Genetic risk factors associated with thrombosis in children with congenital neurologic disorders.
Thromboembolic events during the perinatal period are responsible for irreversible brain damage owing to cerebral hypoxia and neuronal necrosis. We investigated the presence of thrombophilia risk factors in children with congenital neurologic disorders. Nineteen children (9 males and 10 females), aged 1 to 14 years (median 4.5 years), who had presented with symptoms and signs of congenital neurologic disorders were studied. Thirty-five age-matched healthy children recruited from the same geographic area served as controls. Three patients of 19 (15.8%) were carrying the factor V Leiden mutation compared with 2 children among the controls (5.7%). One patient was heterozygous for the prothrombin G20210A variant (5.2%) compared with one child who was heterozygous among the controls. Three patients were homozygous (15.8%) and 11 were heterozygous (57.9%) for the C677T 5,10-methylenetetrahydrofolate reductase gene mutation compared with 4 (11.5%) and 18 (51.4%), respectively, among the controls. Three patients of 19 (15.8%) were carrying more than one mutation. We found 18 mutations in 79% (15/19) of the patients and 25 mutations in 69% (24/35) of the healthy children. Among the individuals carrying the homozygous 677TT 5,10-methylenetetrahydrofolate reductase genotype, we found 7 mutations in 32% (6/19) of the patients and 7 mutations in 20% (7/35) of the healthy children (P > .05). In one patient, lupus anticoagulant and antiphospholipid antibodies of IgG isotype were detected. Reduced activities of protein C, protein S, or antithrombin III were not observed in either the patient or the control group. Although, among our cases, we found some well-known risk factors associated with thrombosis in adults, the pathogenesis of these clinical entities remains obscure.
Tzoufi
Meropi
M
Department of Pediatrics, Unit of Molecular Biology, University Hospital of Ioannina, Ioannina, Greece.
Giotopoulou
Stella
S
Papadimitriou
Photeini
P
Dokou
Eleni
E
Kolaitis
Nikolaos I
NI
Siamopoulou
Antigoni
A
Vartholomatos
George
G
D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2) / Q000235:genetics; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005165:Factor V / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D009422:Nervous System Diseases / Q000150:complications* / Q000151:congenital* / Q000235:genetics; D011516:Prothrombin / Q000235:genetics; D012307:Risk Factors; D013923:Thromboembolism / Q000209:etiology* / Q000235:genetics*
D005819:Genetic Markers; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2)