Inherited Thrombophilia Associated With Ischemic Pediatric Stroke in Parent-Child Pairs

We aimed to examine inherited thrombophilia frequencies by extending genetic profile to previously rarely or not investigated polymorphisms in children with ischemic pediatric stroke (IPS) and their parents.

The study included 33 children: 23 with perinatal arterial ischemic stroke (PAIS), eight with childhood arterial ischemic stroke (CAIS), and two with sinovenous thrombosis and their parents (33 mother-child, 12 father-child, and 12 mother-father-child pairs). Genotyping of FV-Leiden, FV-H1299R, FII-G20210A, β-fibrinogen-455G>A, FXIII-A-Val34Leu, PAI-1(4G/5G), HPA-1, MTHFR-C677T, MTHFR-A1298C, ACE(I/D), and APOE(ε2-4) was performed using CVD Strip assay (ViennaLab, Austria).

At least one and up to seven simultaneously present polymorphisms were observed in all children with IPS, mothers, and fathers. More than five simultaneously present polymorphisms were identified threefold more frequently in children with IPS (10 of 33; 30%) compared with the child control group (17 of 150; 11%), yielding a statistically significant difference between the two groups (odds ratio [OR] = 3.40; 95% confidence interval [CI] = 1.39 to 8.35; P = 0.012). Stronger association was revealed for PAIS (OR = 4.17; 95% CI = 1.55 to 11.29; P = 0.008) and CAIS subgroups (OR = 7.82; 95% CI = 1.79 to 34.20; P = 0.012). Complete match of polymorphisms was not identified in any parent-child pair. A partial match (one to four mutual polymorphisms) was found in 11 of 12 parent-child pairs where until three mutual polymorphisms was present in 11 of 12 (91.7%) father-child compared with 21 of 33 (63.6%) mother-child pairs.

According to obtained results the simultaneous presence of more than five polymorphisms is associated with a higher risk for IPS occurrence, suggesting the risk enhancement for PAIS in the presence of pregnancy complications or for CAIS in conjunction with maternal comorbidity and positive family history. The presence of up to three mutual polymorphisms more frequently in father-child than mother-child pairs suggests significant paternal contribution of inherited thrombophilia to increased risk of IPS.