PP09.7 - 2375: Phenotypic heterogeneity in two large Roma families with a congenital myasthenic syndrome due to CHRNE1267delG mutation. A long-term follow-up

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• 作者：D. Natera-de Benito ; J. Domí ; nguez-Carral ; N. Muelas ; J. Colomer ; A. Nascimento ; T. Jaijo ; R. Arteaga ; C. Ortez ; J. Ví ; lchez
• 刊名：European Journal of Paediatric Neurology
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：19
• 期：supp_S1
• 页码：S66
• 全文大小：83 K

文摘

Mutations in CHRNE are the cause of approximately 50% of CMS. ɛ1267delG frameshifting mutation is present on at least one allele of 60% of patients with CHRNE mutations. We here present a description of the clinical features of the CMS caused by the homozygous 1267delG mutation in the AChR ɛ subunit in 13 members of two large Roma kindreds.

Methods

Thirteen patients from two unrelated families were followed up over a mean period of 9.9 years.

Results

We trace 65 and 108 members in six and seven generations of each family, respectively. We interviewed and examined 13 clinically affected family members, 9 women and 4 men. Disease onset ranged from first weeks after birth to 12 years (mean 3.7 years; median 2 years). Ophthalmoparesis was observed in nine patients and subjective diplopia was present in all thirteen cases. Bilateral symmetric ptosis was found in ten patients. Facial weakness was encountered in eleven patients. Mild bulbar symptoms were reported in ten patients. Proximal muscle weakness was found in ten patients. It entailed restricted ambulation in 8 patients. A rapid progression of the disease was noted in two patients. The disease course have remained stable in eight patients. Three patients had a significant fluctuation of their symptoms. All the thirteen patients responded positively to pyridostigmine. In 6 patients, addition of 3,4-diaminopyridine resulted in further clinical improvement.

Conclusion

Founder European Roma mutation 1267delG leads to an heterogeneous phenotype with a varying severity. It is further characterized by ophthalmoplegia and a good response to anticholinesterase drugs and 3,4-DAP; but also by ptosis, facial weakness, bulbar symptoms, neck muscle weakness, and proximal muscle weakness that entails the loss of ambulation in 63% of our adult patients. The disease course can be stable but also progressive in nearly 40%, with or without fluctuations.