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Shwachman-Diamond syndrome (SDS)

Written2005-03Markus Schmugge, David Betts
Department of Oncology, University Children's Hospital, Steinwiesstr. 75, CH-8032 Zürich, Switzerland

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Atlas_Id 10058
Genes implicated inSBDS  
Inheritance Autosomal recessive inheritance. Male to female ratio 1.7 : 1


Note 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 <50%)
  • Other manifestations include delayed puberty, rib and thoracic bone abnormalities 30-50%, metaphyseal dysostosis 50-75%, dental dyplasia, hepatomegaly 10-60%, elevated liver transaminases 50-75%, Ichtyosis severe and recurrent viral, bacterial and fungal infections 50-75% and developmental delay.
  • 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.
    Treatment 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.
    Prognosis 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 conditions Rare reports of increase in spontaneous chromosomal breakage.
    Cytogenetics of cancer
  • 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

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

    Gene NameSBDS (SBDS, ribosome maturation factor)
    Location 7q11.21
    Description 5 exons spanning 7.9kb
    Description Predicted protein is 28.8 kD
    Function Member of highly conserved protein family of unknown function.
    Germinal Various mutations have been described, including mutations resulting in stop codons and simple amino acid substitution.


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    PMID 16534111
    Mutations in SBDS are associated with Shwachman-Diamond syndrome.
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    PMID 12496757
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    PMID 12120235
    Does isochromosome 7q mandate bone marrow transplant in children with Shwachman-Diamond syndrome?
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    PMID 12472589
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    PMID 12181037
    Immune function in patients with Shwachman-Diamond syndrome.
    Dror Y, Ginzberg H, Dalal I, Cherepanov V, Downey G, Durie P, Roifman CM, Freedman MH
    British journal of haematology. 2001 ; 114 (3) : 712-717.
    PMID 11553003
    Bone marrow transplantation in Shwachman-Diamond syndrome.
    Hsu JW, Vogelsang G, Jones RJ, Brodsky RA
    Bone marrow transplantation. 2002 ; 30 (4) : 255-258.
    PMID 12203143
    Intermittent 20q- and consistent i(7q) in a patient with Shwachman-Diamond syndrome.
    Smith A, Shaw PJ, Webster B, Lammi A, Gaskin K, Diaz S, Sharma P
    Pediatric hematology and oncology. 2002 ; 19 (7) : 525-528.
    PMID 12217199
    Shwachman-Diamond syndrome.
    Smith OP
    Seminars in hematology. 2002 ; 39 (2) : 95-102.
    PMID 11957191
    Cytogenetic characterization of acute myeloid leukemia in Shwachman's syndrome. A case report.
    Spirito FR, Crescenzi B, Matteucci C, Martelli MF, Mecucci C
    Haematologica. 2000 ; 85 (11) : 1207-1210.
    PMID 11064470
    A case of Shwachman syndrome with increased spontaneous chromosome breakage.
    Tada H, Ri T, Yoshida H, Ishimoto K, Kaneko M, Yamashiro Y, Shinohara T
    Human genetics. 1987 ; 77 (3) : 289-291.
    PMID 3119460
    Abnormal telomere shortening in leucocytes of children with Shwachman-Diamond syndrome.
    Thornley I, Dror Y, Sung L, Wynn RF, Freedman MH
    British journal of haematology. 2002 ; 117 (1) : 189-192.
    PMID 11918553


    This paper should be referenced as such :
    Schmugge, M ; Betts, D
    Shwachman-Diamond syndrome (SDS)
    Atlas Genet Cytogenet Oncol Haematol. 2005;9(2):182-183.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    External links

    OrphanetShwachman-Diamond syndrome
    Other databaseShwartzman phenomenon (GARD)
    Genes implicated inSBDS   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  

    REVIEW articlesautomatic search in PubMed
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