Palmoplantar Keratoderma, Norrbotten Recessive Type

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

Clinical Features

In a study of palmoplantar keratoderma in the northernmost county of Sweden (Norrbotten), Gamborg Nielsen (1985) observed a seemingly recessive and unusually severe form that differed from the picture of mal de Meleda (248300) in 6 patients from 2 families. Affected individuals had a very thick horny layer with a distinct demarcation to normal skin, bordered by a bluish-red zone in 4 patients; in 1 patient the hyperkeratosis extended to the dorsum of the hand. Knuckle pads were found on the dorsal finger joints. Three of the patients had dermatophytosis on their soles, and 1 had mutilating palmoplantar keratoderma.

Kastl et al. (1990) studied 5 patients from 3 Swedish families with diffuse palmoplantar keratoderma. Affected individuals showed a very thick horny layer, with the transition to normal skin distinctly demarcated by a bluish-red border. Some patients exhibited transgression of the hyperkeratoses to the dorsum of the hands and feet. Knuckle pads were present on the dorsal finger and toe joints. Elbows and knees were uninvolved, hair and teeth were normal, and there was no mental retardation. Biopsies of hyperkeratotic skin from the soles of affected individuals showed a highly acanthotic epidermis with a focally broadened granular layer and an increased amount of tonofibrils. Keratohyalin granules were unevenly distributed within the granular cells. Between the granular and horny layers several 'clear cells' were seen, which had a more loosely arranged cell content and lower amount of tonofibrils than the adjacent granular cells. The horny layer was orthohyperkeratotic and there were occasional spinelike protrusions of granular cells into the horny layer. Ultrastructural findings included an increase in the amount of tonofibrils, beginning in the mid-spinous layer and reaching a maximum in the upper stratum granulosum. The granular layer consisted of up to 11 cell layers, with neighboring cells showing considerable variation in amount, size, and ultrastructure of keratohyaline granules. Cells of the granular, transit, and horny layer possessed some lipid droplets, and desmosomes had already transformed into desmosomal discs beginning in the upper granular layers. In addition to lipid droplets, the lower horny cells often contained cell remnants or granular material, and had thickened plasma membranes. The cells themselves were intensely interlocked and thicker than normal, and chains of desmosomal discs could be detected in the intercellular spaces. Skin biopsies from clinically unaffected obligatory heterozygotes showed no changes by light microscopy, but 4 of the 5 individuals examined exhibited ultrastructural alterations, including an unbalanced distribution of tonofibrils within cells of the spinous and granular layers, with differences in amount and aggregation. Variable amounts of keratohyalin were found in the granular layer and the granules showed a spongy texture with different sizes of less electron-dense areas and sometimes a granular border as well.