Hereditary palmoplantar keratodermas. Part I. Non‐syndromic palmoplantar keratodermas: classification, clinical and genetic features

Abstract The term palmoplantar keratoderma ( PPK ) indicates any form of persistent thickening of the epidermis of palms and soles and includes genetic as well as acquired conditions. We review the nosology of hereditary PPK s that comprise an increasing number of entities with different prognoses, and a multitude of associated cutaneous and extracutaneous features. On the basis of the phenotypic consequences of the underlying genetic defect, hereditary PPK s may be divided into the following: (i) non‐syndromic, isolated PPK s, which are characterized by a unique or predominant palmoplantar involvement; (ii) non‐syndromic PPK s with additional distinctive cutaneous and adnexal manifestations, here named complex PPK s; (iii) syndromic PPK s, in which PPK is associated with specific extracutaneous manifestations. To date, the diagnosis of the different hereditary PPK s is based mainly on clinical history and features combined with histopathological findings. In recent years, the exponentially increasing use of next‐generation sequencing technologies has led to the identification of several novel disease genes, and thus substantially contributed to elucidate the molecular basis of such a heterogeneous group of disorders. Here, we focus on hereditary non‐syndromic isolated and complex PPK s. Syndromic PPK s are reviewed in the second part of this 2‐part article, where other well‐defined genetic diseases, which may present PPK among their phenotypic manifestations, are also listed and diagnostic and therapeutic approaches for PPK s are summarized.