Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (774 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
An inherited syndrome characterized by exocrine pancreatic insufficiency; hematologic abnormalities (e.g., bone marrow hypoplasia), and skeletal abnormalities (e.g., metaphyseal chondroplasia). germline mutations in the SBDS gene are associated with Shwachman-Diamond Syndrome.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Shwachman Syndrome; Pancreatic Insufficiency and Bone Marrow Dysfunction; Shwachman-Bodian Syndrome; Shwachman Bodian Syndrome; Congenital Lipomatosis of Pancreas; Pancreas Congenital Lipomatoses; Pancreas Congenital Lipomatosis; Metaphyseal Chondrodysplasia, Shwachman Type.
Where it fits in the MeSH classification
- Broader topics
- Exocrine Pancreatic Insufficiency; Congenital Bone Marrow Failure Syndromes; Lipid Metabolism, Inborn Errors; Lipomatosis
Related concepts
- Exocrine Pancreatic Insufficiency
- Germline Mutations
Research landscape
PubMed indexes 255 records tagged with the MeSH heading “Shwachman-Diamond Syndrome” (counts retrieved 2026-10-31). 109 of them (42.7%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 149 records.
Reviews account for 48 records (18.8%) and meta-analyses for 1. Randomized controlled trials number 0 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 0 |
| 2010-2019 | 149 |
| 2020 onward | 109 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 48 | 18.8% |
| Meta-analyses | 1 | 0.4% |
| Randomized controlled trials | 0 | 0.0% |
Method: PubMed query "Shwachman-Diamond Syndrome"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in digestive system and liver
Gut and liver research ranges from laboratory studies of the microbiome to large trials of drugs and surgery. Symptoms such as pain, reflux or bowel change are reported by patients and overlap between conditions, and diet and microbiome studies are mostly observational. Check whether the study measured symptoms, tissue findings or long-term outcomes, how the diagnosis was made and how long people were followed. Nothing here replaces advice from a qualified clinician.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome | 2021 | Research article Design not recorded in structured metadata | 157 | cc by PMID 33637765 · DOI · PMC7910481 |
| Somatic genetic rescue of a germline ribosome assembly defect | 2021 | Research article Design not recorded in structured metadata | 64 | cc by PMID 34413298 · DOI · PMC8377010 |
| Loss of Sbds in zebrafish leads to neutropenia and pancreas and liver atrophy | 2020 | Research article Design not recorded in structured metadata | 18 | cc by PMID 32759502 · DOI · PMC7526460 |
| Homozygous Pathogenic Variant in Elongation Factor-Like 1 (EFL1) as a Causal Factor in Shwachman-Diamond Syndrome 2 in a Palestinian Child, With Distinct Ocular Manifestations | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 42043893 · DOI · PMC13117211 |
Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome [1]
Abstract reading summary — source excerpts
- Opening excerpt
- To understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age.
- Closing excerpt
- These results mechanistically link leukemia predisposition to germline genetic constraints on cellular fitness, and provide a rational framework for clinical surveillance strategies.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (175 words)
To understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age. To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. Here we report that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53. We show that germline SBDS deficiency establishes a fitness constraint that drives selection of somatic clones via two distinct mechanisms with different clinical consequences. EIF6 inactivation mediates a compensatory pathway with limited leukemic potential by ameliorating the underlying SDS ribosome defect and enhancing clone fitness. TP53 mutations define a maladaptive pathway with enhanced leukemic potential by inactivating tumor suppressor checkpoints without correcting the ribosome defect. Subsequent development of leukemia was associated with acquisition of biallelic TP53 alterations. These results mechanistically link leukemia predisposition to germline genetic constraints on cellular fitness, and provide a rational framework for clinical surveillance strategies.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33637765 · DOI · PMC7910481
Somatic genetic rescue of a germline ribosome assembly defect [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Indirect somatic genetic rescue (SGR) of a germline mutation is thought to be rare in inherited Mendelian disorders.
