Two sons of a consanguineous marriage developed biventricular cardiomyopathy. 
One boy died of severe heart failure at the age of 6 years, the other was 
transplanted because of severe heart failure at the age of 10 years. In 
addition, focal palmoplantar keratoderma and woolly hair were apparent in both 
boys. As similar phenotypes have been described in Naxos disease and Carvajal 
syndrome, respectively, the genes for plakoglobin (JUP) and desmoplakin (DSP) 
were screened for mutations using direct genomic sequencing. A novel homozygous 
2 bp deletion was identified in an alternatively spliced region of DSP. The 
deletion 5208_5209delAG led to a frameshift downstream of amino acid 1,736 with 
a premature truncation of the predominant cardiac isoform DSP-1. This novel 
homozygous truncating mutation in the isoform-1 specific region of the DSP 
C-terminus caused Carvajal syndrome comprising severe early-onset heart failure 
with features of non-compaction cardiomyopathy, woolly hair and an acantholytic 
form of palmoplantar keratoderma in our patient. Congenital hair abnormality and 
manifestation of the cutaneous phenotype in toddler age can help to identify 
children at risk for cardiac death.