Hirschsprung's disease (HD) or aganglionosis of the intestine is the most common cause of surgically addressed constipation in neonates, infants, and children. The pathology is a lack of migration, differentiation, and maturation of ganglion cells populating the enteric nervous system. This lack of ganglion cells or dysplasia results in disordered motility, constipation, and possibly enterocolitis and death if un-treated. It's genetic transmission is poorly understood, although familial inheritance is recognized and accepted. The workup and evaluation of infants with siblings or parents with HD is often delayed causing morbidity due to this lack of acceptance and understanding. The incidence of familial inheritance of HD ranges from 3% to 7%. The extent of involvement of the aganglionosis, i.e., total colon, increases the likelihood of inherited HD to as high as 20%. Reports exist in the literature of multiple occurrences of HD in documented multigenerational families. Factors that influence phenotypic variability in "single" gene disorders are protein-activity thresholds, modifier genes, and systems dynamics. With the involvement of multiple genes and various mutations and sequence variations in the phenotype, and with patterns of inheritance including dominant, recessive, and polygenic, Hirschsprung's disease represents a model for genetic diseases spanning the spectrum from simple to complex.
Although stem cell properties have been characterized in many tissues, we are only beginning to understand how stem cell function is regulated at the molecular level. (Natarajan, C. Marcos-Gutierrez, V. Pachnis, E. de Graaff, 51) Gene expression profiles have been described for uncultured hematopoietic stem cells and cultured central nervous system neurospheres, but not for prospectively identified, uncultured neural stem cells. O. (N. Suslov, V. C. Kukekov, T. N. Ignatova, D. A. Steindler 394) Because stem cell properties change in culture, the gene expression profile of uncultured neural stem cells might better reflect their properties in vivo. (M. Ramalho-Santos, S. Yoon, Y. Matsuzaki, R. C. Mulligan, D. A. Melton 597)..............
