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Shwachman-Diamond syndrome (SDS)
2005-03-01
Markus Schmugge
 ,
David Betts
 
Affiliation
Department of Oncology, University Childrens Hospital, Steinwiesstr. 75, CH-8032 Zürich, Switzerland
Identity
Name
Shwachman-Diamond syndrome (SDS)
Inheritance
Autosomal recessive inheritance. Male to female ratio 1.7 : 1
Omim
260400
Mesh
C537330
Orphanet
811 Shwachman-Diamond syndrome
Umls
-
Clinics
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
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%.
Cytogenetics
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
Note
Additional reported findings
Over-expression of
p53
protein
Abnormal telomeric shortening
Increased apoptosis mediated through the Fas pathway
Genes involved and Proteins
Description
5 exons spanning 7.9kb
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.
Article Bibliography
Pubmed ID
Last Year
Title
Authors
External Links
GARD
ERN GENTURIS
OMIM
ORPHANET
MeSH
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