Long-term follow-up of patients with congenital myasthenic syndrome caused by COLQ mutations

• Published in: Neuromuscular disorders : NMD 2012-04, Vol.22 (4), p.318-324
• Main Authors: Wargon, I, Richard, P, Kuntzer, T, Sternberg, D, Nafissi, S, Gaudon, K, Lebail, A, Bauche, S, Hantaï, D, Fournier, E, Eymard, B, Stojkovic, T
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Acetylcholinesterase - deficiency; Acetylcholinesterase - genetics; Acetylcholinesterase - metabolism; Adolescent; Adult; Age; Cellular Biology; Child; Child, Preschool; Collagen; Collagen - genetics; Collagen - metabolism; COLQ; Congenital defects; Congenital myasthenic syndrome; Data processing; Disease Progression; Ephedrine; esterase; Female; Follow-Up Studies; Genetic Association Studies; Hereditary diseases; Humans; Life Sciences; Male; Middle Aged; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscles; Mutation; Mutation - genetics; Mutations; Myasthenia; Myasthenic Syndromes, Congenital - diagnosis; Myasthenic Syndromes, Congenital - genetics; Neurology; Neuromuscular junctions; neuromuscular system; Phenotype; Pregnancy; Puberty; Recurrence; Relapse; Subcellular Processes; Treatment Outcome; Young Adult
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2011.09.002

Abstract Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous inherited disorders characterized by impaired neuromuscular transmission. Mutations in the acetylcholinesterase (AChE) collagen-like tail subunit gene ( COlQ ) cause recessive forms of synaptic CMS with end plate AChE deficiency. We present data on 15 COLQ -mutant CMS carrying 16 different mutations (9 novel ones identified) followed-up for an average period of 10 years. The mean age at the first examination was 19 years old (range from 3 to 48). We report relapses during short or long-term periods characterized by worsening of muscle weakness sometimes associated with respiratory crises. All the relapses ended spontaneously or with 3–4 DAP or ephedrine with no residual impairment. The triggering factors identified were esterase inhibitors, effort, puberty or pregnancy highlighting the importance of hormonal factors. There was no genotype–phenotype correlation. At the end of the follow-up, 80% of patients were ambulant and 87% of patients had no respiratory trouble in spite of severe relapses.