PDF(Pubmed)
Abstract：
Introduction: The inherited bone marrow failure syndromes (IBMFSs) are a group of rare disorders characterized by bone marrow failure (BMF), physical abnormalities, and an increased risk of neoplasia. The National Institute of Pediatrics (INP) is a major medical institution in Mexico, where patients with BMF receive a complete approach that includes paraclinical tests. Readily recognizable features, such as the hematological and distinctive physical phenotypes, identified by clinical dysmorphologists, remain crucial for the diagnosis and management of these patients, particularly in circumstances where next-generation sequencing (NGS) is not easily available. Here, we describe a group of Mexican patients with a high clinical suspicion of an IBMFS. Methods: We performed a systematic retrospective analysis of the medical records of patients who had a high IBMFS suspicion at our institution from January 2018 to July 2021. An initial assessment included first ruling out acquired causes of BMF by the Hematology Department and referral of the patient to the Department of Human Genetics for physical examination to search for specific phenotypes suggesting an IBMFS. Patients with high suspicion of having an IBMFS were classified into two main groups: 1) specific IBMFS, including dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), Shwachman-Diamond syndrome (SDS), thrombocytopenia with absent radii (TAR), and severe congenital neutropenia (SCN); 2) undefined IBMFS (UI). Results: We established a high suspicion of having an IBMFS in 48 patients. At initial evaluation, the most common hematologic features were bicytopenia (20%) and aplastic anemia (16%); three patients received hematopoietic stem cell transplantation. Among patients with a suspicion of an IBMFS, the most common physical abnormality was minor craniofacial features in 83% of patients and neurodevelopmental disorders in 52%. The specific suspicions that we built were DBA (31%), SDS (18%), DC (14%), TAR (4%), and SCN (4%), whereas 27% of cases remained as undefined IBMFS. SDS, TAR, and SCN were more commonly suspected at an earlier age (<1 year), followed by DBA (2 years) and DC (5 years). Conclusions: Thorough examination of reported clinical data allowed us to highly suspect a specific IBMFS in approximately 70% of patients; however, an important number of patients remained with suspicion of an undefined IBMFS. Implementation of NGS and telomere length measurement are forthcoming measures to improve IBMFS diagnosis in Mexico.
摘要：
简介：遗传性骨髓衰竭综合征（IBMFSs）是一组以骨髓衰竭（BMF）为特征的罕见疾病，身体异常,和肿瘤形成的风险增加。国家儿科学研究所（INP）是墨西哥的主要医疗机构，BMF患者接受包括临床旁检查在内的完整方法。容易识别的特征，如血液学和独特的身体表型，由临床畸形学家鉴定，对于这些患者的诊断和管理仍然至关重要，特别是在下一代测序（NGS）不容易获得的情况下。这里,我们描述了一组临床高度怀疑IBMFS的墨西哥患者.方法：我们对2018年1月至2021年7月在我们机构怀疑IBMFS高的患者的病历进行了系统的回顾性分析。初步评估包括首先排除血液科获得的BMF原因，并将患者转诊至人类遗传学部门进行身体检查，以寻找提示IBMFS的特定表型。高度怀疑患有IBMFS的患者分为两大类：1）特异性IBMFS，包括先天性角化障碍（DC），Diamond-Blackfan贫血(DBA),Shwachman-Diamond综合征(SDS),伴桡骨缺失的血小板减少症(TAR),和严重的先天性中性粒细胞减少症（SCN）；2）未定义的IBMFS（UI）。结果：我们高度怀疑48例患者患有IBMFS。初步评估时,最常见的血液学特征是双红细胞减少症(20%)和再生障碍性贫血(16%);3例患者接受了造血干细胞移植.在怀疑IBMFS的患者中，最常见的身体异常是83％的患者的轻微颅面特征和52％的神经发育障碍。我们建立的具体怀疑是DBA（31％），SDS（18％），DC（14%），TAR（4%），和SCN（4%），而27%的病例仍然是未定义的IBMFS。SDS,TAR,和SCN更常见于较早的年龄(<1岁)，其次是DBA（2年）和DC（5年）。结论：对报告的临床数据进行彻底检查使我们能够高度怀疑大约70％的患者的特定IBMFS；但是，仍有相当数量的患者怀疑有未定义的IBMFS.NGS和端粒长度测量的实施是即将采取的措施，以改善墨西哥的IBMFS诊断。
