Teo Juliana T, Klaassen Robert, Fernandez Conrad V, Yanofsky Rochelle, Wu John, Champagne Josette, Silva Mariana, Lipton Jeffrey H, Brossard Jossee, Samson Yvan, Abish Sharon, Steele Macgregor, Ali Kaiser, Athale Uma, Jardine Lawrence, Hand John P, Tsangaris Elena, Odame Isaac, Beyene Joseph, Dror Yigal
Marrow Failure and Myelodysplasia Program, Division of Haematology, Research Institute, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Pediatrics. 2008 Jul;122(1):e139-48. doi: 10.1542/peds.2007-3415.
Unclassified inherited bone marrow failure syndromes are a heterogeneous group of genetic disorders that represent either new syndromes or atypical clinical courses of known inherited bone marrow failure syndromes. The relative prevalence of the unclassified inherited bone marrow failure syndromes and their characteristics and the clinical and economic challenges that they create have never been studied.
We analyzed cases of inherited bone marrow failure syndrome in the Canadian Inherited Marrow Failure Registry that were deemed unclassifiable at study entry.
From October 2001 to March 2006, 39 of the 162 patients enrolled in the Canadian Inherited Marrow Failure Registry were registered as having unclassified inherited bone marrow failure syndromes. These patients presented at a significantly older age (median: 9 months) than the patients with classified inherited bone marrow failure syndrome (median: 1 month) and had substantial variation in the clinical presentations. The hematologic phenotype, however, was similar to the classified inherited bone marrow failure syndromes and included single- or multiple-lineage cytopenia, severe aplastic anemia, myelodysplasia, and malignancy. Grouping patients according to the affected blood cell lineage(s) and to the presence of associated physical malformations was not always sufficient to characterize a condition, because affected members from several families fit into different phenotypic groups. Compared with the classified inherited bone marrow failure syndromes, the patients with unclassified inherited bone marrow failure syndromes had 3.2 more specific diagnostic tests at 4.5 times higher cost per evaluated patient to attempt to categorize their syndrome. At last follow-up, only 20% of the unclassified inherited bone marrow failure syndromes were ultimately diagnosed with a specific syndrome on the basis of the development of new clinical findings or positive genetic tests.
Unclassified inherited bone marrow failure syndromes are relatively common among the inherited bone marrow failure syndromes and present a major diagnostic and therapeutic dilemma.
未分类的遗传性骨髓衰竭综合征是一组异质性的遗传疾病，代表新的综合征或已知遗传性骨髓衰竭综合征的非典型临床病程。从未对未分类的遗传性骨髓衰竭综合征的相对患病率、其特征以及它们所带来的临床和经济挑战进行过研究。
我们分析了加拿大遗传性骨髓衰竭登记处中在研究入组时被认为无法分类的遗传性骨髓衰竭综合征病例。
从2001年10月至2006年3月，加拿大遗传性骨髓衰竭登记处登记的162例患者中有39例被登记为患有未分类的遗传性骨髓衰竭综合征。这些患者的就诊年龄（中位数：9个月）明显大于已分类遗传性骨髓衰竭综合征患者（中位数：1个月），临床表现差异很大。然而，血液学表型与已分类的遗传性骨髓衰竭综合征相似，包括单系或多系血细胞减少、严重再生障碍性贫血、骨髓发育异常和恶性肿瘤。根据受影响的血细胞谱系和相关身体畸形的存在对患者进行分组并不总是足以表征一种疾病，因为来自几个家庭的受影响成员符合不同的表型组。与已分类的遗传性骨髓衰竭综合征相比，未分类的遗传性骨髓衰竭综合征患者为试图对其综合征进行分类，每个评估患者的特定诊断测试多3.2项，成本高出4.5倍。在最后一次随访时，基于新的临床发现或阳性基因检测，只有20%的未分类遗传性骨髓衰竭综合征最终被诊断为特定综合征。
未分类的遗传性骨髓衰竭综合征在遗传性骨髓衰竭综合征中相对常见，并带来了重大的诊断和治疗难题。
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