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Shwachman-Diamond syndrome

Zora R Rogers, MD
Section Editors
Donald H Mahoney, Jr, MD
William J Klish, MD
Deputy Editor
Jennifer S Tirnauer, MD


Shwachman-Diamond syndrome (SDS, also known as Shwachman-Diamond-Oski syndrome) generally presents in infancy with exocrine pancreatic dysfunction and bone marrow failure. Since its initial description in the early 1960s [1-3], clinical features associated with SDS have been identified. In addition, advances in molecular genetics have established that SDS is an autosomal recessive disorder.

The genetic abnormalities, clinical manifestations, diagnosis, and management of Shwachman-Diamond syndrome will be reviewed here.


Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder. In approximately 90 percent of affected patients who have been studied, mutations have been detected in the Shwachman-Bodian-Diamond syndrome (SBDS) gene located on chromosome 7q11 [4,5]. The SBDS gene has an adjacent pseudogene (a nonfunctional but almost identical gene) and, in the majority of cases, gene conversion mutations recombine portions of the pseudogene and SBDS gene, resulting in a dysfunctional SBDS gene [5]. At the present time, there is no known correlation between identified mutations and severity of disease [6].

The SBDS gene is highly conserved throughout evolution and is expressed in all human tissues tested to date [5,7,8]. The SBDS protein has been implicated in ribosome biogenesis and mitotic spindle stabilization [5,7-13]. Using human and animal models, investigators have shown that the SBDS gene product has an important role in the maturation of the 60S ribosomal subunit and ribosome assembly [14-18]. How this defect in ribosomal function leads to the clinical manifestations of SDS has not been established. One hypothesis is that the high protein secretory capacity of neutrophils, pancreatic acinar cells, and chondrocytes makes them particularly vulnerable to defects in ribosomal assembly [19]. SBDS protein colocalizes with the mitotic spindle and binds to and stabilizes purified microtubules [11,20]. It is currently unclear which functions of SBDS contribute to marrow failure.  

In a mouse model, homozygous expression of SBDS gene mutations leads to early fetal death [21] consistent with an essential role for SBDS in early mammalian development.


