The odyssey of complex neurogenetic disorders: From undetermined to positive.

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.

Esclerosis temporo mesial, evaluación diagnóstica y resultados / Temporus mesial sclerosis, diagnostic evaluation and results

La esclerosis temporo-mesial (ETM), dentro de las epilepsias del lóbulo temporal, es el tipo de epilepsia sintomática focal más frecuente, especialmente en formas parciales resistentes a los medicamentos, siendo la cirugía un tratamiento efectivo para la misma con resolución completa entre un 60 a 90% 1 Su fisiopatogenia es debido a la pérdida neuronal segmental y gliosis en el hipocampo; algunos estudios postmortem indican que estos hallazgos también están presentes en una proporción de pacientes en la amígdala, corteza entorrinal y corteza temporal 2 . Se ha demostrado un aumento de la patología en pacientes que presentaron antecedentes de convulsiones febriles en edad pediátrica, predominando en niños con crisis atípicas, hipoxia perinatal o infecciones en del sistema nervioso central.

The temporo-mesial sclerosis (MTS), within the epilepsies of the temporal lobe, is the type of focal symptomatic epilepsy more frequent, especially in partial forms resistant to the medicines, being the surgery an effective treatment for the same with complete resolution between 60 to 90%. Its pathophysiology is due to segmental neuronal loss and gliosis in the hippocampus; Some postmortem studies indicate that these findings are also present in a proportion of patients in the amygdala, entorhinal cortex and temporal cortex. An increase in the pathology has been demonstrated in patients who had a history of febrile convulsions in the pediatric age, predominantly in children with atypical crises, perinatal hypoxia or infections in the central nervous system.