Comparative analysis of Shwachman‐Diamond syndrome to other inherited bone marrow failure syndromes and genotype–phenotype correlation |
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| Authors: | R Klaassen CV Fernandez R Yanofsky E Shereck J Champagne M Silva JH Lipton J Brossard Y Samson S Abish M Steele K Ali N Dower U Athale L Jardine JP Hand J Beyene Y Dror |
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| Affiliation: | 1. Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada;2. Isaak Walton Killam Hospital for Children, Halifax, Nova Scotia, Canada;3. CancerCare Manitoba, Winnipeg, Manitoba, Canada;4. British Columbia Children's Hospital, Vancouver, British Columbia, Canada;5. H?pital Ste. Justine, Montréal, Québec, Canada;6. Queen's University, Kingston, Ontario, Canada;7. Princess Margaret Hospital, Toronto, Ontario, Canada;8. Centre U Sante de l’Estrie‐Fleur, Sherbrooke, Quebec, Canada;9. Centre Hospital University Quebec‐Pav CHUL, Sainte‐Foy, Quebec, Canada;10. Montreal Children's Hospital, Montreal, Québec, Canada;11. Alberta Children's Hospital, Calgary, Alberta, Canada;12. University of Saskatchewan, Saskatoon, Saskatchewan, Canada;13. University of Alberta/Health Sciences Centre, Edmonton, Alberta, Canada;14. McMaster Children's Hospital/McMaster University Health Sciences Centre, Hamilton, Ontario, Canada;15. Children's Hospital of Western Ontario, London, Ontario, Canada;16. Janeway Child Health Centre, St. John's, Newfoundland, Canada;17. Population Health Sciences, Research Institute, The Hospital For Sick Children, Toronto, Ontario, Canada;18. Marrow Failure and Myelodysplasia Program, Division of Haematology/ Oncology and Cell Biology Program, Research Institute, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada |
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| Abstract: | Hashmi SK, Allen C, Klaassen R, Fernandez CV, Yanofsky R, Shereck E, Champagne J, Silva M, Lipton JH, Brossard J, Samson Y, Abish S, Steele M, Ali K, Dower N, Athale U, Jardine L, Hand JP, Beyene J, Dror Y. Comparative analysis of Shwachman‐Diamond syndrome to other inherited bone marrow failure syndromes and genotype–phenotype correlation. Our knowledge of the phenotypes of inherited bone marrow failure syndromes (IBMFSs) derives from case reports or case series in which only one IBMFS was studied. However, the substantial phenotypic overlap necessitates comparative analysis between the IBMFSs. Shwachman–Diamond syndrome (SDS) is an IBMFS that the appreciation of what comprises its clinical phenotype is still evolving. In this analysis we used data on 125 patients from the Canadian Inherited Marrow Failure Study (CIMFS), which is a prospective multicenter population‐based study. Thirty‐four cases of SDS patients were analyzed and compared to other patients with the four most common IBMFSs on the CIMFS: Diamond Blackfan anemia, Fanconi anemia (FA), Kostmann/severe congenital neutropenia and dyskeratosis congenita (DC). The diagnosis of SDS, FA and DC was often delayed relative to symptoms onset; indicating a major need for improving tools to establish a rapid diagnosis. We identified multiple phenotypic differences between SDS and other IBMFSs, including several novel differences. SBDS biallelic mutations were less frequent than in previous reports (81%). Importantly, compared to patients with biallelic mutations, patients with wild type SBDS had more severe hematological disease but milder pancreatic disease. In conclusion, comprehensive study of the IBMFSs can provide useful comparative data between the disorders. SBDS‐negative SDS patients may have more severe hematological failure and milder pancreatic disease. |
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| Keywords: | Diamond Blackfan anemia dyskeratosis congenita Fanconi anemia genetic genotype phenotype correlation inherited bone marrow failure syndromes Kostmann neutropenia Shwachman Diamond syndrome |
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