[Congenital myasthenic syndrome related to SLC25A1 gene variant: two cases report and literature review].

Objective: To investigate the clinical characteristics and genetic features of congenital myasthenic syndrome (CMS) related to SLC25A1 gene variant. Methods: The clinical data of two SLC25A1 gene variant related CMS patients treated at the Children's Hospital of Fudan University between January 2015 and June 2019 were analyzed retrospectively. A literature search with "SLC25A1" and "congenital myasthenic syndrome" as key words was conducted at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and Pubmed (up to June 2020). The clinical characteristics and genetic features of congenital myasthenic syndrome related to SLC25A1 gene variant were summarized. Results: Two patients were all males, aged 9 years and 2 years respectively and the onset age was in infancy. In addition to typical CMS symptoms (fatigable muscular weakness, including bilateral ptosis, strabismus, masticatory weakness, low voice and limb weakness), the two patients both had developmental delay along with metabolic abnormalities (elevated urinary 2-ketoglutarate (2-KG), elevated lactic acid levels or 2-hydroxyglutaric aciduria). Trio whole-exome sequencing (WES) revealed two novel pathogenic variants of SLC25A1(c.628C>T, p.R210X; c.145G>A, p.V49M) in case 1 and (c.145G>A, p.V49M; microdeletion) in case 2. After literature search, 15 cases in 3 English articles were found, which made up the complete case data of 17 patients (including these 2 cases). Seventeen patients had very early onset with the age of 2 years. Mild intellectual disability was recorded in 9 patients, and mild developmental delay was observed in one patient. 5 SLC25A1 gene variants (three missense, one nonsense and one microdeletion) were identified in these cases. Twelve patients from 6 pedigrees harbored one same variant (c.740G>A, p.R247Q) and two cases had the other variant (c.145G>A, p.V49M). Conclusions: Patients diagnosed with SLC25A1 related CMS have very early onset, and most of them have intellectual disability or developmental delay. Part of patients had metabolic abnormalities. The variants (c.740G>A, p.R247Q and c.145G>A, p.V49M) are recurrent.