Identification of Monogenic Causes of Arterial Ischemic Stroke in Children with Arteriopathies by Next-Generation Sequencing

The leading causes of pediatric arterial ischemic stroke (PAIS) are arteriopathies, which refer to pathologies of the arterial walls in the brain. Since traditional risk factors for cardiovascular diseases in children play a smaller role than in adults, it can be supposed that genetic factors may be of particular importance in this age group. Therefore, this study aimed to identify mutations affecting the formation of vascular wall pathologies, which can subsequently lead to ischemic stroke. The study used a database of 92 Caucasian children diagnosed with ischemic stroke. From this group, 25 children with arteriopathies were selected. The study had an exploratory and descriptive design, with the aim of characterizing rare genetic variants in a selected cohort, without attempting formal statistical association testing. The sequencing was performed using the Illumina NextSeq 550 platform. A panel of 161 genes known to be associated with stroke or arteriopathies was selected for further analysis. We identified 10 pathogenic or likely pathogenic mutations in 15 patients. Among these, three are likely monogenic causes of stroke (ELN, SCN5A, and VHL genes), two are considered risk factors (FV and ADAMTS13), two have conflicting interpretations (ACAD9 and ENG), and three are most likely benign (CBS, PMM2, and PKD1). The frequency of genetic variants underlying ischemic stroke or acting as risk factors for the disease in the studied group is significantly higher than the estimated frequency of monogenic forms of stroke in young adults and higher than in the general population. NGS testing is worth considering, especially in patients who exhibit certain symptoms that may suggest the presence of mutations.