Risk of Down syndrome among second- and third-degree relatives of a proband with trisomy 21

Previous studies indicate that parents who have had one child with trisomy 21 have an increased risk of having another affected child. To establish whether sibs, aunts, uncles, and cousins of an index case with trisomy 21 are also at increased risk for having an affected child, 219 kindreds of trisomy 21 probands were surveyed and compared with a control group of 247 kindreds. Control kindreds were ascertained through a child with a nonchromosomal disorder. Empiric risks were obtained and a risk interval calculated for each type of relationship. The results of this study suggest that for most families who have had a child with trisomy 21, the risk to second- and third-degree relatives is increased somewhat but still low (less than 1%). Analysis of those rare families who present with one or more affected second- or third-degree relative with trisomy 21 in addition to the proband suggests that they represent a small subpopulation with a markedly increased risk. Sibs and second-degree relatives in such families should be offered the option of amniocentesis, regardless of maternal age.