The Experts below are selected from a list of 1713 Experts worldwide ranked by ideXlab platform
Akiko Shimamura - One of the best experts on this subject based on the ideXlab platform.
-
Clinical spectrum and molecular pathophysiology of Shwachman-Diamond Syndrome.
Current Opinion in Hematology, 2020Co-Authors: James N. Huang, Akiko ShimamuraAbstract:PURPOSE OF REVIEW Shwachman Diamond Syndrome (SDS) is an inherited bone marrow failure and cancer predisposition Syndrome that affects multiple organ systems. Mutations in the SBDS gene are found in the majority of patients, but the molecular function of the SBDS protein product remains unclear. Here, we review recent progress in the clinical and molecular characterization of SDS.
-
Variable Clinical Presentation of Shwachman–Diamond Syndrome: Update from the North American Shwachman–Diamond Syndrome Registry
The Journal of Pediatrics, 2013Co-Authors: Kasiani C. Myers, Audrey Anna Bolyard, Barbara Otto, Trisha E. Wong, Amanda T. Jones, Richard E. Harris, Stella M. Davies, David C. Dale, Akiko ShimamuraAbstract:Objectives To investigate the range of clinical presentations for Shwachman–Diamond Syndrome (SDS) with the long-term goal of improving diagnosis. Study design We reviewed the North American Shwachman–Diamond Syndrome Registry. Genetic reports of biallelic Shwachman–Bodian–Diamond Syndrome mutations confirming the diagnosis of SDS were available for 37 patients. Results Neutropenia was the most common hematologic abnormality at presentation (30/37, 81%); however, only 51% (19/37) of patients presented with the classic combination of neutropenia and steatorrhea. Absence of pancreatic lipomatosis on ultrasound or computed tomography scan, normal fecal elastase levels, and normal skeletal survey do not rule out the diagnosis of SDS. SDS was diagnosed in 2 asymptomatic siblings of SDS probands. Twenty-four of 37 patients (65%) had congenital anomalies. Conclusion Our cohort reveals a broad range of clinical presentation for SDS. Clues to the underlying diagnosis of SDS included cytopenias with a hypocellular marrow, congenital anomalies, family history, and myelodysplasia with clonal abnormalities frequently found in SDS. Reliance on classic clinical criteria for SDS would miss or delay diagnosis of a significant subset of patients with SDS.
-
Clinical Spectrum and Molecular Pathophysiology of Shwachman-Diamond Syndrome
Blood, 2013Co-Authors: Akiko ShimamuraAbstract:Shwachman-Diamond Syndrome (SDS) is an inherited marrow failure Syndrome associated with exocrine pancreatic dysfunction and leukemia predisposition. SDS patients may also manifest additional non-hematologic abnormalities. Autosomal recessive mutations in the SBDS gene are found in over 90 percent of patients fitting the classical clinical phenotype of SDS. The advent of genetic testing has revealed an unexpectedly broad range of SDS phenotypes. Through the Shwachman-Diamond Syndrome Registry, we found that diagnosis may be obscured by cryptic or non-classical presentations of SDS. The timely diagnosis of SDS carries profound ramifications for medical management and treatment. We are developing assays utilizing massively parallel next generation sequencing to address this challenging diagnostic problem. Clinical applications of next generation sequencing to the diagnostic algorithm for marrow failure or myelodysplastic Syndrome and implications for medical treatment will be explored. Disclosures: No relevant conflicts of interest to declare.
-
Variable Clinical Presentation of Shwachman-Diamond Syndrome: Update From the North-American Shwachman-Diamond Syndrome Registry.
