Lipoprotein (a) and genetic polymorphisms of clotting factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of spontaneous ischemic stroke in childhood

Ischemic stroke is a rare event in childhood. In approximately one third of cases no obvious underlying cause or disorder can be detected. We investig ated the importance of genetic risk factors of venous thromboembolism in ch ildhood or stroke in adulthood as risk factors for spontaneous ischemic str oke in children. One hundred forty-eight Caucasian infants and children (ag ed 0.5 to 16 years) with stroke and 296 age-matched controls from the same geographic areas as the patients were analyzed for increased lipoprotein (a ) [Lp(a)] levels >30 mg/dL; for the presence of the factor V (FV) G1691A mu tation, the prothrombin (PT) G20210A variant, and the TT677 genotype of met hylenetetrahydrofolate reductase (MTHFR); and deficiencies of protein C, pr otein S, and antithrombin. The following frequencies (patients v controls), odds ratios (ORs), and confidence intervals (Cls) of single risk factors w ere found: Lp(a) >30 mg/dL (26.4% v 4.7%; OR/Cl, 7.2/3.8 to 13.8; P <.0001) , RI G1691A (20.2% v 4%; OR/Cl, 6/2.97 to 12.1; P <.0001), protein C defici ency (6% v 0.67%; OR/Cl, 9.5/2 to 44.6; P =.001), PT G20210A (6% v1.3%; OR/ Cl, 4.7/1.4 to 15.6; P =.01), and the MTHFR TT677 genotype (23.6% v 10.4%; OR/Cl, 2.4/1.53 to 4.5; P <.0001). A combination of the heterozygous FV G16 91A mutation with increased Lp(a) in = 11) or the MTHFR Tr677 genotype in = 5) was found in 10.8% of cases, but only 0.3% of controls (OR/Cl, 35.75/4. 7 to 272; P <.0001). Increased Lp (a) levels, the FV G1691A mutation, prote in C deficiency, the prothrombin G20210A variant and the MTHFR TT677 are im portant risk factors for spontaneous ischemic stroke in childhood. (C) 1999 by The American Society of Hematology.