Résumé :
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Communication n° 188 Introduction: The majority of postsynaptic congenital myasthenic syndromes (CMS) result from deficiency of acetylcholine receptors (AChR) at the endplate, due to mutations of the gene encoding the epsilon subunit of the AChR (CHRNE).Synaptic CMS are caused by mutations of the gene encoding the collagenic tail subunit of endplate acetylcholinesterase (COLQ). We report tree patients affected by mutations in the CHRNE gene and another with mutation in the COLQ gene. Patients, method and results: The current age of the two girls and the boy with CHRNE mutations are respectively 8, 12 and 14 year old. Only the boy presented clinical symptoms at the neonatal period with decremented response to repetitive nerve stimulation and no clear response to AChE inhibitors. By sequencing of the CHRNE gene a heterozygous missense mutation L269F acting as slow-channel syndrome was identified. The two girls carried the same heterozygous frameshift mutations: 70insG in exon 2 and 1293insG in exon of the CHRNE gene.Slight ptosis were apparent at 12 and 22 months and the ophtalmoplegia appeared at 36 and 12 months respectively. The response to AChE inhibitors was evident at the age of 4 years in one being slightly in the other. The 8 month old male patient with mutation in the COLQ gene presented with feeding difficulties, hypotonic, slight ptosis and fatigability. He showed decrement with repetitive stimulation and clinical worsening with AChE inhibitors. The genetic studies revealed a homozygous frameshift mutation (158insC) in exon 2. This mutation has not been described in the literature so far. Conclusions: Only half of the patients presented symptoms and responses compatibles with CMS before one year of age. The slight ptosis, the delayed appearance of the ophtalmoplegia and the mild improvement with AChE inhibitors in some of them hampered diagnosis of CMS. The genotype characterization helps to adequate therapy.
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