- Closing excerpt
- Our data suggest that SGR is a universal phenomenon that may influence the clinical evolution of diverse Mendelian disorders and support eIF6 suppressor mimics as a therapeutic strategy in SDS.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (184 words)
Indirect somatic genetic rescue (SGR) of a germline mutation is thought to be rare in inherited Mendelian disorders. Here, we establish that acquired mutations in the EIF6 gene are a frequent mechanism of SGR in Shwachman-Diamond syndrome (SDS), a leukemia predisposition disorder caused by a germline defect in ribosome assembly. Biallelic mutations in the SBDS or EFL1 genes in SDS impair release of the anti-association factor eIF6 from the 60S ribosomal subunit, a key step in the translational activation of ribosomes. Here, we identify diverse mosaic somatic genetic events (point mutations, interstitial deletion, reciprocal chromosomal translocation) in SDS hematopoietic cells that reduce eIF6 expression or disrupt its interaction with the 60S subunit, thereby conferring a selective advantage over non-modified cells. SDS-related somatic EIF6 missense mutations that reduce eIF6 dosage or eIF6 binding to the 60S subunit suppress the defects in ribosome assembly and protein synthesis across multiple SBDS-deficient species including yeast, Dictyostelium and Drosophila. Our data suggest that SGR is a universal phenomenon that may influence the clinical evolution of diverse Mendelian disorders and support eIF6 suppressor mimics as a therapeutic strategy in SDS.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34413298 · DOI · PMC8377010
Loss of Sbds in zebrafish leads to neutropenia and pancreas and liver atrophy [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, neutropenia, and skeletal abnormalities.
- Closing excerpt
- A variety of stress responses, some associated with Tp53, contribute to pathophysiology of SDS.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (242 words)
Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, neutropenia, and skeletal abnormalities. Biallelic mutations in SBDS, which encodes a ribosome maturation factor, are found in 90% of SDS cases. Sbds-/- mice are embryonic lethal. Using CRISPR/Cas9 editing, we created sbds-deficient zebrafish strains. Sbds protein levels progressively decreased and became undetectable at 10 days postfertilization (dpf). Polysome analysis revealed decreased 80S ribosomes. Homozygous mutant fish developed normally until 15 dpf. Mutant fish subsequently had stunted growth and showed signs of atrophy in pancreas, liver, and intestine. In addition, neutropenia occurred by 5 dpf. Upregulation of tp53 mRNA did not occur until 10 dpf, and inhibition of proliferation correlated with death by 21 dpf. Transcriptome analysis showed tp53 activation through upregulation of genes involved in cell cycle arrest, cdkn1a and ccng1, and apoptosis, puma and mdm2. However, elimination of Tp53 function did not prevent lethality. Because of growth retardation and atrophy of intestinal epithelia, we studied the effects of starvation on WT fish. Starved WT fish showed intestinal atrophy, zymogen granule loss, and tp53 upregulation - similar to the mutant phenotype. In addition, there was reduction in neutral lipid storage and ribosomal protein amount, similar to the mutant phenotype. Thus, loss of Sbds in zebrafish phenocopies much of the human disease and is associated with growth arrest and tissue atrophy, particularly of the gastrointestinal system, at the larval stage. A variety of stress responses, some associated with Tp53, contribute to pathophysiology of SDS.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32759502 · DOI · PMC7526460
Homozygous Pathogenic Variant in Elongation Factor-Like 1 (EFL1) as a Causal Factor in Shwachman-Diamond Syndrome 2 in a Palestinian Child, With Distinct Ocular Manifestations [4]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundShwachman-Diamond syndrome type 2 (SDS2) is a rare ribosomopathy caused by biallelic mutations in the EFL1 gene.
