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

Abstract

We report on a family with a rare form of cardiac and non-cardiac disease that shed new lights on the clinical spectrum associated with desomomal gene mutations, usually related to arrhythmogenic right ventricular cardiomyopathy. The 29-year-old patient presented with woolly hair from infancy and palmoplantar keratoderma, leuconychia (hands and feet) and oligodontia (agenesis of 4 teeth). Global cardiac biventricular involvement was present on echocardiography and MRI. Late potentials were present on signal-average ECG and ventricular premature beats (PVB) on Holter-ECG (>10/24h). A single-chamber prophylactic implantable cardioverter-defibrillator was implanted. The son of the patient had palmoplantar keratoderma, woolly hair, oligodontia (agenesis of 10 teeth) and brittle nails. At 10 years of age, a diagnosis of acute myocarditis was made (chest pain, cardiac troponin elevation, multiple isolated PVB, typical sign on MRI). RV infundibulum was dilated on Echocardiography. Evolution was unremarkable after medical treatment. A heterozygous missense mutation (c.1691C>T, p. Thr564Ile) was identified in the desmoplakin gene (both in father and son). No additional mutation was identified in other desomosomal genes. Carvajal/Naxos syndromes are usually recessive and characterized by wooly hair, palmoplantar keratoderma and a cardiomyopathy. We report on a family with unique features associated with a new mutation of desmoplakin gene. First, mode of inheritance is autosomal dominant and not recessive. Second, clinical expression is associating not only the usual Carvajal/Naxos syndrome but also oligodentia and leuconychia. This report (i) extends the phenotype associated with desmosomal gene mutations, (ii) demonstrates that leuconychia and oligodentia may be associated with severe cardiomyopathy and may therefore require systematic cardiac examination, (iii) suggests that desmoplakin gene is involved in the normal and abnormal development of teeth and nails.