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Pancreatitis is a complex condition with multiple potential causes. When pancreatitis occurs in multiple closely related individuals, it warrants further investigation, which may include genetic counseling and/or genetic testing. The diagnosis of hereditary or familial pancreatitis should include the collection of a 3-generation family history and evaluation for other causes of pancreatitis in the family (e.g., gallstones, heavy alcohol use, cystic fibrosis). Genetic testing may help determine the presence of hereditary pancreatitis or familial pancreatitis in a family. Although they sound similar, there are important differences between these two diagnoses.
Hereditary pancreatitis is a rare and aggressive form of pancreatitis that typically presents in childhood. However, families with hereditary pancreatitis have substantial variability in age of onset, severity, and more. A diagnosis of hereditary pancreatitis [1, 2] requires (a) demonstration of a clear pattern of autosomal dominant inheritance in a family and/or (b) finding a known disease-causing variant in the PRSS1 gene. This presentation of disease in a family should be consistent with autosomal dominant inheritance – i.e. two or more individuals with recurrent acute or chronic pancreatitis across two or more generations of a family. The gene most commonly related to a hereditary pancreatitis diagnosis is PRSS1. Under normal circumstances, PRSS1 provides the body with instructions to make an important digestive enzyme. This enzyme is referred to as trypsinogen in its inactive form and trypsin in its activated form; variants in PRSS1 may cause trypsinogen to activate prematurely, causing damage to the tissue of the pancreas. However, some families with hereditary pancreatitis don’t yet have an identifiable genetic cause.
Familial pancreatitis is used to describe families with a higher incidence of pancreatitis than expected by chance. A diagnosis of familial pancreatitis requires at least two or more first- or second-degree family members with idiopathic pancreatitis not attributed to obstructive or environmental causes. Additional causes of pancreatitis that should be ruled out include PRSS1-hereditary pancreatitis and a CFTR-related disorder. Idiopathic refers to the unknown etiology, or cause, of the pancreatitis attacks. To rule out other causes, your healthcare provider may ask questions about your lifestyle behaviors, medications you’ve been on, and other details about your life. Genetic testing may be indicated to look for genetic variants associated with familial and/or hereditary pancreatitis.
The distinction between hereditary and familial pancreatitis is important to determine the cause of pancreatitis in a family and risk to other family members. Ultimately, the risk for family members to develop pancreatitis depends on both the presentation of pancreatitis within the family and the presence of known genetic contributions. Although genetic variants are expected to contribute to pancreatitis in hereditary and familial pancreatitis kindreds, not all families have a known genetic cause due to limitations in testing and research. Still, avoiding certain lifestyle behaviors like drinking alcohol or smoking cigarettes may reduce the severity of attacks or slow the progression of chronic pancreatitis even in individuals with genetic forms of pancreatitis. Speak to your healthcare provider if you have questions surrounding your diagnosis or the diagnosis of a loved one.