P.415 - Congenital myasthenia syndromes: clinical description of a pediatric cohort

Abstract

Congenital myasthenic syndromes (CMS) are a group of heterogeneous diseases caused by mutations in genes encoding for proteins involved in the neuromuscular junction that lead to an impaired signal transmission. We describe the clinical and paraclinical history of 12 patients with genetically confirmed CMS (1 CHRND, 2 AGRN, 1 DOK7, 1 MUSK, 4 RAPSN, 1 DPAGT1, 2 COLQ). Fatigable weakness was mentioned in all patients. The first symptom appeared at the latest in the first month of life (extremes: antenatal to less than 1 month of life). 4 patients had neonatal stridor. 11 patients had at least one severe respiratory decompensation with intubation. 8 had been tracheotomized. One patient died (COLQ mutation). 5 patients had arthrogryposis, 1 postural syndrome. Ptosis was reported in 11 patients. 9 of 10 patients who had reached the age of gait walked, (average age: 40 months; median age: 24 months). All patients with RAPSN mutation had clinodactyly. Electromyographic analysis showed neuromuscular junction abnormalities in 9 of 11 patients. Stimulated single fiber was always abnormal (done in 5 patients). Muscle biopsy exhibited mainly type 1 fibers predominance. Histology study of motor endplate performed in 2 patients was abnormal. Diagnostic delay was 35 months on average with a median at 9 months. From a therapeutic point of view, patients with mutations in the RAPSN gene were all significantly improved by anticholinesterasic monotherapy. A bi or triple therapy was required in the others (anticholinesterase, salbutamol / ephedrine, 3–4 DAP). Anticholinesterase drugs aggravated myasthenic syndrome in 3 patients (AGRN, DOK7 and COLQ mutations). The diagnosis of SMC is challenging due to life threatening complications, especially since a specific treatment exists.