Clinical presentations and pathophysiological mechanisms of dystroglycanopathy: advancing therapeutic strategies.

Dystroglycanopathies are muscular dystrophies with varying clinical severities, ranging from congenital-onset to adult limb-girdle muscular dystrophy. Dystroglycanopathies are caused by a loss of function of the extracellular matrix receptor α-dystroglycan, a widely expressed cell-surface glycoprotein required for the formation and function of various muscle and non-muscle tissues. In severe clinical presentations, individuals with dystroglycanopathy experience, in addition to muscle weakness and cardiac involvement, structural ocular and CNS malformations, leading to intellectual disability and epilepsy. Currently, management is only symptomatic. Advances in the understanding of the pathophysiology and genetics have identified new therapeutic targets. Emerging therapeutic approaches, including adeno-associated virus gene therapy for limb-girdle muscular dystrophy associated with pathogenic variants in FKRP (the most common form of dystroglycanopathy) and ribitol-based therapies, are being evaluated in clinical trials and could expand treatment options.