SNP Shot: Genomic Insights

Hereditary pancreatitis is a genetic disorder characterized by repeated episodes of pancreas inflammation (pancreatitis). The pancreas is responsible for producing digestive enzymes and insulin, a hormone regulating blood sugar (glucose) levels. Pancreatitis episodes can cause lasting tissue damage and impaired pancreatic function.

The condition typically manifests in late childhood with an acute pancreatitis attack. This sudden attack can cause abdominal pain, fever, nausea, or vomiting, usually lasting one to three days, although some experience more prolonged and severe episodes. Hereditary pancreatitis progresses to recurrent acute pancreatitis, characterized by multiple attacks over at least a year, with varying frequencies among individuals. This recurrent form can lead to chronic pancreatitis, a state of persistent pancreatic inflammation, typically developing by early adulthood. Symptoms of chronic pancreatitis include abdominal pain (occasional or frequent, with varying intensity), flatulence, and bloating. Many individuals with hereditary pancreatitis also develop calcium deposits in the pancreas (pancreatic calcifications) by early adulthood.

Over years, the inflammation damages the pancreas, leading to scar tissue formation (fibrosis) that replaces functional pancreatic tissue. This fibrosis often impairs the pancreas's ability to produce digestive enzymes, disrupting digestion and leading to fatty stools (steatorrhea), weight loss, and vitamin and protein deficiencies. Furthermore, due to reduced insulin production, about a quarter of those with hereditary pancreatitis develop type 1 diabetes mellitus by mid-adulthood, and the risk increases with age.

Chronic pancreatic inflammation and damage increase the risk of pancreatic cancer, particularly in those who also smoke, consume alcohol, have type 1 diabetes, or have a family history of cancer. Pancreatic cancer, if it develops, is typically diagnosed in mid-adulthood in affected individuals.

The most frequent causes of death in individuals with hereditary pancreatitis are complications from pancreatic cancer and type 1 diabetes mellitus. However, it is believed that individuals with this condition can still have a normal life expectancy.

Inheritance:

Hereditary pancreatitis caused by PRSS1 gene mutations follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene in each cell is sufficient to cause the disorder. An affected person may inherit the mutation from one affected parent, or it may arise from a new mutation in the gene, occurring in individuals with no family history of the condition. Notably, approximately 20 percent of individuals carrying the altered PRSS1 gene never experience a pancreatitis episode. This phenomenon is called reduced penetrance, and the reasons why some individuals with the mutated gene do not develop symptoms are not fully understood.