Pseudotumor cerebri (PTC) is a syndrome characterized by symptoms and signs of isolated intracranial hypertension leading to catastrophic effects on the visual system without clinical, laboratory, or radiological evidence of a space-occupying lesion or hydrocephalus. The clinical picture is caused by raised cerebrospinal fluid (CSF) pressure but the pathogenesis is not clear with the most widely accepted hypothesis being reduced CSF absorption through the arachnoid villi. Although the majority of cases are non-familial, there are reports of familial PTC that raise the possibility of some genetic defect that may become clinically manifested after exposure to a precipitating agent. We hypothesize that PTC is a multifactorial disorder with an underlying genetic thrombotic risk factor that predisposes the patients to local thrombus lining arachnoid villi that leads to increased intracranial pressure without demonstrable cerebral venous thrombosis when the patient is exposed the factors known to precipitate PTC. Coagulation Factor V is an enzyme cofactor with pivotal functions in hemostasis. A number of polymorphisms/mutations have been identified among the 25 exons of the Factor V gene. Altered activity of mutated Factor V is the most common hereditary blood coagulation disorder predisposing to thrombosis. A number of mutations/polymorphisms of the Factor V gene, including V Hong Kong (Arg306Gly), V Cambridge (Arg306Thr), Arg485Lys, V Leiden (Arg506Gln), and the R2 allele (Arg-1299), known to be associated with thrombotic risk are located in exons 7, 10, and13. We scanned exons 7 and 10 of Factor V gene for mutations in 51 PTC patients and 69 controls from Turkey. The G 1628 A single nucleotide substitution (Arg485Lys replacement) in exon 10 previously indicated to be associated with increased risk of coronary artery heart diseases in the Chinese population [Le et al., Clin Genet, 57(2000)296] was found to be significantly associated with the development of PTC in the Turkish population (p smaller than 0.05) (OR=3.1, 95% CI -0.08 to 24.7 %). This is the first study to document a genetic risk factor for PTC. We are in the process of scanning exon 13 of Factor V as well as exons of the Factor II gene, which is also an important modifier in thrombosis development.
