Clinical Guidance

High-penetrance

PRSS1 pathogenic variants include and . Lower-penetrance PRSS1 pathogenic variants include p.Ala16Val and Asp22Gly, p.Lys23Arg, p.Asn29Thr, and p.Arg122Cys . Note: Other PRSS1 variants have been associated with pancreatitis, but typically require additional risk factors to cause disease and do not segregate as autosomal dominant hereditary pancreatitis.

Source: GeneReviews — "PRSS1-Related Hereditary Pancreatitis"

Penetrance

The reported penetrance of PRSS1-related HP varies :

• Spain. Forty percent for p.Arg122Cys

• France. Ninety-three percent for p.Asn29Ile and p.Arg122His

• England. Eighty percent to 96% for p.Asn29Ile and p.Arg122His

• Europe. Forty-three percent for p.Ala16Val

• United States. Eighty percent for p.Asn29Ile and p.Arg122His to 83.4% for p.Arg122His (83.9%), p.Asn29Ile (11.5%), and others

Source: GeneReviews — "PRSS1-Related Hereditary Pancreatitis"

Diagnostic Criteria

The clinical features of PRSS1-related hereditary pancreatitis (HP) are clinically indistinguishable from other forms of acute and chronic pancreatitis. The diagnosis is established by family history and PRSS1 molecular testing.

Suggestive Findings

PRSS1-related HP should be suspected in individuals with the following:

• Acute pancreatitis occurring in childhood

• Recurrent acute attacks of pancreatitis of unknown cause

• Chronic pancreatitis of unknown cause, particularly with onset before age 25 years

• A family history of recurrent acute pancreatitis, chronic pancreatitis, and/or childhood pancreatitis consistent with autosomal dominant inheritance

• A family history of pancreatitis, diabetes mellitus, or pancreatic cancer

Source: GeneReviews — "PRSS1-Related Hereditary Pancreatitis"

Differential Diagnosis

The morphologic features and laboratory findings of PRSS1-related hereditary pancreatitis (HP) are the same as those of pancreatitis associated with other monogenetic (e.g., SPINK1), multifactorial/polygenic, and acquired causes of pancreatitis. See Pancreatitis Overview, Risk Factors and Etiologies of Recurrent Acute Pancreatitis / Chronic Pancreatitis for other genes and risk factors to consider in the differential diagnosis of PRSS1-related HP.

Source: GeneReviews — "PRSS1-Related Hereditary Pancreatitis"

Management Guidelines

No clinical practice guidelines for PRSS1-related hereditary pancreatitis (HP) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with PRSS1-related HP, the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

Source: GeneReviews — "PRSS1-Related Hereditary Pancreatitis"

Clinical Guidance

Alcohol and tobacco. Smoking doubles the risk for all forms of pancreatitis, including HP . In combination, smoking and alcohol use increases the risk of developing pancreatitis eightfold . Tobacco use also doubles the risk of pancreatic cancer and is associated with earlier-onset pancreatic cancer . Dehydration worsens episodes of AP, and in severe cases can contribute to complications such as acute kidney injury and cardiovascular shock. Physical and emotional stresses aggravate pancreatitis . Avoiding these stressors in individuals with PRSS1-related HP may prevent or delay worsening of symptoms and progression of disease.

Source: GeneReviews — "PRSS1-Related Hereditary Pancreatitis"

Therapies Under Investigation

A recognition of the need for new treatments and the challenges in developing classic pharmaceutical trials for rare diseases led to an NIH workshop during PancreasFest 2018 [, , , , ]. Although there are many potential treatments and enthusiastic research physicians, major funding for potential well-powered clinical trials is lacking. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "PRSS1-Related Hereditary Pancreatitis"

Surveillance Guidelines

Surveillance for pancreatic cancer may benefit individuals with PRSS1-related HP age 40 years and older who have long-standing CP and a strong family history of pancreatic cancer . Because long-standing CP results in pancreatic scarring and fibrosis that make assessment of abnormalities difficult , it is recommended that concerned individuals be referred to a surveillance program that includes biomarker research and other new techniques.

Source: GeneReviews — "PRSS1-Related Hereditary Pancreatitis"