Hirschsprung Disease and Other Enteric Dysganglionoses

Abstract

Hirschsprung disease has become a paradigm for multigene disorders because the same basic phenotype is associated with mutations in at least seven distinct genes. As such, the condition poses distinct challenges for clinicians, patients, diagnostic pathologists, and basic scientists, who must cope with the implications of this genetic complexity to comprehend the pathogenesis of the disorder and effectively manage patients. This review focuses on the anatomic pathology, genetics, and pathogenesis of Hirschsprung disease and related conditions. The nature and functions of “Hirschsprung disease genes” are examined in detail and emphasis is placed on the importance of animal models to this field. Where possible, potential uses and limitations of new data concerning molecular genetics and pathogenesis are discussed as they relate to contemporary medical practices.

KEYWORDS: :

• aganglionosis
• megacolon
• pseudoobstruction
• intestinal neuronal dysplasia
• hypoganglionosis
• enteric nervous system
• ret
• endothelin
• neurocristopathy.