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Genetic-epidemiologic study of omphalocele and gastroschisis: evidence for heterogeneity
P Yang1, T H Beaty, M J Khoury
1Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Insights
Omphalocele (OM) and gastroschisis (GA) are distinct abdominal wall defects. Isolated cases suggest genetic inheritance, while multiple defects indicate a sporadic, non-genetic cause.
Area of Science:
- Medical Genetics
- Pediatric Surgery
- Birth Defects Research
Background:
- Omphalocele (OM) and gastroschisis (GA) are congenital abdominal wall defects.
- These conditions are generally considered pathogenetically distinct.
- OM is frequently associated with other malformations, unlike GA.
Purpose of the Study:
- To investigate heterogeneity between isolated and multiple defect cases of OM and GA.
- To analyze epidemiologic characteristics and familial risks associated with OM and GA.
- To determine the inheritance patterns for isolated versus multiple defect cases.
Main Methods:
- Analysis of epidemiologic data from a population-based study (82 OM, 81 GA cases).
- Stratification of infants into isolated and multiple defect groups.
- Examination of birth year, sex, race, and maternal age.
- Application of regressive logistic models to assess familial aggregation of birth defects.
Main Results:
- Significant differences in maternal age were observed between isolated OM and isolated GA cases.
- No significant maternal age differences were found between OM/GA cases with other defects.
- An autosomal recessive model best explained familial aggregation for isolated OM and GA.
- A sporadic, non-genetic model was most suitable for families with multiple defects.
Conclusions:
- Findings suggest heterogeneity within OM and GA based on the presence of other malformations.
- Isolated OM and GA may have different genetic underpinnings than cases with multiple defects.
- Results aid in estimating familial risk for these major birth defects.
Abstract:
On the basis of clinical manifestations, epidemiologic characteristics, and the presence of additional malformations, omphalocele (OM) and gastroschisis (GA) are considered casually and pathogenetically distinct abdominal wall defects. More than 50% of infants with OM have additional defects, but only about 15% of those with GA do. To evaluate whether there is heterogeneity between isolated and multiply affected cases of OM and GA, we analyzed epidemiologic characteristics and familial risks of major defects for 82 OM and 81 GA cases drawn from a population-based study in the Maryland-Washington, DC-Northern Virginia area and born from 1980 through June 1987. We examined year of birth, sex, race, and maternal age distributions after stratifying the infants into isolated and multiple defect groups. We found significant differences in maternal age between cases with isolated OM and GA, but not between cases with GA or OM who had other defects. Using regressive logistic models, we analyzed familial aggregation of birth defects among relatives of infants with OM and GA. An autosomal recessive model of inheritance was found to be the most parsimonious explanation for the families of infants with isolated OM or GA. However, for families of infants with multiple defects, a sporadic or nongenetic model fit best. These findings are not only useful for estimating familial risk of major birth defects, but they also suggest further heterogeneity of infants with OM and GA according to the presence of other malformations.