Genetic and environmental risk factors for sagittal craniosynostosis

The authors investigated whether genetic and environmental factors influence risk for sagittal craniosynostosis. Cases were ascertained from craniofacial clinics in the Baltimore-Washington metropolitan region. Controls were recruited from the Johns Hopkins newborn nursery and a large pediatric practice in Baltimore County. Forty-two probands with isolated, nonsyndromic sagittal craniosynostosis born in the mid-Atlantic region were included in this analysis. Controls are infants born in Maryland without any known birth defects (n = 182). Odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated. Cases were genotyped at several loci implicated in malformation syndromes including craniosynostosis. There were no elevated risks for craniosynostosis related to maternal or paternal smoking or maternal vitamin usage. Case mothers consumed less alcohol (OR = 0.38, 95% CI = 0.17-0.85) and had less education than control mothers (P < 0.001). All cases that were sequenced were negative for mutations at the following genes: FGFR1 exon IIIa 755C->G, FGFR2 (exons IIIa and IIIc, , FGFR3 exon IIIa, and TWIST exon 1. These findings suggest that whereas TWIST and the FGFR genes are important for syndromic craniosynostosis, they are unlikely to be involved in isolated sagittal craniosynostosis. Parental education and alcohol consumption were associated with sagittal craniosynostosis in this study.