Inidcations for prenatal diagnosis in relatives of patients with neural tube defects

Abstract

We have reviewed the family histories of children with neural tube defects to determine which relatives are at sufficient risk to be offered amniocentesis for prenatal diagnosis. The recurrence risks for sibs was 6%; therefore, women with one affected child should be made aware of the availability of this test for monitoring subsequent pregnancies. The empiric recurrence risks for various groups of second and third degree relative exceeds 1% only for mothers' sisters' children. The lower values for the other groups may reflect either true biologic differences of reporting biases. Unit the matter is clarified, all sibs of affected children and all sibs of the parents of affected children should be informed of the availability of amniocentesis for monitoring their (or their spouse's) pregnancies.

PIP: To assess the risk for 2nd- and 3rd-degree relatives of patients with open neural tube defects and thereby identify appropriate candidates for prenatal diagnosis, the histories of 133 families having at least 1 offspring with anencephaly or spina bifida and 13 having disorders unrelated to neural tube defects were reviewed. Mothers of the affected children had a total of 598 pregnancies yielding 364 full and 13 half sibs (12.5% miscarriage rate). 22 of the full sibs were themselves affected with anencephaly or spina bifida, giving a 6% overall recurrence rate among sibs. This statistic is higher than the 4-5% usually cited, due perhaps to the small sample size or the high prevalence of these disorders in the Quebec population. Previous miscarriage does not seem to be a significant factor in determining recurrence risk. The defect rate among 1st cousins (parents' sibs' children) was 0.7% overall, with the rate for maternal cousins (0.9%) higher than that for paternal cousins (0.5%) and the risk for mothers' sisters' children (1.3%) especially high. There were no cases of neural tube defects among mothers' sibs, but a 0.7% rate among fathers' sibs, giving an overall risk of 0.4% for 2nd-degree relatives. This finding is striking since recall biases and a maternal effect should enrich the sample for affected sibs of the mother. It is concluded that although the recurrence risk exceeds 1% (the current criteria for candidates for prenatal testing) only for mothers' sisters' children, all 2nd- and 3rd-degree relatives should be given the option of amniotic AFP testing until it can be determined whether the lower risk values for other groups reflect true biologic differences or reporting biases.