Anorectal malformations associated with enteric dysganglionosis in Danforth's short tail (Sd) mice.

BACKGROUND: The spontaneous mutant Danforth's short tail (Sd) mouse has been studied over the last 60 years from the morphological, embryological, and genetic point of view. The Sd mutation affects a gene essential to notochordal development, and the Sd mouse phenotype represents an analogue of human caudal regression syndrome. The Sd/Sd mouse presents different types of anorectal malformations (ARM) and was suggested as a simple and cheap model of investigation of ARM morphology and embryology. In the current study, the Sd mouse enteric nervous system (ENS) was thoroughly investigated with specific immunohistochemical markers. METHODS: Macroscopic analysis, normal histology, and immunohistochemical techniques for detecting neurofilaments (NF) and NOS1 were used to study ENS of 138 Sd mice and 25 controls. RESULTS: The surprising results of this study showed that Sd mutation is associated with different degrees of hypoganglionosis and aganglionosis. In 41% of Sd/SD-affected mice, the rectal pouch was aganglionic and in the remaining 58% was severely hypoganglionic. In addition, 4.1% of heterozygous mice presented a distal aganglionosis and 8.3% hypoganglionosis. CONCLUSIONS: These results suggest that Sd mutation independently affects distinct cell lines during early organogenesis, as notochord cells, ventral hingut endoderm, and neuroblasts migrating from neural crest cells. Comparing the Sd murine model with human pathology, this study confirms that the association between ARM and intestinal dysganglionosis is not rare and underlines the importance of detecting in every ARM patient the innervation abnormalities of rectal pouch and fistulas.

[Constipation and chronic intestinal pseudoobstruction as a clinical expression of intestinal neuronal dysplasia (IND)]. / Stipsi e pseudo-ostruzione intestinale cronica come espressione clinica di displasia neuronale intestinale (IND).

BACKGROUND: Intestinal neuronal dysplasia (IND) belongs to the group of dysganglionosis. It may occur as part of a syndrome of early chronic constipation, neonatal intestinal occlusion, chronic intestinal pseudo obstruction. The aim of this study was to report the cases examined by the Istituto G. Gaslini in Genoa and to discuss the numerous aspects of this disease which are still unclear. METHODS: 787 children were included in the study and underwent biopsy between 1984 and 1997. Rectal biopsies were obtained by suction or in some cases during surgery and were treated using enzymohistochemical techniques, such as acetylcholinesterase, rapid acetylcholinesterase and alpha-naphthylesterase. RESULTS: 574 children were found to be suffering from innervative alterations: 348 (60.6%) presented isolated Hirschsprung's disease, IND was found in 83 (14.5%), in 8 of the latter in association with other dysganglionosis. IND was accompanied by other diseases in 40 cases (48.2%). Over the past three years (since October 1994) a total of 164 dysganglionosis have been diagnosed, including 55 cases of aganglia. During this period IND was the most frequently observed alteration and affected 61 children. CONCLUSIONS: Rectal biopsy is the essential diagnostic test for the diagnosis of intestinal dysganglionosis. Biopsies are performed in outpatient clinics without sedation, and do not represent an invasive procedure for the young patients. Radiological and manometric examinations cannot provide reliable data for the diagnosis of IND. In our experience, the incidence of IND over the past few years has increased and its diagnosis is essential for correct treatment which is not surgical in the majority of cases. The real incidence of IND and its pathogenesis still need to be clarified.