A Novel F5 Gene Variant Associated With Early-Life Ischemic Brain Injury in a Child With a Familial Coagulation...

Perinatal and early-life arterial ischemic stroke are important causes of hemiparesis and lifelong neurodevelopmental morbidity. While many cases are considered idiopathic, inherited thrombophilia is increasingly implicated in selected patients. We report an infant who developed right-sided motor impairment recognized at nine months of age. He was born at term after an uncomplicated pregnancy, although the neonatal period was complicated by transient respiratory distress and a small atrial septal defect requiring brief neonatal intensive care admission. Examination demonstrated right spastic hemiparesis, delayed speech development, mild dysmorphic facial features, and bilateral fifth-finger clinodactyly. Brain magnetic resonance imaging showed left-sided cerebral and cerebellar volume loss with a focal left thalamic lesion, consistent with a remote ischemic insult. Hematologic evaluation identified sickle cell trait. Whole-exome sequencing revealed a heterozygous c.3482G>A (p.Arg1161Gln) variant in the F5 gene, associated with activated protein C resistance and classified as a variant of uncertain significance. No recurrent thrombotic events have occurred to date, and the patient remains clinically stable under conservative hematologic follow-up. This case supports the concept that early-life ischemic brain injury may arise from the interaction of multiple prothrombotic factors rather than a single isolated abnormality. The coexistence of sickle cell trait and a rare F5 variant associated with activated protein C resistance may have contributed to a lowered thrombotic threshold in this patient. Comprehensive thrombophilia and genetic evaluation may therefore provide important diagnostic and risk-stratification value in children with otherwise unexplained early ischemic stroke.