Hirschsprung disease, associated syndromes, and genetics: a review

Hirschsprung disease (HSCR, aganglionic megacolon) is the main genetic caus e of functional intestinal obstruction with an incidence of 1/5000 live bir ths. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intes tine. In the last decades, the development of surgical approaches has drama tically decreased mortality and morbidity, which has allowed the emergence of familial cases. HSCR appeared to be a multifactorial malformation with l ow, sex dependent penetrance and variable expression according to the lengt h of the aganglionic segment, suggesting the involvement of one or more gen e(s) with low penetrance. So far, eight genes have been found to be involve d in HSCR. This frequent congenital malformation now stands as a model for genetic disorders with complex patterns of inheritance.