A narrative review on the role of genetics in children with acute recurrent pancreatitis and chronic pancreatitis

ABSTRACT The incidence of pancreatitis in children has increased over the past two decades. With advances in molecular biological techniques and clinical research, genetic variations have emerged as a pivotal etiological factor in pediatric pancreatitis. This review aims to summarize recent clinical research advancements in understanding pediatric pancreatitis caused by various gene mutations. As of the year 2020, researchers had identified 12 genes implicated in the pathogenesis of pancreatitis. These genes primarily contributed to the development of pancreatitis through three mechanisms. Pancreatitis resulting from these gene mutations exhibits several distinct characteristics, including early onset, a heightened risk of developing pancreatic duct stones, rapid disease progression, and a significantly increased risk of pancreatic endocrine and exocrine dysfunction, as well as pancreatic cancer in the future. Genetic sequencing is recommended for children with pancreatitis based on six indications. The sequencing not only assists in the clinical diagnosis but also enhances our understanding of the pathophysiology of pancreatitis. By 2020, 12 genes were involved in the pathogenesis of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children, especially PRSS1, SPINK1, and CFTR. These genes induce pancreatitis mainly through three mechanisms: trypsin‐dependent pathway, protein misfolding, and ductal abnormalities. Pancreatitis caused by related gene mutations has the characteristics of early onset, high risk of pancreatic duct stones, rapid progression, and significantly increased risk of pancreatic endocrine and exocrine dysfunction and pancreatic cancer in the future. Sequencing‐related genes are helpful in clarifying the etiological diagnosis, monitoring disease progression, and evaluating prognosis in children with ARP and CP. （The illustration was drawn by Figdraw: www.figdraw.com）