The Epidemiology of PRSS1 Hereditary Pancreatitis and its Clinical Implications: A Systematic Review

Objectives: PRSS1-associated hereditary pancreatitis (HP) is a rare autosomal dominant disorder characterized by early disease onset. Although PRSS1 variants are recognized pathogenic factors, the epidemiology and clinical phenotype of PRSS1 hereditary pancreatitis remain inconsistently reported. This systematic review consolidates current evidence to define the genetic landscape, clinical profile, and implications for diagnosis and management. Methods: Following PRISMA guidelines, MEDLINE, EMBASE, and Cochrane CENTRAL were searched on 6 January 2025. All observational studies reporting genetic, clinical, or pain outcomes in PRSS1-associated hereditary pancreatitis were included. Methodological quality was appraised using Joanna Briggs Institute tools and data were synthesized narratively due to study heterogeneity. Results: Sixty-eight studies from multiple countries met inclusion criteria. Over 70% of individuals with PRSS1 associated HP presented before age 18, indicating early-onset disease. Pain and reduced quality of life were the most frequently reported clinical features, although assessment methods varied and validated instruments were used only in in few studies. Diabetes prevalence ranged from minimal in children to 14–26% in adults, with inconsistent reporting of diabetes type. PRSS1 R122H and N29I were the most common pathogenic variants, with additional pathogenic, benign, unknown and variants of uncertain significance also reported. Pancreatic cancer was rarely documented despite the elevated lifetime risk in this cohort. Conclusions: PRSS1-associated HP is characterized by early disease onset and substantial pain burden, but clinical reporting remains inconsistent. Standardized outcome measures and longitudinal multicenter studies are needed to improve comparability and prognostic insight