Warburg micro syndrome type 1 associated with peripheral neuropathy and cardiomyopathy

The Warburg micro syndrome (WARBM) is a genetically heterogeneous syndrome linked to at least 4 loci. At the clinical level, WARBM is characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, corpus callosum hypoplasia, severe mental retardation, and hypogonadism. In some families additional clinical features have been reported. The presence of uncommon clinical features (peripheral neuropathy, cardiomyopathy) may result in misdirected molecular diagnostics. Using the next generation sequencing approach (NGS), we were able to diagnose WARBM1 syndrome by detection of a new mutation within the RAB3GAP1 gene. We have detected some DNA variants which may be responsible for cardiomyopathy. We did not find any obvious pathogenic mutation within a set of genes known to be responsible for hereditary motor and sensory neuropathy (HMSN). We conclude that: (i) in clinically delineated syndromes, a classical single-gene oriented approach may be not conclusive especially in the presence of rare clinical features, (ii) peripheral neuropathy and cardiomyopathy are rare additional symptoms coexisting with WARBM1, (iii) a pleiotropic effect of a single point mutation is sufficient to be causative for WARBM1 and (iv) more WARBM-affected patients should be reported to delineate a complete phenotype.