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The gastrointestinal tract
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Hereditary pancreatitis is a rare but important cause of recurrent abdominal pain in childhood and young adults and may predispose to later pancreatic cancer. Predictive genetic testing in someone who is well should be used with caution in view of the great variability of the condition and the scope for gene-gene interaction (as well as the involvement of environmental factors). There is some evidence that the risk of cancer is greater with CFTR-associated than with SPINK1-associated pancreatitis. Type V hyperlipoproteinaemia (autosomal recessive) may also cause recurrent pancreatitis.
Hereditary Pancreatitis
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Hereditary pancreatitis is a rare disorder that is defined as the occurrence of acute recurrent pancreatitis or chronic pancreatitis in at least two first-degree or three second-degree relatives, in two or more generations, without precipitating factors and with a negative workup for known causes of chronic pancreatitis [26,27]. At the molecular level, gain-of-function mutation in PRSS1 (7q34) and loss-of-function mutations in SPINK1 (5q32), CFTR (7q31.2), and CTRC (1p36.21) affecting the structure, function, and level of digestive enzymes in the pancreas underlie the development of hereditary pancreatitis [28,29]. Specifically, gain-of-function PRSS1 mutation induces premature conversion of trypsinogen to active trypsin and also premature activation of inactive pancreatic zymogens in the pancreas; loss-of-function SPINK1 reduces inhibition of active trypsin in the pancreas, and loss-of-function CTRC and CFTR mutations hinders degradation of trypsinogen and trypsin. Together, a continuing presence of elevated levels of active trypsin in the pancreas induces autodigestion of pancreatic parenchyma, formation of pancreatic fibrosis, and development of recurrent acute pancreatitis/chronic pancreatitis as well as pancreatic cancer at an earlier age. Diagnosis of hereditary pancreatitis is based on meeting certain clinical criteria and/or identification of disease-causing or -modifying PRSS1, SPINK1, CFTR, and CTRC pathogenic variants. Treatment of hereditary pancreatitis involves a multidisciplinary approach consisting of surgery, therapeutic endoscopy, chemotherapy, radiotherapy, and other standard medical procedures [30].
Inherited causes of exocrine pancreatic insufficiency in pediatric patients: clinical presentation and laboratory testing
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Tatiana N. Yuzyuk, Heather A. Nelson, Lisa M. Johnson
Hereditary pancreatitis (HP) is a rare genetic gastroenterological disease. Despite its low prevalence, HP is a significant cause of recurrent, AP that often rapidly progresses to chronic pancreatitis in the pediatric population [41]. Although inheritance patterns are complex, HP is associated with pathogenic variants most commonly involving the cationic trypsinogen (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), or chymotrypsin C (CTRC) genes [42]. The shared pathologic mechanism of these gene variants is an excessive activity of digestive enzymes within the pancreas, leading to autodigestion of the pancreatic parenchyma. About 80% of HP is caused by autosomal dominant gain-of-function mutations in PRSS1, resulting in the overactivation of trypsin. In contrast, SPINK1 and CTRC code for proteins that inactivate trypsin, resulting in loss-of-function mutations in SPINK1 or CTRC that are associated with increased susceptibility to autodigestion.
Recognizing and Managing Pancreaticopleural Fistulas in Children
Published in Journal of Investigative Surgery, 2022
Konstantina Dimopoulou, Anastasia Dimopoulou, Nikolaos Koliakos, Andrianos Tzortzis, Dimitra Dimopoulou, Nikolaos Zavras
On admission, a detailed clinical history should be obtained. An accurate history often reveals several previous episodes of intermittent midepigastric pain, sometimes associated with vomit and nausea, whereas in some cases, trauma or abdominal surgery is recorded. A thorough family history should also be taken in order to investigate the possibility of hereditary pancreatitis, which may progress to a chronic condition with a severe clinical course and complications [16]. If three or more patients with pancreatitis are reported in the second generation, genetic screening should be performed [17–19]. Physical examination often shows diminished breath sounds and dullness on percussion on the right or left hemithorax, or even bilateral [2,5,8,9]. On the other hand, abdominal examination is generally normal, apart from distention and mild epigastric tenderness on palpation in some cases [20–22].