Clinical and molecular characterization of patients affected by congenital muscular dystrophies using next generation sequencing strategies

Congenital muscular dystrophies (CMD) are a heterogeneous group of rare conditions clinically characterized by muscle weakness with onset at birth or shortly after, and variable involvement of eyes, heart and central nervous system. An accurate genetic diagnosis in CMD is important in order to facilitate genetic and prenatal counselling, to inform prognosis and aspects of management, as well as to facilitate future treatments. To date the number of proven CMD cases without a genetic diagnosis is still significant. In the last years the advent of next generation sequencing (NGS) technologies led to the discovery of several new genes responsible for different forms of CMD. We report the frequency of the various forms of CMD in our geographic area and we also provide information about the genetic diagnosis of our cohort of patients. Using the modern technologies offered by NGS platforms a genetically confirmed diagnosis of CMD was reached in about 67% of cases (14/21) and LAMA2 was the most common mutated gene in our cohort. The most common subtype of CMD was the group of distroglycanopathies, although we had a low mutation detection rate in that CMD group. Furthermore, we describe new peculiar clinical features identified in patients in whom a genetic diagnosis was reached and we further expand the clinical spectrum associated with mutations in the POMT2 and SYNE1 genes.