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.
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 type||Lifetime risk|
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:
Criteria for evaluating a family for JPS have been established:
Clinical diagnostic criteria have also been developed:
For management recommendations, please refer to:
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: Deletion/duplication analysis covers the promoter region.