Variante patogénica en el gen PCDH19 en una paciente con epilepsia y discapacidad cognitiva / Pathogenic variant in the PCDH19 gene in a patient with epilepsy and cognitive disability

INTRODUCCIÓN: La asociación de casos familiares de epilepsia y discapacidad intelectual (DI) en mujeres fue reportada en 1971. El año 2008, se identificó el rol de variantes patogénicas del gen PCDH19 en algunas familias. La enfermedad se presenta con crisis febriles en cluster, DI y rasgos autistas. La mayoría se debe a variantes de novo, pero hay algunos casos heredados por un modo peculiar de transmisión ligada X. OBJETIVO: Comunicar el caso de una paciente con epilepsia portadora de una variante patogénica en el gen PCDH1 9, revisando la historia natural de la enfermedad y la evidencia disponible para su manejo. CASO CLÍNICO: Paciente femenina, con antecedentes de embarazo y período perinatal normal. A los 6 meses, estando febril, presentó crisis focales motoras en cluster que repitieron a los 14, 18, 21 meses y 3 años siempre asociadas a fiebre, presentando incluso estatus epiléptico. Mantiene biterapia con topiramato y ácido valproico, completando 13 años sin crisis. El estudio del gen SCN1A no mostró anomalías y el estudio del gen PCDH19 reveló una variante patogénica en heterocigosis, "de novo". La paciente ha evolucionado con DI y alteraciones conductuales severas que requieren aten ción de salud mental. CONCLUSIONES: Las variantes patogénicas PCDH19 tienen expresión fenotípica variada. El diagnóstico genético debe sospecharse con la clínica. La morbilidad psiquiátrica a largo plazo puede ser incapacitante.

INTRODUCTION: The association of family cases of epilepsy and intellectual disability in women was reported in 1971. In 2008, the role of pathogenic variants of the PCDH19 gene in some families were identified. The disease presents with febrile seizure clusters, intellectual disability, and autistic features. Most cases are due to de novo variants, however, there are some inherited cases, with an atypical way of X-linked transmission. OBJECTIVE: To report the case of a patient with epilepsy carrier of a pathogenic variant of the PCDH19 gene, reviewing the natural history of this condition and the available evidence for its management. CLINICAL CASE: Female patient, with normal history of pregnancy and perinatal period. At 6 months, while febrile, she presented focal motor seizure clusters that repeated at 14, 18, 21 months and 3 years old, always associated with fever, even presenting status epilepticus. She is on therapy with topiramate and valproic acid, achieving 13 seizure-free years. The analysis of the SCN1A gene showed no abnormalities and the study of the PCDH19 gene revealed a de novo heterozygous pathogenic variant. The patient evolved with intellectual disability and severe behavioral disorders that require mental health team support. CONCLUSIONS: PCDH19 pathogenic variants have varied phenotypic expression. The genetic diagnosis should be guided with the clinical features. Long-term psychiatric morbidity can be disabling.

Nuevos fármacos antiepilépticos en epilepsias de la infancia / New antiepileptic drugs for childhood epilepsies

La epilepsia es una enfermedad neurológica muy frecuente que afecta al 0,5 a 1% de todos los niños. La era moderna de los fármacos antiepilépticos (FAEs), que abarca los últimos 150 años, desde el uso del bromuro hasta el presente, ha visto la introducción de diversos fármacos eficaces y seguros que han proporcionado grandes beneficios a pacientes que sufren epilepsia. En Europa y Estados Unidos están aprobados aproximadamente 31 FAEs, 11 de los cuales han sido aprobados por la FDA en los últimos 20 años. El objetivo general que guía el uso de FAEs es alcanzar la libertad de crisis con mínimos efectos adversos. A pesar de la disponibilidad de nuevas opciones, la tasa de fracaso con el primer FAE usado en epilepsia recién diagnosticada mantiene cifras entre 20 a 40%, tanto por falta de eficacia o por efectos adversos intolerables. En esta revisión de nuevos FAEs, veremos que muchos se encuentran disponibles en el mercado hace más de 10 años, sin embargo aún no han sido registrados ni están disponibles para su uso en Chile. Para cada fármaco se presenta su historia y datos relevantes en relación a farmacocinética, dosificación, evidencias de su utilidad así como los principales efectos adversos reconocidos. La facilidad para acceder a nuevos FAEs, requiere que los clínicos consideren cuidadosamente las opciones evaluando todos estos aspectos. Aunque en pacientes pediátricos puede ser particularmente desafiante, hay una mayor urgencia en el control de crisis, dada la evidencia desde los estudios en animales que indican que el control precoz de las crisis mejora el pronóstico futuro. Palabras clave: fármacos antiepilépticos, anticonvulsivantes, epilepsia, tratamiento de la epilepsia, epilepsia en niños y adolescentes

Epilepsy is a common neurological disease that affects 0.5 to 1% of all children. The modern era of antiepileptic drugs (AED), that covers the last 150 years, from the use of the bromide until the present, has seen the introduction of various effective and safe drugs that have provided large benefits to patients that suffer epilepsy. In Europe and the United States there are approximately 31 approved AED, 11 of which have been approved by the FDA in the past 20 years. The general objective that guides the use of AED is to achieve freedom of crisis with minimal adverse effects. Despite the availability of new options, the failure rate with the first AED used in newly diagnosed epilepsy is still between 20 to 40%, either for lack of efficacy or intolerable adverse effects. In this review of new AED, we will see that there are many drugs that have been available for over 10 years, however they are still not registered or available in Chile. We present the history and relevant information for each drug, in regard to pharmacokinetics, dosage, evidence of its usefulness as well as the main recognized adverse effects. The ease of access to new AED, requires that the physician evaluates these aspects carefully. Although pediatric patients can

Cuidado en sala cuna: impacto sobre la patología respiratoria aguda baja del menor de 2 años / Day care attendance: impact over acute low respiratory pathology in child under 2 years old

Aim: To measure the impact of day care attendance on lower respiratory tract infections in children under 2 years old in 2 urban settings with different degrees of air pollution. Subjects and Methods: a 26 week follow up, during fall and winter of 1991 and 1992, was performed to 98 children (48 attending day care and 50 controls) comming from Santiago, a city affected by severe air pollution and 95 children (46 Attending day care and 49 controls) coming from San felipe and Los Andes (villages with low air pollution). The incidence of lower respiratory infections was recorded by trained personnel and expressed as rates per 100 weeks of follow up. Day care settings in San Felipe and Los Andes were state funded whereas those from Santiago were private. All premises has wooden or plastic floors and smoking was forbidden. During the follow up years, no respiratory epidemic were recorded. Results: The socioeconomic level of children from San Felipe and Los Angeles was better. Children from Santiago were more exposed to tobacco smoke. The highest incidence of lower respiratory infections was found in children attending day care in San Felipe and Los Andes (31.2 episodes/100 weeks of observation), closely followed by control and day care attending children from Santiago (28.7 respectively) and control children from San felipe and Los Andes (18.2). Conclusions: Day care attendance in areas with low air pollution increases the risk of lower respiratory infections. Instead, in highly polluted areas, the infection rates do not increase