HYPOTHESIS - PATHOGENESIS OF SKIP AREAS IN LONG-SEGMENT HIRSCHSPRUNGS-DISEASE

The existence of skip areas in a subset of patients with long-segment Hirschsprung's disease (LSHD) is a rare phenomenon that poses practica l and theoretical challenges. In this paper, three new cases are descr ibed and compared with preceding reports in the medical literature. In addition, an analogous distribution of ganglion cell precursors is re ported in the developing large intestines of murine embryos, homozygou s for the lethal spotted (ls) allele. In ls/ls embryos which were dest ined to have ''classic'' short-segment aganglionosis coli, a transient phase was observed in which ganglion cells were present in the middle colon, but absent from the cecum and distal large intestine. This ''s kip area'' is attributed to an extramural phase of neuroblast migratio n which is unique to the colon. Persistence of an abnormal pattern of neuroblast migration, similar to that observed transiently in ls/ls em bryos, is invoked as an explanation for skip areas in humans with LSHD .