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Etiologic heterogeneity of neural-tube defects
Insights
Genetic counseling for neural tube defects like anencephaly needs careful consideration of underlying causes. Excluding Meckel syndrome cases significantly lowers recurrence risk rates for isolated defects.
Area of Science:
- Medical Genetics
- Developmental Biology
- Public Health
Background:
- Anencephaly, meningomyelocele, meningocele, and encephalocele are serious congenital malformations.
- Accurate etiological classification is crucial for appropriate genetic counseling.
- Previous recurrence risk assessments may not have sufficiently differentiated specific causes.
Purpose of the Study:
- To classify infants with neural tube defects by their underlying causes.
- To determine accurate precurrence and recurrence rates for isolated defects.
- To evaluate the impact of etiological heterogeneity on genetic counseling.
Main Methods:
- Classification of 106 stillborn and live-born infants with neural tube defects.
- Identification of genetic and nongenetic causes, including Meckel syndrome.
- Calculation of precurrence and recurrence rates based on etiological subgroups.
Main Results:
- Six distinct causes were identified, with 12% linked to Meckel syndrome or other genetic/nongenetic disorders.
- Overall precurrence and recurrence rates were 5.2% and 1.7% respectively.
- Excluding Meckel syndrome cases, isolated defect rates in white infants were 1.7% precurrence and 0% recurrence.
Conclusions:
- Etiological classification is essential for accurate genetic counseling regarding neural tube defects.
- Current genetic counseling risk rates (5%) may be overestimated for isolated cases.
- Differentiating Meckel syndrome and other specific causes refines recurrence risk assessment.
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.