ABSTRACT
BACKGROUND: Congenital myasthenic syndromes (CMSs) are a group of clinically and genetically heterogeneous inherited disorders of the neuromuscular junction. Mutations in the acetylcholine transferase (CHAT) gene cause a pre-synaptic CMS, typically associated with episodic apnoea and worsening of myasthenic symptoms during crises caused by infections, fever or stress. Between crises symptoms may be mild and variable. Acetylcholinesterase - inhibitor therapy is reported to improve clinical symptoms and reduce crises. PATIENTS AND METHODS: We present data on the long-term follow-up of 11 patients with a congenital myasthenic syndrome due to nine different CHAT mutations; ten of the patients have not been previously reported. RESULTS AND CONCLUSIONS: Manifestation varied from the neonatal period to the age of two years, follow-up time from nine months to 12 years. This cohort of CHAT patients studied here enabled us to describe two distinct phenotypes: The neonatal-onset group suffers from apnoeic crises, respirator dependency and bulbar weakness. Apnoea should be carefully distinguished from seizures; a CMS should be taken into account early to start appropriate therapy. Infantile-onset patients show mild permanent weakness, but experience apnoeic crises and worsening which resolve with Acetylcholinesterase - inhibitor treatment. However, after several years of treatment proximal muscle strength may decrease and lead to wheelchair dependency despite the continuation of Acetylcholinesterase - inhibitor therapy.
