Novel Desmoplakin c.1789 T>C Mutation in Carvajal Syndrome, A Rare Cause of DCM in Children

• Published in: The Thoracic and Cardiovascular Surgeon
• Main Authors: Dehne, J., Kehl, H. G., Debus, V., Frank, T., Gehrmann, J., Schulze-Bahr, E., Jux, C.
• Format: Conference Proceeding
• Language: English
• Published: 05.06.2015
• ISSN: 0171-6425; 1439-1902
• DOI: 10.1055/s-0035-1556019

We report on a 13 year-old boy with clinical signs of Carvajal Syndrome in whom a novel c.1789 T>C mutation in the desmoplakin gene could be detected. A 13 years old patient presented with dyspnea, fatigue, and vertigo under physical stress. On exam he showed remarkable acantholytic palmoplantar keratoderma and woolly hair. Chest-X-ray, echocardiography and MRI demonstrated severe dilatative cardiomyopathy of both ventricles with non-compactioning disarray and fibrosis. The ECG revealed negative T-waves in II, III aVF and V1-V4 together with polymorphic ventricular extrasystoles. Histologic examination of myocardial biopsies showed chronic damage as in dilatative cardiomyopathy without inflammatory reaction or detection of infectious agents. Genetic investigation revealed a novel heterozygous c.1789 T>C mutation in the desmoplakin-gene on chromosome 6p24 with an exchange of amino acid Ser597Pro in the spectrin binding domain 4 of the protein. Carvajal syndrome is defined by characteristic cardiocutaneous lesions: streaky palmoplantar hyperkeratosis, woolly hair and early onset of primarily left ventricular dilatative cardiomyopathy with high risk of sudden death caused by arrhythmia or heart failure. Naxos Syndrome is a similar syndrome classified by arrhythmogenic right ventricular cardiomyopathy (ARVC) which summarizes diseases with non-functional proteins of the desmosome-complex. Characteristically these diseases show left, right or biventricular cardiomyopathy and are responsible for up to 12,5% of sudden cardiac deaths especially in young people.