The cardiocutaneous conundrum and the role of multidisciplinary management

The heart and skin share structural proteins that maintain integrity under mechanical stress, particularly desmoplakin within desmosomes. Mutations in the DSP gene are classically associated with the autosomal recessive Carvajal syndrome, presenting with woolly hair, palmoplantar keratoderma and dilated cardiomyopathy. More recently, autosomal dominant DSP mutations have been recognized, broadening the phenotypic spectrum. A 40-year-old woman with lifelong palmoplantar keratoderma, woolly hair and hypodontia developed exertional chest pain and dyspnoea at age 24 years. Echocardiography revealed globally impaired left-ventricular systolic function (ejection fraction 30–40%) with normal coronary angiography. Dermatology review raised suspicion of a cardiocutaneous syndrome. She was initially managed medically but re-presented in 2016 with acute-on-chronic heart failure. Repeat echocardiography demonstrated severe left-ventricle dilatation with ejection fraction 15–20%, necessitating eventual cardiac transplantation with pacemaker implantation in 2018. Genetic testing in 2025 identified a heterozygous DSP variant (NM_004415.4: c.1823T>A, p.Ile608Lys) located on chromosome 6:g.7571504(GRCh38), confirming DSP-related cardiomyopathy with woolly hair, palmoplantar keratoderma and tooth agenesis. She was commenced on alitretinoin for symptomatic keratoderma and referred for restorative dental assessment. This case illustrates an autosomal dominant DSP mutation manifesting with both cardiac and cutaneous features. Recognition of the dermatological phenotype can enable early identification of cardiomyopathy, timely genetic testing and family screening. Dermatological signs may precede cardiac disease by decades in DSP-related syndromes. Early multidisciplinary recognition is essential to optimize outcomes and highlight the shared desmosomal pathology linking skin and heart.

Abstract from Crossref