SCN1A Variants as the Underlying Cause of Genetic Epilepsy with Febrile Seizures Plus in Two Multi-Generational Colombian Families.

Genetic epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant disorder with febrile or afebrile seizures that exhibits phenotypic variability. Only a few variants in SCN1A have been previously characterized for GEFS+, in Latin American populations where studies on the genetic and phenotypic spectrum of GEFS+ are scarce. We evaluated members in two multi-generational Colombian Paisa families whose affected members present with classic GEFS+. Exome and Sanger sequencing were used to detect the causal variants in these families. In each of these families, we identified variants in SCN1A causing GEFS+ with incomplete penetrance. In Family 047, we identified a heterozygous variant (c.3530C > G; p.(Pro1177Arg)) that segregates with GEFS+ in 15 affected individuals. In Family 167, we identified a previously unreported variant (c.725A > G; p.(Gln242Arg)) that segregates with the disease in a family with four affected members. Both variants are located in a cytoplasmic loop region in SCN1A and based on our findings the variants are classified as pathogenic and likely pathogenic, respectively. Our results expand the genotypic and phenotypic spectrum associated with SCN1A variants and will aid in improving molecular diagnostics and counseling in Latin American and other populations.

Síndrome de Ondina (hipoventilación central congénita), una amenaza contra la vida al dormir / Ondina syndrome (congenital central hypoventilation) a threat against life when sleeping

RESUMEN El síndrome de Ondina, o síndrome de hipoventilación central congénita, es una enfermedad neurológica rara, donde hay fracaso en el control de la ventilación en el sistema nervioso central, llevando a la hipoxia e hipercapnia que pueden generar problemas del neurodesarrollo y, finalmente, ocasionar la muerte. Puede representar una situación muy dolorosa para los familiares de los pacientes que la padecen, despertando sentimientos difíciles de enfrentar, es por esto que es importante tener conocimiento acerca de esta condición para así impactar en la disminución de su incidencia.

SUMMARY Ondina syndrome, or congenital central hypoventilation syndrome, is a rare neurological disease in which there is a failure in the control of ventilation in the central nervous system, which leads to hypoxia and hypercapnia leading to neurodevelopmental problems and ultimately to death. It can represent a very painful situation for the family of patients who suffer from it, awakening feelings that are difficult to face. Thus, it is important to have adequate knowledge of this condition in order to have an impact on the decrease of its incidence.