Congenital myasthenic syndromes in adults: clinical features, diagnosis and long-term prognosis

作者：Julian Theuriet, Marion Masingue, Anthony Béhin, Ana Ferreiro, Guillaume Bassez, Pauline Jaubert, Oriana Tarabay, Frédéric Fer, Antoine Pégat, Françoise Bouhour, Juliette Svahn, Philippe Petiot, Laurentiu Jomir, G Chauplannaz, Catherine Cornut-Chauvinc, Véronique Manel, Emmanuelle Salort‐Campana, Shahram Attarian, Étienne Fortanier, Annie Verschueren, Ludivine Kouton, Jean‐Philippe Camdessanché, Céline Tard, Armelle Magot, Yann Péréon, Jean‐Baptiste Noury, Marie-Christine Minot-Myhié, Maud Perié, Frédéric Taithe, Yacine Farhat, Anne-Laure Millet, Pascal Cintas, Guilhem Solé, Marco Spinazzi, Florence Esselin, Dimitri Renard, Sabrina Sacconi, Andra Ezaru, Edoardo Malfatti, Martial Mallaret, Laurent Magy, Eva Diab, P. Merle, Maud Michaud, Maxime Fournier, Aleksandra Nadaj Pakleza, Jean‐Baptiste Chanson, Claire Lefeuvre, Pascal Laforêt, Pascale Richard, Damien Sternberg, Rocío‐Nur Villar‐Quiles, Tanya Stojkovic, B. Eymard · 发表于：Brain · 年份：2024 · DOI：10.1093/brain/awae124 · 被引用次数：22 · 研究领域：Myasthenia Gravis and Thymoma、Cellular transport and secretion、Ubiquitin and proteasome pathways

Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous diseases caused by mutations affecting neuromuscular transmission. Even if the first symptoms mainly occur during childhood, adult neurologists must confront this challenging diagnosis and manage these patients throughout their adulthood. However, long-term follow-up data from large cohorts of CMS patients are lacking, and the long-term prognosis of these patients is largely unknown. We report the clinical features, diagnostic difficulties, and long-term prognosis of a French nationwide cohort of 235 adult patients with genetically confirmed CMS followed in 23 specialized neuromuscular centres. Data were retrospectively analysed. Of the 235 patients, 123 were female (52.3%). The diagnosis was made in adulthood in 139 patients, 110 of whom presented their first symptoms before the age of 18. Mean follow-up time between first symptoms and last visit was 34 years [standard deviation (SD) = 15.1]. Pathogenic variants were found in 19 disease-related genes. CHRNE-low expressor variants were the most common (23.8%), followed by variants in DOK7 (18.7%) and RAPSN (14%). Genotypes were clustered into four groups according to the initial presentation: ocular group (CHRNE-LE, CHRND, FCCMS), distal group (SCCMS), limb-girdle group (RAPSN, COLQ, DOK7, GMPPB, GFPT1), and a variable-phenotype group (MUSK, AGRN). The phenotypical features of CMS did not change throughout life. Only four genotypes had a propor...