This is an update on severe epilepsies in infancy that are associated with genetic etiologies, either chromosomal abnormalities or gene mutations. These severe epilepsies may present the clinical and electroencephalographic phenotype of the so called epileptic encephalopathies, although a significant number of cases do not comply with the criteria to be included among the already known categories, as classified by the International League Against Epilepsy. Several chromosomal abnormalities, with or without a characteristic physical phenotype, are associated with epileptic encephalopathies in infants. Many patients are affected by metabolic or structural cerebral diseases of genetic etiology, in which seizures are not the only manifestation. Inborn errors of metabolism, deficiencies in cerebral transporters, mitochondrial encephalopathies, several neuroectodermosis, and part of the brain malformations and disorders of cortical development are examples. Recognition of new gene mutations in infants with epileptic encephalopathies or other severe epilepsies whose brain imaging studies, neurometabolic screenings and conventional cariotypes are normal, is emphasized in this review. An algorhythm for diagnosis and treatment of neonatal seizures with no determined etiology is also included. Finally, the new molecular genetics techniques applied in the diagnostic approach of these conditions, such as Array Comparative Genomic Hybridization, the identification of copy number variations and the eventual sequencing of genes, are commented but not described. The concept for pediatricians and pediatric neurologists is that mutations in one gene may provoke different epileptic syndromes, whereas one epileptic syndrome may be provoked by mutations in different genes.

Las epilepsias graves asociadas con etiologías genéticas, por anomalías cromosómicas o por mutaciones génicas comienzan en los dos primeros años de vida. Pueden presentar el fenotipo clínico-electroencefalográfco de las encefalopatías epilépticas, aunque muchos no se pueden incluir en categorías conocidas. Algunas anomalías cromosómicas, con fenotipo físico o sin él, se asocian a encefalopatías epilépticas en lactantes. En pacientes con enfermedad metabólica o estructural cerebral de etiología genética, las crisis epilépticas no constituyen la única manifestación. Se enfatiza el reconocimiento de nuevas mutaciones génicas en lactantes con crisis epilépticas refractarias a la medicación habitual, con imágenes cerebrales, estudios neurometabólicos y cariotipos convencionales normales. Se comentan nuevas técnicas de genética molecular -la hibridación genómica comparativa- para identificar variaciones en el número de copias y la eventual secuenciación de los genes buscados. El concepto válido para pediatras y neurólogos infantiles es que mutaciones en un mismo gen pueden provocar distintos síndromes epilépticos, y un síndrome epiléptico puede ser provocado por mutaciones en distintos genes.