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.

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Primary panel (2 genes)


BMPR1A: Deletion/duplication analysis covers the promoter region.

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.

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. American Society of Clinical Oncology, Cancer.Net: Juvenile Polyposis Syndrome. Accessed June 2015.
  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. 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
  4. 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
  5. 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
  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. 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: PMID: 20301642
  8. 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
  9. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Colorectal. Accessed September 2015.
  10. National Library of Medicine, Genetics Home Reference: Juvenile Polyposis Syndrome. Accessed June 2015.
  11. 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
  12. 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
  13. 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

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, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

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

BMPR1A: Deletion/duplication analysis covers the promoter region.