BACKGROUND: Hirschsprung disease (HSCR) is a frequent congenital disorder with 
an incidence of 1 in 5000 live births, characterised by the absence of 
parasympathetic intramural ganglion cells in the hindgut resulting in intestinal 
obstruction in neonates and severe constipation in infants and adults. 
Intestinal neuronal dysplasia (IND) shares clinical features with HSCR but the 
submucosal parasympathetic plexus is affected. IND has been proposed as one of 
the most frequent causes of chronic constipation and is often associated with 
HSCR.
METHODS: We examined 29 patients diagnosed with sporadic HSCR, 20 patients with 
IND, and 12 patients with mixed HSCR/IND for mutations in the coding regions of 
the RET, GDNF, EDNRB, and EDN3 genes. The entire coding regions were analysed by 
single strand conformational polymorphism and DNA sequencing.
RESULTS: Only three RET mutations were detected in patients with HSCR. In 
patients with IND or a mixed HSCR/IND phenotype, no mutations in these genes 
were observed. While HSCR and HSCR/IND showed over representation of a specific 
RET polymorphism in exon 2, IND exhibited a significantly lower frequency 
comparable with that of controls.
CONCLUSIONS: The mutation frequency found in our sporadic HSCR patients (10%) 
and the allelic distribution of RET polymorphisms are comparable with earlier 
published data. A significantly different allelic distribution in an established 
HSCR associated polymorphism argues against common genetic pathways for HSCR and 
IND.