SNOMEDCT: 25499005, 394726009; ICD10CM: L82, L82.1; ICD9CM: 702.1; DO: 6498;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3q26.32 | Keratosis, seborrheic, somatic | 182000 | 3 | PIK3CA | 171834 |
A number sign (#) is used with this entry because of evidence that seborrheic keratosis can result from somatic mutations in the FGFR3 gene (134934) or the PIK3CA gene (171834).
Seborrheic keratoses are common benign epidermal lesion that can develop on any part of the body.
Reiches (1952) described 7 families in which seborrheic keratosis was transmitted through 2 or 3 generations. The keratoses were of late onset. The skin lesions of the basal cell nevus syndrome sometimes resemble seborrheic keratoses.
Bedi (1977) observed congenital seborrheic verrucae in 11 members in 3 generations of a family.
Butterworth and Strean (1962) described mother and daughter with seborrheic keratosis and stated that inheritance is autosomal dominant. The transmission pattern of seborrheic keratosis in the families reported by Reiches (1952) and Bedi (1977) was consistent with autosomal dominant inheritance.
Logie et al. (2005) screened a series of 62 seborrheic keratoses and found 39% of samples harbored somatic activating FGFR3 mutations (see, e.g., 134934.0005 and 134934.0013) identical to those associated with skeletal dysplasia syndromes and bladder and cervical neoplasms. The authors implicated FGFR3 activation as a major cause of benign epidermal tumors in humans.
Hafner et al. (2007) identified heterozygous somatic mutations in the PIK3CA gene (see, e.g., 171834.0001 and 171834.0003) in 10 (16%) of 62 seborrheic keratosis lesions. Three of the lesions had concomitant somatic mutations in the FGFR3 gene (see, e.g., R248C; 134934.0005). Histologic analysis identified 8 acanthotic lesions, 1 hyperkeratotic lesion, and 1 adenoid lesion. In 3 patients, multiple individual lesions were analyzed. In 2 patients, all lesions had wildtype PIK3CA and FGFR3 genes, whereas in the third case, 1 lesion had a mutation, and 7 other lesions had wildtype sequences. The findings suggested that, in addition to their role in cancer, oncogenic PIK3CA mutations contribute to the pathogenesis of skin tumors lacking malignant potential.
Logie et al. (2005) targeted an activated FGFR3 mutant, S249C (134934.0013), to basal cells of the epidermis of mice. FGFR3-mutant mice developed benign epidermal tumors with no sign of malignancy. These skin lesions had features in common with acanthosis nigricans and other benign human skin tumors, including seborrheic keratosis.
Bedi, T. R. Familial congenital multiple seborrheic verrucae. Arch. Derm. 113: 1441-1442, 1977. [PubMed: 143912]
Butterworth, T., Strean, L. P. Clinical Genodermatology. Baltimore: Williams and Wilkins (pub.) 1962.
Hafner, C., Lopez-Knowles, E., Luis, N. M., Toll, A., Baselga, E., Fernandez-Casado, A., Hernandez, S., Ribe, A., Mentzel, T., Stoehr, R., Hofstaedter, F., Landthaler, M., Vogt, T., Pujol, R. M., Hartmann, A., Real, F. X. Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern. Proc. Nat. Acad. Sci. 104: 13450-13454, 2007. [PubMed: 17673550] [Full Text: https://doi.org/10.1073/pnas.0705218104]
Logie, A., Dunois-Larde, C., Rosty, C., Levrel, O., Blanche, M., Ribeiro, A., Gasc, J.-M., Jorcano, J., Werner, S., Sastre-Garau, X., Thiery, J. P., Radvanyi, F. Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans. Hum. Molec. Genet. 14: 1153-1160, 2005. [PubMed: 15772091] [Full Text: https://doi.org/10.1093/hmg/ddi127]
Reiches, A. J. Seborrheic keratoses: are they delayed hereditary nevi? Arch. Derm. Syph. 65: 596-600, 1952.