Coincidence of acral peeling skin syndrome and Nagashima‐type palmoplantar keratosis in a Japanese pedigree with acral skin peeling

TL;DR

A Japanese family shows two rare skin conditions, APSS and NPPK, highlighting the need for genetic testing to distinguish similar skin disorders.

Contribution

First report of APSS in East Asia and co-occurrence of APSS and NPPK in a single pedigree.

Findings

Compound heterozygous TGM5 variants confirmed APSS in a Japanese patient.

Compound heterozygous SERPINB7 variants diagnosed NPPK in family members.

Genetic testing is essential for accurate diagnosis of overlapping genodermatoses.

Abstract

Acral peeling skin syndrome (APSS; MIM 609796) is a rare genodermatosis characterized by painless focal cutaneous exfoliation of the dorsal hands and feet, typically displaying autosomal recessive inheritance. While cases associated with a founder mutation in TGM5 are relatively common in European Caucasian populations, no APSS cases have been reported from Japan or other East Asian countries. In contrast, Nagashima‐type palmoplantar keratosis (NPPK; MIM 615598), caused by variants in SERPINB7, is relatively common in East Asia due to founder mutations. We describe a 27‐year‐old Japanese woman with spontaneous focal cutaneous exfoliation of the dorsal hand following prolonged glove use, indicative of APSS. Histopathological examination revealed a cleft between the stratum corneum and stratum granulosum and within the horny layer of the epidermis, supporting this diagnosis. However, her mother and maternal uncle exhibited similar symptoms, and there was no reported consanguinity in the patient's parents or grandparents, prompting suspicion of an autosomal dominant genodermatosis. Whole‐genome sequencing (WGS) revealed compound heterozygous variants in TGM5 (c.1037G>A and c.684 + 1G>A) as suspected causative variants in the patient, leading to an APSS diagnosis, the first reported in East Asia. On the other hand, her mother and maternal uncle were diagnosed with NPPK due to compound heterozygous pathogenic variants in SERPINB7 (c.796C>T and c.455‐1G>A). This case highlights the complexity of diagnosing skin disorders when multiple genodermatoses with similar phenotypes exist within a pedigree. Comprehensive genetic analyses, such as whole‐exome sequencing and WGS, are invaluable for identifying causative variants in such complex cases.

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