Hereditary pancreatitis: current perspectives

Abstract

Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy.

<p>Pancreatic cancer in young adults: changes, challenges, and solutions</p>

“…Risk factors for EOPC development are similar to late-onset pancreatic cancers (LOPC), including tobacco exposure, alcohol abuse, chronic pancreatitis, diabetes mellitus (type 1 and 2), diet, obesity (body mass index over 40 kg/m 2 ), previous radiotherapy, as well as previous cholecystectomy, gastrectomy, and infections 13,14. Nevertheless, intrinsic and genetic-dependent risk factors of PC like familial history15 and hereditary genetic syndromes, such as hereditary pancreatitis,16 are more frequently observed in EOPC 14,17. Therefore, specific germline genetic analyses (like of the breast cancer type 1/2 susceptibility proteins, BRCA) in families with increased incidence of PC could help identify patients with high risk for developing PC and initiate surveillance programs 18…”

The Differential Role of Human Cationic Trypsinogen (PRSS1) p.R122H Mutation in Hereditary and Nonhereditary Chronic Pancreatitis: A Systematic Review and Meta-Analysis

“…PRSS1 mutation was first discovered to be associated with the phenotype of hereditary pancreatitis (HP) twenty years ago [ 7 ]. Carriers with this mutation tend to develop recurrent AP with an early onset of the disease (prior to the second decade of life) and the development of chronic pancreatitis and also have a significantly increased risk for development of pancreatic adenocarcinoma [ 8 , 9 ]. R122H mutation of the PRSS1 gene, detected in more than 50% of the patients with HP, was the most common mutation in patients with HP [ 10 ].…”

Parenchyma Preserving Surgery for Idiopathic Chronic Calcific Pancreatitis in Children: A Report of Three Cases

“…While an autosomal dominant inheritance pattern is the most common form of inheritance, another method of inheritance is in an autosomal recessive fashion whereby 2 mutated parental genes are needed for the phenotypic manifestation (e.g., CFTR gene and SPINK1). 4 The autosomal recessive inheritance is a perplex pattern requiring environmental factors and genetic mutation or a mix of individual mutated genes. 4 In the absence of known mutations, trauma, alcohol consumption, drug intake, infection, or metabolic disorders, it can be referred as idiopathic chronic pancreatitis.…”