Is intestinal neuronal dysplasia a disorder of the neuromuscular junction?

Intestinal neuronal dysplasia (IND) is a malformation of the enteric plexus and clinically resembles Hirschsprung's disease. The pathogenesis of IND is not known. There is no information available regarding the nature of the neuromuscular junction in this disease. The authors examined immunohistochemically full-thickness biopsy specimens from 14 patients (aged 3 weeks to 26 months) with IND and 10 age-matched controls, using monoclonal antibodies to growth associated protein-43 (GAP-43), synaptophysin, and neural-cell adhesion molecule (NCAM) as neuromuscular junction markers. In the normal bowel, GAP-43, synaptophysin, and NCAM immunoreactivity was abundant in the submucous and myenteric plexuses as well as in the muscularis mucosae and circular and longitudinal muscle layers. However, of the biopsy specimens from patients with IND, five had absence of GAP-43, synaptophysin, and NCAM immunoreactivity in muscularis muscosae and the circular and longitudinal muscle layers; five had no immunoreactivity in the longitudinal muscle; and four had no immunoreactivity in the muscularis mucosae. The submucous and myenteric plexuses of all patients with IND displayed strong immunoreactivity for GAP-43, synaptophysin, and NCAM. The findings demonstrate that patients with IND have defective innervation of the neuromuscular junction of the affected bowel.