Blood, 2012Co-Authors: Kasiani C. Myers, Audrey Anna Bolyard, Barbara Otto, Trisha E. Wong, Richard E. Harris, Stella M. Davies, David C. Dale, Nicholas J Dobbins, Amanda L. Jones, Akiko ShimamuraAbstract:Abstract 2367 Background: Shwachman-Diamond Syndrome (SDS) is an autosomal recessively inherited marrow failure Syndrome associated with exocrine pancreatic dysfunction and an increased leukemia risk. SDS is caused by biallelic mutations in the SBDS gene. Timely diagnosis prior to the development of life-threatening complications is essential for optimal medical management and outcomes. SDS hematologic complications such as severe marrow failure or leukemia are treated with a hematopoietic stem cell transplant. SDS patients require reduced intensity conditioning regimens to avoid undue regimen-related toxicities, thus the recognition of the underlying diagnosis of SDS is critical. The common constellation of clinical characteristics reported for SDS includes neutropenia, steatorrhea, and failure to thrive. Hypothesis: With the advent of genetic testing, diagnosis is now possible for patients with non-classical presentations of the inherited marrow failure Syndromes. The aim of this study was to investigate the range of clinical presentations for SDS with the long-term goal of improving diagnosis. Methods: This study was a retrospective review of medical records obtained by the North American Shwachman-Diamond Syndrome Registry (SDSR) which was founded in 2008. The SDS Registry works in partnership with the Severe Chronic Neutropenia International Registry. Results: Genetic reports of biallelic SBDS mutations confirming the diagnosis of SDS were available for 31 patients. This SDS study cohort included 19 male and 12 female patients. Median patient age was 10 years with a range of 2 – 49 years. Radiologic reports were available for 23 patients. Pancreatic lipomatosis was noted in 22/23 patients. One patient had an atrophic pancreas without lipomatosis on CT scan at age 6.9 years. Two patients initially had normal early pancreatic studies by CT or ultrasound at ages 1.3 years and 2.6 years, but subsequently were found to have pancreatic lipomatosis by the same imaging modalities later in life. Fecal elastase has not been previously evaluated as a screen for SDS. 14/17 patients (82%) had low fecal elastase levels while 3/17 patients had normal fecal elastase levels. Serum trypsinogen or pancreatic isoamylase were low in all 18 patients tested. 26/31 patients (84%) presented with failure to thrive. 17/31 (54%) patients presented with diarrhea or steatorrhea. 17/31 patients (55%) had congenital anomalies. Neutropenia was the most common hematologic abnormality at presentation (77%). Strikingly, 2 patients presented with isolated thrombocytopenia, 3 patients presented with severe anemia requiring transfusion support, and 5 patients presented without any cytopenias. One patient presented with the initial diagnosis of MDS with a del 20q clone. One patient presented with short stature and a sibling who died from AML. Interestingly, one patient had very short telomeres ( st percentile for age) across 3 lymphocyte subsets as well as in total lymphocytes, a pattern typically associated with dyskeratosis congenita. Conclusion: Data from the North-American Shwachman Diamond Syndrome Registry reveals an unexpected range of clinical presentation for this rare disorder that expands beyond that which is currently classically recognized. The diagnosis of SDS should be considered even in the absence of neutropenia or diarrhea. In our cohort, clues to the underlying diagnosis of SDS included other cytopenias, congenital anomalies, family history, and the del20q clonal marrow abnormality. Reliance on classical clinical descriptions of SDS would miss or delay diagnosis of a significant subset of SDS patients. Disclosures: Dale: AMGEN: Consultancy.
-
Clinical and molecular pathophysiology of Shwachman-Diamond Syndrome: an update.
Hematology-oncology Clinics of North America, 2012Co-Authors: Kasiani C. Myers, Stella M. Davies, Akiko ShimamuraAbstract:: Shwachman-Diamond Syndrome (SDS) is an inherited neutropenia Syndrome associated with a significant risk of aplastic anemia and malignant transformation. Multiple additional organ systems, including the pancreas, liver, and skeletal and central nervous systems, are affected. Mutations in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene are present in most patients. There is growing evidence that SBDS functions in ribosomal biogenesis and other cellular processes. This article summarizes the clinical phenotype of SDS, diagnostic and treatment approaches, and novel advances in our understanding of the molecular pathophysiology of this disease.
F Goldman - One of the best experts on this subject based on the ideXlab platform.
