Heterozygous Arrhythmogenic Cardiomyopathy-Desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion

This study investigated the cutaneous phenotype of heterozygous carriers of truncation-type variants in the desmoplakin (DSP) gene, which is associated with arrhythmogenic cardiomyopathy (AC). The study included 12 participants (4 women and 8 men) with a mean age of 48 years. While no significant macroscopic changes in skin and hair were observed, the carriers exhibited lower skin temperature and higher transepidermal water loss compared to controls. Skin biopsies revealed widening of intercellular spaces and acantholysis of keratinocytes, along with reduced DSP expression. Additionally, trichograms showed regular nodules indicative of pseudomonilethrix. These findings suggested that heterozygous DSP mutation carriers have distinct subclinical cutaneous changes, regardless of cardiac involvement.