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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 or Shwachman syndrome) is a rare inherited disorder associated with neutropenia that may progress to bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities that generally presents in infancy. Advances in understanding the genetics, pathophysiology, and natural history of the disease since its initial description in the early 1960s have made the importance of accurate diagnosis and management of this disorder more compelling.

This topic review discusses the pathophysiology, clinical manifestations, diagnosis, and clinical management of SDS.

Other inherited bone marrow failure syndromes, and an approach to the evaluation of patients with bone marrow failure, are discussed in separate topic reviews:

(See "Congenital neutropenia".)

(See "Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis".)


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Literature review current through: Sep 2015. | This topic last updated: Oct 1, 2015.
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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. Shen J, Lin K, An Y, et al. [Two cases of Shwachman-Diamond syndrome with genetic confirmation and literature review]. Zhonghua Er Ke Za Zhi 2013; 51:679.
  7. Carvalho CM, Zuccherato LW, Williams CL, et al. Structural variation and missense mutation in SBDS associated with Shwachman-Diamond syndrome. BMC Med Genet 2014; 15:64.
  8. Erdos M, Alapi K, Balogh I, et al. Severe Shwachman-Diamond syndrome phenotype caused by compound heterozygous missense mutations in the SBDS gene. Exp Hematol 2006; 34:1517.
  9. Nicolis E, Bonizzato A, Assael BM, Cipolli M. Identification of novel mutations in patients with Shwachman-Diamond syndrome. Hum Mutat 2005; 25:410.
  10. Hall GW, Dale P, Dodge JA. Shwachman-Diamond syndrome: UK perspective. Arch Dis Child 2006; 91:521.
  11. Kuijpers TW, Alders M, Tool AT, et al. Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship. Blood 2005; 106:356.
  12. 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.
  13. Kawakami T, Mitsui T, Kanai M, et al. Genetic analysis of Shwachman-Diamond syndrome: phenotypic heterogeneity in patients carrying identical SBDS mutations. Tohoku J Exp Med 2005; 206:253.
  14. Austin KM, Leary RJ, Shimamura A. The Shwachman-Diamond SBDS protein localizes to the nucleolus. Blood 2005; 106:1253.
  15. Boocock GR, Marit MR, Rommens JM. Phylogeny, sequence conservation, and functional complementation of the SBDS protein family. Genomics 2006; 87:758.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. Wong CC, Traynor D, Basse N, et al. Defective ribosome assembly in Shwachman-Diamond syndrome. Blood 2011; 118:4305.
  24. 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.
  25. 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.
  26. Ganapathi KA, Austin KM, Lee CS, et al. The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA. Blood 2007; 110:1458.
  27. Burwick N, Coats SA, Nakamura T, Shimamura A. Impaired ribosomal subunit association in Shwachman-Diamond syndrome. Blood 2012; 120:5143.
  28. Asano N, Atsuumi H, Nakamura A, et al. Direct interaction between EFL1 and SBDS is mediated by an intrinsically disordered insertion domain. Biochem Biophys Res Commun 2014; 443:1251.
  29. Gijsbers A, García-Márquez A, Luviano A, Sánchez-Puig N. Guanine nucleotide exchange in the ribosomal GTPase EFL1 is modulated by the protein mutated in the Shwachman-Diamond syndrome. Biochem Biophys Res Commun 2013; 437:349.
  30. Sezgin G, Henson AL, Nihrane A, et al. Impaired growth, hematopoietic colony formation, and ribosome maturation in human cells depleted of Shwachman-Diamond syndrome protein SBDS. Pediatr Blood Cancer 2013; 60:281.
  31. 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.
  32. Stepanovic V, Wessels D, Goldman FD, et al. The chemotaxis defect of Shwachman-Diamond Syndrome leukocytes. Cell Motil Cytoskeleton 2004; 57:158.
  33. Orelio C, Kuijpers TW. Shwachman-Diamond syndrome neutrophils have altered chemoattractant-induced F-actin polymerization and polarization characteristics. Haematologica 2009; 94:409.
  34. Henson AL, Moore JB 4th, Alard P, et al. Mitochondrial function is impaired in yeast and human cellular models of Shwachman Diamond syndrome. Biochem Biophys Res Commun 2013; 437:29.
  35. Booij J, Reneman L, Alders M, Kuijpers TW. Increase in central striatal dopamine transporters in patients with Shwachman-Diamond syndrome: additional evidence of a brain phenotype. Am J Med Genet A 2013; 161A:102.
  36. Sen S, Wang H, Nghiem CL, et al. The ribosome-related protein, SBDS, is critical for normal erythropoiesis. Blood 2011; 118:6407.
  37. Ambekar C, Das B, Yeger H, Dror Y. SBDS-deficiency results in deregulation of reactive oxygen species leading to increased cell death and decreased cell growth. Pediatr Blood Cancer 2010; 55:1138.
