J Genet Med.  2020 Dec;17(2):73-78. 10.5734/JGM.2020.17.2.73.

Wide heterogeneity of congenital myasthenic syndromes: analysis of clinical experience in a tertiary center

• Cho A
• Kim SY
• Lee JS
• Lim BC
• Kim H
• Hwang H
• Chae JH

• KMID: 2509989
• DOI: http://doi.org/10.5734/JGM.2020.17.2.73

Abstract

Purpose
Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of disorders characterized by impaired neuromuscular transmission. This study aims to provide the clue for early diagnosis and improved therapeutic strategies in CMS.
Materials and Methods
Through the targeted panel sequencing including twenty CMS causative genes, eleven patients were genetically confirmed and enrolled in this study. A retrospective medical record review was carried out for the clinical and laboratory data analysis.
Results
The age of patients ranged from 5 to 23 years, with the median age of 16 years. The peak age at onset of symptoms was the neonatal period. Seven out of the eleven patients were symptomatic at birth. The most commonly reported initial finding was generalized hypotonia with poor sucking and crying. Mean time to accurate diagnosis was 9.3±5.0 years. Total fifteen different variants in seven genes associated with CMS (DOK7, AGRN, RAPSN, CHRNE, COLQ, SLC5A7, and GFPT1) were identified.
Conclusion
We describe the clinical and genetic characteristics of CMS patients and treatment outcome in a single tertiary center. High clinical suspicion and timely molecular diagnosis is particularly important for the tailored therapy to maximize clinical improvement in CMS.

Keyword

Congenital myasthenic syndrome; Therapeutic effect; Next generation sequencing