• Test code: 01711
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Juvenile Polyposis Syndrome Panel

Test description

This test analyzes the BMPR1A and SMAD4 genes, which are associated with juvenile polyposis syndrome (JPS). This condition results in the development of gastrointestinal polyps that may become cancerous.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

Order test

Primary panel (2 genes)

Alternative tests to consider

BMPR1A and SMAD4 can also be ordered as part of a broader panel to test for different types of hereditary cancer, including colorectal cancer. Depending on the individual’s family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered for no additional cost.

  • hereditary hemorrhagic telangiectasia (HHT)
  • juvenile polyposis syndrome (JPS)

Juvenile polyposis syndrome (JPS) is a cancer predisposition syndrome characterized by the development of numerous hamartomatous polyps in the gastrointestinal tract. Polyposis typically begins in the mid-teens to late twenties but can also present in childhood. Although individuals with JPS develop polyps at a young age, the term “juvenile” refers to the fact that the majority of polyps remain benign (juvenile) and will not become cancerous. Still, approximately 68% of individuals with JPS will eventually develop cancer, including colorectal and upper gastrointestinal tract cancers.

In some cases, JPS presents in combination with hereditary hemorrhagic telangiectasia (HHT), which is caused by one of the genes associated with JPS (SMAD4). HHT is a condition characterized by arteriovenous malformations (AVMs) due to abnormal blood vessel development; it is characterized by epistaxis (nosebleeds), lung AVMs (in 40% of HHT patients), and, more rarely, brain AVMs.

Although the exact penetrance of JPS is unknown, it appears that the majority of individuals with pathogenic variants in SMAD4 and BMPR1A will develop JPS. JPS is also highly variable, meaning individuals with JPS may present differently, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant.

Cancer typeLifetime risk
Colorectal cancer 38%-68%
Gastric cancer 21%
Pancreatic cancer Elevated

Approximately 20%-25% of individuals with JPS have pathogenic variants in BMPR1A and 20% have pathogenic variants in SMAD4.

JPS is inherited in an autosomal dominant pattern. Most cases are inherited, but approximately 25% occur as the result of a spontaneous de novo mutation.

The prevalence of JPS is estimated at 1 in 16,000 to 1 in 100,000.

Testing for JPS should be considered for individuals with at least one of the following:

  • more than five juvenile polyps of the colorectum
  • multiple juvenile polyps throughout the GI tract
  • any number of juvenile polyps and a family history of juvenile polyps

Criteria for evaluating a family for JPS have been established:

Clinical diagnostic criteria have also been developed:

  1. Walpole, IR, Cullity, G. Juvenile polyposis: a case with early presentation and death attributable to adenocarcinoma of the pancreas. Am. J. Med. Genet. 1989; 32(1):1-8. doi: 10.1002/ajmg.1320320102. PMID: 2705469
  2. Brosens, LA, et al. Risk of colorectal cancer in juvenile polyposis. Gut. 2007; 56(7):965-7. doi: 10.1136/gut.2006.116913. PMID: 17303595
  3. Syngal, S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am. J. Gastroenterol. 2015; 110(2):223-62; quiz 263. doi: 10.1038/ajg.2014.435. PMID: 25645574
  4. Latchford, AR, et al. Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term outcome. Dis. Colon Rectum. 2012; 55(10):1038-43. doi: 10.1097/DCR.0b013e31826278b3. PMID: 22965402
  5. Calva, D, Howe, JR. Hamartomatous polyposis syndromes. Surg. Clin. North Am. 2008; 88(4):779-817, vii. doi: 10.1016/j.suc.2008.05.002. PMID: 18672141
  6. Howe, JR, et al. The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann. Surg. Oncol. 1998; 5(8):751-6. doi: 10.1007/bf02303487. PMID: 9869523
  7. Hampel, H, et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet. Med. 2015; 17(1):70-87. doi: 10.1038/gim.2014.147. PMID: 25394175
  8. Pollock, J, Welsh, JS. Clinical cancer genetics: Part I: Gastrointestinal. Am. J. Clin. Oncol. 2011; 34(3):332-6. doi: 10.1097/COC.0b013e3181dea432. PMID: 20859198
  9. National Comprehensive Cancer Network®, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Colorectal. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Accessed September 2019.
  10. American Society of Clinical Oncology, Cancer.Net: Juvenile Polyposis Syndrome. http://www.cancer.net/cancer-types/juvenile-polyposis-syndrome Accessed September 2019.
  11. National Library of Medicine, Genetics Home Reference: Juvenile Polyposis Syndrome. http://ghr.nlm.nih.gov/condition/juvenile-polyposis-syndrome Accessed June 2015.
  12. Chow, E, Macrae, F. A review of juvenile polyposis syndrome. J. Gastroenterol. Hepatol. 2005; 20(11):1634-40. doi: 10.1111/j.1440-1746.2005.03865.x. PMID: 16246179
  13. Larsen, Haidle, J, Howe, JR. Juvenile Polyposis Syndrome. 2003 May 13. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1469/ PMID: 20301642

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
BMPR1A* NM_004329.2
SMAD4 NM_005359.5

BMPR1A: Deletion/duplication analysis covers the promoter region.