Long-Term Follow-Up of Patients with Congenital Myasthenic Syndromes: What Do We Learn?

Background: Congenital myasthenic syndromes (CMS) form a heterogeneous group of disorders caused by defects of the neuromuscular transmission. The clinical picture of CMS varies widely between mild and life-limiting forms. Until now, data of long-term follow-up are rare.

Patients and Methods: A retrospective analysis (clinical, genetic, and treatment data) of 31 patients with CMS was performed. Additionally, a standardized, not yet validated test to examine 21 patients has been used.

Results: We identified 31 patients with 9 different genetic defects of CMS. We formed different phenotypic groups in consideration of clinical symptoms; 18/31 patients presented ocular problems; 21/31 patients had bulbar symptoms at the beginning. Transient respiratory problems were found in 19/31 patients at onset; 6 had persistent respiratory problems; 18/31 patients showed first symptoms of neonatal (CHRNE [3/7], RAPSN [7/8], CHAT [3/5], COLQ [2/3], CHRND [1/1], CHRNB1 [1/1] mutations and “fast-channel” syndrome [1/1]); 12/18 patients later (between 2 months and 6 years). Despite an early and appropriate treatment, following long-term problems were identified: 12/18 patients suffered from difficulties in eating, 11/31 used a wheelchair, scoliosis developed in 9/31 patients, and 5/31 patients needed respiratory support.

Conclusion: In patients with CMS, there is no direct genotype-phenotype correlation; nonetheless, in this cohort we identified specific phenotypic groups. Not all patients with CMS benefit in the same way from treatment. Some patients developed irrespective of genetic background and despite an appropriate and early therapy long-term problems. The applied test highlighted problems in ocular, bulbar, cervical, and limb muscle additional to neurological examination.