Unproven genotype/phenotype correlation in any genetic defect associated with non-compaction

Abstract

We appreciated to read the report by Klaassen et al. [1] about the detection of MYH7, ACTC, and TNNT2-mutations in 11 of 63 patients and 13 relatives with left-ventricular hypertrabeculation/noncompaction (LVHT). The study raises a number of comments and concerns. Though LVHT is associated with a large number of different genetic defects [2,3codorn18], a causal relation between any of these genetic defects and LVHT has never been proven. A strong argument against a causal relation is rare segregation of LVHT together with a mutation in a single family. To date LVHT has been associated with mutations in at least 30 different genes and >20 different chromosomal abnormalities. To regard LVHT as only autosomal dominantly inherited [1] is not justified given its heterogeneous genetic background and the report of autosomal dominant, X-chromosomal, and maternal traits of inheritance.