Clinical Information

Hereditary pancreatitis (HP) is a rare autosomal dominant disorder associated with approximately 80% penetrance. HP is characterized by early onset acute pancreatitis during childhood or early adolescence. The acute pancreatitis in these patients generally progresses to chronic pancreatitis by adulthood and can eventually lead to both exocrine and endocrine pancreatic insufficiency. Patients with HP are also at an increased risk for developing pancreatic cancer. Studies have estimated the lifetime risk of developing pancreatic cancer to be as high as 40%.

Mutations in the protease serine 1 or cationic trypsinogen (PRSS1) gene are a common cause of HP. It has been reported that as many as 80% of patients with symptomatic hereditary pancreatitis have a causative PRSS1 mutation. HP cannot be clinically distinguished from other forms of pancreatitis. However, PRSS1 mutations are generally restricted to individuals with a family history of pancreatitis. PRSS1 mutations are infrequently found in patients with alcohol-induced and tropical pancreatitis.

Although several mutations have been identified, the R122H, N29I and A16V mutations are the most common disease-causing mutations associated with HP. Data suggest that the R122H mutation results in more severe disease and earlier onset of symptoms than the A16V mutation. Although these 3 alterations account for >90% of mutations detected in the cationic trypsinogen gene, the inability to identify mutations in approximately 20% of families with HP suggests the involvement of other loci or unidentified mutations in the cationic trypsinogen gene.

Mutations in other genes, such as SPINK1, CFTR and CTRC have been associated with hereditary and familial pancreatitis. Abnormalities in these genes are not detected by this assay. However, genetic testing for these genes simultaneously, including PRSS1, is available by ordering HPPAN / Hereditary Pancreatitis Panel.