Abstract A 19-month-old infant came to our attention showing clinical signs consistent with focal keratoderma limited to the palms and soles, dystrophic pachyonychia of all his nails and scalp alopecia characterized by sparse curly hair. His oral cavity examination revealed periodontitis, early tooth decay and notching of the incisor teeth. The patient is the second child of a nonconsanguineous, otherwise healthy couple. No other family members were reported to have similar skin and oral alterations. Based on the characteristic appearance of his cutaneous lesions, he was investigated for a palmoplantar keratoderma disorder and was subjected to genetic testing. Results confirmed a mutation within DSP, a gene responsible for encoding the most abundant component of desmosomes, a major cell adhesion junction, particularly prominent in epidermal and cardiac tissue. Mutations in genes encoding desmosomal components are known to be associated with a broad spectrum of phenotypical alterations of skin and hair structures. The same genetic anomaly accounts for 40–50% of cases of arrhythmogenic cardiomyopathy (Pigors M, Schwieger-Briel A, Cosgarea R et al. Desmoplakin mutations with palmoplantar keratoderma, woolly hair and cardiomyopathy. Acta Derm Venereol 2015; 95:337–40). Despite being asymptomatic, our young patient was referred to cardiology for further investigations and surveillance. At the age of 7 years, routine electrocardiography revealed new conduction abnormalities. An echocardiogram confirmed a dilated cardiomyopathy that, combined with the previously described cutaneous and oral alterations, led to a diagnosis of cardiocutaneous syndrome. An overview of the clinical features associated with desmoplakin mutations reported in medical literature illustrates the complexity of this group of disorders and their genotype–phenotype correlations, which cannot be easily predicted. Our reported case is a paradigmatic example of diagnostic difficulties often encountered when facing concomitant dermatological and oral conditions in the same patient, emphasizing the importance of recognizing oral, dental and skin signs to be a potential risk factor for hidden cardiac diseases.