Hirschsprung's disease is characterized by the absence of ganglion cells in the 
myenteric and submucosal plexuses of the gastrointestinal tract. Genetic 
dissection was successful as nine genes and four loci for Hirschsprung's disease 
susceptibility were identified. Different approaches were used to find these 
loci such as classical linkage in large families, identity by descent mapping in 
an inbred kindred, candidate gene approaches based on naturally occurring mutant 
mice models, and finally the use of model-free linkage and association analyzes. 
In this study, we review the identification of genes and loci involved in the 
non-syndromic common form and syndromic Mendelian forms of Hirschsprung's 
disease. The majority of the identified genes are related to Mendelian syndromic 
forms of Hirschsprung's disease. The non-Mendelian inheritance of sporadic 
non-syndromic Hirschsprung's disease proved to be complex; involvement of 
multiple loci was demonstrated in a multiplicative model. We discuss the 
practical implications of the elucidation of genes associated with 
Hirschsprung's disease susceptibility for genetic counseling. Finally, we 
speculate on possible strategies to identify new genes for Hirschsprung's 
disease.