-
Successful unrelated umbilical cord blood transplantation in children with Shwachman-Diamond Syndrome
Bone Marrow Transplantation, 2005Co-Authors: R Vibhakar, M Radhi, S Rumelhart, D Tatman, F GoldmanAbstract:Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic insufficiency and variable degrees of neutropenia. SDS patients are at risk of developing myelodysplasia, aplastic anemia, and leukemic transformation. The role and timing of allogeneic hematopoietic stem cell transplantation (HSCT) in SDS remain controversial. We report three SDS patients with severe aplasia transplanted using unrelated umbilical cord blood (UCB). Patients received melphalan (180 mg/m^2), etoposide (1200 mg/m^2), anti-thymocyte globulin (90 mg/kg), and total lymphoid irradiation (500 cGy); graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and prednisone. Myeloid engraftment occurred promptly with absolute neutrophil count >500 cells/mm^3 on day 15±5 and all patients displayed 100% donor chimerism by 2 months post transplant. The major complication of transplant was GVHD, with all patients developing grade II or III acute GVHD, one progressing to chronic extensive GVHD. Patients are alive 309, 623, and 2029 days post transplant. Factors important in HSCT outcome for SDS may include transplantation at a young age, avoidance of cyclophosphamide, and adequate GVHD prophylaxis. Importantly, these cases also suggest that unrelated UCB, in the absence of a matched family member, is an excellent alternative stem cell source for SDS patients undergoing HSCT.
Kasiani C. Myers - One of the best experts on this subject based on the ideXlab platform.
-
Clinical features and outcomes of patients with Shwachman-Diamond Syndrome and myelodysplastic Syndrome or acute myeloid leukaemia: a multicentre, retrospective, cohort study.
The Lancet Haematology, 2019Co-Authors: Kasiani C. Myers, Elissa Furutani, Edie Weller, Bradford Siegele, Ashley Galvin, Valérie Arsenault, Blanche P. Alter, Farid Boulad, Carlos E. Bueso-ramos, Lauri BurroughsAbstract:Summary Background Data to inform surveillance and treatment for leukaemia predisposition Syndromes are scarce and recommendations are largely based on expert opinion. This study aimed to investigate the clinical features and outcomes of patients with myelodysplastic Syndrome or acute myeloid leukaemia and Shwachman-Diamond Syndrome, an inherited bone marrow failure disorder with high risk of developing myeloid malignancies. Methods We did a multicentre, retrospective, cohort study in collaboration with the North American Shwachman-Diamond Syndrome Registry. We reviewed patient medical records from 17 centres in the USA and Canada. Patients with a genetic (biallelic mutations in the SBDS gene) or clinical diagnosis (cytopenias and pancreatic dysfunction) of Shwachman-Diamond Syndrome who developed myelodysplastic Syndrome or acute myeloid leukaemia were eligible without additional restriction. Medical records were reviewed between March 1, 2001, and Oct 5, 2017. Masked central review of bone marrow pathology was done if available to confirm leukaemia or myelodysplastic Syndrome diagnosis. We describe the clinical features and overall survival of these patients. Findings We initially identified 37 patients with Shwachman-Diamond Syndrome and myelodysplastic Syndrome or acute myeloid leukaemia. 27 patients had samples available for central pathology review and were reclassified accordingly (central diagnosis concurred with local in 15 [56%] cases), 10 had no samples available and were classified based on the local review data, and 1 patient was excluded at this stage as not eligible. 36 patients were included in the analysis, of whom 10 (28%) initially presented with acute myeloid leukaemia and 26 (72%) initially presented with myelodysplastic Syndrome. With a median follow-up of 4·9 years (IQR 3·9–8·4), median overall survival for patients with myelodysplastic Syndrome was 7·7 years (95% CI 0·8–not reached) and 0·99 years (95% CI 0·2–2·4) for patients with acute myeloid leukaemia. Overall survival at 3 years was 11% (95% CI 1–39) for patients with leukaemia and 51% (29–68) for patients with myelodysplastic Syndrome. Management and surveillance were variable. 18 (69%) of 26 patients with myelodysplastic Syndrome received upfront therapy (14 haematopoietic stem cell transplantation and 4 chemotherapy), 4 (15%) patients received no treatment, 2 (8%) had unavailable data, and 2 (8%) progressed to acute myeloid leukaemia before receiving treatment. 