Palmoplantar Keratoderma, Nonepidermolytic, Focal 2

A number sign (#) is used with this entry because of evidence that focal nonepidermolytic palmoplantar keratoderma-2 (FNEPPK2) is caused by heterozygous mutation in the TRPV3 gene (607066) on chromosome 17p13. One such family has been reported.

Heterozygous mutation in the TRPV3 gene can also cause Olmsted syndrome (OLMS; 614594), which is also known as mutilating palmoplantar keratoderma with periorificial keratotic plaques.

For a discussion of phenotypic and genetic heterogeneity of palmoplantar keratoderma, see epidermolytic PPK (144200).

Clinical Features

He et al. (2015) reported a Chinese father and son with focal palmoplantar keratoderma. The 37-year-old father exhibited distinct hyperkeratotic lesions on his palms and soles, and his son also had focal hyperkeratosis on his fingers, palms, and toes. Neither patient had any other abnormalities. Histopathologic examination of a biopsy from the sole of the father's foot showed prominent hyperkeratosis, thickened stratum spinosum layer with reduced stratum granulosum, disadhesion of cells in the suprabasal layers, elongation of rete ridges, and sparse lymphocyte infiltration in the dermis.

Molecular Genetics

In a Chinese family in which a father and son had focal palmoplantar keratoderma, He et al. (2015) performed whole-genome sequencing and identified heterozygosity for a missense mutation in the TRPV3 gene (Q580P; 607066.0005). The mutation was de novo in the father and present in the affected son, but it was not found in the unaffected paternal grandparents, an unaffected paternal uncle, or an unaffected sister. Noting the mild clinical presentation associated with the Q580P mutation compared with other mutations in TRPV3 that have been reported to cause Olmsted syndrome, He et al. (2015) suggested that different mutations might lead to functional differences in TRPV3.