Pancreatitis Panel

Last Literature Review: February 2022 Last Update:
  • Use for individuals with a personal history of idiopathic pancreatitis
  • Use to detect sequence variants in the CFTR, CTRC, PRSS1, and SPINK1 genes

If a familial sequence variant has been previously identified, targeted sequencing for that variant may be appropriate; refer to the Laboratory Test Directory for additional information.

Pancreatitis is a relatively common disorder with multiple etiologies that causes inflammation in the pancreas. Acute pancreatitis (AP) is a result of sudden inflammation, and patients may present with increased pancreatic enzyme concentrations. Chronic pancreatitis (CP) is a syndrome of progressive inflammation that may lead to permanent damage to pancreatic structure and function. Genetic testing can be utilized to determine a genetic cause of idiopathic or hereditary AP or CP and/or to assess risk of disease in family members.

Disease Overview

Incidence/Prevalence

  • Chronic pancreatitis
    • Incidence: Approximately 4-12/100,000 per year 
    • Prevalence: Approximately 37-42/100,000 

Symptoms and Etiology

  Symptoms/Presentation Etiologies
AP

Sudden onset of pain in the upper abdomen, nausea and vomiting, orthostatic hypotension, confusion, and shortness of breath

Duration is <6 months

Increased concentrations of pancreatic enzymes (ie, lipase, amylase)

Characteristic findings of pancreatic inflammation on abdominal imaging

Most acute pancreatitis is caused by gallstones, alcohol use, hypertriglyceridemia, or is idiopathic
RAP >1 episode of acute pancreatitis, separated by ≥3 months

Nonhereditary RAP and CP are typically associated with ≥1 risk factor, divided into the following TIGAR-O categories:

  • Toxic-metabolic
  • Idiopathic
  • Autoimmune
  • Recurrent or severe acute pancreatitis
  • Obstructive
44-65% of CP cases are alcohol-related ; alcohol use and smoking are independent risk factors but together have a multiplicative effect on risk 
CP

Abdominal pain, nausea, vomiting, weight loss, diarrhea, oily stools

Duration is >6 months

At advanced stages, pain often decreases, and malabsorption and diabetes may occur

Patients with CP have an increased risk of pancreatic cancer after age 50

RAP, recurrent acute pancreatitis

Source: Conwell, 2014 ; Shelton, 2020 ; Shelton, 2019 

Genetics

Genes

  • CFTR (NM_000492), CTRC (NM_007272), PRSS1 (NM_002769), SPINK1 (NM_003122)
    • 90% of individuals affected with PRSS1-related hereditary pancreatitis have the PRSS1 sequence variant R122H (p.Arg122His) 
    • Other genes (CLDN2, CPA1, CASR, CEL, TRPV6) have been reported to be associated with CP but are not currently assessed at ARUP Laboratories. 

Inheritance

  • PRSS1: autosomal dominant with gain-of-function variants
  • CFTR, CTRC, SPINK1: autosomal recessive/digenic

Test Interpretation

Methodology

This test is performed using the following sequence of steps:

  • Selected genomic regions, primarily coding exons and exon-intron boundaries, from the targeted genes are isolated from extracted genomic DNA using a probe-based hybrid capture enrichment workflow.
  • Enriched DNA is sequenced by massively parallel sequencing (MPS; also known as next generation sequencing [NGS]) followed by paired-end read alignment and variant calling using a custom bioinformatics pipeline.
  • Sanger sequencing is performed as necessary to fill in regions of low coverage or known low quality, and in certain other situations to confirm variant calls.

Sensitivity/Specificity

Clinical Sensitivity

CFTR, CTRC, PRSS1, and SPINK1 pathogenic variants which contribute to or explain idiopathic pancreatitis: ~48% 

Analytic Sensitivity

Variant Class Analytic Sensitivity (PPA) Estimatea (%)
and 95% Credibility Region (%)		 Analytic Specificity (NPA) (%)

SNVs

>99 (96.9-99.4)

>99.9

Deletions 1-10 bpb

93.8 (84.3-98.2)

>99.9

Insertions 1-10 bpb

94.8 (86.8-98.5)

>99.9

aGenes included on this test are a subset of a larger methods-based validation from which the PPA values are derived.

bVariants greater than 10 bp may be detected, but the analytical sensitivity may be reduced.

bp, base pairs; NPA, negative percent agreement; PPA, positive percent agreement; SNVs, single nucleotide variants

Results

Result Interpretation
Positive

One of the following:

  • One PRSS1 pathogenic variant or copy number variant detected
  • Two pathogenic CFTR, SPINK1, or CTRC gene variants detected
  • Two pathogenic variants detected, one in each of two different genes (digenic inheritance)
  • One pathogenic variant detected in CFTR, CTRC, or SPINK1 genes (may increase the risk for pancreatitis but is not causative)
Negative No pathogenic variants detected in any of the genes; reduces the risk for hereditary pancreatitis but genetic etiology is not excluded
Uncertain Variant(s) of uncertain clinical significance detected; may be disease-causing or benign

Limitations

  • A negative result does not exclude a genetic etiology for pancreatitis.
  • Diagnostic errors can occur due to rare sequence variations.
  • Interpretation of this test result may be impacted if this patient has had an allogeneic stem cell transplantation.
  • The following will not be evaluated:
    • Variants outside the coding regions and intron-exon boundaries of targeted genes
    • Regulatory region and deep intronic variants other than 5T (IVS8), c.1680-886A>G (c.1679+1.6kbA>G), and c.3718-2477C>T in the CFTR gene
    • Large deletions/duplications in any of the tested genes
    • Variants in currently unknown genes that may be associated with pancreatitis
  • The following may not be detected:
    • Deletions/duplications/insertions of any size by massively parallel sequencing
    • Noncoding transcripts
    • Low-level somatic variants
    • Certain other variants due to technical limitations in the presence of pseudogenes or repetitive/homologous regions

References

Related Information
Acute Pancreatitis
Chronic Pancreatitis