Juvenile Polyposis Syndrome: SMAD4 Gene Deletion/Duplication
Test code: 7923
Turnaround time: 3 weeks
Juvenile polyposis syndrome (JPS) is an autosomal dominant condition characterized by predisposition to hamartomatous polyps in the gastrointestinal (GI) tract, specifically in the stomach, small intestine, colon, and rectum. The term “juvenile” refers to the type of polyp rather than to the age of onset of polyps. Most individuals with JPS have some polyps by age 20 years; some may have only four or five polyps over their lifetime, whereas others in the same family may have more than a hundred. If the polyps are left untreated, they may cause bleeding and anemia. Most juvenile polyps are benign; however, malignant transformation can occur. Most of this increased risk is attributed to colon cancer, but cancers of the stomach, upper GI tract, and pancreas have been reported. The incidence of colorectal cancer is 17%-22% by age 35 years and approaches 68% by age 60 years. The median age is 42 years. The incidence of gastric cancer is 21% in those with gastric polyps.
JPS is clinically diagnosed if any one of the three following findings is present: 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. Juvenile polyps are hamartomas with a distinct histology that differs from that of adenomas. The genes known to be associated with JPS are SMAD4 and BMPR1A. Approximately 20% of individuals with JPS have mutations in SMAD4(18q21.1); approximately 20% have mutations in BMPR1A. Recent studies suggest that deletion/duplication testing can identify an additional 9%-14% of mutations in SMAD4. Approximately 75% of individuals with JPS have an affected parent; approximately 25% of probands with JPS have no previous history of polyps in the family and may have the disorder as the result of a new gene mutation.
A combined syndrome of JPS and hereditary hemorrhagic telangiectasia (HHT) (termed JPS/HHT) may be present in 15%-22% of individuals with an SMAD4mutation. Some clinicians suggest that patients with juvenile polyposis who have a SMAD4 mutation should be screened for the vascular lesions associated with hereditary hemorrhagic telangiectasia, especially occult arteriovenous malformations in visceral organs that may otherwise present suddenly with serious medical consequences.
This test is indicated for:
- Confirmation of a clinical diagnosis of juvenile polyposis syndrome in individuals who have tested negative for sequence analysis
- Individuals at-risk for juvenile polyposis syndrome due to family history who have tested negative for sequence analysis
DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.
Please note that a “backbone” of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off- target copy number variants causative of disease may be identified that may or may not be related to the patient’s phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient’s clinical and/or biochemical phenotype.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
In EDTA (purple top) or ACD (yellow top) tube: Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
Submit copies of diagnostic biochemical test results with the sample, if appropriate. Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed by another third party provider, please submit a copy of the sequencing report with the test requisition.
• Sequencing analysis of the SMAD4 gene is available (test code: 4156) and is required before deletion/duplication analysis.