Familial and Hereditary Pancreatitis

Hereditary and familial pancreatitis are related but distinct. Hereditary pancreatitis is associated with an inherited disease-causing genetic variant, most commonly in the PRSS1 gene that codes for trypsinogen (or trypsin when activated). Familial pancreatitis describes a pattern in which multiple family members have pancreatitis, even when a specific genetic cause has not been identified.

‍

Hereditary Pancreatitis

Hereditary pancreatitis is a rare genetic condition that can cause repeated episodes of acute pancreatitis and may progress to chronic pancreatitis.

‍

Most hereditary pancreatitis is associated with disease-causing variants in the PRSS1 gene that increase activation of trypsin or delay it's inactivation. To much active trypsin within the pancreas caused acute pancreatitis. A limited number of PRSS1 genetic variants increase trypsin activity and are usually inherited in an autosomal dominant pattern, meaning a person only needs one disease-causing variant to be at risk. However, not everyone with a gain-of-function PRSS1 variant develops pancreatitis, and the risk varies depending on the specific variant and other factors.

‍

Hereditary pancreatitis can also occur without a family history. In some cases, a genetic change occurs for the first time in an individual, or a parent carries the variant without having symptoms.

‍

Familial Pancreatitis

Familial pancreatitis describes a pattern in which pancreatitis occurs in multiple members of the same family, even when no specific genetic cause has been identified.

‍

Familial pancreatitis may be related to genetic factors that have not yet been identified, a combination of genetic and environmental factors, or other shared risk factors. Some families have multiple genetic risk factors that increase risk of pancreatitis when they multiple genetic variants are in one person. An example is CFTR-related pancreatitis caused by mild mutations in the cystic fibrosis gene (CFTR) that affect the pancreas, but not other organs such as the lungs. Other common predisposing genetic variants are in genes such as SPINK1, CTRC, and others

Symptoms of hereditary and familial pancreatitis are similar to those of other forms of pancreatitis and can include severe abdominal pain, nausea, and vomiting. Acute pancreatitis often causes sudden, severe pain in the upper abdomen that may spread to the back. People who develop chronic pancreatitis may have ongoing or recurring abdominal pain, unintended weight loss, oily or fatty stools, and diabetes.
‍

In hereditary pancreatitis, pancreatitis often begins during childhood or young adulthood, although the age of onset varies. Symptoms and age of onset can also vary among members of the same family.

Hereditary Pancreatitis

Diagnosis may involve a history of recurrent or chronic pancreatitis and genetic testing that identifies a disease-causing PRSS1 variant. A family history can provide additional information, but it is not required.

Genetic testing may be considered when pancreatitis occurs at a young age, is recurrent or unexplained, or there is a strong family history of pancreatitis or pancreatic cancer. Most PRSS1 variant do NOT cause hereditary pancreatitis, so results should be interpreted by a healthcare professional or genetic counselor familiar with pancreatitis genetics.

Pancreatic Cancer Risk

People with hereditary pancreatitis have an increased risk of pancreatic cancer, particularly after years of chronic inflammation. The level of risk varies among individuals with higher risk linked to smoking and alcohol use. People with PRSS1-related hereditary pancreatitis should discuss pancreatic cancer risk and appropriate surveillance with their healthcare team.

‍

Familial Pancreatitis

When evaluating familial pancreatitis, healthcare providers may ask about relatives with pancreatitis, pancreatic cancer, diabetes, or other pancreatic conditions. They may also consider other possible risk factors, including gallstones, alcohol use, smoking, hypertriglycerides (high blood fat levels), certain medications, metabolic conditions, and cystic fibrosis.

Genetic testing may be recommended when pancreatitis occurs at a young age, is recurrent or unexplained, or there is a strong family history. A genetic counselor can help determine whether testing is appropriate and explain what the results may mean for the individual and their family.

Treatment for both hereditary and familial pancreatitis focuses on managing symptoms, treating episodes of pancreatitis, and reducing the risk of complications.

‍

When a genetic cause is identified, the results may help guide care and inform discussions with family members. Genetic counseling can help individuals and their families understand inheritance, testing options, and what genetic test results may mean for relatives. A care team may include a pancreas specialist, dietitian, and genetic counselor who can help coordinate care and treatment.

The risk of developing pancreatitis can depend on several factors, including family history, genetic variants, and environmental factors. Avoiding triggers such as alcohol and smoking may help reduce the risk or severity of pancreatitis and may help slow the progression of chronic pancreatitis.

Talk with your healthcare provider or a genetic counselor if you have questions about your diagnosis or the potential risk to family members.