Immunogenetic Bases of Congenital Malformations: Association of HLA-B27 with Spina Bifida

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Abstract
Summary: A random sample of 46 families with single and multiple cases of spina bifida has been selected from families referred to the Institute of Pediatrics for genetic counseling. This sample constituted a group of 92 parents and 102 offspring: 41 normal, 46 with spina bifida, and 13 with spina bifida occulta. Routine HLA typing was performed on the parents and their children. For each case, 13 HLA specifities from locus A and 15 from locus B were determined. Segregation analysis in families showed excellent agreement with the expected values. HLA gene frequencies in the affected children as compared with a control population of 240 normal adults, revealed significantly higher frequency for HLA-B27 allele: X2 = 11.9515, P (corrected for the number of alleles) < 0.028. A significant relative risk of spina bifida development for a given HLA-B27 antigen was 2.7. In view of the presented results, routine HLA typing might be recommended for genetic counseling as a new tool for identification of high risk families. Speculation: A number of developmental genes mapped at the T locus in mice may interact in heterozygotes to produce offspring which are tailless or have spina bifida. Close chromosomal proximity of the T locus and the H-2 complex, as well as their evolutionary relationship, suggest that H-2 antigens might be considered as genetic markers of developmental events. The great homology between the H-2 chromosomal region in mice and the human HLA complex suggested the investigations on association between his-tocompatibility antigens and birth defects in man.