The ketogenic diet is a good option in the treatment of refractory epilepsy. After discontinuing the diet, seizures recurrence occurred in few patients.

No abstract

have received fees for teaching activities from the pharmaceutical company that markets the drug for the disease subject of this update.

The genetic and phenotypic heterogeneity of neurogenetic diseases forces patients and their families into a "diagnostic odyssey." An increase in the variability of genetic disorders and the corresponding gene-disease associations suggest the need to periodically re-evaluate the significance of variants of undetermined pathogenicity. Here, we report the diagnostic and clinical utility of Targeted Gene Panel Sequencing (TGPS) and Whole Exome Sequencing (WES) in 341 patients with suspected neurogenetic disorders from centers in Buenos Aires and Cincinnati over the last 4 years, focusing on the usefulness of reinterpreting variants previously classified as of uncertain significance. After a mean of ±2years (IC 95:0.73-3.27), approximately 30% of the variants of uncertain significance were reclassified as pathogenic. The use of next generation sequencing methods has facilitated the identification of both germline and mosaic pathogenic variants, expanding the diagnostic yield. These results demonstrate the high clinical impact of periodic reanalysis of undetermined variants in clinical neurology. K E Y W O R D S diagnostic odyssey, mosaicism, targeted gene panel sequencing, variants of unknown significance, whole exome sequencing 1 | INTRODUCTION Neurogenetic diseases encompass a vast group of entities with marked genetic and phenotypic heterogeneity. Nowadays, the process of establishing a diagnosis for this subset of neurological conditions requires extensive clinical, radiological, and genetic evaluations, often becoming a "diagnostic odyssey" for the patient and the family (Carmichael, Tsipis, Windmueller, Mandel, & Estrella, 2015). Next Generation Sequencing (NGS) has become a widely used tool for obtaining genetic diagnosis in clinical medicine (Might &

Mutations in PEX3 usually result in a severe, early lethal phenotype. We report a patient compound heterozygous for two novel mutations in the PEX3 gene, who is less affected than previously reported patients with a defect in the PEX3 gene. Our findings indicate that PEX3 defects may cause a disease spectrum similar as previously observed for other PEX gene defects.