Acantholysis in Striate Keratoderma as a Clue to the Diagnosis of a Genetic Abnormality

To the Editor: The role of histopathological diagnosis of inherited palmoplantar keratodermas (PPKs) has been traditionally limited. With the advent of molecular genetics, this may have changed. An example is epidermolytic PPK in which the epidermolytic changes along with dyskeratosis may lead to the identification of the correct KRT gene mutation.1 Another example is the PPKs associated with DSG1 mutations such as striate PPK.2 Striate PPKs (OMIM 148700) are an uncommon group of genodermatoses with autosomal dominant inheritance. This group of diseases is characterized by linear hyperkeratosis of the palms running the length of each finger and focal to diffuse thickening of the soles. The disease usually presents during the first or second decade of life and is typically exacerbated by heavy manual labor.3 Causative mutations in genes encoding desmoglein 1 (Dsg1), desmoplakin (DSP), and keratin 1 (KRT1) have been reported in a small number of families of diverse ethnic origin.4–9 In a retrospective histopathological analysis of 4 PPK cases with different DSG1 mutations, we demonstrated that the involved epidermis is characterized by partial acantholysis.2 Consequently, we are now using histopathology successfully as an adjunct to the diagnosis of inherited PPKs. The following is an example: A 21-year-old man, otherwise healthy, presented with PPK. The keratoderma has been present since childhood and increased in severity over the years. The condition worsened after physical effort and was accompanied by both pain and cosmetic concern. His skin examination revealed thickened, yellowish hyperkeratotic bands with a verrucous appearance on his palms (Fig. 1), and keratotic plaques on the weight-bearing areas of his soles. No other skin, nail, hair, or dental abnormalities were found. He reported that his deceased father and grandmother, 2 uncles, and 1 aunt were afflicted by a similar condition. Several cousins had a milder form of keratoderma involving the soles only.FIGURE 1: Thick, yellowish hyperkeratotic bands with a verrucous appearance on the palms.A punch biopsy obtained from his palm demonstrated epidermal papillomatosis and orthohyperkeratosis, as well as partial acantholysis in the granular and spinous cell layers, compatible with striate PPK (Fig. 2).2 Direct sequencing of DSG1 demonstrated in exon 5, a single nucleotide change c.395C>A converting a serine residue (TCA) to stop codon (TAA), causing a nonsense mutation designated S132X. This mutation was previously reported to underlie striate keratoderma.10FIGURE 2: A biopsy from a hyperkeratotic band on the palms showing partial acantholysis in the granular and spinous cell layers.This case study confirms the usefulness of a skin biopsy in the diagnosis of PPKs associated with DSG1 mutations.