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

Abstract

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.

Congenital myasthenic syndrome–associated agrin variants affect clustering of acetylcholine receptors in a domain-specific manner

“…A similarly affected younger sister died at 1 year of age of respiratory failure. The genetic results of this patient were previously reported (24).…”

Congenital myasthenic syndromes in Turkey: Clinical clues and prognosis with long term follow-up

“…As such, our population does not include some types of CMS, such as rapsyn deficiency and we very rarely see patients with ChAT deficiency. However, many patients with ChAT deficiency were reported from other pediatric neurology centers in Turkey [8]. Rapsyn deficiency may be mild in older children and adults and are often misdiagnosed as seronegative MG. Our CMS cohort would likely increase if all undiagnosed myopathy patients were evaluated for a defect of neuromuscular transmission by RNS and/or single fiber EMG, and if all seronegative myasthenic patients were re-evaluated for CMS.…”

“…Defects in no fewer than 30 genes are currently known to cause CMS with 90% being in one of the following genes: CHRNE, RAPSN, COLQ, DOK7, GFPT1 , and CHAT [1-2, 6-7]. To date, a limited number of CMS patients have been identified in Turkey [8-10], but the genotype/phenotype features of the CMS in this population remain unclear. Recently, a series of CMS patients was reported from Israel, another country in the region [11].…”

Clinical and Genetic Features of Congenital Myasthenic Syndromes due to CHAT Mutations: Case Report and Literature Review

“…The presynaptic genetic alterations most frequently observed are mutations of the choline acetyltransferase (CHAT) gene, located on chromosome 10q11.2. 3,4 Typically, CMS caused by CHAT mutations present in early infancy with respiratory distress and episodic apnea. The attacks of respiratory distress and apnea may be triggered by fever, infections, or stress.…”