12 patients received treatment for acute myeloid leukaemia—including the two patients initially diagnosed with myelodysplastic who progressed— two (16%) received HSCT as initial therapy and ten (83%) received chemotherapy with intent to proceed with HSCT. 33 (92%) of 36 patients (eight of ten with leukaemia and 25 of 26 with myelodysplastic Syndrome) were known to have Shwachman-Diamond Syndrome before development of a myeloid malignancy and could have been monitored with bone marrow surveillance. Bone marrow surveillance before myeloid malignancy diagnosis was done in three (33%) of nine patients with leukaemia for whom surveillance status was confirmed and 11 (46%) of 24 patients with myelodysplastic Syndrome. Patients monitored had a 3-year overall survival of 62% (95% CI 32–82; n=14) compared with 28% (95% CI 10–50; n=19; p=0·13) without surveillance. Six (40%) of 15 patients with available longitudinal data developed myelodysplastic Syndrome in the setting of stable blood counts. Interpretation Our results suggest that prognosis is poor for patients with Shwachman-Diamond Syndrome and myelodysplastic Syndrome or acute myeloid leukaemia owing to both therapy-resistant disease and treatment-related toxicities. Improved surveillance algorithms and risk stratification tools, studies of clonal evolution, and prospective trials are needed to inform effective prevention and treatment strategies for leukaemia predisposition in patients with Shwachman-Diamond Syndrome. Funding National Institute of Health.
-
Diagnosis, Treatment, and Molecular Pathology of Shwachman-Diamond Syndrome.
Hematology-oncology Clinics of North America, 2018Co-Authors: Adam S. Nelson, Kasiani C. MyersAbstract:: Shwachman-Diamond Syndrome (SDS) is an inherited bone marrow failure Syndrome classically associated with exocrine pancreatic dysfunction and neutropenia, with a predisposition toward progressive marrow failure, risk of myelodysplastic Syndrome, and leukemia. Most patients carry biallelic mutations in the Shwachman-Bodian-Diamond Syndrome gene, which is an integral component of ribosome maturation and biogenesis. This article reviews the diagnosis, clinical characteristics, and treatment modalities of SDS, and reports advances in the understanding of the molecular pathophysiology of SDS.
-
The North American Shwachman-Diamond Syndrome Registry: Genetically Undefined Shwachman-Diamond Syndrome
Blood, 2015Co-Authors: Kasiani C. Myers, Audrey Anna Bolyard, Richard E. Harris, Stella M. Davies, Jamie Leung, Joan Moore, Sara Loveless, Leann Mount, Siobán B. Keel, David C. DaleAbstract:Shwachman-Diamond Syndrome (SDS) is an inherited marrow failure Syndrome associated with exocrine pancreatic dysfunction and an increased risk of myelodysplasia and leukemia. The majority of individuals with SDS carry biallelic SBDS gene mutations, however a subset of patients remain genetically undefined. The objective of this study was to compare the clinical characteristics of patients with and without SBDS mutations. To address these questions, we conducted a retrospective study of patients enrolled on the North American Shwachman-Diamond Syndrome Registry (SDSR). Clinical data from the SDSR were available for 55 individuals with biallelic SBDS mutations and 16 individuals who fulfilled clinical diagnostic criteria for SDS but lacked biallelic mutations in the SBDS gene. Study subject ages for SBDS mutation positive and negative cohorts span 2-52.4 and 2.8-21.4 years with median ages of 12.4 and 10.9 years respectively. Cytopenias were present for both SBDS mutation positive and negative cohorts, with neutropenia the most common event in 94% and 81% respectively. Bone marrow hypocellularity was reported in 91% of those with SBDS mutations and 69% of those without. Marrow dysplasia was reported in 65% of those with SBDS mutations and none of those without. Clonal abnormalities were present in 44% and 25% of those with and without SBDS mutations with median age of initial appearance at 9 years (0.8-45.1) and 7 years (1.2-14) respectively. Abnormalities included del7q and del20q in both groups as well as iso7q, trisomy 8 and others in the SBDS mutation positive group. Clonal abnormalities were all transient in the SBDS mutation negative cohort. One SBDS mutation positive individual developed AML. None of the SBDS mutation negative individuals developed malignancy or progressed to require HSCT thus far. Pancreatic dysfunction determined by low serum trypsinogen or pancreatic isoamylase was similar in both cohorts 79% vs 80%. However, only 27% (15/55) of SBDS mutation positive individuals reported requiring enzyme therapy with 33% (18/55) documenting failure to thrive, in contrast to 75% (12/16) of SBDS mutation negative individuals with 73% (11/15) having failure to thrive. A broad spectrum of congenital anomalies were reported in 55% and 56% of SBDS mutation positive and negative individuals respectively, with skeletal anomalies being the most common in both groups. Medical comorbidities commonly reported in both groups included eczema and endocrinopathies. Elevated liver transaminases were seen in 27% of SBDS mutation positive individuals but this was not seen in the SBDS mutation negative cohort. Conclusion: Patients with genetically undefined ( SBDS mutation negative) SDS share clinical characteristics with SBDS mutation positive patients; however, the risk of leukemia in the genetically undefined patients remains unclear due to low patient numbers with short follow-up. Further studies of this young cohort are required to inform medical management and to advance our understanding of genetic etiology, mechanism, disease pathophysiology and treatment of these marrow failure disorders. Disclosures Dale: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau.
