[Congenital Myasthenic Syndromes]

Area of Science:

• Neurology
• Genetics
• Molecular Biology

Context:

• Congenital myasthenic syndromes (CMS) represent a group of rare genetic disorders.
• These syndromes arise from defects in neuromuscular signal transmission.
• Pathogenic variants in 36 genes have been identified as causative agents.

Purpose:

• To provide an overview of Congenital Myasthenic Syndromes (CMS).
• To highlight recently identified forms of CMS, including TOR1AIP1-CMS, CHD8-CMS, PURA-CMS, and TEFM-CMS.
• To emphasize the importance of genetic analysis for diagnosis and treatment.

Summary:

• CMS are characterized by impaired neuromuscular signal transmission due to genetic variants.
• Both autosomal recessive and dominant inheritance patterns exist, with some dominant forms presenting in adulthood.
• Differential diagnosis should consider CMS in congenital myopathies, especially with muscle hypotrophy or atypical myasthenic features.
• Diagnostic tools include repetitive nerve stimulation and muscle biopsy, with elevated serum CK in some cases.
• Identification of causative gene variants is essential for targeted therapies.

Impact:

• Facilitates differential diagnosis of congenital myopathies and other neuromuscular conditions.
• Underscores the need for genetic testing in suspected CMS cases.
• Informs clinicians about the diverse genetic basis and clinical presentations of CMS.
• Highlights the availability of rational therapies, contingent on accurate genetic diagnosis.