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. 2022 Mar;29(3):833-842.
doi: 10.1111/ene.15173. Epub 2021 Nov 17.

Congenital myasthenic syndrome: Correlation between clinical features and molecular diagnosis

Eduardo P Estephan  1   2   3 , Antonio A Zambon  1 , Rachel Thompson  4 , Kiran Polavarapu  4 , Danny Jomaa  4   5 , Ana Töpf  6 , Paulo V P Helito  7 , Carlos O Heise  1 , Cristiane A M Moreno  1   2   3 , André M S Silva  1 , Joao A Kouyoumdjian  8 , Maria da Penha Morita  8 , Umbertina C Reed  1 , Hanns Lochmüller  4   9   10   11   12 , Edmar Zanoteli  1
Affiliations

Congenital myasthenic syndrome: Correlation between clinical features and molecular diagnosis

Eduardo P Estephan et al. Eur J Neurol. 2022 Mar.

Abstract

Objectives: To present phenotype features of a large cohort of congenital myasthenic syndromes (CMS) and correlate them with their molecular diagnosis.

Methods: Suspected CMS patients were divided into three groups: group A (limb, bulbar or axial weakness, with or without ocular impairment, and all the following: clinical fatigability, electrophysiology compatible with neuromuscular junction involvement and anticholinesterase agents response), group B (limb, bulbar or axial weakness, with or without ocular impairment, and at least one of additional characteristics noted in group A) and group C (pure ocular syndrome). Individual clinical findings and the clinical groups were compared between the group with a confirmed molecular diagnosis of CMS and the group without molecular diagnosis or with a non-CMS molecular diagnosis.

Results: Seventy-nine patients (68 families) were included in the cohort: 48 in group A, 23 in group B and 8 in group C. Fifty-one were considered confirmed CMS (30 CHRNE, 5 RAPSN, 4 COL13A1, 3 DOK7, 3 COLQ, 2 GFPT1, 1 CHAT, 1 SCN4A, 1 GMPPB, 1 CHRNA1), 7 probable CMS, 5 non-CMS and 16 unsolved. The chance of a confirmed molecular diagnosis of CMS was significantly higher for group A and lower for group C. Some individual clinical features, alterations on biopsy and electrophysiology enhanced specificity for CMS. Muscle imaging showed at least mild alterations in the majority of confirmed cases, with preferential involvement of soleus, especially in CHRNE CMS.

Conclusions: Stricter clinical criteria increase the chance of confirming a CMS diagnosis, but may lose sensitivity, especially for some specific genes.

Keywords: congenital myasthenic syndromes; muscle MRI; neuromuscular disorders; neuromuscular junction; phenotype/genotype correlation.

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References

REFERENCES

    1. Rodríguez Cruz PM, Palace J, Beeson D. The neuromuscular junction and wide heterogeneity of congenital myasthenic syndromes. Int J Mol Sci. 2018;19(6):1677. doi:10.3390/ijms19061677
    1. McMacken G, Abicht A, Evangelista T, Spendiff S, Lochmüller H. The increasing genetic and phenotypical diversity of congenital myasthenic syndromes. Neuropediatrics. 2017;48(4):294-308. doi:10.1055/s-0037-1602832
    1. Janas JS, Barohn RJ. A clinical approach to the congenital myasthenic syndromes. J Child Neurol. 1995;10(2):168-169. doi:10.1177/088307389501000221
    1. Evangelista T, Hanna M, Lochmüller H. Congenital myasthenic syndromes with predominant limb girdle weakness. J Neuromuscul Dis. 2015;2(Suppl 2):S21-S29.
    1. Engel AG, Lambert EH, Mulder DM, et al. A newly recognized congenital myasthenic syndrome attributed to a prolonged open time of the acetylcholine-induced ion channel. Ann Neurol. 1982;11(6):553-569.

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