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Keywords:

  • congenital malformations;
  • neural tube defects;
  • spina bifida cystica;
  • autosomal dominant inheritance;
  • likelihood analysis of causal factors

Abstract

Four families were selected randomly on the basis of the occurrence of spina bifida cystica and/or spina bifida occulta in one or more family members. Sixty-three relatives were studied clinically and roentgenologically; their roentgenograms were evaluated blindly. Twenty-eight were clinically and roentgenologically normal; 35 were diagnosed as having spina bifida occulta (SBO), spina bifida cystica (SBC), vertebral anomalies, and/or external defects usually interpreted as evidence for SBO. Excluding one proband we found the frequency of SBO to be 19/51 (37%) and the frequency of all types of spinal/vertebral defects (excluding five probands) to be 30/58 (52%). The distribution of these defects in the four families was analyzed using likelihood methods corrected for random ascertainment.

The log likelihood values for sporadic, recessive, and dominant models were −26.69, −20.95, and −18.90, respectively, indicating a higher likelihood of autosomal dominant inheritance than sporadic occurrence or recessive inheritance. The penetrance probability in this dominant model, estimated by maximum likelihood, is 0.749 ± 0.100. Further examination of these data suggests that SBO and SBC represent different expressions of the same dominant gene in these kindreds.