Cancer prone diseases
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Shwachman-Diamond syndrome (SDS)
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 <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.
The risk for
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%.
Rare reports of increase in spontaneous chromosomal breakage.
Clonal aberrations are common and frequently involve chromosome 7, typically in form of i(7)(q10).
represents the second most common aberration, often occurring as secondary event to
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).
Additional reported findings
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.
Increasing the specificity of diagnostic criteria for schwannomatosis.
Baser ME et al
Mutations in SBDS are associated with Shwachman-Diamond syndrome.
Boocock GR et al
Shwachman-Diamond syndrome: clinical phenotypes.
Cipolli M et al
Does isochromosome 7q mandate bone marrow transplant in children with Shwachman-Diamond syndrome?
Cunningham J et al
Dror Y et al
Immune function in patients with Shwachman-Diamond syndrome.
Dror Y et al
Bone marrow transplantation in Shwachman-Diamond syndrome.
Hsu JW et al
Intermittent 20q- and consistent i(7q) in a patient with Shwachman-Diamond syndrome.
Smith A et al
Smith OP et al
Cytogenetic characterization of acute myeloid leukemia in Shwachman's syndrome. A case report.
Spirito FR et al
A case of Shwachman syndrome with increased spontaneous chromosome breakage.
Tada H et al
Abnormal telomere shortening in leucocytes of children with Shwachman-Diamond syndrome.
Thornley I et al
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