AUTOANTIBODIES IN DOWN'S SYNDROME AND GONADAL DYSGENESIS *

Increased frequency of thyroid antibodies has been noted both in patients with Down’s and in those with gonadal dysgenesis.6-8 In general terms, the association could be explained by one of two mechanisms. Aneuploidy in an individual may predispose him to develop thyroid autoantibodies, or alternatively, thyroid antibodies or a related factor may predispose him to aneuploidy. In the latter case, it is necessary to postulate that a factor associated with thyroid antibodies in a parent predisposes to aneuploidy in the child. The increased frequency of maternal thyroid dysfunction, claimed by many, but not all, studies of the mothers of patients with Down’s syndrome, would be compatible with this sugge~tion.~,9-14 No reports of parental thyroid evaluation in gonadal dysgenesis have yet appeared, but several observers have noted examples of parental thyroid antibodies.8J5816 These observations suggested that a large group of parents of children with chromosomal abnormalities should be tested for thyroid antibodies. If the antibodies in patients with chromosomal aberrations are secondary to these aberrations, then one need not expect to find thyroid antibodies in the parents who do not themselves have chromosomal disorders. On the other hand, an increased frequency of thyroid antibodies would be compatible with the suggestion that a factor related to the antibodies predisposes these parents to having a child with a chromosomal abn0rma1ity.l~ Initially we measured thyroid antibodies in the families of children with Down’s ~yndrome,~J* primarily because they were more available to us than families of patients with gonadal dysgenesis. In that study of 148 mothers of children with Down’s syndrome and 148 controls, a significantly increased frequency of thyroid antibodies was noted in the mothers of children with Down’s syndrome. Since that time our study has been expanded to include 242 families of patients with Down’s syndrome and the data have been analyzed in relation to maternal age. Antinuclear factors, gastric parietal-cell antibodies, and rheumatoid factors have also been measured. In addition, a smaller group of families with gonadal dysgenesis has been tested.