Expanding the phenotype associated with a desmoplakin dominant mutation: Carvajal/Naxos syndrome associated with leukonychia and oligodontia

We report the case of a 29-year-old Caucasian man with a rare form of cardiac and non-cardiac disease that sheds new light on the clinical spectrum associated with desmosomal gene mutations, usually related to arrhythmogenic right ventricular cardiomyopathy (ARVC) [ ]. Dilated cardiomyopathy with left ventricular dysfunction was first diagnosed in this patient when he was 12 years old (incidental finding of an enlarged heart on chest X-ray). The patient was referred to our institution a few years later for further investigations. The patient presented with woolly hair from infancy and palmoplantar keratoderma, confirmed by skin biopsy (Fig. 1). He also had leukonychia (hands and feet) (Fig. 1) and oligodontia, characterized by the absence of third molars (agenesis of 4 teeth). The patient did not experienced episodes of syncope nor palpitations. The 12-lead electrocardiogram demonstrated QRS complex prolongation and depolarization abnormalities (Fig. 1). Echocardiographic examination demonstrated dilatation and hypokinesia of both ventricles. Left ventricular ejection (LV) fraction was 35% and LV end-diastolic diameter was 61 mm. Severe global dilatation and reduced ejection fraction of right ventricular (RV) were observed (fractional area change 32%), associated with dilatation (40 mm) and akinesia of RV infundibulum (Fig. 1), apical aneurism and excessive trabeculations. These structural alterations were confirmed by cardiac magnetic resonance imaging (MRI) (Fig. 1), which also demonstrated extensive myocardial late gadolinium enhancement in both ventricles. Late potentials by signal-average ECG were positive for two out of three criteria. Premature ventricular beats were registered on Holter-ECG (>500/day). The diagnosis of ARVC was made according to the 2010 International Task Force diagnostic criteria [ ]. A single-chamber prophylactic implantable cardioverter-defibrillator was implanted, and no arrhythmia occurred to date.