Novel Genes of Early-Onset Epileptic Encephalopathies: From Genotype to Phenotypes

• Published in: Pediatric neurology Vol. 53; no. 2; pp. 119 - 129
• Main Author: Mastrangelo, Mario
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2015
• Subjects: children; early-onset epileptic encephalopathies; epilepsy; Genetic Predisposition to Disease - genetics; Genotype; Humans; Infant; Mutation - genetics; Neurology; next-generation sequencing; Pediatrics; Phenotype; PubMed - statistics & numerical data; Spasms, Infantile - genetics; Spasms, Infantile - physiopathology; epilepsy; early-onset epileptic encephalopathies; next-generation sequencing; children
• ISSN: 0887-8994; 1873-5150
• DOI: 10.1016/j.pediatrneurol.2015.04.001

Early-onset epileptic encephalopathies are severe disorders in which seizure recurrence impairs motor, cognitive, and sensory development. In recent years, next-generation sequencing technologies have led to the detection of several pathogenic new genes. A PubMed search was carried out using the entries “early onset epileptic encephalopathies,” “early infantile epileptic encephalopathies,” and “next generation sequencing.” The most relevant articles written on this subject between 2000 and 2015 were selected. Here we summarize the related contents concerning the pathogenic role and the phenotypic features of 20 novel gene-related syndromes involved in the pathogenesis of early-onset epileptic encephalopathy variants. Despite the increasing number of single early-onset epileptic encephalopathy genes, the clinical presentations of these disorders frequently overlap, making it difficult to picture a systematic diagnostic evaluation. In any case, a progressive approach should guide the choice of molecular genetic investigations. It is suggested that clinicians pay particular attention to mutated genes causing potentially treatable conditions in order to take advantage of expert counseling.