Faivre Laurence, Portnoï Marie France, Pals Gerard, Stoppa-Lyonnet Dominique, Le Merrer Martine, Thauvin-Robinet Christel, Huet Frédéric, Mathew Christopher G, Joenje Hans, Verloes Alain, Baumann Clarisse
Centre de Génétique, Hôpital d'Enfants, Dijon, France.
Am J Med Genet A. 2005 Aug 15;137(1):55-8. doi: 10.1002/ajmg.a.30853.
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 (café au 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.
VACTERL综合征的特征是一种非随机的缺陷模式，包括以下至少三种主要特征：脊柱异常、肛门闭锁、心血管畸形、气管食管瘘、肾脏和肢体异常，据推测这是一种高度异质性疾病。这些缺陷也可被视为范可尼贫血（FA）谱系的一部分。虽然伴有脑积水的VACTERL综合征已明确与FA相关，但在不伴有脑积水的VACTERL综合征中，染色体断裂研究的指征尚不清楚。我们报告了3例具有VACTERL表型且确诊为FA的非亲缘关系患者。结合从一项欧洲FA基因型-表型相关性研究中提取的13例类似病例的数据以及文献报道的4例病例的数据，我们发现：（i）在一系列已证实患有FA的个体中，5%（13/245）也具有VACTERL表型；（ii）所有患者均有桡骨射线异常，这13例患者中有12例至少表现出FA的1项其他特征（咖啡牛奶斑、生长发育迟缓、小头畸形、畸形）；（iii）VACTERL表型在FA互补组D1、E和F中似乎过度存在。由于FA的诊断对于患者的遗传咨询和早期治疗干预很重要，我们得出结论，不仅在伴有脑积水的VACTERL综合征病例中，而且在伴有桡骨射线异常的VACTERL综合征病例中，尤其是个体有其他与FA相关的表现如皮肤色素沉着异常、生长发育迟缓、小头畸形或小眼症时，都应进行染色体断裂研究。
