Both of these disorders are more common in Hirschsprungs patients than in the general population. One function that RET controls is the travel of the neural crest cells through the intestines in the developing fetus. The earlier the RET mutation occurs in Hirschsprungs disease, the more severe the disorder becomes. Other genes
Common and rare DNA variations in the neuregulin 1 (NRG1) and NRG3 (NRG3) were first shown to be associated with the disease in Chinese patients through a Genome Wide Association Study by the Hong Kong team in 2009  and 2012, respectively Subsequent studies in both Asian and Caucasian patients confirmed the initial findings by the University of Hong Kong. Both rare and common variants in these two genes have been identified in additional Chinese, Thai, Korean, Indonesian, and Spanish patients. These two genes are known to play a role in the formation of the enteric nervous system; thus, they are likely to be involved in the pathology of Hirschsprungs disease, at least in some cases.Another gene associated with this condition is NADPH oxidase, EF-hand calcium binding domain 5 (NOX5). This gene is located on the long arm of chromosome 15 (15q23). Pathophysiology
During normal prenatal development, cells from the neural crest migrate into the large intestine (colon) to form the networks of nerves called the myenteric plexus (Auerbach plexus) (between the smooth muscle layers of the gastrointestinal tract wall) and the submucosal plexus (Meissner plexus) (within the submucosa of the gastrointestinal tract wall).
Surgery is also a treatment option. In epilepsy surgery (focal resection or hemispherectomy) the part of the brain which creates the abnormal electrical current through the brain must be resected, but the surgery is very complicated and needs to be performed by expert surgeons in epilepsy reference centers. None of these treatments, with the exception of some metabolic disorders with specific treatments available, have shown any efficacy at avoid long-term consequences of the disease. Prognosis
The prognosis is usually poor. Mortality rate is high during early infancy and almost half of the children die by 2 years of age. In the patient with severe phenotype, even when optimal treatment is initiated promptly, the prognosis remains poor. Most of the survivors suffer from psychomotor impairment and develop electroclinical features of other epilepsy syndromes (i.e Lennox- Gastaut syndrome). In patients with reduced phenotype, if there is early treatment initiated the better developmental outcome can be observed. Epidemiology
The prevalence estimates among EME are of <1 / 1 000 000. References


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