Alternative titles; symbols
SNOMEDCT: 722285005; ORPHA: 998;
Cytogenetic location: Xq24-q26 Genomic coordinates (GRCh38): X:117,400,001-138,900,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| Xq24-q26 | Albinism-deafness syndrome | 300700 | X-linked | 2 |
Margolis (1962) described a 'new' X-linked syndrome--deaf-mutism (profound deafness) and total albinism. Also from Israel, Ziprkowski et al. (1962) described an X-linked syndrome consisting of congenital deafness and partial albinism (without ocular albinism). They were reporting on the same family. The albinism is shown by the photographs to be 'partial,' as described by Ziprkowski and colleagues. Indeed, the pigmentary disorder might be called 'piebald.'
Woolf (1965) reported albinism and deafness in 2 Hopi American Indian brothers. Woolf et al. (1965) gave a further description of these 2 brothers with congenital deafness and a remarkably similar pattern of pigmentary variegation of the piebald type. Another brother and both parents were normal and no other cases are known in Southwest Indians. The deafness was subtotal nerve type. Dolowitz (1966) stated that the 'Hopi children showed no marked decrease in vestibular function as judged by calorics with the Hallpike-Cawthorn test.' Gorlin (1988) was of the opinion that the disorder reported by Woolf (1965) 'has nothing whatsoever to do with the X-linked disorder that Ziprkowski and colleagues documented in 1962.'
Hearing impairment in heterozygotes with ADFN was demonstrated by Fried et al. (1969). Studying the original family with ADFN (Margolis, 1962; Ziprkowski et al., 1962), Litvak et al. (1987) found a specific pattern of hearing impairment in carrier females.
Zlotogora (1995) pointed out that although this syndrome is clinically very unusual and relatively easy to diagnose, there may have been only one other report of the condition, and that in an isolated patient (Campbell et al., 1962). This raised the possibility that this syndrome represents only 1 clinical aspect of another allelic X-linked disorder. Zlotogora (1995) proposed Waardenburg syndrome type II (see 193510) as its possible allelic syndrome. He was impressed with the similarity between affected members in the original family (Margolis, 1962; Ziprkowski et al., 1962) and the patient with homozygous WS1 reported by Zlotogora et al. (1995). He suggested that the albinism-deafness syndrome is an X-linked dominant form of Waardenburg syndrome 2, defining WS2 on phenotypic grounds characterized particularly by the absence of dystopia canthorum.
From linkage studies using DNA probes in the original family with ADFN (Margolis, 1962; Ziprkowski et al., 1962), Litvak et al. (1987) suggested that the disorder locus is on Xq, probably in the region Xq13-q26. Also in the original family, Shiloh et al. (1988, 1990) placed the ADFN gene in the region Xq26.3-q27.1 by further linkage studies with RFLP markers. One of the DNA probes, that which detects the DXS91 locus, had been previously localized to Xq11-q13, which would be inconsistent with the linkage data. Shiloh et al. (1990) showed by hybridization of the probe to a panel of somatic cell hybrids containing different portions of the X chromosome that the locus is in fact at Xq24-q26.
Campbell, B., Campbell, N. R., Swift, S. Waardenburg syndrome: a variation of the first arch syndrome. Arch. Derm. 86: 718-724, 1962. [PubMed: 14018109] [Full Text: https://doi.org/10.1001/archderm.1962.01590120016003]
Dolowitz, D. A. Personal Communication. Salt Lake City, Utah 1966.
Fried, K., Feinmesser, M., Tsitsianov, J. Hearing impairment in female carriers of the sex-linked syndrome of deafness with albinism. J. Med. Genet. 6: 132-134, 1969. [PubMed: 5801459] [Full Text: https://doi.org/10.1136/jmg.6.2.132]
Gorlin, R. J. Personal Communication. Minneapolis, Minn. 7/18/1988.
Litvak, G., Sandkuyl, L., Ott, J., Buchris, V., Hildesheimer, M., Shiloh, Y. Localization of X-linked albinism-deafness syndrome (ADFN) to Xq by linkage with DNA markers. (Abstract) Cytogenet. Cell Genet. 46: 652, 1987.
Margolis, E. A new hereditary syndrome--sex-linked deaf-mutism associated with total albinism. Acta Genet. Statist. Med. 12: 12-19, 1962. [PubMed: 14469778] [Full Text: https://doi.org/10.1159/000151176]
Reed, W. B., Stone, V. M., Boder, E., Ziprkowski, L. Pigmentary disorders in association with congenital deafness. Arch. Derm. 95: 176-186, 1967. [PubMed: 6018993]
Shiloh, Y., Litvak, G., Ziv, Y., Lehner, T., Sandkuyl, L., Hildesheimer, M., Buchris, V., Cremers, F. P. M., Szabo, P., White, B. N., Holden, J. J. A., Ott, J. Genetic mapping of X-linked albinism-deafness syndrome (ADFN) to Xq26.3-q27.1. Am. J. Hum. Genet. 47: 20-27, 1990. [PubMed: 2349949]
Shiloh, Y., Sandkuyl, L., Litvak, G., Ziv, Y., Hildesheimer, M., Buchris, V., Ott, J. Localization of X-linked albinism-deafness syndrome (ADFN) to the region Xq26.3-27.1 by linkage analysis. (Abstract) Am. J. Hum. Genet. 43: A158, 1988.
Woolf, C. M. Albinism among Indians in Arizona and New Mexico. Am. J. Hum. Genet. 17: 23-35, 1965. [PubMed: 14255554]
Woolf, C. M., Dolowitz, D. A., Aldous, H. E. Congenital deafness associated with piebaldness. Arch. Otolaryng. 82: 244-250, 1965. [PubMed: 14327022] [Full Text: https://doi.org/10.1001/archotol.1965.00760010246005]
Ziprkowski, L., Krakowski, A., Adam, A., Costeff, H., Sade, J. Partial albinism and deaf-mutism due to a recessive sex-linked gene. Arch. Derm. 86: 530-539, 1962. [PubMed: 14003785] [Full Text: https://doi.org/10.1001/archderm.1962.01590100144027]
Zlotogora, J. X-linked albinism-deafness syndrome and Waardenburg syndrome type II: a hypothesis. (Letter) Am. J. Med. Genet. 59: 386-387, 1995. [PubMed: 8599367] [Full Text: https://doi.org/10.1002/ajmg.1320590321]
Zlotogora, J., Lerer, I., Bar-David, S., Ergaz, Z., Abeliovich, D. Homozygosity for Waardenburg syndrome. Am. J. Hum. Genet. 56: 1173-1178, 1995. [PubMed: 7726174]