NEURAL TUBE DEFECTS (NTD): FAMILY STUDIES

Abstract

A population of 360 families, with at least one child with anencephaly and/or myelomeningocele or encephalomeningocele was ascertained by multiple selection in the Southern Poland where the birth prevalence of NTD is 0.89/1000. The probability of ascertairment π equalled 0:64; The population birth prevalence of NTD and the prevalence of NTD among the probands' sibs were used to calculate the relative risk and heritability. Complex segregation analysis by the method of maximum likelihood was applied in an attempt to discriminate between the hypotheses of single locus and that of quasi-continuity under multifactorial inheritance. A special program YUKONS in FORTRAN for Cyber 72 CDC computer was preapred. The recurrence risk of NTD among the probands' sibs was 3.4% ± 1.6, being about 39 times (X2 = 181.31 p < 0.0005) the population prevalence at birth. The heritability calculated on the regression of siblings on propositi was 76% ± 7. The results of complex segregation analysis excluded the hypothesis of multifactorial inheritance (X2= 18.186 df=46). The hypotheses of two allele model at a single autosomal locus fit the data with much better degree of exactness. Among the eight hypotheses the best conformity (X2 = 9.375 df=45) was observed for additive model (d = 0.5) with penetrance t=0.605 and frequency of phenocopies x = 0.546. These results suggest that major additive genes might be responsible for NTD inheritance.