Etiologic Heterogeneity of Neural-Tube Defects

TLDR

The study classified 106 infants with anencephaly, meningomyelocele, meningocele and encephalocele by their recognized etiologic categories. Six distinct etiologies were identified, with 12 % of cases involving nongenetic disorders or Meckel syndrome, leading to recurrence rates of 1.7 % for isolated defects—much lower than the 5 % risk currently used in genetic counseling.

Abstract

We classified 106 stillborn and live-born infants with anencephaly, meningomyelocele, meningocele and encephalocele according to the recognized causes of these malformations. Six different causes were identified, including both genetic and nongenetic disorders; 12 per cent had nongenetic disorders, a chromosome abnormality, or an encephalocele as part of the autosomal recessive Meckel syndrome. Therefore, for this 12 per cent genetic counseling normally provided for isolated anencephaly, meningomyelocele or encephalocele would have been incorrect. If all infants were considered together regardless of cause, the precurrence and recurrence rates of similar malformations in the sibs were 5.2 and 1.7 per cent respectively. However, if infants with other disorders, especially the Meckel syndrome, were excluded, the precurrence and recurrence rates for isolated anencephaly, meningomyelocele and encephalocele among white infants were only 1.7 per cent and 0 per cent. These rates are much lower than the risk of 5 per cent currently being used in genetic counseling in the United States.