Should chromosome breakage studies be performed in patients with VACTERL association?
Should chromosome breakage studies be performed in patients with VACTERL association?
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DOI：
10.1002/ajmg.a.30853
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发表时间：
2005-08-15
影响因子：
2
通讯作者：
Baumann, C
中科院分区：
文献类型：
--
作者：
Faivre, L;Portnoï, MF;Baumann, C
VACTERL关联的特点是缺陷的非随机模式，包括至少以下三个主要特征：椎体异常、肛门闭锁、心血管畸形、气管食管瘘、肾脏和肢体异常，并且被认为是一种非常异质性的疾病。这些缺陷也可视为范可尼贫血（FA）谱的一部分。虽然伴有脑积水的VACTERL明显与FA相关，但染色体断裂研究的指征在无脑积水的VACTERL中尚不明确。我们报告了三名不相关的VACTERL表型患者和FA的确诊诊断。结合从欧洲FA基因型-表型相关研究中提取的13例类似病例的数据和文献中报道的4例病例的数据，我们表明(i)在一系列被证明患有FA的个体中，5%（13/245）也具有VACTERL表型，（ii）所有患者都有放射线异常，这13名受试者中有12名至少表现出FA的其他1种特征（咖啡斑和斑点、生长迟缓、小头畸形、畸形）。（iii） VACTERL表型似乎在FA互补组D1、E和f中过度代表。由于FA的诊断对患者的遗传咨询和早期治疗干预很重要，我们得出结论，染色体断裂研究应该进行，而不仅仅是在VACTERL合并脑积水的情况下，但也适用于有放射线异常的VACTERL，特别是如果个体有额外的FA相关表现，如皮肤色素沉着异常、生长迟缓、小头畸形或小眼。(c) 2005 Wiley-Liss, Inc。
The VACTERL association is characterized as a non-random pattern of defects including at least three of the following cardinal features: vertebral anomalies, anal atresia, cardiovascular malformations, tracheoesophageal fistula, renal and limb anomalies, and is postulated to be a very heterogeneous disorder. These defects can also be seen as part of the Fanconi anemia (FA) spectrum. Although VACTERL with hydrocephaly has clearly been associated with FA, the indication for chromosome breakage studies is not clear in VACTERL without hydrocephaly. We report on three unrelated patients with the VACTERL phenotype and the confirmed diagnosis of FA. Together with the data of 13 similar cases extracted from a European genotype-phenotype correlation study for FA and those from the four reported cases of the literature, we show that (i) in a series of individuals proven to have FA, 5% (13/245) also have the VACTERL phenotype, (ii) all have radial ray anomalies and 12 of these 13 subjects show at least 1 other feature of FA (cafe an lait spots, growth retardation, microcephaly, dysmorphism), and (iii) the VACTERL phenotype appears to be over represented in the FA complementation groups D1, E, and F. Since the diagnosis of FA is important for genetic counseling and early therapeutic intervention in patients, we conclude that chromosomal breakage studies should be performed, not only in cases of VACTERL with hydrocephaly, but also in cases VACTERL with radial-ray anomalies and especially if the individual has additional FA associated manifestations such as skin pigmentation abnormalities, growth retardation, microcephaly, or microphthalmia. (c) 2005 Wiley-Liss, Inc.