The gastrointestinal tract in Down syndrome.

Down Syndrome is recognized as one of the most common predisposing conditions for a group of serious gastrointestinal (GI) anomalies. Tracheo-esophageal fistula, duodenal obstruction with or without pyloric stenosis, annular pancreas, imperforate anus and Hirschsprung's disease are the most prevalent lesions. Understanding of the morphogenetic mechanisms responsible for this range of abnormalities is far from clear, as none of the lesions is specific to the trisomic state and the underlying defects (i.e., failure of foregut canalization, failure of neural crest cell migration into the myenteric and submucosal plexuses or malformation of the anterior abdominal wall, etc) are encountered in unaffected infants. Segregation analysis of inheritance patterns points to multi-factorial traits and random genetic action provide appropriate models (to a certain extent) for describing the observations. Furthermore, intestinal anomalies can be found in many other genetic disorders, with recent evidence suggesting the presence of GI developmental regulatory genes on chromosome 13q. A possible common pathway to the observed anomalies might be enhanced epithelial adhesiveness, as demonstrated in vitro experiments with fibroblasts. Molecular genetic techniques applied to the smallest human autosome could provide the needed insight into the ultimate mechanisms determining morphogenesis. The development of a murine model is a promising tool for the successful approach to these extraordinarily complex questions.