About Neuromuscular Disorders (NMDs)
Neuromuscular disorders (NMDs) are a heterogeneous group of genetic disorders that affect around 1 in 1000 individuals worldwide. Although collectively common, each individual condition is rare, with an overall prevalence estimated to be 37 per 10000 in the general population. NMDs result from genetic variations including insertions, deletions, duplications, or repeat expansions that disrupt the function of peripheral nerves, motor neurons, neuromuscular junctions, or skeletal muscles, leading to progressive muscle weakness and degeneration. There are around 715 different genes resulting in 1240 NMDs. NMDs are mostly monogenic, inherited as autosomal dominant (Myotonic dystrophy), autosomal recessive (LGMD 2), X-linked (DMD), mitochondrial (MERRF, MELAS) or can be sporadic (Nemaline Myopathy).
The onset, severity, and clinical presentation of NMDs vary widely. Disorders, such as congenital myopathies and congenital muscular dystrophies (CMDs), manifest at birth or in early infancy with hypotonia, delayed milestones, or respiratory insufficiency, while others, such as limb girdle muscular dystrophy (LGMD) or facioscapulohumeral muscular dystrophy (FSHD), present during adolescence or adulthood. Duchenne Muscular Dystrophy (DMD), the most prevalent and severe form, affects approximately 1 in 3500 male children and typically presents before the age of five with progressive proximal muscle weakness, calf hypertrophy, and elevated Creatinine phosphokinase (CPK) levels. CMDs, though less common (0.6-0.9 per 100000), present with Central nervous system (CNS), ocular, and cardiac involvement. Mitochondrial myopathies, by contrast, are linked to defects in oxidative phosphorylation, presenting with exercise intolerance, myalgias, or metabolic decompensation during illness or fasting. Similarly, Hereditary Spastic Paraplegias (HSPs) occur in about 1-9 per 100000 individuals and are characterized by progressive spastic paraplegias due to distal axonal degeneration. Systemic involvement also aids recognition and early intervention, for example, cardiac manifestations in DMD and myotonic dystrophy, hepatomegaly in metabolic storage disorders, early respiratory failure in nemaline myopathy, and contractures in Emery-Dreifuss muscular dystrophy.