  38. Ball HL, Zhang B, Riches JJ, et al. Shwachman-Bodian Diamond syndrome is a multi-functional protein implicated in cellular stress responses. Hum Mol Genet 2009; 18:3684.
  39. 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.
  40. Minelli A, Nicolis E, Cannioto Z, et al. Incidence of Shwachman-Diamond syndrome. Pediatr Blood Cancer 2012; 59:1334.
  41. Tsangaris E, Klaassen R, Fernandez CV, et al. Genetic analysis of inherited bone marrow failure syndromes from one prospective, comprehensive and population-based cohort and identification of novel mutations. J Med Genet 2011; 48:618.
  42. 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.
  43. 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.
  44. 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.
  45. Shimamura A. Shwachman-Diamond syndrome. Semin Hematol 2006; 43:178.
  46. 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.
  47. Myers KC, Davies SM, Shimamura A. Clinical and molecular pathophysiology of Shwachman-Diamond syndrome: an update. Hematol Oncol Clin North Am 2013; 27:117.
  48. 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.
  49. Myers K, Bolyard AA, Wong T, et al. The North American Shwachman-Diamond Syndrome Registry: Five years of follow up. Pediatr Blood Cancer 2015; 62:S26.
  50. Aggett PJ, Cavanagh NP, Matthew DJ, et al. Shwachman's syndrome. A review of 21 cases. Arch Dis Child 1980; 55:331.
  51. Mack DR, Forstner GG, Wilschanski M, et al. Shwachman syndrome: exocrine pancreatic dysfunction and variable phenotypic expression. Gastroenterology 1996; 111:1593.
  52. Smith OP, Hann IM, Chessells JM, et al. Haematological abnormalities in Shwachman-Diamond syndrome. Br J Haematol 1996; 94:279.
  53. Cipolli M, D'Orazio C, Delmarco A, et al. Shwachman's syndrome: pathomorphosis and long-term outcome. J Pediatr Gastroenterol Nutr 1999; 29:265.
  54. 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.
  55. Aggett PJ, Harries JT, Harvey BA, Soothill JF. An inherited defect of neutrophil mobility in Shwachman syndrome. J Pediatr 1979; 94:391.
  56. 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.
  57. Dror Y, Ginzberg H, Dalal I, et al. Immune function in patients with Shwachman-Diamond syndrome. Br J Haematol 2001; 114:712.
  58. Rochowski A, Sun C, Glogauer M, Alter BP. Neutrophil functions in patients with inherited bone marrow failure syndromes. Pediatr Blood Cancer 2011; 57:306.
  59. 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.
  60. 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.
  61. Toiviainen-Salo S, Mäyränpää MK, Durie PR, et al. Shwachman-Diamond syndrome is associated with low-turnover osteoporosis. Bone 2007; 41:965.
  62. 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.
  63. Grinspan ZM, Pikora CA. Infections in patients with Shwachman-Diamond syndrome. Pediatr Infect Dis J 2005; 24:179.
  64. 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.
  65. Dror Y. Shwachman-Diamond syndrome. Pediatr Blood Cancer 2005; 45:892.
  66. 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.
  67. 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.
  68. Ryan TD, Jefferies JL, Chin C, et al. Abnormal circumferential strain measured by echocardiography is present in patients with Shwachman-Diamond syndrome despite normal shortening fraction. Pediatr Blood Cancer 2015; 62:1228.
  69. 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.
  70. Kent A, Murphy GH, Milla P. Psychological characteristics of children with Shwachman syndrome. Arch Dis Child 1990; 65:1349.
  71. 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.
  72. Gana S, Sainati L, Frau MR, et al. Shwachman-Diamond syndrome and type 1 diabetes mellitus: more than a chance association? Exp Clin Endocrinol Diabetes 2011; 119:610.
  73. Singh SA, Vlachos A, Morgenstern NJ, et al. Breast cancer in a case of Shwachman Diamond syndrome. Pediatr Blood Cancer 2012; 59:945.
  74. Sack JE, Kuchnir L, Demierre MF. Dermatofibrosarcoma protuberans arising in the context of Shwachman-Diamond syndrome. Pediatr Dermatol 2011; 28:568.
  75. Sharma A, Sadimin E, Drachtman R, Glod J. CNS lymphoma in a patient with Shwachman Diamond syndrome. Pediatr Blood Cancer 2014; 61:564.
  76. Rothbaum R, Perrault J, Vlachos A, et al. Shwachman-Diamond syndrome: report from an international conference. J Pediatr 2002; 141:266.
  77. 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.
  78. Mehta P, Locatelli F, Stary J, Smith FO. Bone marrow transplantation for inherited bone marrow failure syndromes. Pediatr Clin North Am 2010; 57:147.
  79. 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.
  80. 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.
  81. 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.
  82. 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.