Genetics of cerebral venous thrombosis

Cerebral venous thrombosis (CVT) is rare compared to arterial causes of stroke. It is often encountered in young patients and may occur in children and neonates. Predisposition to CVT also has a genetic basis and inherited thrombophilias are known to cause 22.4% of the CVT cases. Inherited thrombophilias should be suspected if a patient has recurrent CVT, is less than 45 years age, has a family history of venous thrombosis or has no apparent acquired risk factor. Factor V Leiden (FVL) is the most common genetic risk factor, followed by the prothrombin gene mutation G20210A. Other less common inherited venous thrombophilias include deficiencies of Protein S, Protein C and antithrombin III. FVL, the G20210A prothrombin gene mutation and a deficiency of protein S and C, cause a reduction in the control of thrombin generation. Deficiency of antithrombin causes a decreased neutralization of thrombin. Both these mechanisms are responsible for venous thrombosis. Inherited thrombophilias with concomitant acquired risk factors like surgery, trauma, prolonged immobilization, pregnancy and puerperium, oral contraceptives, antiphospholipid antibodies and hyperhomocysteinemia may increase the risk of CVT manifold. Similarly the co-inheritance of two or more known mutations also increases the risk markedly. FVL, prothrombin G20210A mutation, increased factor VIIIc, protein C & S deficiency and antithrombin III deficiency have all been reported to cause neonatal stroke due to CVT. Maternal and foetal testing is suggested when CVT occurs in neonates.