Hereditary pancreatitis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]
Overview
Pathophysiology
Hereditary pancreatitis 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 known germline pathogenic variant.[1]
Pathogenesis
- Hereditary pancreatitis involves atleast 3 different patterns of inheritance:[2][3][4][5][6][7][8][9]
| Mode of inheritance | Genes involved |
|---|---|
| Autosomal dominant | Serine protease 1 gene (PRSS1) |
| Autosomal recessive | Serine protease inhibitor Kazal type 1 gene (SPINK1, also called pancreatic secretory trypsin inhibitor gene) |
| Complex genetics | A combination of genetic and environmental factors |
Mutations in PRSS1 gene:
Mutations in SPINK1 gene:
Mutations in CFTR gene:
Mutations in CTRC gene:
Mutations in other genes:
Genetics
- The most common disease associated mutations in PRSS1 gene include:[3][4][10]
- R122H
- N29I
- Other genes may include:
- PRSS2, the anionic trypsinogen gene
- CFTR, the cystic fibrosis transmembrane conductance regulator gene
Associated Conditions
Hereditary pancreatitis may be associated with following syndromes:
- Shwachman-Diamond syndrome (SDS)
- Pearson marrow pancreas syndrome
- CEL maturity-onset diabetes of the young (CEL-MODY)
- Johanson-Blizzard syndrome
Gross Pathology
- On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
- On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
References
- ↑ Whitcomb DC, Ulrich CD (1999). "Hereditary pancreatitis: new insights, new directions". Baillieres Best Pract Res Clin Gastroenterol. 13 (2): 253–63. PMID 11030605.
- ↑ Whitcomb DC, Preston RA, Aston CE, Sossenheimer MJ, Barua PS, Zhang Y, Wong-Chong A, White GJ, Wood PG, Gates LK, Ulrich C, Martin SP, Post JC, Ehrlich GD (1996). "A gene for hereditary pancreatitis maps to chromosome 7q35". Gastroenterology. 110 (6): 1975–80. PMID 8964426.
- ↑ 3.0 3.1 Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD (1996). "Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene". Nat. Genet. 14 (2): 141–5. doi:10.1038/ng1096-141. PMID 8841182.
- ↑ 4.0 4.1 Gorry MC, Gabbaizedeh D, Furey W, Gates LK, Preston RA, Aston CE, Zhang Y, Ulrich C, Ehrlich GD, Whitcomb DC (1997). "Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis". Gastroenterology. 113 (4): 1063–8. PMID 9322498.
- ↑ Howes N, Lerch MM, Greenhalf W, Stocken DD, Ellis I, Simon P, Truninger K, Ammann R, Cavallini G, Charnley RM, Uomo G, Delhaye M, Spicak J, Drumm B, Jansen J, Mountford R, Whitcomb DC, Neoptolemos JP (2004). "Clinical and genetic characteristics of hereditary pancreatitis in Europe". Clin. Gastroenterol. Hepatol. 2 (3): 252–61. PMID 15017610.
- ↑ LaFemina J, Roberts PA, Hung YP, Gusella JF, Sahani D, Fernández-del Castillo C, Warshaw AL, Thayer SP (2009). "Identification of a novel kindred with familial pancreatitis and pancreatic cancer". Pancreatology. 9 (3): 273–9. doi:10.1159/000201553. PMC 3713708. PMID 19407482.
- ↑ LaRusch J, Barmada MM, Solomon S, Whitcomb DC (2012). "Whole exome sequencing identifies multiple, complex etiologies in an idiopathic hereditary pancreatitis kindred". JOP. 13 (3): 258–62. PMC 3651649. PMID 22572128.
- ↑ Schneider A, Larusch J, Sun X, Aloe A, Lamb J, Hawes R, Cotton P, Brand RE, Anderson MA, Money ME, Banks PA, Lewis MD, Baillie J, Sherman S, Disario J, Burton FR, Gardner TB, Amann ST, Gelrud A, George R, Rockacy MJ, Kassabian S, Martinson J, Slivka A, Yadav D, Oruc N, Barmada MM, Frizzell R, Whitcomb DC (2011). "Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis". Gastroenterology. 140 (1): 162–71. doi:10.1053/j.gastro.2010.10.045. PMC 3171690. PMID 20977904.
- ↑ Rosendahl J, Landt O, Bernadova J, Kovacs P, Teich N, Bödeker H, Keim V, Ruffert C, Mössner J, Kage A, Stumvoll M, Groneberg D, Krüger R, Luck W, Treiber M, Becker M, Witt H (2013). "CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis: is the role of mutated CFTR overestimated?". Gut. 62 (4): 582–92. doi:10.1136/gutjnl-2011-300645. PMID 22427236.
- ↑ Teich N, Mössner J, Keim V (1998). "Mutations of the cationic trypsinogen in hereditary pancreatitis". Hum. Mutat. 12 (1): 39–43. doi:10.1002/(SICI)1098-1004(1998)12:1<39::AID-HUMU6>3.0.CO;2-P. PMID 9633818.