Congenital myasthenic syndrome in Israel: Genetic and clinical characterization

Aharoni, Sharon; Sadeh, Menachem; Shapira, Yehuda; Edvardson, Simon; Daana, Muhannad; Dor-Wollman, Talia; Mimouni-Bloch, Aviva; Halevy, Ayelet; Cohen, Rony; Sagie, Liora; Argov, Zohar; Rabie, Malcolm; Spiegel, Ronen; Chervinsky, Ilana; Orenstein, Naama; Engel, Andrew G.; Nevo, Yoram

doi:10.1016/j.nmd.2016.11.014

Cited by 30 publications

(35 citation statements)

References 25 publications

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“…However, these figures may vary between countries and regions under investigation. In a study of 34 CMS families from Israel the genes most frequently mutated were RAPSN ( n = 13), COLQ ( n = 11), and CHRNE ( n = 7) [15]. All other mutated proteins may contribute with less than 1% of the CMS cases to the general group of CMS.…”

Section: Resultsmentioning

confidence: 99%

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Congenital myasthenic syndromes

Finsterer

2019

Orphanet J Rare Dis

139

154

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Objectives Congenital myasthenic syndromes (CMSs) are a genotypically and phenotypically heterogeneous group of neuromuscular disorders, which have in common an impaired neuromuscular transmission. Since the field of CMSs is steadily expanding, the present review aimed at summarizing and discussing current knowledge and recent advances concerning the etiology, clinical presentation, diagnosis, and treatment of CMSs. Methods Systematic literature review. Results Currently, mutations in 32 genes are made responsible for autosomal dominant or autosomal recessive CMSs. These mutations concern 8 presynaptic, 4 synaptic, 15 post-synaptic, and 5 glycosilation proteins. These proteins function as ion-channels, enzymes, or structural, signalling, sensor, or transporter proteins. The most common causative genes are CHAT, COLQ, RAPSN, CHRNE, DOK7, and GFPT1. Phenotypically, these mutations manifest as abnormal fatigability or permanent or fluctuating weakness of extra-ocular, facial, bulbar, axial, respiratory, or limb muscles, hypotonia, or developmental delay. Cognitive disability, dysmorphism, neuropathy, or epilepsy are rare. Low- or high-frequency repetitive nerve stimulation may show an abnormal increment or decrement, and SF-EMG an increased jitter or blockings. Most CMSs respond favourably to acetylcholine-esterase inhibitors, 3,4-diamino-pyridine, salbutamol, albuterol, ephedrine, fluoxetine, or atracurium. Conclusions CMSs are an increasingly recognised group of genetically transmitted defects, which usually respond favorably to drugs enhancing the neuromuscular transmission. CMSs need to be differentiated from neuromuscular disorders due to muscle or nerve dysfunction.

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Section: Resultsmentioning

confidence: 99%

“…One of her siblings with a similar presentation had died at age 11 m [59]. Two further patients were reported in a study of CMS patients from Israel but no clinical details were provided [15].…”

Section: Resultsmentioning

confidence: 99%

Congenital myasthenic syndromes

Finsterer

2019

Orphanet J Rare Dis

139

154

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“…Since next generation methods are increasingly available, this method will fasten the diagnosis of CMS cases where genetic mutations are heterogeneous. 21 …”

Section: Discussionmentioning

confidence: 99%

Genetic Landscape of Congenital Myasthenic Syndromes From Turkey: Novel Mutations and Clinical Insights

et al. 2017

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Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous disorders of neuromuscular transmission. Most are treatable, but certain subtypes worsen with cholinesterase inhibitors. This underlines the importance of genetic diagnosis. Here, we report on cases with genetically proven CMS from Turkey. We retrospectively reviewed our experience of all patients with CMS, referred over a 5-year period (2011–2016) to the Child Neurology Department of Dokuz Eylül University, Izmir, Turkey. In addition, PubMed was searched for published cases of genetically proven CMS originating from Turkey. In total, we identified 43 (8 new patients, 35 recently published patients) cases. Defects in the acetylcholine receptor (n=15; 35%) were the most common type, followed by synaptic basal-lamina associated (n=14; 33%) and presynaptic syndromes (n=10; 23%). We only had 3 cases (7%) who had defects in endplate development. One patient had mutation GFPT1 gene (n=1; 2%). Knowledge on CMS and related genes in Turkey will lead to prompt diagnosis and treatment of these rare neuromuscular disorders.

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“…Clinical details were obtained from medical records. Neurophysiological studies were performed according to standard procedures 7, 8…”

Section: Methodsmentioning

confidence: 99%

Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome

Salpietro

Lin

Vedove³

et al. 2017

Annals of Neurology

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We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC in a Kuwaiti family and c.146G>C in an Israeli family. VAMP1 is crucial for vesicle fusion at presynaptic neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials and presynaptic impairment. We assessed the effect of the nonsense mutation on mRNA levels and evaluated the NMJ transmission in VAMP1 lew/lew mice, observing neurophysiological features of presynaptic impairment, similar to the patients. Taken together, our findings highlight VAMP1 homozygous mutations as a cause of presynaptic CMS. Ann Neurol 2017;81:597–603

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Congenital myasthenic syndrome in Israel: Genetic and clinical characterization

Cited by 30 publications

References 25 publications

Congenital myasthenic syndromes

Congenital myasthenic syndromes

Genetic Landscape of Congenital Myasthenic Syndromes From Turkey: Novel Mutations and Clinical Insights

Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome

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