Waardenburg syndrome type 2 is an autosomal dominant auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the ocular inner canthi, ... Waardenburg syndrome type 2 is an autosomal dominant auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the ocular inner canthi, which is seen in some other forms of WS (reviews by Read and Newton, 1997 and Pingault et al., 2010). Waardenburg syndrome type 2A is caused by mutation in the MITF gene (156845). - Clinical Variability of Waardenburg Syndrome Types 1-4 Waardenburg syndrome has been classified into 4 main phenotypes. Type I Waardenburg syndrome (WS1; 193500) is characterized by pigmentary abnormalities of the hair, including a white forelock and premature graying; pigmentary changes of the iris, such as heterochromia iridis and brilliant blue eyes; congenital sensorineural hearing loss; and 'dystopia canthorum.' WS type II (WS2) is distinguished from type I by the absence of dystopia canthorum. WS type III (WS3; 148820) has dystopia canthorum and is distinguished by the presence of upper limb abnormalities. WS type IV (WS4; 277580), also known as Waardenburg-Shah syndrome, has the additional feature of Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010). - Genetic Heterogeneity of Waardenburg Syndrome Type 2 Waardenburg syndrome type 2 is a genetically heterogeneous disorder. WS2B (600193) has been mapped to chromosome 1p, WS2C (606662) has been mapped to chromosome 8p23, WSD (608890) is caused by mutation in the SNAI2 gene (602150) on chromosome 8q11, and WS2E (611584) is caused by mutation in the SOX10 gene (602229) on chromosome 22q13.
Arias (1971) suggested the existence of 2 types of Waardenburg syndrome based in the presence or absence of dystopia canthorum. Hageman and Delleman (1977) presented family data supporting delineation of 2 types: type I, with dystopia canthorum; and ... Arias (1971) suggested the existence of 2 types of Waardenburg syndrome based in the presence or absence of dystopia canthorum. Hageman and Delleman (1977) presented family data supporting delineation of 2 types: type I, with dystopia canthorum; and type II, without dystopia canthorum. The frequency of deafness was higher in type II. In a personally studied series of 81 individuals from 21 families with WS type II in comparison with 60 personally studied patients from 8 families with type I, Liu et al. (1995) concluded that sensorineural hearing loss (77%) and heterochromia iridum (47%) were more common in WS type II than in type I. On the other hand, white forelock and skin patches were more frequent in type I. Reynolds et al. (1995) reviewed their collection of 26 WS1 and 8 WS2 families. Deafness was more frequent and more severe in the WS2-affected individuals than had been found previously. No one in either group had neural tube defects or cleft lip and/or palate. However, 12 individuals in 5 families had some signs or symptoms of Hirschsprung megacolon (WS4). Their data led Reynolds et al. (1995) to conclude that use of the W-index to discriminate between affected WS1 and WS2 individuals may be problematic since 1) ranges of W-index scores of affected and unaffected individuals overlapped considerably within both WS1 and WS2 families, and 2) a considerable number of both affected and unaffected WS2 individuals exhibited W-index scores consistent with dystopia canthorum. Tassabehji et al. (1994) reported 2 unrelated families with WS type 2. Both had typical WS2, with various combinations of hearing loss, heterochromia irides, white forelock, skin hypopigmentation, and premature greying. Neither had dystopia canthorum.
Tassabehji et al. (1994) demonstrated heterozygous mutations in the MITF gene (156845.0001 and 156845.0002) in affected members of 2 families with Waardenburg syndrome type 2A. One of the families had been reported by Hughes et al. (1994). Inheritance ... Tassabehji et al. (1994) demonstrated heterozygous mutations in the MITF gene (156845.0001 and 156845.0002) in affected members of 2 families with Waardenburg syndrome type 2A. One of the families had been reported by Hughes et al. (1994). Inheritance was autosomal dominant. - Exclusion Studies Farrer et al. (1994) typed microsatellite markers within and flanking the PAX3 gene (606597) on chromosome 2q35 in 41 WS1 kindreds and 26 WS2 kindreds defined on the basis of presence or absence of dystopia canthorum according to the W index of patients. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that in 60% of all WS families and in 100% of WS1 families, the phenotype was linked to PAX3. None of the WS2 families were linked to the PAX3 gene.