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This webinar was presented on Wednesday 28 September 2022 by Dr. Roxana Rassouli-Kirchmeier from the Amalia Children’s Hospital in Nijmegen and Dr. Thomas Menter from the Institute of Medical Genetics and Pathology at University Hospital Basel. It is aimed at healthcare professionals. In this webinar, the pathophysiology of Hirschsprung disease is discussed in order to provide a deeper inside and understanding of the mechanisms of the disease. The presenters discuss their approach to an adequate work-up of biopsies taken to confirm or rule out this diagnosis. This approach is based on enzyme-histochemistry in order to evaluate the presence of neurons of the enteric nerve system and to evaluate the parasympathetic innervation. In addition, they demonstrate the respective findings by performing live microscopy of illustrative cases The ARM webinar series covers all aspects of paediatric colorectal surgery, in particular (congenital) anorectal malformations. They are joint presentations between ERNs eUROGEN and ERN ERNICA, and are supported by ARM-Net. ERN eUROGEN is the ERN for rare and complex urorectogenital diseases and conditions. For more information, visit www.eurogen-ern.eu. ERN ERNICA is the ERN for rare Inherited and Congenital (digestive and gastrointestinal) Anomalies. For more information, visit https://ern-ernica.eu. The ARM-Net Consortium is a group of professionals and patient representatives that aim to exchange data and knowledge to improve clinical care and to perform research on congenital anorectal malformations. For more information, visit https://www.arm-net.eu