Birth defects in uncles and aunts from Irish families with neural tube defects

Previous studies suggested an excess of matrilineal cases of neural tube defects among distant relatives in NTD families. There is little information on patterns of heredity of other birth defects among distant relatives.

Between 1995 and 2003, 78 nuclear families and 373 uncles and aunts were interviewed about birth defects among uncles and aunts in Irish families with an NTD.

Among 783 total uncles and aunts, those related through the mother had more birth defects overall than those related through the father (8.4 vs. 4.0%, p = 0.01). The excess persisted after controlling with logistic regression models for maternal and paternal age, gender of uncle/aunt, proband's NTD diagnosis, and year of birth (OR 2.52; 95% CI: 1.29, 4.91; p = 0.007). Among individual birth defects, significant excesses over expected rates were seen for spina bifida, congenital heart defects, and syndactyly.

This study of reported birth defects suggests that maternal uncles and aunts in Irish families have significantly more birth defects than paternal uncles and aunts. These results, if confirmed, support the hypothesis that NTD relatives carry a susceptibility to other birth defects, preferentially on the mother's side of the family, suggesting opportunities for prevention. Birth Defects Research (Part A) 2008.