Neuromuscular disorders comprehensive panel

Hereditary neuromuscular disorders form a clinically and genetically heterogeneous spectrum in which the primary anatomical site of pathology determines the phenotype. Muscle involvement manifests as proximal or distal weakness, often with elevated creatine kinase; motor-neuron forms present with hypotonia, denervation, and atrophy; peripheral-nerve forms produce a chronic distal motor and sensory polyneuropathy beginning typically in the first to third decade; and neuromuscular-junction forms cause fatigable weakness. Age of onset across the spectrum is markedly heterogeneous and spans congenital and infantile presentations (e.g.,, severe spinal muscular atrophy, congenital muscular dystrophies, congenital myasthenic syndromes), childhood-onset entities (e.g., , milder spinal muscular atrophy forms), and adolescent-to-adult onset (e.g., , , , late-onset distal myopathies).

Precise epidemiological data are lacking because of high genetic heterogeneity and variable and overlapping clinical presentations for each genetic entity.

A large number of genes have been associated with neuromuscular disorders. The genetic forms span muscle, motor neuron, peripheral nerve, and neuromuscular junction disorders. Frequently identified examples include (DMD; X-linked dystrophinopathy with progressive weakness), spinal muscular atrophy (SMN1; anterior-horn motor neuron degeneration), and (PMP22; demyelinating motor and sensory polyneuropathy).

Neuromuscular disorders follow diverse inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked inheritance, depending on the underlying genetic entity.

• Where neuromuscular disorders are suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

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