Is there a familial link between Down's syndrome and neural tube defects? Population and familial survey.

OBJECTIVE To verify whether Down's syndrome and neural tube defects arise more often in the same family than expected by chance. DESIGN Population and familial survey. SETTING Network of maternity hospitals in the Latin American collaborative study of congenital malformations (ECLAMC) in Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Paraguay, Peru, Uruguay, and Venezuela between 1982 and 2000. PROBANDS 2421 cases of neural tube defects, 952 of hydrocephalus, and 3095 of Down's syndrome registered from a total of 1 583 838 live births and stillbirths. MAIN OUTCOME MEASURES Observed number of cases of Down's syndrome among siblings of probands with a neural tube defect or hydrocephalus and number expected on the basis of maternal age; observed number of cases of neural tube defects or hydrocephalus among siblings of probands with Down's syndrome and number expected according to the prevalence in the same population. RESULTS Five cases of Down's syndrome occurred among 5404 pregnancies previous to a case of neural tube defect or hydrocephalus, compared with 5.13 expected after adjustment by maternal age. Twelve cases of neural tube defect or hydrocephalus occurred among 8066 pregnancies previous to a case of Down's syndrome, compared with 17.18 expected on the basis of the birth prevalence for neural tube defects plus hydrocephalus in the same population. CONCLUSION No association occurred between families at risk of neural tube defects and those at risk of Down's syndrome.