Palmoplantar Keratoderma, Nonepidermolytic, Focal 1 Q83.4

NEPPK1 is a rare, autosomal dominant inherited palmoplantar keratosis characterized by focal, pressure point localized, callus-like, hyperkeratoses on palms and soles. Furthermore, focal forms of PPK associated with esophageal carcinoma (148500) and with gingival hyperplasia (148730) have been described.

Very rare, only a few families are described.

In two families with identical clinical phenotypes of focal NEPPK with follicular and orogenital hyperkeratoses, one of which was the large multigenerational family linked to chromosome 17q12-q21 previously studied by Stevens et al. (1994), Shamsher et al. (1995) sequenced the KRT16 gene and identified heterozygosity for two different missense mutations in affected individuals. The mutations were not found in unaffected family members or in 30 unrelated control subjects. Shamsher et al (1995) noted that the clinical manifestations of focal NEPPK are very similar to those of pachyonychia congenita type1, with the only significant difference being the extent of nail involvement. In this one, a mutation in the KRT16 gene is also detectable. McLean (1997) noted that the two families studied by Shamsher et al. (1995) had mild nail changes similar to those seen in a much more severe form in pachyonychia congenita. In a third-generation family with mild FNEPPK, Smith et al. (2000) identified a complex deletion in the KRT16 gene. The authors found that the deletion, which removes a keratin 16 helix termination motif (HTM), unexpectedly resulted in a relatively mild phenotype.

Histopathological examination shows marked hyperkeratosis, thickened stratum spinosum with reduced stratum granulosum, loss of cell adhesion in the suprabasal layers, elongation of the rete ridges, and sparse lymphocyte infiltration in the dermis.

1. Kelsell D P et al (1995) Genetic linkage studies in non-epidermolytic palmoplantar keratoderma: evidence for heterogeneity. Hum Molec Genet 4: 1021-1025
2. Shamsher MK et al (1995) Novel mutations in keratin 16 gene underly focal nonepidermolytic palmoplantar keratoderma (NEPPK) in two families. Hum. Molec. Genet 4: 1875-1881.
3. Smith FJD et al. (2000) Novel keratin 16 mutations and protein expression studies in pachyonychia congenita type 1 and focal palmoplantar keratoderma. Exp Derm 9: 170-177
4. Stevens HP et al (1994) Keratin staining and linkage of non-epidermolytic focal palmoplantar keratodermas (PPK) to 17q. Brit J Derm 131: 425