Challenges and progress in the diagnosis of Congenital Muscular Dystrophies

Introduction. An accurate assessment of clinical presentation and genetic causes of congenital muscular dystrophy (CMD) has been achieved through a systematic review of literature and analysis of the current state of the art. This review reflects the diagnostic progress in the CMD field, with a recent classification based on gene discoveries. Areas covered. CMD affects children, with weakness starting in infancy or early-onset hypotonia with frequent brain involvement. Three major categories are represented and covered: cases due to merosin deficiency, cases with dystroglycan deficiency (including Fukuyama CMD, Muscle-Eye-Brain disease, and Walker-Warburg-syndrome), and collagen 6-related myopathies. The forms related to mutations in SEPN1 and LMNA genes are less frequent. Expert opinion. We present clues for CMD diagnosis either from clinical features or from muscle biopsy and brain imaging. When such studies do not yield diagnosis, new technologies such as next generation sequencing can be recommended for genetic characterization.