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Literature review current through: Aug 2015. | This topic last updated: Jan 23, 2014.
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  3. NEZELOF C, WATCHI M. [Lipomatous congenital hypoplasia of the exocrine pancreas in children. (2 cases and review of the literature)]. Arch Fr Pediatr 1961; 18:1135.
  4. Woloszynek JR, Rothbaum RJ, Rawls AS, et al. Mutations of the SBDS gene are present in most patients with Shwachman-Diamond syndrome. Blood 2004; 104:3588.
  5. Boocock GR, Morrison JA, Popovic M, et al. Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nat Genet 2003; 33:97.
  6. Hall GW, Dale P, Dodge JA. Shwachman-Diamond syndrome: UK perspective. Arch Dis Child 2006; 91:521.
  7. Austin KM, Leary RJ, Shimamura A. The Shwachman-Diamond SBDS protein localizes to the nucleolus. Blood 2005; 106:1253.
  8. Boocock GR, Marit MR, Rommens JM. Phylogeny, sequence conservation, and functional complementation of the SBDS protein family. Genomics 2006; 87:758.
  9. Savchenko A, Krogan N, Cort JR, et al. The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism. J Biol Chem 2005; 280:19213.
  10. Shammas C, Menne TF, Hilcenko C, et al. Structural and mutational analysis of the SBDS protein family. Insight into the leukemia-associated Shwachman-Diamond Syndrome. J Biol Chem 2005; 280:19221.
  11. Austin KM, Gupta ML Jr, Coats SA, et al. Mitotic spindle destabilization and genomic instability in Shwachman-Diamond syndrome. J Clin Invest 2008; 118:1511.
  12. Rujkijyanont P, Adams SL, Beyene J, Dror Y. Bone marrow cells from patients with Shwachman-Diamond syndrome abnormally express genes involved in ribosome biogenesis and RNA processing. Br J Haematol 2009; 145:806.
  13. Hesling C, Oliveira CC, Castilho BA, Zanchin NI. The Shwachman-Bodian-Diamond syndrome associated protein interacts with HsNip7 and its down-regulation affects gene expression at the transcriptional and translational levels. Exp Cell Res 2007; 313:4180.
  14. Wong CC, Traynor D, Basse N, et al. Defective ribosome assembly in Shwachman-Diamond syndrome. Blood 2011; 118:4305.
  15. Finch AJ, Hilcenko C, Basse N, et al. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes Dev 2011; 25:917.
  16. Menne TF, Goyenechea B, Sánchez-Puig N, et al. The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. Nat Genet 2007; 39:486.
  17. Ganapathi KA, Austin KM, Lee CS, et al. The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA. Blood 2007; 110:1458.
  18. Burwick N, Coats SA, Nakamura T, Shimamura A. Impaired ribosomal subunit association in Shwachman-Diamond syndrome. Blood 2012; 120:5143.
  19. Tulpule A, Kelley JM, Lensch MW, et al. Pluripotent stem cell models of Shwachman-Diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction. Cell Stem Cell 2013; 12:727.
  20. Orelio C, Verkuijlen P, Geissler J, et al. SBDS expression and localization at the mitotic spindle in human myeloid progenitors. PLoS One 2009; 4:e7084.
  21. Zhang S, Shi M, Hui CC, Rommens JM. Loss of the mouse ortholog of the shwachman-diamond syndrome gene (Sbds) results in early embryonic lethality. Mol Cell Biol 2006; 26:6656.
  22. Goobie S, Popovic M, Morrison J, et al. Shwachman-Diamond syndrome with exocrine pancreatic dysfunction and bone marrow failure maps to the centromeric region of chromosome 7. Am J Hum Genet 2001; 68:1048.
  23. Alter BP. Inherited Bone Marrow Failure Syndromes. In: Nathan and Oski's Hematology of Infancy and Childhood, Nathan DG, Orkin SH, Ginsburg D, Look AT (Eds), W.B. Saunders, Philadelphia 2003. p.280.
  24. Myers KC, Bolyard AA, Otto B, et al. Variable clinical presentation of Shwachman-Diamond syndrome: update from the North American Shwachman-Diamond Syndrome Registry. J Pediatr 2014; 164:866.
  25. Ginzberg H, Shin J, Ellis L, et al. Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar. J Pediatr 1999; 135:81.
  26. Aggett PJ, Cavanagh NP, Matthew DJ, et al. Shwachman's syndrome. A review of 21 cases. Arch Dis Child 1980; 55:331.
  27. Mack DR, Forstner GG, Wilschanski M, et al. Shwachman syndrome: exocrine pancreatic dysfunction and variable phenotypic expression. Gastroenterology 1996; 111:1593.
  28. Smith OP, Hann IM, Chessells JM, et al. Haematological abnormalities in Shwachman-Diamond syndrome. Br J Haematol 1996; 94:279.
  29. Cipolli M, D'Orazio C, Delmarco A, et al. Shwachman's syndrome: pathomorphosis and long-term outcome. J Pediatr Gastroenterol Nutr 1999; 29:265.
  30. Ip WF, Dupuis A, Ellis L, et al. Serum pancreatic enzymes define the pancreatic phenotype in patients with Shwachman-Diamond syndrome. J Pediatr 2002; 141:259.
  31. Mäkitie O, Ellis L, Durie PR, et al. Skeletal phenotype in patients with Shwachman-Diamond syndrome and mutations in SBDS. Clin Genet 2004; 65:101.
  32. Toiviainen-Salo S, Mäyränpää MK, Durie PR, et al. Shwachman-Diamond syndrome is associated with low-turnover osteoporosis. Bone 2007; 41:965.
  33. Toiviainen-Salo S, Durie PR, Numminen K, et al. The natural history of Shwachman-Diamond syndrome-associated liver disease from childhood to adulthood. J Pediatr 2009; 155:807.
