PDF(Pubmed)
Abstract：
BACKGROUND: Myotonia congenita is the most common form of nondystrophic myotonia and is caused by Mendelian inherited mutations in the CLCN1 gene encoding the voltage-gated chloride channel of skeletal muscle.
OBJECTIVE: The study aimed to describe the clinical and genetic spectrum of Myotonia congenita in a large pediatric cohort.
METHODS: Demographic, genetic, and clinical data of the patients aged under 18 years at time of first clinical attendance from 11 centers in different geographical regions of Türkiye were retrospectively investigated.
RESULTS: Fifty-four patients (mean age:15.2 years (±5.5), 76% males, with 85% Becker, 15% Thomsen form) from 40 families were included. Consanguineous marriage rate was 67%. 70.5% of patients had a family member with Myotonia congenita. The mean age of disease onset was 5.7 (±4.9) years. Overall 23 different mutations (2/23 were novel) were detected in 52 patients, and large exon deletions were identified in two siblings. Thomsen and Becker forms were observed concomitantly in one family. Carbamazepine (46.3%), mexiletine (27.8%), phenytoin (9.3%) were preferred for treatment.
CONCLUSIONS: The clinical and genetic heterogeneity, as well as the limited response to current treatment options, constitutes an ongoing challenge. In our cohort, recessive Myotonia congenita was more frequent and novel mutations will contribute to the literature.
OBJECTIVE: The study aimed to describe the clinical and genetic spectrum of Myotonia congenita in a large pediatric cohort.
METHODS: Demographic, genetic, and clinical data of the patients aged under 18 years at time of first clinical attendance from 11 centers in different geographical regions of Türkiye were retrospectively investigated.
RESULTS: Fifty-four patients (mean age:15.2 years (±5.5), 76% males, with 85% Becker, 15% Thomsen form) from 40 families were included. Consanguineous marriage rate was 67%. 70.5% of patients had a family member with Myotonia congenita. The mean age of disease onset was 5.7 (±4.9) years. Overall 23 different mutations (2/23 were novel) were detected in 52 patients, and large exon deletions were identified in two siblings. Thomsen and Becker forms were observed concomitantly in one family. Carbamazepine (46.3%), mexiletine (27.8%), phenytoin (9.3%) were preferred for treatment.
CONCLUSIONS: The clinical and genetic heterogeneity, as well as the limited response to current treatment options, constitutes an ongoing challenge. In our cohort, recessive Myotonia congenita was more frequent and novel mutations will contribute to the literature.
摘要：
背景：先天性肌强直是最常见的非营养不良性肌强直形式，由编码骨骼肌电压门控氯通道的CLCN1基因的孟德尔遗传突变引起。
目的：该研究旨在描述一个大型儿科队列中先天性肌强直症的临床和遗传谱。
方法：人口统计学，遗传,回顾性调查了来自Türkiye不同地理区域的11个中心的首次临床就诊时年龄在18岁以下的患者的临床数据。
结果：54名患者（平均年龄：15.2岁（±5.5），76%的男性,85%的贝克尔,包括来自40个家庭的15％汤姆森形式）。近亲婚姻率为67%。70.5％的患者有一个先天性肌强直症的家庭成员。平均发病年龄为5.7(±4.9)岁。在52例患者中检测到23种不同的突变（2/23是新的），在两个兄弟姐妹中发现了大量外显子缺失。在一个家庭中同时观察到汤姆森和贝克尔形式。卡马西平(46.3%),美西律（27.8%），优选苯妥英(9.3%)用于治疗.
结论：临床和遗传异质性，以及对当前治疗方案的反应有限，构成了持续的挑战。在我们的队列中，隐性先天性肌强直症更为频繁，新的突变将为文献做出贡献。
目的：该研究旨在描述一个大型儿科队列中先天性肌强直症的临床和遗传谱。
方法：人口统计学，遗传,回顾性调查了来自Türkiye不同地理区域的11个中心的首次临床就诊时年龄在18岁以下的患者的临床数据。
结果：54名患者（平均年龄：15.2岁（±5.5），76%的男性,85%的贝克尔,包括来自40个家庭的15％汤姆森形式）。近亲婚姻率为67%。70.5％的患者有一个先天性肌强直症的家庭成员。平均发病年龄为5.7(±4.9)岁。在52例患者中检测到23种不同的突变（2/23是新的），在两个兄弟姐妹中发现了大量外显子缺失。在一个家庭中同时观察到汤姆森和贝克尔形式。卡马西平(46.3%),美西律（27.8%），优选苯妥英(9.3%)用于治疗.
结论：临床和遗传异质性，以及对当前治疗方案的反应有限，构成了持续的挑战。在我们的队列中，隐性先天性肌强直症更为频繁，新的突变将为文献做出贡献。
