Hirschsprung’s Disease—Recent Understanding of Embryonic Aspects, Etiopathogenesis and Future Treatment Avenues

Hirschsprung’s disease is a neurocristopathy, caused by defective migration, proliferation, differentiation and survival of neural crest cells, leading to gut aganglionosis. It usually manifests rapidly after birth, affecting 1 in 5000 live births around the globe. In recent decades, there has been a significant improvement in the understanding of its genetics and the association with other congenital anomalies, which share the pathomechanism of improper development of the neural crest. Apart from that, several cell populations which do not originate from the neural crest, but contribute to the development of Hirschsprung’s disease, have also been described, namely mast cells and interstitial cells of Cajal. From the diagnostic perspective, researchers also focused on “Variants of Hirschsprung’s disease”, which can mimic the clinical signs of the disease, but are in fact different entities, with distinct prognosis and treatment approaches. The treatment of Hirschsprung’s disease is usually surgical resection of the aganglionic part of the intestine, however, as many as 30–50% of patients experience persisting symptoms. Considering this fact, this review article also outlines future hopes and perspectives in Hirschsprung’s disease management, which has the potential to benefit from the advancements in the fields of cell-based therapy and tissue engineering.