Waardenburg syndrome type I (WS-I)
Incidence
1:32,400 and 1:42,000. It is the most common form of inherited congenital deafness. It is inherited in an autosomal dominant pattern with variable penetrance. More than 1500 cases of WS, representing all ethnic groups, have been reported up to 1991.
Clinical Characteristics
Based on clinical classification at least three distinct types have been identified, of which WS type I (WS-I) is the most common. Clinically, WS-I is characterized by depigmentation of the hair and skin, heterochromia irides, dystopia canthorum, congenital deafness, a broad nasal root, and confluent eye brows. The absence of dystopia canthorum has been the distinguishing feature of WS-II, and upper-limb abnormalities are characteristic of WS-III.
The frequency of the syndrome has been estimated between 1:32,400 and 1:42,000. The most frequent cutaneous pigmentary abnormality is a white forelock; the skin beneath the forelock is usually depigmented. Premature graying, occurring as early as the teens, can involve the scalp, eyebrows, ciliary body of the eye, and body hair. Patches of depigmentation on the face, neck, anterior chest, abdomen, and limbs are also a common feature. The patches of depigmentation are similar to those observed in piebaldism. Hyperpigmented macules may occur on depigmented or normal skin. Partial or total heterochromia irides is found in more than 20 percent of the reported cases. Unilateral depigmentation of the irides typically gives rise to irides of different colors, one usually being slate-blue. Bilateral involvement results in pale-blue eyes. In addition, confluent eyebrows and broadened nasal root are two fairly common facial features. Sensorineural deafness occurs in 9 to 37.5 percent of the patients. The deafness may be unilateral or bilateral, moderate or severe. Auditory brain-stem responses typically demonstrate sensorineural deafness without any particular distinguishing features unique to this syndrome. Histopathological study of the inner ear from one patient with WS revealed absence of the organ of Corti, atrophy of the spinal ganglion and nerve, and absence of melanocytes. Numerous anomalies have been reported in WS type I. These include cleft lip and palate, Hirschsprung disease, facial asymmetry, facial palsy, hypoplasia of the middle ear ossicles, iris coloboma, genitourinary abnormalities, and neural-tube defects. Histopathological findings in WS include absent or reduced number of melanocytes in depigmented skin. Abnormal migration of neural crest cells has been suggested. Histologic analysis of the temporal bones from two cases of WS revealed atrophy of the vestibular neuroepithelia and stria vascularis of the inner ear.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
It is a clinical diagnosis. The identification of a paracentric inversion of chromosome 2 in a WS-I patient and linkage studies allowed the mapping of the WS-I gene to human chromosome 2q37. Genetic heterogeneity for WS-I was demonstrated based on the finding that only 45 percent of WS-I families show linkage to chromosome 2q.