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 bee n 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 infan t 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 compatib le with a hypothesis that genetic risk factors for cerebral thrombosis coul d cause microinfarction in the brain stem during the first month of life, a ffecting vital centers or their blood supply. The presence of three common point mutations seen in families with thrombophilia (1691G-->A in the coagu lation factor V gene, 677C-->T in the methylenetetrahydrofolate reductase g ene, and the 20210G-->A mutation in the prothrombin gene) could increase th e risk for thrombosis in the child. This prompted us to investigate these g enetic markers of thromboembolic disease in 121 cases of sudden infant deat h syndrome and in relevant controls, in the expectation of a more frequent occurrence of these markers if thrombosis is an etiological factor in sudde n infant death syndrome. The frequency of homozygous 1691G-->A mutation in SIDS cases was higher than expected (odds ratio: 7.3, 95% confidence interv al, 1.2-45.8), The allele frequencies (theta) in cases of sudden infant dea th 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 all ele 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) diff ered significantly from that in cases of sudden infant death syndrome. In 5 ,251,027 inhabitants in Denmark, the incidence of venous thromboembolism wa s 0.9 per 1000 per year in the back ground population, and less than one-th ousandth of these were children. Consequently it is not likely that venous thrombosis is a major cause of sudden infant death syndrome. On the other h and, this does not exclude other known or unknown risk factors for thrombos is 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 su dden infant death syndrome if the phenomenon of sudden infant death syndrom e is to be ascribed to a specific hereditary disorder. (C) 2000 Elsevier Sc ience Ltd, All rights reserved.