Shwachman-Diamond Syndrome

Shwachman-Diamond syndrome is an inherited multisystem hematology-oncology disorder that can affect the pancreas, blood, bone marrow, and skeletal system.  Because of the broad range of clinical findings (even within the same family), confirming a clinical diagnosis can greatly impact medical management.  

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Shwachman-Diamond syndrome is an inherited multisystem hematology-oncology disorder that can affect the pancreas, blood, bone marrow, and skeletal system.  Because of the broad range of clinical findings (even within the same family), confirming a clinical diagnosis can greatly impact medical management.  

Disease Name 
Shwachman-Diamond Syndrome (SDS)
Shwachman-Bodian-Diamond Syndrome
Shwachman-Bodian syndrome
Shwachman’s syndrome
Congenital lipomatosis of the pancreas
Disease Information 

Shwachman-Diamond Syndrome (SDS) is an inherited multisystem disorder occurring in approximately 1/76,000 births.1  Symptoms include pancreatic insufficiency, blood abnormalities including bone marrow failure and leukemia, and skeletal changes.2  Diagnosis is often made in early childhood due to failure to thrive, abnormal stools, and recurrent infections.1  Historically, diagnosis was based upon clinical findings.  However, individuals may have mutations in the gene that causes SDS (SBDS) and not show classical clinical findings, illustrating the importance of genetic testing in confirming a diagnosis, testing at-risk family members, and planning healthcare management.2

Rib cage abnormalities and short stature are common signs of irregular bone growth and maturation that characterize SDS. Enlarged liver and elevated liver enzymes are found in many very young patients, but these tend to resolve in later childhood.   Approximately half of patients show pancreatic insufficiency.1-3  Blood disorders, including neutropenia (low neutrophil count), thrombocytopenia (low platelets) or anemia (low red blood cells), are present in nearly all patients.4 Also, at least one quarter of patients develop more serious blood conditions: aplastic anemia, myelodysplastic syndrome, or leukemia.4

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.2

SBDS gene mutations are passed through families in an autosomal recessive pattern.  An estimated 1 in 139 people worldwide is a carrier for this disorder.2  Over 90% of people with a clinical diagnosis of SDS will have mutations in this gene.2

Testing Benefits & Indication 

Because of the wide range of clinical findings, even within the same family, genetic testing is a very important part of evaluation and management for SDS, and identification of at-risk family members.2

Gene sequencing of the SBDS gene may be considered for:

  • Diagnostic confirmation in patients suspected to have SDS
  • Mutation identification in known affected patients
  • Other at-risk family members, including prenatal testing for known familial mutations 
Test Description 

Ambry’s Shwachman-Diamond syndrome testing uses 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 5  bases into the 5’ and 3’ ends of all the introns. The assay design prevents unwanted amplification of the pseudogene. Specific Site Analysis for individual SBDS mutations known to be in the family is also available.

Mutation Detection Rate 

Mutations in SBDS account for >99.9% of Shwachman-Diamond syndrome (clinical sensitivity).2  Ambry’s SBDS analysis can detect >99.9% of described mutations in the gene, when present (analytical sensitivity).2          

Specimen Requirements 

Complete specimen requirements are available here* or by downloading the PDF found above on this page.

*NOTE: It is recommended that patients wait at least 2 weeks after a packed cell or platelet transfusion, and at least 4 weeks after a whole blood transfusion procedure prior to blood draw for testing at Ambry. Testing quality may be affected if patients have received chemotherapy within the last 120 days. For patients who have had a bone marrow transplant, please send cultured fibroblasts. Blood or saliva cannot be accepted for transplant patients. 

Turnaround Time 
TEST CODE TECHNIQUE TURNAROUND TIME
1440 SBDS Gene Sequence Analysis 14-28 Days

 

Genes 
SBDS
Techniques 
References 
  1. Necchi V, et al.  Ubiquitin-proteasome-rich cytoplasmic structures in neutrophils of patients with Shwachman-Diamond syndrome.  Haematologica. 2012 Jul;97(7):1057-63.
     
  2. Myers, K.  Shwachman-Diamond syndrome.  GeneReviews. 2008, updated 2014. Pagon RA, Adam MP, Ardiner HH et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2014.
     
  3. Dror Y. Shwachman-Diamond syndrome. Pediatr Blood Cancer. 2005;45:892-901.
     
  4. Kawakami T, et al. Genetic analysis of Shwachman-Diamond syndrome: phenotypic heterogeneity in patients carrying identical SBDS mutations. Tohoku J Exp Med. 2005;206:253-259.