria: 1) congenital sensorineural hearing loss that is present at birth; 2) heterochromia iridis either complete, partial, or segmental; 3) isohypochromia iridis defined as pale blue eyes; 4) pigmentary abnormalities of the fundus of the eye; and/or 5) white forelock and loss of hair color.

Clinical aspects

Patient affected with this ...

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