Alter B P, Rosenberg P S
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Md., USA.
Mol Syndromol. 2013 Feb;4(1-2):87-93. doi: 10.1159/000346035.
Patients with Fanconi anemia (FA) often have birth defects that suggest the diagnosis of VATER association. A review of 2,245 cases of FA reported in the literature from 1927 to 2012 identified 108 cases with at least 3 of the defining features of VATER association; only 29 had been so noted by the authors. The FA VATER signature was the significantly higher frequency of renal and limb (radial and/or thumb) anomalies (93% of cases had both) compared with less than 30% of VATER patients; the presence of one or both of these birth defects should lead to testing for FA. The relative frequencies of the genotypes of the patients with FA VATER were strikingly different from those expected from the general FA population; only 19% were FANCA, while 21% were FANCB, 14% FANCD1/BRCA2, and 12% FANCD2. Consistent with their genotypes, those with the FA VATER phenotype had a worse prognosis than FA patients with milder phenotypes, with shorter median survival and earlier onset of malignancies. The early identification of FA patients among infants with VATER association should lead to earlier more proactive management, such as cancer surveillance and genetic counseling.
范可尼贫血（FA）患者常伴有先天性缺陷，提示可能患有VATER综合征。回顾1927年至2012年文献报道的2245例FA病例，发现108例具有至少3项VATER综合征的典型特征；但作者仅指出其中29例。FA-VATER特征是肾脏和肢体（桡骨和/或拇指）异常的发生率显著更高（93%的病例两者都有），而VATER患者中该比例不到30%；出现这一种或两种先天性缺陷应进行FA检测。FA-VATER患者的基因型相对频率与一般FA人群预期的显著不同；只有19%为FANCA型，而21%为FANCB型，14%为FANCD1/BRCA2型，12%为FANCD2型。与他们的基因型一致，具有FA-VATER表型的患者预后比表型较轻的FA患者更差，中位生存期更短，恶性肿瘤发病更早。在患有VATER综合征的婴儿中早期识别FA患者应能实现更早期、更积极的管理，如癌症监测和遗传咨询。
