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Introduction Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterised by autonomic dysfunction and impaired respiratory control. While advances in ventilatory support have improved survival, risk factors for mortality remain incompletely understood. Our objective was to investigate the impact of genetic and clinical parameters on mortality in children and young adults with genetically confirmed CCHS.Methods Data were collected from the European CCHS Consortium registry, encompassing patient information collected from 2012 to 2021. This dataset included information for 240 patients with genetically confirmed CCHS. Complete outcome data were available for 211 patients. Survival outcomes were analysed using Kaplan-Meier curves and Cox proportional hazards regression models.Results The overall mortality rate was 14% (95% CI 9% to 19%), with most deaths occurring in early childhood. The 25-year survival probability was 89% (95% CI 79% to 100%) for children and young adults with isolated CCHS, compared with 26% (95% CI 6% to 100%) for those with CCHS and Hirschsprung disease (HSCR), corresponding to a 6.8-fold increased risk of mortality (95% CI 2.2 to 21.1) associated with HSCR. In multivariable Cox models including genotype and HSCR as covariates, mortality risk was consistently associated with HSCR. While respiratory signs at initial presentation were comparable between groups, children with both CCHS and HSCR exhibited signs of more severe autonomic dysfunction, requiring more frequent resuscitation and intubation at birth.Conclusions HSCR is a key determinant of increased mortality in children with CCHS, likely because of its association with more extensive autonomic dysfunction.