Risks to sibs of probands with neural tube defects: Data for clinic populations in British Columbia

Abstract

The purpose of this study is to determine whether couples receiving genetic counselling because of a child with a neural tube defect (NTD) are a selected group and therefore not representative of the general population with respect to sib risks for NTDs. British Columbia (B.C.) provides an excellent opportunity to look at this for several reasons. Firstly, genetic counselling services are centralized. Secondly, there is virtually complete ascertainment of all infants with NTDs in the province. Thirdly, sib risks for NTDs in the general population have been derived previously [McBride, 1979] and, therefore, are available for comparison with the risks for sibships in the clinic populations. In the present study, data were available on 398 sibships in which the index case had anencephaly and/or spina bifida. In all instances, sib risks for the clinic populations did not differ significantly from those for the general population. In addition, congenital malformations other than NTDs did not occur among sibs of index cases more often than expected, based on provincial incidence data.

An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure

“…For human NTDs, the degree to which anencephaly and spina bifida aperta share the same genetic risk factors or have risk factors specific to only the cranial or only the caudal neural tube is not known. Among human families with two NTD siblings, in the decades before folate supplementation, 30 to 50% had one sibling with anencephaly and one with spina bifida (McBride,1979; Keena et al,1986; Drainer et al,1991). The data suggest that some families have risk of only anencephaly or only spina bifida, but that the genetic liability in many families likely creates a risk for both defects.…”

Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects

“…For human NTDs, it appears that 30–50% of families with two affected sibs have one with anencephaly and one with spina bifida (McBride, 1979; Czeizel and Metnecki, 1984; Keena et al, 1986; Drainer et al, 1991). If the risk is equal, within these families, for anencephaly and spina bifida, the probability of having one of each type is simply calculated as 50%.…”

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“…Canada became part of an international trial to examine this question, and the clinical genetics and prenatal diagnostic services of BC were included (114). This allowed us to accumulate a great deal of information and to recognize subgroups of neural tube defects with increased risk (79,103,114,130,131). Based on mouse work done in BC that showed multiple neural tube closure sites, we published our BC data on human families in which fetuses exhibited vulnerabilities at certain developmental sites (143).…”