Dataset Information

Clinical and Genetic Spectrum of Myotonia Congenita in Turkish Children.

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.

SUBMITTER: Oz Tuncer G

PROVIDER: S-EPMC10578252 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Clinical and Genetic Spectrum of Myotonia Congenita in Turkish Children.

Öz Tunçer Gökçen G Sanri Aslıhan A Aydin Seren S Hergüner Özlem M ÖM Özgün Nezir N Kömür Mustafa M İçağasioğlu Dilara F DF Toker Rabia Tütüncü RT Yilmaz Sanem S Arslan Elif Acar EA Güngör Mesut M Kutluk Gültekin G Erol İlknur İ Mert Gülen Gül GG Polat Burçin Gönüllü BG Aksoy Ayşe A

Journal of neuromuscular diseases 20230101 5

<h4>Background</h4>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.<h4>Objective</h4>The study aimed to describe the clinical and genetic spectrum of Myotonia congenita in a large pediatric cohort.<h4>Methods</h4>Demographic, genetic, and clinical data of the patients aged under 18 years at time of first clinical attendance from 11 centers in differ ...[more]

PMID: 37355912

Similar Datasets

Project description:Background: CLCN1-related myotonia congenita (MC) is one of the most common forms of non-dystrophic myotonia, in which muscle relaxation is delayed after voluntary or evoked contraction. However, there is limited data of clinical and molecular spectrum of MC patients in China. Patients and Methods: Five patients with myotonia congenita due to mutations in CLCN1 gene were enrolled, which were identified through trio-whole-exome sequencing or panel-based next-generation sequencing test. The clinical presentation, laboratory data, electrophysiological tests, muscular pathology feature, and genetic results were collected and reviewed. We also searched all previously reported cases of MC patients with genetic diagnosis in Chinese populations, and their data were reviewed. Results: The median onset age of five patients was 3.0 years old, ranging from 1.0 to 5.0 years old, while the median age of admit was 5.0 years old, ranging from 3.5 to 8.8 years old. Five patients complained of muscle stiffness when rising from chairs or starting to climb stairs (5/5, 100.0%), four patients complained of delayed relaxation of their hands after forceful grip (4/5, 80.0%), all of which improved with exercise (warm-up phenomenon) (5/5, 100%). Electromyogram was conducted in five patients, which all revealed myotonic change (100%). Genetic tests revealed nine potential disease-causing variants in CLCN1 gene, including two novel variants: c.962T>A (p.V321E) and c.1250A>T (p.E417V). Literature review showed that 43 MC Chinese patients with genetic diagnosis have been reported till now (including our five patients). Forty-seven variants in CLCN1 gene were found, which consisted of 33 missense variants, 6 nonsense variants, 5 frame-shift variants, and 3 splicing variants. Variants in exon 8, 15, 12, and 16 were most prevalent, while the most common variants were c.892G>A (p.A298T) (n = 9), c.139C>T (p.R47W) (n = 3), c.1205C>T(p.A402V) (n = 3), c.1657A>T (p.I553F) (n = 3), c.1679T>C (p.M560T) (n = 3), c.350A>G (p.D117G) (n = 2), c.762C>G (p.C254W) (n = 2), c.782A>G (P.Y261C) (n = 2), and c.1277C>A (p.T426N) (n = 2). Conclusion: Our results reported five CLCN1-related MC patients, which expanded the clinical and genetic spectrum of MC patients in China. Based on literature review, 43MC Chinese patients with genetic diagnosis have been reported till now, and variants in exon eight were most prevalent in Chinese MC patients while c.892G>A (p.A298T) was probably a founder mutation.

Dataset Information

Clinical and Genetic Spectrum of Myotonia Congenita in Turkish Children.

Background

Objective

Methods

Results

Conclusions

Publications

Clinical and Genetic Spectrum of Myotonia Congenita in Turkish Children.

Similar Datasets

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