Sudden infant death syndrome, childhood thrombosis, and presence of genetic risk factors for thrombosis.
Sudden infant death syndrome or "cot death" has until the late eighties been a significant cause of death in children between the ages of 1 month and 1 year. Approximately two per 1000 children born alive dies of sudden infant death syndrome each year in Western Europe, North America, and Australia. The vulnerability of the infant brain stem to ischemia has been suggested to be a conceivable cause of sudden infant death syndrome. This is compatible with a hypothesis that genetic risk factors for cerebral thrombosis could cause microinfarction in the brain stem during the first month of life, affecting vital centers or their blood supply. The presence of three common point mutations seen in families with thrombophilia (1691G-->A in the coagulation factor V gene, 677C-->T in the methylenetetrahydrofolate reductase gene, and the 20210G-->A mutation in the prothrombin gene) could increase the risk for thrombosis in the child. This prompted us to investigate these genetic markers of thromboembolic disease in 121 cases of sudden infant death syndrome and in relevant controls, in the expectation of a more frequent occurrence of these markers if thrombosis is an etiological factor in sudden infant death syndrome. The frequency of homozygous 1691G-->A mutation in SIDS cases was higher than expected (odds ratio: 7.3, 95% confidence interval, 1.2-45.8). The allele frequencies (theta;) in cases of sudden infant death syndrome of the 1691G-->A, 677C-->T, and 20210G-->A alleles was 2.6% (1.0-5.5), 32.6% (26.8-38.9), and 0.9% (0.1-3.4), respectively. None of the allele frequencies found in the background population (3.4% for the 1691G-->A allele, 29% for the 677C-->T allele, and 1% for the 20210G-->A allele) differed significantly from that in cases of sudden infant death syndrome. In 5,251,027 inhabitants in Denmark, the incidence of venous thromboembolism was 0.9 per 1000 per year in the background population, and less than one-thousandth of these were children. Consequently it is not likely that venous thrombosis is a major cause of sudden infant death syndrome. On the other hand, this does not exclude other known or unknown risk factors for thrombosis as possible etiological factors for sudden infant death syndrome. It is likely that we must continuously employ the exclusion principle on possible etiological causes in genetic material from a large group of victims of sudden infant death syndrome if the phenomenon of sudden infant death syndrome is to be ascribed to a specific hereditary disorder.
Larsen
T B
TB
Department of Clinical Biochemistry, Vejle County Central Hospital, Vejle, Denmark. tblarsen@dadlnet.dk
Nørgaard-Pedersen
B
B
Lundemose
J B
JB
Rüdiger
N
N
Gaustadnes
M
M
Brandslund
I
I
D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003718:Denmark / Q000453:epidemiology; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007020:Hypoprothrombinemias / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency / Q000235:genetics; D010661:Phenylketonurias / Q000453:epidemiology; D017354:Point Mutation; D015995:Prevalence; D011446:Prospective Studies; D011516:Prothrombin / Q000235:genetics*; D012307:Risk Factors; D013398:Sudden Infant Death / Q000209:etiology*; D013923:Thromboembolism / Q000453:epidemiology; D019851:Thrombophilia / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D020246:Venous Thrombosis / Q000453:epidemiology
D020413:3' Untranslated Regions; D005819:Genetic Markers; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)