Prevalence and genetic subtypes of congenital myasthenic syndromes in the pediatric population of Slovenia

Gergeli, Anja Troha; Neubauer, David; Golli, Tanja; Butenko, Tita; Loboda, Tanja; Maver, Aleš; Osredkar, Damjan

doi:10.1016/j.ejpn.2020.02.002

Cited by 16 publications

(17 citation statements)

References 20 publications

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“…A total of 48 studies fulfilled the inclusion and exclusion criteria mentioned in the methods’ section. Among the 48 articles selected [ 2 , 3 , 6 , 14 - 58 ], most are case reports, and none are randomized controlled trials. A total of 208 CMS patients with CHRNE mutations were treated with ten different pharmacological strategies in these studies.…”

Section: Resultsmentioning

confidence: 99%

“…Congenital myasthenic syndromes (CMSs) are a heterogeneous group of inherited disorders in which the safety margin of neuromuscular transmission is impaired due to mutations of proteins involved in the organization, function, maintenance, and modulation of the neuromuscular junction (NMJ) [ 1 ]. The incidence of CMSs was estimated to be 1.8 per million in a total population [ 2 , 3 ] and 2.3 to 22.2 per million in the pediatric population [ 4 - 6 ], but due to complexity of the procedures that are used to reach an accurate diagnosis, these incidence rates are likely underestimations. Currently, approximately 30 proteins are involved in various types of CMSs; these proteins are either located at the presynaptic, synaptic, or postsynaptic part of the NMJ or they undergo abnormal glycosylation (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological Strategy for Congenital Myasthenic Syndrome with CHRNE Mutations: A Meta-Analysis of Case Reports

Huang

Luo

et al. 2021

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Background: Congenital myasthenic syndromes (CMSs) are a heterogeneous group of neuromuscular disorders. Mutations of the nicotinic acetylcholine receptor epsilon subunit gene (CHRNE) are the most common causes of these disorders. CMSs are gaining increasing recognition by clinicians. However, pharmacological treatment of CMS with CHRNE mutations has only been discussed in a small number of case reports. Objective: This study aims to determine how to choose an appropriate pharmacological strategy for CMS with CHRNE mutations. Methods: A meta-analysis was performed. The PubMed, MEDLINE, Web of Science, and Cochrane Library databases were searched for studies published in English prior to June 1, 2020. The extracted data included clinical information, gene mutations, pharmacological treatment, and treatment effects. Results: A total of 48 studies and 208 CMS patients with CHRNE mutations were included in our meta-analysis. Ten different pharmacological strategies were used in these patients. Our research found that β2-adrenergic receptor agonists had the best treatment effect for CMS patients with CHRNE mutations, especially in patients with primary AChR deficiency. In addition, our analysis found no evidence that age at disease onset influences the treatment results. Conclusions: This meta-analysis provides evidence that (1) β2-adrenergic receptor agonist therapy could be the first choice of pharmacological strategy for treating CMS with CHRNE mutations; (2) a single-drug-regime, rather than a combination therapy, should be the first choice of treatment; and (3) it is never too late to initiate pharmacological treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacological Strategy for Congenital Myasthenic Syndrome with CHRNE Mutations: A Meta-Analysis of Case Reports

Huang

Luo

et al. 2021

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“…Congenital myasthenic syndrome (CMS) encompasses a heterogeneous group of inherited disorders affecting nerve transmission across the neuromuscular junction 1 . The incidence of CMS was estimated to be 1.8–22.2 per million; however, due to the complexity of the procedures that are used to obtain an accurate diagnosis, incidence rates are likely underestimated 2–6 . Currently, more than 30 proteins are known to be involved in various types of CMS.…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological‐genetic features of congenital myasthenic syndrome from a Chinese neuromuscular centre

