Inflammatory manifestations in patients with Shwachman-Diamond syndrome: A novel phenotype

Am J Med Genet A. 2020 Jul;182(7):1754-1760. doi: 10.1002/ajmg.a.61593. Epub 2020 Apr 15.


Shwachman-Diamond syndrome (SDS) is an autosomal recessive multisystem disorder characterized by exocrine pancreatic dysfunction, bone marrow failure, and leukemia predisposition. Approximately 90% of cases are due to biallelic mutations in the Shwachman-Bodian-Diamond (SBDS) gene. Additional phenotypic features variably associated with SDS include skeletal, neurologic, hepatic, cardiac, endocrine, and dental abnormalities. We report five subjects with SDS who developed a range of inflammatory manifestations. Three patients developed inflammatory eye conditions. Single cases of juvenile idiopathic arthritis, chronic recurrent multifocal osteomyelitis, and scleroderma were also noted. Clinical presentation and treatment responses are described. Proteomic analysis revealed increased inflammatory signatures in SDS subjects as compared to controls. Treatment of inflammatory manifestations in patients with SDS may be complicated by potential myelosuppressive toxicities of anti-rheumatic medications. Further research is needed to better understand the potential link between inflammatory disorders and SDS to inform effective treatment strategies.

Keywords: Shwachman-Diamond syndrome; autoimmune; inflammation; neutropenia.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / pathology
  • Bone Marrow Diseases / diagnosis
  • Bone Marrow Diseases / genetics
  • Child
  • Child, Preschool
  • Endocrine System / pathology
  • Female
  • Humans
  • Inflammation / diagnosis
  • Inflammation / genetics*
  • Inflammation / pathology
  • Lipomatosis / diagnosis
  • Lipomatosis / genetics
  • Lipomatosis / pathology
  • Male
  • Mutation / genetics
  • Phenotype
  • Proteins / genetics*
  • Proteomics
  • Shwachman-Diamond Syndrome / diagnosis
  • Shwachman-Diamond Syndrome / genetics*
  • Shwachman-Diamond Syndrome / pathology
  • Young Adult


  • Proteins
  • SBDS protein, human