*3.1.1 Genetic causes*

Genetic conditions that predispose to recurrent episodes of pancreatitis are the cystic fibrosis transmembrane conductance regulator-gene (CFTR-gene), PRSS1 gene and SPINK1-gene mutations.

**CFTR-gene** mutations occur in about 5% of Western populations and cause an altered function of the product of this gene with a defect in the transmembrane epithelial chloride ion transfer. This dysregulation affects different organs including the pancreas and results in an abnormal production of viscous exocrine secretions that lead to ductal obstructions. Mutations in the cationic trypsinogen gene (**PRSS1-gene**) have been matched in patients with hereditary pancreatitis. The pancreas is unable to contrast an excessive trypsin activation because of the lack of protective mechanism predisposing patients to recurrent episodes of pancreatitis in childhood.

**SPINK1-gene** mutations predispose to the development pancreatitis and involve the serine protease inhibitor Kazal type I gene (SPINK1). This mutation results in a defect of the protective action in the pancreas mediated by SPINK1 protein that represents a feedback inhibitor of trypsin activation. Approximately 16–23% of patients with idiopathic pancreatitis have SPINK1 mutations instead [18].
