Mild phenotype of CHAT -associated congenital myasthenic syndrome: case series.

Autor:	Murtazina A; Research Centre for Medical Genetics, Moscow, Russia., Borovikov A; Research Centre for Medical Genetics, Moscow, Russia., Marakhonov A; Research Centre for Medical Genetics, Moscow, Russia., Sharkov A; Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Moscow, Russia.; Genomed Ltd., Moscow, Russia., Sharkova I; Research Centre for Medical Genetics, Moscow, Russia., Mirzoyan A; Republican Research and Clinical Center of Neurology and Neurosurgery, Minsk, Belarus., Kulikova S; Republican Research and Clinical Center of Neurology and Neurosurgery, Minsk, Belarus., Ganieva R; Research Centre for Medical Genetics, Moscow, Russia., Zabnenkova V; Research Centre for Medical Genetics, Moscow, Russia., Ryzhkova O; Research Centre for Medical Genetics, Moscow, Russia., Nikitin S; Research Centre for Medical Genetics, Moscow, Russia., Dadali E; Research Centre for Medical Genetics, Moscow, Russia., Kutsev S; Research Centre for Medical Genetics, Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Frontiers in pediatrics [Front Pediatr] 2024 Jan 18; Vol. 12, pp. 1280394. Date of Electronic Publication: 2024 Jan 18 (Print Publication: 2024).
DOI:	10.3389/fped.2024.1280394
Abstrakt:	Congenital myasthenic syndrome with episodic apnea is associated with pathogenic variants in the CHAT gene. While respiratory disorders and oculomotor findings are commonly reported in affected individuals, a subset of patients only present with muscle weakness and/or ptosis but not apneic crises. In this case series, we describe five individuals with exercise intolerance caused by single nucleotide variants in the CHAT gene. The age of onset ranged from 1 to 2.5 years, and all patients exhibited a fluctuating course of congenital myasthenic syndrome without disease progression over several years. Notably, these patients maintained a normal neurological status, except for the presence of abnormal fatigability in their leg muscles following prolonged physical activity. We conducted a modified protocol of repetitive nerve stimulation on the peroneal nerve, revealing an increased decrement in amplitude and area of compound muscle action potentials of the tibialis anterior muscle after 15-20 min of exercise. Treatment with 3,4-diaminopyridine showed clear improvement in two children, while one patient experienced severe adverse effects and is currently receiving a combination of Salbutamol Syrup and pyridostigmine with slight positive effects. Based on our findings and previous cases of early childhood onset with muscle fatigability as the sole manifestation, we propose the existence of a mild phenotype characterized by the absence of apneic episodes. Competing Interests: AS is employed by Genomed Ltd., Russia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2024 Murtazina, Borovikov, Marakhonov, Sharkov, Sharkova, Mirzoyan, Kulikova, Ganieva, Zabnenkova, Ryzhkova, Nikitin, Dadali and Kutsev.)
Databáze:	MEDLINE
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