To identify the yield of genetic testing and time to genetic diagnosis in infantile spasms (IS).

We elaborate results of genetic evaluation for IS in a tertiary care center with specialized epilepsy genetics clinics.

We conducted a retrospective review of charts between 2015-2020 for patients with IS (onset between 2-24 months). Patients were included if they had MRI and, of those without MRI evidence of an acquired etiology, at least one form of genetic testing, such as chromosomal microarray (CMA), karyotype, epilepsy panel, whole exome sequencing. Subjects were categorized as treatment responders (resolution of electroclinical spasms after one or two standard therapies) or and non-responders (non-resolution of spasms, and/or relapse of spasms after initial response to at least two treatments).

A total of 127 cases (60% males) were included with 42 (33%) responders and 85 (67%) non-responders. Underlying etiology was identified in 81% (103/127) of the overall cohort (34/42 of responders and 69/85 of non-responders). An acquired etiology was noted in 15% (19/127) (9/42 among responders and 10/85 in non-responders). Excluding acquired etiologies, some form of genetic testing was performed in 104/108 (96%) patients. Genetic diagnosis was identified in 55% (57/104) ( 15/33 in responders and 42/71 in non-responders). Diagnosis was established by CMA/karyotype in 20% (17/87), with gene panels (epilepsy panels/region of interest panel) in 26% (21/80) and with WES in 40% (19/48).  Mean time to genetic diagnosis was 5.8±9.6 months in the responders and 8.9±8.5 months in non-responders. Genetic testing and its yield did not differ between the responder and non-responder groups, but it took longer to arrive at an etiology in the latter (p=0.03).

In our study, neuroimaging along with high utilization of the genetic testing led to a higher yield of etiologic diagnosis in both treatment-responsive and treatment-resistant IS. Time to diagnosis was longer in the non-responders.