Diagnostic yields of genetic testing and related benefits in infantile epileptic spasms syndrome: A systematic review and meta-analysis.

BACKGROUND

Diagnostic yields for infantile epileptic spasms syndrome (IESS) are notably heterogeneous across different testing modalities and studies. To investigate the proportion of individuals with IESS harboring causative/pathogenic genetic variants identified using whole-exome sequencing (WES), multi-gene panels (MGPs), and chromosomal microarray (CMA), thereby providing evidence to inform guidelines for genetic testing strategies.

METHODS

The study team searched PubMed, Embase, and Cochrane Central Register of Controlled Trials between January 2012- October2023. Data were extracted and synthesized by two investigators following the preferred reporting items for systematic reviews and meta-analyses guideline. The primary outcome was the pooled diagnostic rate of individual WES, MGPs, and CMA across studies. Subgroup analyses were performed based on the inclusion of cases with tuberous sclerosis complex and the number of genes included on MGPs.

RESULTS

Our study included 30 studies, involving 2 738 participants. The diagnostic rates in IESS for WES (13 studies, n = 799), MGPs (13 studies, n = 1 117), and CMA (13 studies, n = 629) were 26 % (95 % CI = 21 %-31 %), 20 % (95 % CI = 15 %-27 %), and 14 % (95 % CI = 11 %-16 %), respectively. WES and MGPs showed comparable diagnostic yields (P = 0.34). Our results indicated that 61.6 % of individuals with genetic IESS may potentially benefit from genetic diagnosis in terms of clinical management.

CONCLUSIONS

Our results showed that WES and MGPs exhibited comparable genetic diagnostic yields. Therefore, either method could be equally recommended as a first-tier testing approach for IESS cases with suspected genetic or unknown etiologies, especially considering the potential clinical benefits derived from genetic diagnosis.