An observational longitudinal study of congenital myasthenic syndromes.

Congenital Myasthenic Syndromes (CMS) are a group of inherited disorders characterised by fatigable muscle weakness. There are currently no validated outcome measures in CMS. We conducted a prospective exploratory observational study in 49 CMS patients. The primary aim was to explore relevant and reliable outcome measures for assessing and monitoring change. Assessments included Quantitative Myasthenia Gravis score, Myasthenia Gravis Activities of Daily Living, six-minute-walk-test and sit to stand in one minute, in addition to others. Patients were seen 2-4 times over a 2-year period. Median age was 25.5 (range 1-72) years. Subtypes included AChR-deficiency (n = 15), AGRN-DOK7 clustering complex (n = 15), RAPSN (n = 6), COLQ (n = 5), others (n = 8). Ptosis was highest in AChR-deficiency and limb fatigue was highest in AGRN-DOK7 and COLQ. Median sit to stand in one minute was 22 (range 6-45), median total distance walked in six-minute-walk-test was 434 metres (range 0-711 m). A correlation was noted between sit to stand and six-minute-walk-test (R² = 0.291, p-value <0.001) and between total Quantitative Myasthenia Gravis and Myasthenia Gravis Activities of Daily Living scores (R² = 0.2851, p-value <0.001). This is the first study exploring the use of outcome measures in a CMS population, highlighting the variability in fatigue across CMS subtypes and the limitations of outcome measures validated in myasthenia gravis for CMS.