Juvenile polyposis syndrome (JPS) is an autosomal dominant disorder occurring in 1/100,000-1/160,000 individuals that predisposes to development of polyps in the gastrointestinal tract. Juvenile polyps are hamartomas that develop from normal tissue. Therefore most are benign but malignant transformation can occur with risk of gastrointestinal cancer ranging from 9% to 50%. Polyps are almost always found in the colon and rectum but also occur in the stomach and small intestine. Juvenile polyposis of infancy involves the entire digestive tract and has the poorest prognosis. Most other patients develop symptoms by age 20 though some are not diagnosed until the third decade of life. Common symptoms include gastrointestinal bleeding, anemia, diarrhea, and abdominal pain. Early detection of JPS allows for better surveillance of at-risk individuals and treatment of polyps.

Defects in the SMAD4 gene account for approximately 22% of JPS, with mutations detected throughout the gene’s coding region. Mutations in the BMPR1A gene, not tested here, cause an approximately equal number of cases of JPS.

SMAD4 also contributes to Hereditary Hemorrhagic Telangiectasia (HHT). For further information, please see our HHT page in the Test Directory section.

The Ambry Test is full gene sequence analysis of the SMAD4 gene. Turn-around-time is 10-21 days. Familial mutation testing is available.

The following CPT Codes for the Ambry Test reflects Ambry Genetics’ interpretation of CPT coding requirements based on AMA guidelines:

Ambry Test: SMAD4-Related Juvenile Polyposis
83891, 83894, 83898, 83904, 83909, 83912

CPT codes are provided only as a guide to assist you in billing. CPT coding is the sole responsibility of the billing party.

Disclaimer for SMAD4:

This test was developed and its performance characteristics were determined by Ambry Genetics Corporation. The laboratory is regulated under the Clinical Laboratory Improvement Amendments 2003 as qualified to perform nonwaived testing. The Ambry Test: SMAD4 analyzes the following types of mutations: nucleotide substitutions, small deletions, small insertions, and small indels. It is not intended to analyze the following types of mutations: gross deletions and insertions, gross rearrangements, deep intronic variations, and other unknown abnormalities. The pattern of mutation types varies with the gene tested and the Ambry Test detects a high but variable percentage of known and unknown mutants of the classes stated. A negative result from the analysis cannot rule out the possibility that the tested individual carries a rare unexamined mutation or mutation in the undetectable group. The Ambry Test: SMAD4 is designed and validated to be capable of detecting about 94% of described mutations in SMAD4 (considering less than 6% to be the other types of mutations). These detectable mutations account for approximately 22% of JPS cases and 2-3% of HHT. JPS and HHT are complex clinical disorders, which in some cases are due to alterations in SMAD4 gene generally detected by the Ambry Test: SMAD4 except as noted above. Mutations in other genes or the regions not tested by the Ambry Test: SMAD4 can also give rise to clinical conditions similar to JPS or HHT. Although molecular tests are highly accurate, rare diagnostic errors may occur. Possible diagnostic errors include sample mix-up, erroneous paternity identification, technical errors, clerical errors, and genotyping errors. Genotyping errors can result from trace contamination of PCR reactions, from maternal cell contamination in fetal samples, from rare genetic variants, which interfere with analysis, or from other sources. This report does not represent medical advice. Any questions, suggestions, or concerns regarding interpretation of results should be forwarded to a genetic counselor, medical geneticist, or physician skilled in interpretation of the relevant medical literature.