Huang

Duan

et al. 2022

J Cellular Molecular Medi

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Congenital myasthenic syndrome (CMS) encompasses a heterogeneous group of inherited disorders affecting nerve transmission across the neuromuscular junction. 1 The incidence of CMS was estimated to be 1.8-22.2 per million; however, due to the complexity of the procedures that are used to obtain an accurate diagnosis, incidence rates are likely underestimated. [2][3][4][5][6] Currently, more than 30 proteins are known to be involved in various types of CMS. Generally, proteins related to CMS are located at the presynaptic, synaptic or postsynaptic region of the neuromuscular junction (NMJ), or they undergo abnormal glycosylation. Among them, mutations in CHRNE, RAPSN and COLQ are the most frequent, accounting for half of CMS cases in a large-scale analysis including 680 patients. 7 Mutations in CMS-related genes can be used to accurately diagnose CMS.Generally, CMS is characterized by fatigability or skeletal muscle weakness with an onset at birth to early childhood.Electromyographic findings of a decrease in repetitive nerve stimulation (RNS) and increased jitter on single-fibre electromyography (EMG) may support the diagnosis. 8 Genetic testing or whole-exome sequencing could establish a diagnosis of CMS and guide pharmacological treatment. For example, β2-receptor agonist therapy could

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“…Congenital myasthenic syndromes (CMS) are a group of diseases in which the signal transduction at the neuromuscular junction (NMJ) is disrupted by congenital mutations of genes. In a recent review, the prevalence of this disease was estimated to be 25-125 individuals per 1 million people (Troha Gergeli et al, 2020). This indicates that the disease is not extremely rare, and there is a likelihood of many undiagnosed patients.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, approximately 40 different causative genes have been identified. CMS are classified as presynaptic (CHAT, LC18A3, MUNC13-1, SNAP25, SYB1, SYT2, SLC5A7, VAMP1), synaptic (COLQ, COL13A1, LAMA5, LAMB2), postsynaptic (CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, FCCMS, SCCMS, DOK7, MUSK, MYO9A, AGRN, LRP4, PREPL, SCN4A, RAPSN, PLEC1), protein glycosylation defects (ALG2, ALG14, DPAGT1, GFPT1, GMPPB), and other syndromes (PREPL, SCL25A1, BIN1, MTM1, DNM2, TPM3, RYR) (Engel, 2018;Troha Gergeli et al, 2020). The abnormalities in the gene products lead to defects in acetylcholine resynthesis or vesicular packaging, terminal acetylcholine esterase (AChE) deficiency, slow channel syndrome, acetylcholine receptor (AChR) deficiency, low-affinity fast AChR channel syndrome, and skeletal muscle sodium channel mutation.…”

Section: Introductionmentioning

confidence: 99%

The longest reported sibling survivors of a severe form of congenital myasthenic syndrome with the ALG14 pathogenic variant

Katata

Uneoka

Saijyo

et al. 2021

American J of Med Genetics Pt A

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Congenital myasthenic syndromes (CMS) is a group of diseases that causes abnormalities at the neuromuscular junction owing to genetic anomalies. The pathogenic variant in ALG14 results in a severe pathological form of CMS causing end-plate acetylcholine receptor deficiency. Here, we report the cases of two siblings with CMS associated with a novel variant in ALG14. Immediately after birth, they showed hypotonia and multiple joint contractures with low Apgar scores. Ptosis, low-set ears, and high-arched palate were noted. Deep tendon reflexes were symmetrical. They showed worsening swallowing and respiratory problems; hence, nasal feeding and tracheotomy were performed. Cranial magnetic resonance imaging scans revealed delayed myelination and cerebral atrophy. Exome sequencing indicated that the siblings had novel compound heterozygous missense variants, c.590T>G (p.Val197Gly) and c.433G>A (p.Gly145Arg), in exon 4 of ALG14. Repetitive nerve stimulation test showed an abnormal decrease in compound muscle action potential. After treatment with pyridostigmine, the time off the respirator increased. Their epileptic seizures were well controlled by anti-epileptic drugs. Their clinical course is stable even now at the ages of 5 and 2 years, making them the longest reported survivors of a severe form of CMS with the ALG14 variant thus far.

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Prevalence and genetic subtypes of congenital myasthenic syndromes in the pediatric population of Slovenia

Cited by 16 publications

References 20 publications

Pharmacological Strategy for Congenital Myasthenic Syndrome with CHRNE Mutations: A Meta-Analysis of Case Reports

Pharmacological Strategy for Congenital Myasthenic Syndrome with CHRNE Mutations: A Meta-Analysis of Case Reports

Clinicopathological‐genetic features of congenital myasthenic syndrome from a Chinese neuromuscular centre

The longest reported sibling survivors of a severe form of congenital myasthenic syndrome with the ALG14 pathogenic variant

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