Marrow Failure and Myelodysplasia Program, Division of Haematology/ Oncology and Cell Biology Program, Research Institute, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
Clin Genet. 2011 May;79(5):448-58. doi: 10.1111/j.1399-0004.2010.01468.x.
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.
我们对遗传性骨髓衰竭综合征（IBMFSs）表型的了解来自于仅研究一种 IBMFS 的病例报告或病例系列。然而，大量的表型重叠需要对 IBMFSs 进行比较分析。Shwachman-Diamond 综合征（SDS）是一种 IBMFS，对其临床表型的认识仍在不断发展。在这项分析中，我们使用了来自加拿大遗传性骨髓衰竭研究（CIMFS）的 125 名患者的数据，这是一项前瞻性的多中心基于人群的研究。对 34 例 SDS 患者进行了分析，并与 CIMFS 上四种最常见的 IBMFSs（Diamond Blackfan 贫血、范可尼贫血（FA）、Kostmann/严重先天性中性粒细胞减少症和先天性角化不良症（DC））的其他患者进行了比较。SDS、FA 和 DC 的诊断相对于症状发作往往被延迟；这表明迫切需要改进工具以快速诊断。我们确定了 SDS 与其他 IBMFSs 之间的多种表型差异，包括一些新的差异。SBDS 双等位基因突变的频率低于之前的报告（81%）。重要的是，与双等位基因突变的患者相比，野生型 SBDS 患者的血液系统疾病更严重，但胰腺疾病更轻微。总之，对 IBMFSs 的综合研究可以为这些疾病之间提供有用的比较数据。SBDS 阴性的 SDS 患者可能有更严重的血液系统衰竭和更轻微的胰腺疾病。
