Bone marrow nonneoplastic
Alterations in cellularity
Shwachman-Diamond syndrome
Author: Dragos C. Luca, M.D.
Last author update: 1 April 2013
Last staff update: 22 July 2019
Copyright: 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Bone marrow Shwachman-Diamond syndrome [title]
Table of Contents
Definition / general | Clinical features and diagnosis | Case reports | Treatment and prognostic factors | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Luca DC. Shwachman-Diamond syndrome. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrowshwachmandiamond.html. Accessed November 27th, 2024.
Definition / general
- Also known as Shwachman-Bodian-Diamond syndrome (SBDS)
- Rare autosomal recessive childhood stem cell disorder with peripheral cytopenia (particularly neutropenia), ineffective hematopoiesis, variable marrow cellularity; also pancreatic exocrine insufficiency with pancreatic fatty infiltration
- 25% have bone abnormalities (metaphyseal chondrodysplasia leading to short stature)
- Often considered a congenital neutropenia but 25% develop aplastic anemia; may be a myelodysplastic disorder from inception (Arch Pathol Lab Med 2002;126:1157)
Clinical features and diagnosis
- Additional clinical findings: intellectual disability, facial dysmorphism, dental anomalies, ichthyosis, thoracic deformities
- Often presents with infections at birth due to neutropenia, also malabsorption (steatorrhea)
- Normochromic normocytic anemia, increased HgF levels, thrombocytopenia
- Low serum isoamylase and trypsinogen
Case reports
- With successful bone marrow transplant (Eur J Pediatr 1999;158:995)
Treatment and prognostic factors
- 25% develop aplastic anemia, 7% develop myelodysplastic syndrome or acute myeloid leukemia
- Supportive treatment (G-CSF, transfusions, pancreatic enzyme replacement)
- Orthopedic management of skeletal deformities
- Hematopoietic stem cell transplant may be curative
- Variable clinical course: pancreatic insufficiency may improve with time but bone marrow failure tends to progress
Microscopic (histologic) description
- Hypocellular marrow; scattered mild dysplastic changes in all cell lines; may have prominent hematogones (Arch Pathol Lab Med 2000;124:1379)
- May demonstrate shift to immaturity in myeloid series
- Variable bone marrow cellularity including normocellular and even occasional hypercellular cases
- Erythroid and megakaryocytic lineages typically preserved initially
Microscopic (histologic) images
Images hosted on other servers:
Bone marrow aspirate
Decreased bone marrow cellularity
Positive stains
Molecular / cytogenetics description
- Mutations in Shwachman-Bodian-Diamond syndrome (SBDS) gene (7q11) in 90% (Blood 2004;104:3588)
- Two common gene mutations account for 75% of cases due to gene conversion into a pseudogene that is 97% homologous to the normal SBDS gene
- Genetic testing by sequencing the 5 exons of SBDS: at least one converted allele in 90% of patients, 2 converted alleles in 60% (mainly involving exons 2 and 3)
- Development of MDS / AML mostly associated with chromosome 7 abnormalities
Differential diagnosis
