Neuromuscular disorders

Genetic testing is clinically relevant for the following indications, including but not limited to:

Patients with clinical or biochemical features suggestive of a muscular disorder:

• Unexplained progressive muscle weakness
• Delayed motor development or loss of previously acquired motor skills
• Persistent elevation of creatine kinase (CK) levels

Families with a known hereditary muscular disorder who require:

• Diagnostic confirmation
• Carrier testing
• Predictive testing
• Prenatal diagnosis

Testing is typically requested by paediatricians, (paediatric) neurologists, and clinical geneticists.

Genetic testing is considered when a hereditary neuromuscular disorder is suspected but cannot be resolved by clinical examination, electrophysiology, and muscle imaging alone. Establishing a molecular diagnosis can help clarify prognosis and recurrence risk and guides treatment decisions, including eligibility for gene-targeted therapies.

• A pathogenic or likely pathogenic variant establishes the specific molecular diagnosis, identifying the causative gene and condition.
• A variant of uncertain significance (VUS) is an unclear finding: current evidence is insufficient to classify it as likely benign or likely pathogenic, and reanalysis can be offered after a few years as evidence accumulates.
• In other cases, no clinically significant variant is detected in the analysed genes. The presence of such a variant cannot, however, be entirely excluded: the causative change may lie in a gene not yet linked to the condition, or in a regulatory region that current methods cannot reliably capture.
• Each variant is classified according to ACMG/AMP criteria, incorporating disease- and gene-specific specifications developed by where available.

Identifying a pathogenic or likely pathogenic variant confirms the diagnosis, helps refine the prognosis, and enables anticipation of multisystem complications such as cardiac or respiratory involvement that may require regular surveillance. It can also determine eligibility for disease-specific and gene-targeted therapies, and enable predictive and carrier testing in relatives, supporting informed reproductive decision-making, including prenatal or preimplantation options. In cases with syndromic or multisystem features, care is guided by condition-specific multidisciplinary management.

is an important part of the testing process. It helps patients and families understand the purpose and implications of testing, interpreting results, and making well-informed medical decisions, while supporting physicians in providing appropriate care. Availability of genetic counselling services may vary by country. Please to check out access in your region.

Testing is performed using based multi-gene panels; for some disorders, additional diagnostic methods are required, such as repeat expansion testing.

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