Etiopathological aspects of achalasia: lessons learned with Hirschsprung's disease

The etiology of primary esophageal achalasia is largely unknown. There is increasing evidence that genetic alterations might play an important but underestimated role. Current knowledge of the genetic base of Hirschsprung's disease in contrast is far more detailed. The two enteric neuropathies have several clinical features in common. This association may also exist on a cellular and molecular level. The aim of this review is to enlighten those etiopathogenetic concepts of Hirschsprung's disease that seem to be useful in uncovering the pathological processes causing achalasia. Three aspects are looked at: (i) the genetic base of Hirschsprung's disease, particularly its major susceptibility gene rearranged during transfection and its potential reference to achalasia; (ii) the altered motor functions in both conditions with loss of inhibitory innervation and interstitial cell pathology; and (iii) the involvement of these motility disorders in genetic syndromes.