- Closing excerpt
- It highlights the need for broader awareness of SDS2 among endocrinologists and ophthalmologists due to the novel clinical manifestations observed.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (173 words)
BackgroundShwachman-Diamond syndrome type 2 (SDS2) is a rare ribosomopathy caused by biallelic mutations in the EFL1 gene. This condition presents with features similar to classic SDS1 such as pancreatic insufficiency and haematologic abnormalities.Case presentationWe report a Palestinian female infant admitted to the NICU at H-Clinic Hospital, Ramallah, in January 2023, with a homozygous mutation in the EFL1 gene (c.3284G>A; p.Arg1095Gln), identified through whole exome sequencing and confirmed by Sanger sequencing. In addition to typical SDS2 features-pancytopenia, pancreatic insufficiency and growth failure-the patient exhibited unique manifestations, including ROP-like retinal changes, infantile esotropia with inferior oblique overaction, and elevated ACTH and 17-hydroxyprogesterone levels, indicating adrenal dysfunction.FindingsThese findings expand the SDS2 phenotype to include novel ocular and endocrine involvement. No other pathogenic variants were identified by bioinformatic analysis. The recurrence of this variant in unrelated Palestinian families suggests a possible founder effect.ConclusionThis case underscores the importance of extended genetic testing and multidisciplinary evaluation in rare syndromes. It highlights the need for broader awareness of SDS2 among endocrinologists and ophthalmologists due to the novel clinical manifestations observed.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42043893 · DOI · PMC13117211
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Mechanisms of leukemic transformation in congenital neutropenia [5]
- Research article Shwachman-Diamond syndrome and solid tumors: Three new patients from the French Registry for Severe Chronic Neutropenia and literature review [6]
- Research article Emerging genetic technologies informing personalized medicine in Shwachman-Diamond syndrome and other inherited BMF disorders [7]
- Research article [Allogeneic hematopoietic stem cell transplantation for Shwachman-Diamond syndrome: a report of three cases and literature review] [8]
- Research article Clinical and genetic characteristics of Chinese patients with Shwachman Diamond syndrome: a literature review of Chinese publication [9]
- Research article A child with haemophilia A and Shwachman-Diamond syndrome with literature review of combined haematologic diseases in children [10]
References
- Kennedy AL, Myers KC, Bowman J, Gibson CJ, Camarda ND, Furutani E, et al.. Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome. . 2021. PMID 33637765 · DOI · PMC7910481
- Tan S, Kermasson L, Hilcenko C, Kargas V, Traynor D, Boukerrou AZ, et al.. Somatic genetic rescue of a germline ribosome assembly defect. . 2021. PMID 34413298 · DOI · PMC8377010
- Oyarbide U, Shah AN, Amaya-Mejia W, Snyderman M, Kell MJ, Allende DS, et al.. Loss of Sbds in zebrafish leads to neutropenia and pancreas and liver atrophy. . 2020. PMID 32759502 · DOI · PMC7526460
- Taha I, Minelli A, Danesino C, Swalmeh A, Huraibat K, Al-Labadi L, et al.. Homozygous Pathogenic Variant in Elongation Factor-Like 1 (EFL1) as a Causal Factor in Shwachman-Diamond Syndrome 2 in a Palestinian Child, With Distinct Ocular Manifestations. . 2026. PMID 42043893 · DOI · PMC13117211
- Link DC. Mechanisms of leukemic transformation in congenital neutropenia. Curr Opin Hematol. 2019. PMID 30431463 · DOI · PMC6447304
- Bou Mitri F, Beaupain B, Flejou JF, Patient M, Okhremchuck I, Blaise D, et al.. Shwachman-Diamond syndrome and solid tumors: Three new patients from the French Registry for Severe Chronic Neutropenia and literature review. Pediatr Blood Cancer. 2021. PMID 33871916 · DOI
- Cull AH, Kent DG, Warren AJ. Emerging genetic technologies informing personalized medicine in Shwachman-Diamond syndrome and other inherited BMF disorders. Blood. 2024. PMID 38905596 · DOI
- Feng AH, Shi JM, Fu HR, Yu J, Zheng WY, Zhu YY, et al.. [Allogeneic hematopoietic stem cell transplantation for Shwachman-Diamond syndrome: a report of three cases and literature review]. Zhonghua Xue Ye Xue Za Zhi. 2024. PMID 39231775 · DOI · PMC11388119
- Wang L, Jin Y, Chen Y, Zhao P, Shang X, Liu H, et al.. Clinical and genetic characteristics of Chinese patients with Shwachman Diamond syndrome: a literature review of Chinese publication. Exp Biol Med (Maywood). 2024. PMID 38651168 · DOI · PMC11033403
- Turudic D, Kelecic J, Omerza L, Vukovic J, Bilic M, Bilic E. A child with haemophilia A and Shwachman-Diamond syndrome with literature review of combined haematologic diseases in children. Haemophilia. 2019. PMID 31523886 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-11-04; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-11-04.
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Evidence strength
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