Test the grandfather! Incidental in-frame DMD deletions in three asymptomatic families

The DMD gene, the largest gene in the human genome, is particularly prone to exonic deletions or duplications due to recombination events during gametogenesis, with frameshift deletions typically seen in Duchenne muscular dystrophy (DMD) and in-frame deletions with Becker muscular dystrophy or X-linked dilated cardiomyopathy. Dystrophic changes in the muscles result in elevated creatine kinase levels. DMD deletions are also associated with cognitive challenges. In this case series, we present three unrelated families with the incidental finding of in-frame DMD deletions on chromosome microarray, two involving exons 49–51 and one involving exons 45–60. All of the children are asymptomatic or minimally symptomatic with normal echocardiograms and inherited the deletion from their maternal grandfathers who are asymptomatic into their 60s. The identification of incidental DMD deletions on chromosome microarray can have important implications in terms of diagnosis, screening and follow-up, prognostication and family planning. The finding of a familial in-frame DMD deletion in an asymptomatic maternal grandfather is reassuring with regard to prognosis and disease course. When a maternally inherited in-frame DMD deletion is identified in an asymptomatic young male, or unexpectedly at the time of invasive prenatal testing, it is crucial to test both maternal grandparents.