Genetic variants underlying congenital Zika syndrome and severe microcephaly: a systematic review and meta-analysis

Congenital Zika syndrome (CZS) is a condition caused by the infection of the Zika virus (ZIKV) during pregnancy, with severe microcephaly as an additional condition commonly associated with CZS. Although not all embryos or fetuses exposed to ZIKV infection develop CZS, various genetic factors have been linked to the condition, which can cause other neurodevelopmental disorders. In this study, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was employed to gather a total of 7191 studies from different sources, which were then filtered to 2794 unique studies after the removal of 4397 duplicates. From these studies, 107 met the inclusion criteria and were used to examine the relationship between genetic variants and CZS and severe microcephaly conditions. Subsequently, 32 studies were selected for meta-analysis to determine the statistical significance of the genes associated with microcephaly and CZS. The results of the meta-analysis revealed that microcephaly was significantly associated with genetic variation primarily found in ASPM, WDR62, STIL, and CEP135 genes, while the CDK5RAP2 gene did not demonstrate a statistically significant association with microcephaly. The study concluded that mutations in the assembly factor for the spindle microtubules (ASPM) gene frequently cause microcephaly across different geographical locations. The analysis also identified 39 genes reported in 580 cases, and the meta-analysis of the prime genes showed a direct association with microcephaly.

The online version contains supplementary material available at 10.1007/s13337-025-00924-y.