Shwachman-Diamond syndrome (SDS)

2005-03-01   Markus Schmugge , David Betts 

Department of Oncology, University Childrens Hospital, Steinwiesstr. 75, CH-8032 Zürich, Switzerland



Shwachman-Diamond syndrome (SDS)


Autosomal recessive inheritance. Male to female ratio 1.7 : 1






811 Shwachman-Diamond syndrome





Bone marrow failure syndrome with exocrine pancreatic dysfunction and growth retardation, many phenotypic features often present at birth.

Phenotype and clinics

  • Intermittent neutropenia is the most common haematological finding (85-100%); in addition aplastic anemia (80%), increased hemoglobin F levels (80%), thrombocytopenia (25-85%) and impaired neutrophil chemotaxis, B- and T-cell defects can be found.
  • Fluctuating or persistent exocrine pancreatic dysfunction (with low serum amylase in 50-75%, low serum trypsinogen in 70-98% and abnormal pancreatic stimulation test in nearly 100%),
  • Growth retardation (shortness 60%, weight 50%, microcephalus
  • Neoplastic risk

    The risk for AML in SDS is estimated to be 15-25%. MDS has been found in small cohorts of SDS patients in 10-44%. The predilection to malignant myeloid transformation is higher in SDS patients with evolving pancytopenia and can already occur during infancy.


    Pancreatic insufficiency can be treated with pancreatic enzyme replacement. Periodic monitoring for the occurrence of haematological manifestations and supportive care for pancytopenia are mandatory. GCSF is used for individuals with severe neutropenia and recurrent infections. Because of the possible underlying liver abnormalities androgen-therapy is not recommended. Bone marrow transplantation from a family- or alternative donor is the only curative option for severe bone marrow failure and is recommended in SDS patients with severe pancytopenia and evolving haematological malignancies.


    Morbidity and mortality in infancy is related to infections, maldigestion and malabsorbtion and thoracic dystrophy. Pancreatic insufficiency that can be severe in infancy improves with increasing age in up to 50% of patients. In older children and adults, the main cause for morbidity and mortality are haematological. MDS and AML in patients with SDS has a poor prognosis, with a survival rate of < 20%.


    Inborn condition

    Rare reports of increase in spontaneous chromosomal breakage.

    Cancer cytog

  • Clonal aberrations are common and frequently involve chromosome 7, typically in form of i(7)(q10).
  • Del(20q) represents the second most common aberration, often occurring as secondary event to i(7)(q10).
  • Clonal aberrations need not indicate imminent transformation to MDS\/AML and can be transient in nature.
  • Over 60% of transformed cases will have an abnormal clone that includes aberrations of either chromosome 7 and\/or del(20q).
  • Other Findings


    Additional reported findings
  • Over-expression of p53 protein
  • Abnormal telomeric shortening
  • Increased apoptosis mediated through the Fas pathway
  • Genes involved and Proteins


    5 exons spanning 7.9kb


    Member of highly conserved protein family of unknown function.


    Various mutations have been described, including mutations resulting in stop codons and simple amino acid substitution.


    Pubmed IDLast YearTitleAuthors
    165341112006Increasing the specificity of diagnostic criteria for schwannomatosis.Baser ME et al
    124967572003Mutations in SBDS are associated with Shwachman-Diamond syndrome.Boocock GR et al
    121202352001Shwachman-Diamond syndrome: clinical phenotypes.Cipolli M et al
    124725892002Does isochromosome 7q mandate bone marrow transplant in children with Shwachman-Diamond syndrome?Cunningham J et al
    121810372002Shwachman-diamond syndrome.Dror Y et al
    115530032001Immune function in patients with Shwachman-Diamond syndrome.Dror Y et al
    122031432002Bone marrow transplantation in Shwachman-Diamond syndrome.Hsu JW et al
    122171992002Intermittent 20q- and consistent i(7q) in a patient with Shwachman-Diamond syndrome.Smith A et al
    119571912002Shwachman-Diamond syndrome.Smith OP et al
    110644702000Cytogenetic characterization of acute myeloid leukemia in Shwachman's syndrome. A case report.Spirito FR et al
    31194601987A case of Shwachman syndrome with increased spontaneous chromosome breakage.Tada H et al
    119185532002Abnormal telomere shortening in leucocytes of children with Shwachman-Diamond syndrome.Thornley I et al