  34. Kerr EN, Ellis L, Dupuis A, et al. The behavioral phenotype of school-age children with shwachman diamond syndrome indicates neurocognitive dysfunction with loss of Shwachman-Bodian-Diamond syndrome gene function. J Pediatr 2010; 156:433.
  35. Durie PR, Rommens JM. Shwachman-Diamond Syndrome. In: Pediatric Gastrointestinal Disease, 4th, Walker WA, Goulet O, Kleinman RE, et al (Eds), BC Decker, Hamilton 2004. p.1624.
  36. Toiviainen-Salo S, Raade M, Durie PR, et al. Magnetic resonance imaging findings of the pancreas in patients with Shwachman-Diamond syndrome and mutations in the SBDS gene. J Pediatr 2008; 152:434.
  37. Calado RT, Graf SA, Wilkerson KL, et al. Mutations in the SBDS gene in acquired aplastic anemia. Blood 2007; 110:1141.
  38. Stepanovic V, Wessels D, Goldman FD, et al. The chemotaxis defect of Shwachman-Diamond Syndrome leukocytes. Cell Motil Cytoskeleton 2004; 57:158.
  39. Orelio C, Kuijpers TW. Shwachman-Diamond syndrome neutrophils have altered chemoattractant-induced F-actin polymerization and polarization characteristics. Haematologica 2009; 94:409.
  40. Aggett PJ, Harries JT, Harvey BA, Soothill JF. An inherited defect of neutrophil mobility in Shwachman syndrome. J Pediatr 1979; 94:391.
  41. Rothbaum RJ, Williams DA, Daugherty CC. Unusual surface distribution of concanavalin A reflects a cytoskeletal defect in neutrophils in Shwachman's syndrome. Lancet 1982; 2:800.
  42. Dror Y, Ginzberg H, Dalal I, et al. Immune function in patients with Shwachman-Diamond syndrome. Br J Haematol 2001; 114:712.
  43. Rochowski A, Sun C, Glogauer M, Alter BP. Neutrophil functions in patients with inherited bone marrow failure syndromes. Pediatr Blood Cancer 2011; 57:306.
  44. Kuijpers TW, Alders M, Tool AT, et al. Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship. Blood 2005; 106:356.
  45. Dror Y. Shwachman-Diamond syndrome. Pediatr Blood Cancer 2005; 45:892.
  46. Woods WG, Krivit W, Lubin BH, Ramsay NK. Aplastic anemia associated with the Shwachman syndrome. In vivo and in vitro observations. Am J Pediatr Hematol Oncol 1981; 3:347.
  47. Kuijpers TW, Nannenberg E, Alders M, et al. Congenital aplastic anemia caused by mutations in the SBDS gene: a rare presentation of Shwachman-Diamond syndrome. Pediatrics 2004; 114:e387.
  48. Singh SA, Vlachos A, Morgenstern NJ, et al. Breast cancer in a case of Shwachman Diamond syndrome. Pediatr Blood Cancer 2012; 59:945.
  49. Sack JE, Kuchnir L, Demierre MF. Dermatofibrosarcoma protuberans arising in the context of Shwachman-Diamond syndrome. Pediatr Dermatol 2011; 28:568.
  50. Myers KC, Rose SR, Rutter MM, et al. Endocrine evaluation of children with and without Shwachman-Bodian-Diamond syndrome gene mutations and Shwachman-Diamond syndrome. J Pediatr 2013; 162:1235.
  51. Grinspan ZM, Pikora CA. Infections in patients with Shwachman-Diamond syndrome. Pediatr Infect Dis J 2005; 24:179.
  52. Kent A, Murphy GH, Milla P. Psychological characteristics of children with Shwachman syndrome. Arch Dis Child 1990; 65:1349.
  53. Toiviainen-Salo S, Mäkitie O, Mannerkoski M, et al. Shwachman-Diamond syndrome is associated with structural brain alterations on MRI. Am J Med Genet A 2008; 146A:1558.
  54. Rothbaum R, Perrault J, Vlachos A, et al. Shwachman-Diamond syndrome: report from an international conference. J Pediatr 2002; 141:266.
  55. Dror Y, Donadieu J, Koglmeier J, et al. Draft consensus guidelines for diagnosis and treatment of Shwachman-Diamond syndrome. Ann N Y Acad Sci 2011; 1242:40.
  56. Dror Y, Durie P, Ginzberg H, et al. Clonal evolution in marrows of patients with Shwachman-Diamond syndrome: a prospective 5-year follow-up study. Exp Hematol 2002; 30:659.
  57. Shimamura A. Shwachman-Diamond syndrome. Semin Hematol 2006; 43:178.
  58. Donadieu J, Leblanc T, Bader Meunier B, et al. Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. Experience of the French Severe Chronic Neutropenia Study Group. Haematologica 2005; 90:45.
  59. Adachi N, Tsuchiya H, Nunoi H, et al. rhG-CSF for Shwachman's syndrome. Lancet 1990; 336:1136.
  60. Burroughs L, Woolfrey A, Shimamura A. Shwachman-Diamond syndrome: a review of the clinical presentation, molecular pathogenesis, diagnosis, and treatment. Hematol Oncol Clin North Am 2009; 23:233.
  61. Donadieu J, Michel G, Merlin E, et al. Hematopoietic stem cell transplantation for Shwachman-Diamond syndrome: experience of the French neutropenia registry. Bone Marrow Transplant 2005; 36:787.
  62. Cesaro S, Oneto R, Messina C, et al. Haematopoietic stem cell transplantation for Shwachman-Diamond disease: a study from the European Group for blood and marrow transplantation. Br J Haematol 2005; 131:231.
  63. Vibhakar R, Radhi M, Rumelhart S, et al. Successful unrelated umbilical cord blood transplantation in children with Shwachman-Diamond syndrome. Bone Marrow Transplant 2005; 36:855.
  64. Mehta P, Locatelli F, Stary J, Smith FO. Bone marrow transplantation for inherited bone marrow failure syndromes. Pediatr Clin North Am 2010; 57:147.
  65. Bhatla D, Davies SM, Shenoy S, et al. Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman-Diamond syndrome. Bone Marrow Transplant 2008; 42:159.