Congenital myasthenic syndromes in a Southeast Asian Adult Neurology Clinic: A long road to diagnosis and therapy
Congenital myasthenic syndromes (CMS) are rare genetic disorders caused by pathogenic variants in proteins expressed at the neuromuscular junction. Current literature surrounding adult CMS remains limited, primarily derived from Western cohorts. We present a Southeast Asian cohort of adult patients with CMS evaluated at a tertiary neuromuscular center. This is a retrospective cohort study of adults with CMS diagnosed at our center. Patient demographics, clinical and electrodiagnostic features, autoantibodies, and molecular results were reported. From a cohort of 639 adults with clinical myasthenia or congenital myopathy, we identified seven (1.1%) with CMS. Four had adult onset of symptoms, of whom two manifested in late adulthood. Six were initially misdiagnosed. A genetic diagnosis was achieved in five patients with a median diagnostic delay of 17.8 years (range 1- 38 years). Three patients were identified to have COLQ-CMS, one patient with CHRNE-CMS, and one patient with CHRNA1-CMS. Two patients with COLQ-CMS had a multiphasic clinical course. We reclassified two variants as likely pathogenic based on the American College of Medical Genetics criteria. CMS is challenging to diagnose in the adult neurology setting. We discuss the clinical and genotypic features of seven adults with CMS.
Congenital myasthenic syndromes (CMS) are rare genetic disorders caused by pathogenic variants in proteins expressed at the neuromuscular junction. Current literature surrounding adult CMS remains limited, primarily derived from Western cohorts. We present a Southeast Asian cohort of adult patients with CMS evaluated at a tertiary neuromuscular center. This is a retrospective cohort study of adults with CMS diagnosed at our center. Patient demographics, clinical and electrodiagnostic features, autoantibodies, and molecular results were reported. From a cohort of 639 adults with clinical myasthenia or congenital myopathy, we identified seven (1.1%) with CMS. Four had adult onset of symptoms, of whom two manifested in late adulthood. Six were initially misdiagnosed. A genetic diagnosis was achieved in five patients with a median diagnostic delay of 17.8 years (range 1- 38 years). Three patients were identified to have COLQ-CMS, one patient with CHRNE-CMS, and one patient with CHRNA1-CMS. Two patients with COLQ-CMS had a multiphasic clinical course. We reclassified two variants as likely pathogenic based on the American College of Medical Genetics criteria. CMS is challenging to diagnose in the adult neurology setting. We discuss the clinical and genotypic features of seven adults with CMS.
Duke-NUS Graduate Medical School, Singapore