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Major congenital malformations in Down syndrome
B Källén1, P Mastroiacovo, E Robert
1Tornblad Institute, University of Lund, Sweden.
Insights
Infants with Down syndrome (DS) have significantly higher risks for specific congenital malformations like annular pancreas and duodenal atresia. However, risks for neural tube defects and hydrocephaly are not increased in DS infants.
Area of Science:
- Medical Genetics
- Developmental Biology
- Pediatrics
Background:
- Down syndrome (DS) is associated with a spectrum of congenital anomalies.
- Understanding the specific malformation risks in DS is crucial for early diagnosis and management.
- Previous studies have identified some common malformations in DS, but comprehensive risk analysis across multiple malformation types is needed.
Purpose of the Study:
- To quantify the risk of 23 major congenital malformations in infants with Down syndrome (DS).
- To compare malformation prevalence in DS infants with non-DS infants using data from three congenital malformation registers.
- To investigate the influence of maternal age and sex on malformation occurrence in DS.
Main Methods:
- Retrospective analysis of major malformations in 5,581 infants with Down syndrome (DS).
- Comparison of birth prevalence rates for 23 malformations between DS and non-DS infants.
- Statistical analysis to determine risk ratios and investigate demographic factors.
Main Results:
- DS infants showed substantially increased risks (3-300 times) for annular pancreas, cataracts, duodenal atresia, megacolon, small choanal atresia, esophageal atresia, anal atresia, small bowel atresia, preaxial polydactyly, and omphalocele.
- Elevated risk ratios (3-5) were observed for cleft palate, cleft lip/palate, and limb deficiencies.
- No increased risk was found for neural tube defects, hydrocephaly, microtia, renal agenesis/dysgenesis, hypospadias, or non-preaxial polydactyly. Cardiac defects occurred in 26% of DS infants.
- Younger maternal age (<25 years) was linked to increased megacolon risk, while older maternal age showed a trend towards increased esophageal/anal atresia risk.
- Teenage mothers had a decreased risk for cardiac defects in DS infants, particularly endocardial cushion and ventricular septal defects.
Conclusions:
- Down syndrome is associated with a highly variable risk profile for congenital malformations, with some conditions being exceptionally common.
- Specific malformations like annular pancreas, duodenal atresia, and certain gastrointestinal atresias represent significant risks in DS.
- Maternal age influences the risk of certain malformations in DS infants, highlighting potential etiological factors and the need for tailored prenatal counseling.
Abstract:
We studied major malformations in 5,581 infants with Down syndrome (DS) from three registers of congenital malformations. THe prevalence at birth of 23 different malformations was compared with the program-specific rates for each malformation in non-DS infants. An about 300 times risk increase was seen for annular pancreas, cataracts and duodenal atresia and an about 100 times risk increase for megacolon and small choanal atresia. Esophageal, anal and small bowel atresia, preaxial polydactyly, and omphalocele all showed risk increases between 10 and 30 times. Statistically significantly elevated risk ratios around 3-5 were seen for cleft palate, cleft lip/palate, and limb deficiencies. No increased risk was seen for neural tube defects, hydrocephaly, microtia, renal agenesis or severe dysgenesis, hypospadias or polydactyly other than preaxial. Oral clefts were more often present in DS in the Swedish material than in the other two materials. Cardiac defects were registered in 26% of all cases (varying between programs) but 28% of the cardiac defects were unspecified. DS infants born to women younger than 25 years had a significantly increased risk for megacolon and there was a trend increasing risk for esophageal or anal atresia with maternal age. A decreased risk for cardiac defect in DS infants born to teenage mothers was found, quite pronounced for endocardial cushion defects and ventricular septum defects. There were no statistically significant differences in the sex distribution of specific malformations in infants with DS and in non-DS infants.