Nagashima-type palmoplantar keratoderma is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis, first described by Nagashima (1977) in the Japanese literature. It is characterized by well-demarcated diffuse erythematous hyperkeratosis that extends onto the dorsal surfaces of the palms and ... Nagashima-type palmoplantar keratoderma is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis, first described by Nagashima (1977) in the Japanese literature. It is characterized by well-demarcated diffuse erythematous hyperkeratosis that extends onto the dorsal surfaces of the palms and feet and the Achilles tendon area. Involvement of the elbows and knees has also been reported, and there is a high frequency of hyperhidrosis on the palms and soles. In contrast to other types of transgressive diffuse hyperkeratosis such as mal de Meleda (248300) and the Gamborg Nielsen type of recessive PPK (PPK Norrbotten; 244850), PPKN shows only mild hyperkeratosis that is nonprogressive after the second decade and does not involve flexion contractures or constricting bands (summary by Kubo et al., 2013). For a discussion of phenotypic and genetic heterogeneity of palmoplantar keratoderma, see epidermolytic PPK (144200).
Kabashima et al. (2008) reported a 17-year-old Japanese boy who had bilateral reddish palmoplantar hyperkeratotic lesions that extended onto the dorsum of the hands and Achilles tendon area. The lesions, which developed within the first 2 years of ... Kabashima et al. (2008) reported a 17-year-old Japanese boy who had bilateral reddish palmoplantar hyperkeratotic lesions that extended onto the dorsum of the hands and Achilles tendon area. The lesions, which developed within the first 2 years of life and had progressed until age 14 or 15, were associated with hyperhidrosis on the palms and soles and were accompanied by a distinct odor and maceration. The patient was otherwise healthy, and family history was negative for similar disorders. Biopsy from the erythematous skin on the dorsum of the hand showed orthokeratotic hyperkeratosis with acanthosis, hypergranulosis, and mild perivascular inflammation, as well as a moderate lymphocytic infiltrate in the upper dermis. Kabashima et al. (2008) stated that this was the first case report of PPKN in the English-language literature, and tabulated 18 cases of Nagashima-type PPK that had previously been reported in the Japanese literature. Review of the PPKN cases showed a male-to-female ratio of 9:10, an onset of disease from birth to 3 years of age, associated hyperhidrosis, and a high frequency of tinea pedis. Involvement of other sites, such as elbows and knees, was noted in 13 of the 19 reported cases. Isoda et al. (2009) reported 2 sisters, aged 31 and 29 years, who presented with bilateral reddish palmoplantar hyperkeratotic lesions. The manifestations, which began within the first 3 years of life and gradually progressed until the late teens, were associated with hyperhidrosis of the palms and soles that had a distinct odor and maceration. There was no involvement of the elbows, knees, hair, teeth, or nails. Their nonconsanguineous parents were healthy, and there were no other cases in the family. Biopsy of the medial sole from the younger sister showed orthokeratosis, mild hypergranulosis, acanthosis, and a sparse lymphocytic infiltrate in the upper dermis. Isoda et al. (2009) concluded that the clinical features and histology were consistent with Nagashima-type PPK; the patients declined genetic analysis. Nakamizo et al. (2010) studied a family in which 5 individuals were affected over 3 generations. A 5-year-old boy and his 40-year-old father presented with bilateral reddish palmar hyperkeratotic lesions, which in the father extended to the dorsum of the hand but in the son were limited to the palm; the father also had erythematous hyperkeratosis of the soles. The father's manifestations began at birth and progressed until his late teens, whereas the son's lesions were noted at birth and were still progressing. Both patients had hyperhidrosis of the palms and soles, with distinct odors and maceration. There was no involvement of the elbows, knees, hair, teeth, or nails. The paternal grandfather and 2 paternal aunts had similar lesions, whereas the mother and the boy's older sister did not. Biopsy of the medial sole from the father showed orthokeratotic hyperkeratosis, mild hypergranulosis, acanthosis, and a sparse lymphocytic infiltrate in the upper dermis. Kubo et al. (2013) studied 13 unrelated Japanese patients with PPKN and mutations in the SERPINB7 gene (see MOLECULAR GENETICS). Lesions were noted at birth or in early infancy in 10 of the patients; the latest onset of lesions was at 9 to 10 years of age in 1 patient. In 9 patients, there was involvement of the knees, and in 6 of those patients, the elbows were involved as well. Exposure of lesional skin to water showed a whitish spongy change in the stratum corneum. Transepidermal water loss analysis before and after water exposure in 3 patients suggested that water permeation into the stratum corneum is specifically facilitated in PPKN lesional skin.
Kubo et al. (2013) performed whole-exome sequencing in 3 unrelated Japanese patients with Nagashima-type PPK, known to be negative for mutation in the SLURP1 gene (606119), and identified homozygosity or compound heterozygosity for mutations in the SERPINB7 gene ... Kubo et al. (2013) performed whole-exome sequencing in 3 unrelated Japanese patients with Nagashima-type PPK, known to be negative for mutation in the SLURP1 gene (606119), and identified homozygosity or compound heterozygosity for mutations in the SERPINB7 gene (603357.0001-603357.0003) in all 3 patients, which were confirmed by Sanger sequencing. Analysis of SERPINB7 in 10 additional unrelated Japanese individuals with PPKN who were negative for mutation in SLURP1 revealed homozygosity or compound heterozygosity for the same mutations identified in the initial 3 patients. All of the patients carried the nonsense mutation R266X (603357.0001) on at least 1 allele; this variant was identified as a SNP in the 1000 Genomes Project (dbSNP rs142859678) with a minor allele frequency of 0.4%. R266X was present in heterozygosity in 2 of 89 Japanese individuals, 4 of 97 Han Chinese individuals from Beijing, and 2 of 100 Han Chinese individuals from southern China, but was not found in any of 806 non-Asian individuals, suggesting that R266X is a founder mutation causing PPKN in Asian populations. - Exclusion Studies In a 17-year-old Japanese boy with PPKN, Kabashima et al. (2008) sequenced the SLURP1 gene but identified no mutations.