Premium
Dravet syndrome and its mimics: Beyond SCN 1A
Author(s) -
Steel Dora,
Symonds Joseph D.,
Zuberi Sameer M.,
Brunklaus Andreas
Publication year - 2017
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13889
Subject(s) - dravet syndrome , phenotype , mendelian inheritance , omim : online mendelian inheritance in man , gene , epilepsy , genetics , epilepsy syndromes , encephalopathy , biology , bioinformatics , medicine , neuroscience , psychiatry
Summary Objective Dravet syndrome ( DS ) is a severe developmental and epileptic encephalopathy characterized by the onset of prolonged febrile and afebrile seizures in infancy, and evolving to drug‐resistant epilepsy with accompanying cognitive, behavioral, and motor impairment. Most cases are now known to be caused by pathogenic variants in the sodium channel gene SCN 1A , but several other genes have also been implicated. This review examines current understanding of the role of non‐ SCN 1A genes in DS , and what is known about phenotypic similarities and differences. We discuss whether these are best thought of as minority causes of DS , or as similar but distinct conditions. Methods Based on a review of literature, a list of genes linked to DS was compiled and PubMed was searched for reports of DS ‐like phenotypes arising from variants in each. Online Mendelian Inheritance in Man ( OMIM ) was used to identify further reports relevant to each gene. Results Genes that have been reported to cause DS ‐like phenotypes include SCN 2A, SCN 8A, SCN 9A, SCN 1B, PCDH 19, GABRA 1, GABRG 2, STXBP 1, HCN 1, CHD 2 , and KCNA 2 . Many of these genes, however, appear to be associated with their own, different, clinical picture. Other candidate genes for DS have been reported, but there is currently an insufficient body of literature to support their causative role. Significance Although most cases of DS arise from SCN 1A variants, numerous other genes cause encephalopathies that are clinically similar. Increasingly, a tendency is noted to define newly described epileptic disorders primarily in genetic terms, with clinical features being linked to genotypes. As genetic diagnosis becomes more readily available, its potential to guide pathophysiologic understanding and therapeutic strategy cannot be ignored. Clinical assessment remains essential; the challenge now is to develop a gene‐based taxonomy that complements traditional syndromic classifications, allowing elements of both to inform new approaches to treatment.