-
Variable Clinical Presentation of Shwachman–Diamond Syndrome: Update from the North American Shwachman–Diamond Syndrome Registry
The Journal of Pediatrics, 2013Co-Authors: Kasiani C. Myers, Audrey Anna Bolyard, Barbara Otto, Trisha E. Wong, Amanda T. Jones, Richard E. Harris, Stella M. Davies, David C. Dale, Akiko ShimamuraAbstract:Objectives To investigate the range of clinical presentations for Shwachman–Diamond Syndrome (SDS) with the long-term goal of improving diagnosis. Study design We reviewed the North American Shwachman–Diamond Syndrome Registry. Genetic reports of biallelic Shwachman–Bodian–Diamond Syndrome mutations confirming the diagnosis of SDS were available for 37 patients. Results Neutropenia was the most common hematologic abnormality at presentation (30/37, 81%); however, only 51% (19/37) of patients presented with the classic combination of neutropenia and steatorrhea. Absence of pancreatic lipomatosis on ultrasound or computed tomography scan, normal fecal elastase levels, and normal skeletal survey do not rule out the diagnosis of SDS. SDS was diagnosed in 2 asymptomatic siblings of SDS probands. Twenty-four of 37 patients (65%) had congenital anomalies. Conclusion Our cohort reveals a broad range of clinical presentation for SDS. Clues to the underlying diagnosis of SDS included cytopenias with a hypocellular marrow, congenital anomalies, family history, and myelodysplasia with clonal abnormalities frequently found in SDS. Reliance on classic clinical criteria for SDS would miss or delay diagnosis of a significant subset of patients with SDS.
-
Variable Clinical Presentation of Shwachman-Diamond Syndrome: Update From the North-American Shwachman-Diamond Syndrome Registry.
