Health-Related Quality of Life in Georgian Children with Mendelian Disorders of the Epigenetic Machinery: A Cross-Sectional Study

Abstract

Background: Mendelian disorders of the epigenetic machinery (MDEMs) represent a heterogeneous group of rare neurodevelopmental syndromes caused by pathogenic variants in genes encoding key components of the epigenetic apparatus. These conditions are commonly associated with intellectual disability, behavioral problems, multisystem comorbidities, and functional limitations, all of which are expected to affect health-related quality of life (HRQL) negatively. Objectives: To evaluate HRQL in children with MDEMs in Georgia using the Patient-Reported Outcomes Measurement Information System (PROMIS). Methods: In this cross-sectional study, 12 children aged 5–17 years with a diagnosis of MDEMs were enrolled. HRQL was assessed using PROMIS Parent Proxy Profile measures across five domains: anxiety, depressive symptoms, fatigue, pain interference, and physical functioning. Associations between HRQL domains and demographic and clinical variables were explored using correlation analyses. Results: PROMIS assessments demonstrated reduced HRQL across all evaluated domains. The highest symptom burden was observed in fatigue (M=62.4) and pain interference (M=60.2), followed by anxiety (M=58.1) and depressive symptoms (M=54.0). Physical functioning was reduced (M= 38.3). Conclusions: Children with MDEMs in Georgia exhibit markedly compromised HRQL. Routine assessment of HRQL may support more comprehensive clinical care. Further studies with larger cohorts are needed to better define HRQL patterns in individuals with MDEMs.