Alternative titles; symbols
SNOMEDCT: 400085009; ORPHA: 79151; DO: 0050606;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12q24.11 | Acrokeratosis verruciformis | 101900 | Autosomal dominant | 3 | ATP2A2 | 108740 |
A number sign (#) is used with this entry because of evidence that acrokeratosis verruciformis (AKV) is caused by heterozygous mutation in the ATP2A2 gene (108740) on chromosome 12q24.
Darier-White disease (DAR; 124200) is also caused by mutation in the ATP2A2 gene.
Acrokeratosis verruciformis of Hopf (AKV) is a localized disorder of keratinization affecting the distal extremities. Onset occurs early in life (Dhitavat et al., 2003).
In the family with acrokeratosis verruciformis of Hopf reported by Niedelman (1947) and Niedelman and McKusick (1962), the dorsum of the hands was affected first and most conspicuously. Older individuals tended to have hyperkeratosis of the elbows and knees. The nails were pearly white in early years and become horny, brown, ridged, and grooved in later life. In older affected persons the palms and soles became involved.
Although histology of acrokeratosis verruciformis lesions shows no evidence of dyskeratosis, Herndon and Wilson (1966) emphasized the phenotypic overlap between this entity and Darier-White disease (124200) and even proposed that they may not be separate entities. In the family they studied, 7 persons had typical acrokeratosis verruciformis, 1 or possibly 2 had Darier disease, and 3 had minor disturbances of keratinization (white nails from subungual hyperkeratosis, or punctate keratoses of palms or soles). Also see benign familial pemphigus (169600).
The pedigree with acrokeratosis verruciformis studied by Niedelman (1947) and Niedelman and McKusick (1962) contained instances of male-to-male transmission as well as unaffected daughters of affected males, consistent with autosomal dominant inheritance.
Dhitavat et al. (2003) studied a family with acrokeratosis verruciformis in 6 generations and identified a heterozygous missense mutation in the ATP2A2 gene (P602L; 108740.0011). This mutation predicted a nonconservative amino acid substitution in the ATP binding domain of the molecule. The mutation segregated with the disease phenotype in the family and was not found in 50 controls. Moreover, functional analysis of the P602L mutant showed that it had lost its ability to transport Ca(2+). This result demonstrated loss of function of the sarco(endo)plasmic reticulum Ca(2+) ATPase2 mutant in acrokeratosis verruciformis, thus providing evidence that acrokeratosis verruciformis and Darier disease are allelic disorders.
In an 11-year-old Afghan boy with AKV, Berk et al. (2010) identified a heterozygous missense mutation in the ATP2A2 gene (A698V; 108740.0013).
Berk, D. R., Taube, J. M., Bruckner, A. L., Lane, A. T. A sporadic patient with acrokeratosis verruciformis of Hopf and a novel ATP2A2 mutation. (Letter) Brit. J. Derm. 163: 653-654, 2010. [PubMed: 20518781] [Full Text: https://doi.org/10.1111/j.1365-2133.2010.09876.x]
Dhitavat, J., Macfarlane, S., Dode, L., Leslie, N., Sakuntabhai, A., MacSween, R., Saihan, E., Hovnanian, A. Acrokeratosis verruciformis of Hopf is caused by mutation in ATP2A2: evidence that it is allelic to Darier's disease. J. Invest. Derm. 120: 229-232, 2003. [PubMed: 12542527] [Full Text: https://doi.org/10.1046/j.1523-1747.2003.t01-1-12045.x]
Herndon, J. H., Jr., Wilson, J. D. Acrokeratosis verruciformis (Hopf) and Darier's disease: genetic evidence for a unitary origin. Arch. Derm. 93: 305-310, 1966.
Niedelman, M. L., McKusick, V. A. Acrokeratosis verruciformis (Hopf): a follow-up study. Arch. Derm. 86: 779-782, 1962. [PubMed: 13938495] [Full Text: https://doi.org/10.1001/archderm.1962.01590120077013]
Niedelman, M. L. Acrokeratosis verruciformis (Hopf): report of fourteen cases in one family in four generations, with a review of the literature. Arch. Derm. Syph. 56: 48-63, 1947. [PubMed: 20251558] [Full Text: https://doi.org/10.1001/archderm.1947.01520070051005]