Genetic heterogeneity in infantile spasms

• Published in: Epilepsy research Vol. 156; p. 106181
• Main Authors: Muir, Alison M., Myers, Candace T., Nguyen, Nancy T., Saykally, Julia, Craiu, Dana, De Jonghe, Peter, Helbig, Ingo, Hoffman-Zacharska, Dorota, Guerrini, Renzo, Lehesjoki, Anna-Elina, Marini, Carla, Møller, Rikke S., Serratosa, Jose, Štěrbová, Katalin, Striano, Pasquale, von Spiczak, Sarah, Weckhuysen, Sarah, Mefford, Heather C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2019
• Subjects: Epilepsy; Genetic diagnosis; Infantile spasms; Targeted sequencing; West syndrome; AC; ACMG; DEE; EEG; Epilepsy; NLES; IS; Genetic diagnosis; West syndrome; Infantile spasms; smMIPs; MIPs; Targeted sequencing
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2019.106181

•Infantile spams is genetically heterogeneous; variants in the majority of genes account for only a small number of cases.•De novo variants in TBL1XR1 and KIF1A can cause infantile spasms.•Larger cohorts or the use of online tools to connect researchers are needed to identify additional genetic causes of IS. Infantile spasms (IS) is a developmental and epileptic encephalopathy with heterogeneous etiologies including many genetic causes. Genetic studies have identified pathogenic variants in over 30 genes as causes of IS. Many of these genetic causes are extremely rare, with only one reported incidence in an individual with IS. To better understand the genetic landscape of IS, we used targeted sequencing to screen 42 candidate IS genes and 53 established developmental and epileptic encephalopathy genes in 92 individual with IS. We identified a genetic diagnosis for 7.6% of our cohort, including pathogenic variants in KCNB1 (n = 2), GNAO1 (n = 1), STXBP1 (n = 1), SLC35A2 (n = 1), TBL1XR1 (n = 1), and KIF1A (n = 1). Our data emphasize the genetic heterogeneity of IS and will inform the diagnosis and management of individuals with this devastating disorder.