Alter BP
Division of Pediatric Hematology/Oncology, The University of Texas Medical Branch at Galveston, Galveston, Texas, 77555-0361, USA.
Oncologist. 1996;1(6):361-366.
Inherited bone marrow failure syndromes (BMFs) comprise at least one-fourth of children with aplastic anemia, and perhaps up to 10% of adults. The most common syndrome is Fanconi's anemia (FA), with more than 1,000 reported cases. FA is autosomal recessive, with birth defects in approximately 75% of patients. It is a DNA repair syndrome, diagnosed by finding chromosomal aberrations in cells treated with clastogenic agents. The major problems in FA are, in order, aplastic anemia, leukemia, and other cancers. There are at least five complementation groups; the gene for Group C has been cloned. Carrier identification and gene therapy are beginning in families at risk for FAC mutations. Dyskeratosis congenita (DC) is primarily X-linked (at Xq28), with autosomal recessive and dominant cases as well. Patients classically have reticulated hyperpigmented skin, dystrophic nails, and mucous membrane leukoplakia. approximately 50% develop aplastic anemia, sometimes prior to the DC phenotype, and approximately 10% develop cancer. Shwachman-Diamond syndrome consists of exocrine pancreatic insufficiency with neutropenia; approximately 25% develop aplastic anemia and 5%-10% develop leukemia. Amegakaryocytic thrombocytopenia presents in infancy, and often evolves into aplastic anemia and/or leukemia. Single cytopenias include Diamond-Blackfan anemia (DBA), which is inherited pure red cell aplasia; transient erythroblastopenia of childhood; Kostmann's syndrome (KS) or infantile genetic agranulocytosis, and thrombocytopenia with absent radii in which there is neonatal thrombocytopenia and absent radii. DBA and KS, particularly the latter treated with G-CSF, may develop leukemia, and solid tumors have been reported in DBA. Treatment for the various BMFs includes bone marrow transplantation, androgens, and hematopoietic cytokines such as G-CSF. These inherited syndromes thus include various combinations of marrow failure and premalignancy.
遗传性骨髓衰竭综合征（BMFs）至少占再生障碍性贫血患儿的四分之一，在成人中可能占比高达10%。最常见的综合征是范可尼贫血（FA），报告病例超过1000例。FA是常染色体隐性遗传，约75%的患者伴有出生缺陷。它是一种DNA修复综合征，通过在用致裂剂处理的细胞中发现染色体畸变来诊断。FA的主要问题依次为再生障碍性贫血、白血病和其他癌症。至少有五个互补组；C组的基因已被克隆。在有FAC突变风险的家庭中，携带者鉴定和基因治疗已开始。先天性角化不良（DC）主要是X连锁（位于Xq28），也有常染色体隐性和显性病例。患者典型表现为网状色素沉着过度的皮肤、营养不良性指甲和黏膜白斑。约50%的患者会发展为再生障碍性贫血，有时在出现DC表型之前，约10%的患者会患癌症。施瓦赫曼-戴蒙德综合征包括外分泌性胰腺功能不全伴中性粒细胞减少；约25%的患者会发展为再生障碍性贫血，5%-10%的患者会患白血病。无巨核细胞性血小板减少症在婴儿期出现，常发展为再生障碍性贫血和/或白血病。单一血细胞减少症包括钻石-黑范贫血（DBA），即遗传性纯红细胞再生障碍；儿童期短暂性红细胞生成减少症；科斯特曼综合征（KS）或婴儿遗传性粒细胞缺乏症，以及桡骨缺如伴血小板减少症，其特征为新生儿血小板减少和桡骨缺如。DBA和KS，尤其是后者经粒细胞集落刺激因子（G-CSF）治疗后，可能会发展为白血病，DBA患者还曾有实体瘤的报告。各种BMFs的治疗方法包括骨髓移植、雄激素以及造血细胞因子如G-CSF。因此，这些遗传性综合征包括骨髓衰竭和癌前病变的各种组合。
