Tietz Albinism-Deafness Syndrome

A number sign (#) is used with this entry because of evidence that Tietz albinism-deafness syndrome (TADS) is caused by heterozygous mutation in the MITF gene (156845) on chromosome 3p13.

A highly overlapping disorder, Waardenburg syndrome type 2A (WS2A; 193510), is also caused by heterozygous mutation in the MITF gene.

Clinical Features

Tietz (1963) described 14 persons in 6 generations with albinism and complete nerve deafness. The albinism was generalized but did not affect the eyes. The irides were blue. Nystagmus and other ocular abnormalities were absent. The medial canthi and nasal bridge were normal. The eyebrows were almost totally lacking. The albinism in this trait is hypopigmentation and not true albinism; the affected individuals tan, for example. Reed et al. (1967) thought this might have been merely a dominant type of deafness in unusually blond persons.

Amiel et al. (1998) presented detailed clinical findings on the affected mother and son reported by Tassabehji et al. (1995) and noted that, although they fulfilled diagnostic criteria for Waardenburg syndrome type II (see 193510), they more closely resembled the family reported by Tietz (1963). Both mother and son had severe congenital sensorineural hearing loss. The mother had red hair as a child but underwent uniform premature graying at age 16 years, and had generalized hypopigmentation with numerous orange freckles. She had no dysmorphic features, and there was no dystopia canthorum. Her eyes were blue with no nystagmus or photophobia, and the irides did not transilluminate. The fundi in both patients were striking with lack of retinal pigmentation and enlarged, irregular optic discs.

Smith et al. (2000) reascertained the family reported by Tietz (1963) and confirmed the existence of the syndrome through at least 4 generations. All affected individuals were born 'snow white,' but gradually gained some pigmentation, with fair skin and blond hair. Eyebrows and eyelashes remained blond. Eyes were blue with albinoid fundi, but no nystagmus or other visual problems were encountered. Craniofacial appearance was normal: specifically there was no dystopia canthorum. Hearing loss was always bilateral, congenital, and profound, and communication was primarily through signing. There was no variation in expression and penetrance was complete.

Izumi et al. (2008) reported a blue-eyed, fair-haired 24-year-old woman with generalized pigment loss, congenital complete sensorineural hearing loss, and lack of retinal pigmentation on funduscopic examination. Histologic examination of skin biopsy specimens revealed the presence of melanocytes, suggesting that the migration of melanocyte stem cells from the neural crest to the epidermal layer occurred normally. In the hypopigmented regions, however, a reduction in the number of melanosomes in keratinocytes adjacent to the melanocytes suggested a disruption in the transfer of melanosomes from the melanocytes to the keratinocytes; and in the hyperpigmented regions, an increase in the number of melanosomes in the keratinocytes adjacent to HMB45-positive melanocytes pointed to a high level of melanogenesis.

Inheritance

The transmission pattern of albinism and deafness in the family reported by Tietz (1963) was consistent with autosomal dominant inheritance.

Molecular Genetics

In a family with partial albinism and sensorineural deafness, Tassabehji et al. (1995) identified an in-frame 3-bp deletion in the MITF gene (delR217; 156845.0003). Izumi et al. (2008) identified the delR217 mutation in an affected 24-year-old woman. The authors noted that dimerization between mutant and wildtype protein would reduce the number of intact wildtype dimers with access to the nucleus to 25% of normal.

In the family originally reported by Tietz (1963), Smith et al. (2000) demonstrated significant linkage to the region of the MITF gene and identified mutations in the MITF gene (156845.0006).