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Pancreatitis Overview.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2014 Mar 13.

Author information

1
Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania
2
Genetic Counselor, GeneDx, Gaithersburg, Maryland
3
Departments of Medicine, Cell Biology & Physiology, and Human Genetics, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh & University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Excerpt

CLINICAL CHARACTERISTICS:

Pancreatitis is inflammation of the pancreas that progresses from acute (sudden onset; duration <6 months) to recurrent acute (>1 episode of acute pancreatitis) to chronic (duration >6 months). The range of symptoms and disease course vary from person to person. Familial pancreatitis, defined as pancreatitis from any cause that occurs in a family with an incidence that is greater than would be expected by chance alone, can be non-genetic or genetic, the latter including autosomal dominant hereditary pancreatitis and pancreatitis syndromes characterized by pancreatitis or pancreatic insufficiency. The majority of familial pancreatitis appears to have a complex, multigenic, or gene-environmental etiology with a variable number of germline pathogenic variants in genes that affect trypsin regulation, including CASR, CTRC, and CLDN2. Hereditary pancreatitis (HP) is defined as either two or more individuals with pancreatitis in two or more generations of a family (i.e., an autosomal dominant pattern of inheritance) or pancreatitis associated with a germline PRSS1 disease-causing gain-of-function variant. The phenotype of hereditary pancreatitis is increased susceptibility to acute pancreatitis, with complications such as chronic inflammation, fibrosis, and chronic pain in some affected individuals. Heterozygous pathogenic variants in PRSS1 are found in 60%-100% of families with hereditary pancreatitis, and most large families with pancreatitis spanning multiple generations; biallelic pathogenic variants in SPINK1 or biallelic pathogenic variants in CFTR result in autosomal recessive pancreatitis. Syndromes in which pancreatitis is a finding include: Pearson marrow pancreas syndrome, CEL maturity-onset diabetes of the young (CEL-MODY), and Johanson-Blizzard syndrome. Shwachman-Diamond syndrome, an autosomal recessive disorder, includes pancreatic exocrine insufficiency as well as other features. Idiopathic sporadic pancreatitis is a single occurrence of pancreatitis in a family for which no etiology is identified.

DIAGNOSIS/TESTING:

Establishing the diagnosis and cause of hereditary pancreatitis relies on medical history, family history, and/or molecular genetic testing, which can be either single-gene (monogenic) testing or use of a multigene panel. Although a multigene panel that includes PRSS1 along with SPINK1, CFTR, and CTRC may be considered, it should be noted that (1) the presence of isolated pathogenic variants in the latter three genes is insufficient to cause pancreatitis and (2) many variants of uncertain significance are likely to be identified.

GENETIC COUNSELING:

Hereditary pancreatitis can occur as part of a rare genetic syndrome or as an isolated finding. The risk to family members depends on the underlying etiology. Pathogenic variants associated with an increased risk for pancreatitis as an isolated finding may be inherited in an autosomal dominant, autosomal recessive, or multigene manner; such pathogenic variants may be classified as disease causing, conferring susceptibility, or disease modifiers.

MANAGEMENT:

Treatment of manifestations: Management for hereditary pancreatitis is currently similar to that for non-hereditary pancreatitis. Treatment of acute pancreatitis usually focuses on pain management and discontinuation of smoking and alcohol use to slow the rate of progression and to decrease the likelihood of complications, including pancreatic cancer. Treatment of chronic pancreatitis focuses on improving quality of life by managing pancreatic pain, maldigestion, and diabetes mellitus. Total pancreatectomy with islet autotransplantation (TPIAT) should be used only as a last resort to manage patients with severe manifestations of pancreatitis. Prevention of primary manifestations: The ability to prevent the primary manifestations of hereditary pancreatitis (regardless of genetic cause) is limited. The following recommendations (beginning in early childhood) for individuals with (or at risk for) hereditary pancreatitis can help prevent attacks of acute pancreatitis: Low-fat diet, multiple small meals, good hydration, antioxidants, and cessation/abstinence from smoking and alcohol use. Agents/circumstances to avoid: Alcohol and tobacco use, dehydration, and physical and emotional stresses Evaluation of relatives at risk: It is recommended that relatives at risk for PRSS1-related hereditary pancreatitis be offered molecular genetic testing for the family-specific germline PRSS1 pathogenic variant to allow early diagnosis, prevention, and management of symptoms

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