Blood, 2012Co-Authors: Kasiani C. Myers, Audrey Anna Bolyard, Barbara Otto, Trisha E. Wong, Richard E. Harris, Stella M. Davies, David C. Dale, Nicholas J Dobbins, Amanda L. Jones, Akiko ShimamuraAbstract:Abstract 2367 Background: Shwachman-Diamond Syndrome (SDS) is an autosomal recessively inherited marrow failure Syndrome associated with exocrine pancreatic dysfunction and an increased leukemia risk. SDS is caused by biallelic mutations in the SBDS gene. Timely diagnosis prior to the development of life-threatening complications is essential for optimal medical management and outcomes. SDS hematologic complications such as severe marrow failure or leukemia are treated with a hematopoietic stem cell transplant. SDS patients require reduced intensity conditioning regimens to avoid undue regimen-related toxicities, thus the recognition of the underlying diagnosis of SDS is critical. The common constellation of clinical characteristics reported for SDS includes neutropenia, steatorrhea, and failure to thrive. Hypothesis: With the advent of genetic testing, diagnosis is now possible for patients with non-classical presentations of the inherited marrow failure Syndromes. The aim of this study was to investigate the range of clinical presentations for SDS with the long-term goal of improving diagnosis. Methods: This study was a retrospective review of medical records obtained by the North American Shwachman-Diamond Syndrome Registry (SDSR) which was founded in 2008. The SDS Registry works in partnership with the Severe Chronic Neutropenia International Registry. Results: Genetic reports of biallelic SBDS mutations confirming the diagnosis of SDS were available for 31 patients. This SDS study cohort included 19 male and 12 female patients. Median patient age was 10 years with a range of 2 – 49 years. Radiologic reports were available for 23 patients. Pancreatic lipomatosis was noted in 22/23 patients. One patient had an atrophic pancreas without lipomatosis on CT scan at age 6.9 years. Two patients initially had normal early pancreatic studies by CT or ultrasound at ages 1.3 years and 2.6 years, but subsequently were found to have pancreatic lipomatosis by the same imaging modalities later in life. Fecal elastase has not been previously evaluated as a screen for SDS. 14/17 patients (82%) had low fecal elastase levels while 3/17 patients had normal fecal elastase levels. Serum trypsinogen or pancreatic isoamylase were low in all 18 patients tested. 26/31 patients (84%) presented with failure to thrive. 17/31 (54%) patients presented with diarrhea or steatorrhea. 17/31 patients (55%) had congenital anomalies. Neutropenia was the most common hematologic abnormality at presentation (77%). Strikingly, 2 patients presented with isolated thrombocytopenia, 3 patients presented with severe anemia requiring transfusion support, and 5 patients presented without any cytopenias. One patient presented with the initial diagnosis of MDS with a del 20q clone. One patient presented with short stature and a sibling who died from AML. Interestingly, one patient had very short telomeres ( st percentile for age) across 3 lymphocyte subsets as well as in total lymphocytes, a pattern typically associated with dyskeratosis congenita. Conclusion: Data from the North-American Shwachman Diamond Syndrome Registry reveals an unexpected range of clinical presentation for this rare disorder that expands beyond that which is currently classically recognized. The diagnosis of SDS should be considered even in the absence of neutropenia or diarrhea. In our cohort, clues to the underlying diagnosis of SDS included other cytopenias, congenital anomalies, family history, and the del20q clonal marrow abnormality. Reliance on classical clinical descriptions of SDS would miss or delay diagnosis of a significant subset of SDS patients. Disclosures: Dale: AMGEN: Consultancy.
R Vibhakar - One of the best experts on this subject based on the ideXlab platform.
-
Successful unrelated umbilical cord blood transplantation in children with Shwachman-Diamond Syndrome
Bone Marrow Transplantation, 2005Co-Authors: R Vibhakar, M Radhi, S Rumelhart, D Tatman, F GoldmanAbstract:Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic insufficiency and variable degrees of neutropenia. SDS patients are at risk of developing myelodysplasia, aplastic anemia, and leukemic transformation. The role and timing of allogeneic hematopoietic stem cell transplantation (HSCT) in SDS remain controversial. We report three SDS patients with severe aplasia transplanted using unrelated umbilical cord blood (UCB). Patients received melphalan (180 mg/m^2), etoposide (1200 mg/m^2), anti-thymocyte globulin (90 mg/kg), and total lymphoid irradiation (500 cGy); graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and prednisone. Myeloid engraftment occurred promptly with absolute neutrophil count >500 cells/mm^3 on day 15±5 and all patients displayed 100% donor chimerism by 2 months post transplant. The major complication of transplant was GVHD, with all patients developing grade II or III acute GVHD, one progressing to chronic extensive GVHD. Patients are alive 309, 623, and 2029 days post transplant. Factors important in HSCT outcome for SDS may include transplantation at a young age, avoidance of cyclophosphamide, and adequate GVHD prophylaxis. Importantly, these cases also suggest that unrelated UCB, in the absence of a matched family member, is an excellent alternative stem cell source for SDS patients undergoing HSCT.
Yigal Dror - One of the best experts on this subject based on the ideXlab platform.
-
Draft consensus guidelines for diagnosis and treatment of Shwachman-Diamond Syndrome.
