Congenital myasthenic syndrome with mild intellectual disability caused by a recurrent SLC25A1 variant

Abstract: Congenital myasthenic syndromes (CMS) are a clinically and genetically heterogeneous group of disorders caused by mutations which lead to impaired neuromuscular transmission. SLC25A1 encodes a mitochondrial citrate carrier, associated mainly with the severe neurometabolic disease combined D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA). We previously reported a single family with a homozygous missense variant in SLC25A1 with a phenotype restricted to relatively mild CMS with intellectual disability, but to date no additional cases of this CMS subtype had been reported. Here, we performed whole exome sequencing (WES) in three additional and unrelated families presenting with CMS and mild intellectual disability to identify the underlying causative gene. The WES analysis revealed the presence of a homozygous c.740G>A; p.(Arg247Gln) missense SLC25A1 variant, the same SLC25A1 variant as identified in the original family with this phenotype. Electron microscopy of muscle from two cases revealed enlarged and accumulated mitochondria. Haplotype analysis performed in two unrelated families suggested that this variant is a result of recurrent mutation and not a founder effect. This suggests that p.(Arg247Gln) is associated with a relatively mild CMS phenotype with subtle mitochondrial abnormalities, while other variants in this gene cause more severe neurometabolic disease. In conclusion, the p.(Arg247Gln) SLC25A1 variant should be considered in patients presenting with a presynaptic CMS phenotype, particularly with accompanying intellectual disability

REtrospective Multicenter INdian Study of Derivo Embolization Device (REMIND): Periprocedural Safety

Purpose The treatment of aneurysms with characteristics such as complex morphology, fusiform, blister-like, wide neck, or large size has been revolutionized with the introduction of flow diverters. Though flow diverters have several advantages over coiling, they also have certain important disadvantages such as the lack of immediate protection against rupture, the risk of ischemic stroke, the need for antiplatelet therapy, and long latency for complete effect. The Derivo Embolization Device (DED) is a second-generation self-expanding device that is claimed to be less thrombogenic than conventional devices. We retrospectively evaluated the periprocedural safety and risks associated with the DED across 5 centers in India. Materials and Methods This is a multicentric, retrospective, observational study of DED, conducted at 5 high volume endovascular therapy centers in India from May 2018 to June 2020. Periprocedural demographic, clinical, and angiographic data were collected from a retrospective review of patient charts. Results A total of 96 patients, including 56 (58.3%) females, aged between 16–80 years (60±12.7 years) harboring 106 aneurysms were studied. Seven (7.3%) were noted to harbor multiple aneurysms: 6 had 3 aneurysms each, while 1 patient had 5 aneurysms. The following aneurysm characteristics were noted: average size, 9.8±8.2 mm; average neck size, 6.9±8.5 mm; wide-necked (>4 mm), 63 (59.4%); giant (>25 mm), 8 (7.5%); and anterior circulation location, 98 (92.5%). Eighteen (17%) of these were ruptured. Additional balloon angioplasty was performed in 5 (5.2%) patients. Intraprocedural problems were encountered in 3 (3.1%), of which only 1 had clinical implications, the device fish-mouthing with stent thrombosis resulting in a malignant middle cerebral artery territory infarction. The modified Rankin scale at 3 months was worse in 1 patient. Conclusion DED is a newer generation flow diverter stent with a low periprocedural complication rate