DISEASE INFORMATION
Shwachman-Diamond Syndrome (SDS) is a recessively-inherited multisystem disorder occurring in approximately 1/75,000 births.¹ This condition is also called Shwachman-Bodian-Diamond Syndrome and was formerly called congenital lipomatosis of the pancreas. Symptoms are exocrine pancreatic insufficiency, hematological abnormalities including bone marrow failure and malignancy, and skeletal defects due to metaphyseal dysostosis.

Diagnosis is often made in early childhood due to failure to thrive, abnormal stools, and recurrent infections. Rib cage abnormalities and short stature are common signs of irregular bone growth and maturation that characterize SDS.  Hepatomegaly and elevated liver enzymes are found in many very young patients, but these tend to resolve in later childhood and approximately half of patients become pancreatic sufficient over time.1 Neutropenia, thrombocytopenia or anemia are present in nearly all patients and at least one quarter of patients develop aplastic anemia, myelodysplastic syndrome, or leukemia.²

Treatments for SDS can include pancreatic enzyme replacement, surgery to improve skeletal function, routine blood and bone marrow analyses for monitoring, blood transfusions, chemotherapy, and hematopoietic stem cell transplant.

Approximately 75% of SDS alleles result from gene conversion events that introduce mutated sequence from a pseudogene into the SBDS gene.³  Genotype does not appear to correlate with phenotype for presence or severity of symptoms.^1-3

TESTING BENEFITS & INDICATIONS

• Diagnostic confirmation in patients suspected to have SDS
• Mutation identification in known affected patients
• Familial mutation testing in relatives to determine carrier status
• Prenatal diagnosis for known carrier couples

TEST DESCRIPTION
The Ambry Test: Shwachman-Diamond Syndrome is a full gene sequence analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1-5 of the SBDS gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns. The assay design prevents unwanted amplification of the pseudogene.  Specific mutation analysis for individual SBDS mutations known to be in the family is also available.

MUTATION DETECTION RATE
The Ambry Test: Shwachman-Diamond Syndrome detects ~95% of the described SBDS mutations.  The detection rate in affected patients is ~78%.^3-5  Approximately 90% of patients will test positive for at least one SBDS mutation.¹

SPECIMEN REQUIREMENTS
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
***For patients who have had a bone marrow transplant, please send whole blood and saliva together.***
DNA: Send 20 µg in TE at 50-100 ng/µl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case. 

REFERENCES
¹ Dror Y. Pediatr Blood Cancer. 2005;45:892-901.
²Kawakami T et al. Tohoku J Exp Med. 2005;206:253-259.
³Kuijpers TW et al. Blood. 2005;106:356-361.
⁴Boocock GRB et al. Nat Genet. 2003;33:97-101.
⁵Woloszynek JR et al. Blood. 2004;104:3588-3590.

DISCLAIMER
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: Shwachman-Diamond Syndrome 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 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: Shwachman-Diamond Syndrome is designed and validated to be capable of detecting ~95% of described SBDS mutations (considering ~5% to be the other types of mutations). The detection rate in affected patients is ~78%. Shwachman-Diamond Syndrome is a complex clinical disorder, which in some cases is due to alterations in the SBDS gene generally detected by the Ambry Test: Shwachman-Diamond Syndrome except as noted above. Mutations in other genes or the regions not tested by the Ambry Test: Shwachman-Diamond Syndrome can also give rise to clinical conditions similar or identical to Shwachman-Diamond Syndrome. 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. References are available upon request.