Annals of the New York Academy of Sciences, 2011Co-Authors: Yigal Dror, Akiko Shimamura, Jean Donadieu, Sanna Toiviainen-salo, Outi Mäkitie, Jutta Köglmeier, John A Dodge, Elizabeth Kerr, Cornelia Zeidler, Neil ShahAbstract:Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic exocrine insufficiency and bone marrow failure, often associated with neurodevelopmental and skeletal abnormalities. Mutations in the SBDS gene have been shown to cause SDS. The purpose of this document is to provide draft guidelines for diagnosis, evaluation of organ and system abnormalities, and treatment of hematologic, pancreatic, dietary, dental, skeletal, and neurodevelopmental complications. New recommendations regarding diagnosis and management are presented, reflecting advances in understanding the genetic basis and clinical manifestations of the disease based on the consensus of experienced clinicians from Canada, Europe, and the United States. Whenever possible, evidence-based conclusions are made, but as with other rare diseases, the data on SDS are often anecdotal. The authors welcome comments from readers.
-
Shwachman-Diamond Syndrome: implications for understanding the molecular basis of leukaemia.
Expert Reviews in Molecular Medicine, 2008Co-Authors: Yigal DrorAbstract:: Inherited bone marrow failure Syndromes provide extremely useful genetic models for understanding leukaemogenesis because the initial genetic defect can be identified and the risk of leukaemia is very high. Shwachman-Diamond Syndrome is one of the most common inherited bone marrow failure Syndromes and an example of such a model. Here, I describe the malignant features of Shwachman-Diamond Syndrome and discuss the potential molecular mechanisms that can lead to leukaemia.
-
Shwachman-Diamond Syndrome: an inherited model of aplastic anaemia with accelerated angiogenesis.
British Journal of Haematology, 2006Co-Authors: Elaine W. Leung, Melvin H. Freedman, Piya Rujkijyanont, Joseph Beyene, Mohamed Abdelhaleem, Yigal DrorAbstract:Summary Bone marrow angiogenesis is increased in myelodysplastic Syndromes (MDS) and acute myeloid leukaemia (AML), but has not been studied in inherited or acquired marrow failure Syndromes. Shwachman–Diamond Syndrome (SDS) carries a high risk of MDS/AML and is characterised by marrow stromal dysfunction. Compared with controls, SDS patients without MDS/AML had higher marrow microvessel density. Stromal VEGF gene expression, stromal vascular endothelial growth factor (VEGF) secretion and VEGF levels in serum and marrow mononuclear cells were normal. Future studies should investigate the mechanism for increased angiogenesis in SDS, and whether SDS marrow, with its increased angiogenesis, promotes progression of malignant clones.
-
Shwachman‐Diamond Syndrome
Pediatric Blood & Cancer, 2005Co-Authors: Yigal DrorAbstract:Shwachman-Diamond Syndrome (SDS) is an inherited marrow failure disorder with varying cytopenia, pancreatic dysfunction, and metaphyseal dysostosis. SDS is also characterized by a risk of myelodysplasia and leukemia in up to one third of the patients. Over the last 5 years, major advances have been made in understanding the bone marrow phenotype. The gene associated with the disease, SBDS, has recently been identified. Herein we provide an update on the clinical features, the hematopoietic defects, and the genetics of the disease as they are currently understood. We also review the diagnostic and therapeutic approaches to the hematological complications in the Syndrome. © 2005 Wiley-Liss, Inc.
-
ErythropoiesisClonal evolution in marrows of patients with Shwachman-Diamond Syndrome: A prospective 5-year follow-up study
Experimental Hematology, 2002Co-Authors: Yigal Dror, Peter R. Durie, Hedy Ginzberg, Rebecca Herman, Anu Banerjee, Martin Champagne, Kevin Shannon, David Malkin, Melvin H. FreedmanAbstract:Objectives Shwachman-Diamond Syndrome (SDS) is characterized by varying degrees of marrow failure. Retrospective studies suggested a high propensity for malignant myeloid transformation into myelodysplastic Syndromes (MDS) and acute myeloid leukemia (AML). The study's aims were to determine the cellular and molecular characteristics as well as the clinical course of malignant myeloid transformation and clonal marrow disease in patients with SDS.
