Infantile spasms are an age-dependent epilepsy that are highly associated with cognitive impairment, autism, and movement disorders. Previous classification systems have focused on a distinction between symptomatic and cryptogenic etiologies, and have not kept pace with the recent discoveries of mutations in genes in key pathways of central nervous system development in patients with infantile spasms. Children with certain genetic syndromes are much more likely to have infantile spasms, and we review the literature to propose a genetic classification of these disorders. Children with these genetic associations with infantile spasms also have phenotypes beyond epilepsy that may be explained by recent advances in the understanding of underlying biological mechanisms. We therefore also propose a biologic classification of the genes highly associated with infantile spasms, and articulate models for infantile spasms pathogenesis based on that data. The two best described pathways of pathogenesis are abnormalities in the gene regulatory network of GABAergic forebrain development, and abnormalities in molecules expressed at the synapse. We intend for these genetic and biologic classifications to be flexible, and hope that they will encourage much needed progress in syndrome recognition, clinical genetic testing, and ultimately the development of new therapies that target specific pathways of pathogenesis.
Keywords: Infantile spasms, developmental epilepsy, autism, movement disorders, gene regulatory networks