Objective:

Our study aims to evaluate the role of methylenetetrahydrofolate reductase gene polymorphism in cryptogenic ischemic stroke among young adult females, assessing for synergistic effects between stroke risk factors and other thrombogenic factors.

Background:

The role of inherited thrombophilia such as methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T and A1298C) in ischemic stroke (IS) is unclear. MTHFR, a vital enzyme involved in converting homocysteine to methionine, regulates homocysteine levels. Literature reports increased stroke risk in young adults with MTHFR polymorphism and elevated homocysteine levels.

Design/Methods:

A retrospective cohort study by querying electronic medical records to identify females with MTHFR gene polymorphism and IS. A descriptive analysis was performed.

Results:

A cohort of 12 females were identified, median age of 32 years (IQR 28,49), with MTHFR polymorphism and cryptogenic IS from 2021 to 2023. The MTHFR gene polymorphism included 3 patients with C677T heterozygosity, 4 with A1298C heterozygosity, 1 with A1298C homozygosity, and 4 with compound heterozygosity. Of these, 5 had experienced large vessel occlusion strokes, and 4 had a history of recurrent strokes while on optimal secondary stroke prevention. Risk factors were hormone therapy (HrT) in 8, migraine with aura in 9, and both migraine and HrT in 7 patients. Diagnostic workup revealed interatrial shunt in 3 patients, 1 with concomitant heterozygous Factor V Leiden and 1 with weakly positive lupus anticoagulant based on prolonged silica clot time. Comprehensive stroke workups with prolonged cardiac monitoring were negative, and all patients had normal homocysteine levels.

Conclusions:

MTHFR genetic polymorphisms, individually or in concert with other stroke risk factors, such as HrT or migraines with aura, may be associated with cryptogenic IS in young adult females. Further work exploring MTHFR polymorphism testing in the evaluation of cryptogenic IS in young adult females is warranted, even with normal serum homocysteine levels.