Jondeau Guillaume, Ropers Jacques, Regalado Ellen, Braverman Alan, Evangelista Arturo, Teixedo Guisela, De Backer Julie, Muiño-Mosquera Laura, Naudion Sophie, Zordan Cecile, Morisaki Takayuki, Morisaki Hiroto, Von Kodolitsch Yskert, Dupuis-Girod Sophie, Morris Shaine A, Jeremy Richmond, Odent Sylvie, Adès Leslie C, Bakshi Madhura, Holman Katherine, LeMaire Scott, Milleron Olivier, Langeois Maud, Spentchian Myrtille, Aubart Melodie, Boileau Catherine, Pyeritz Reed, Milewicz Dianna M
Circ Cardiovasc Genet. 2016 Dec;9(6):548-558. doi: 10.1161/CIRCGENETICS.116.001485. Epub 2016 Nov 21.
The natural history of aortic diseases in patients with TGFBR1 or TGFBR2 mutations reported by different investigators has varied greatly. In particular, the current recommendations for the timing of surgical repair of the aortic root aneurysms may be overly aggressive.
The Montalcino Aortic Consortium, which includes 15 centers worldwide that specialize in heritable thoracic aortic diseases, was used to gather data on 441 patients from 228 families, with 176 cases harboring a mutation in TGBR1 and 265 in TGFBR2. Patients harboring a TGFBR1 mutation have similar survival rates (80% survival at 60 years), aortic risk (23% aortic dissection and 18% preventive aortic surgery), and prevalence of extra-aortic features (29% hypertelorism, 53% cervical arterial tortuosity, and 27% wide scars) when compared with patients harboring a TGFBR2 mutation. However, TGFBR1 males had a greater aortic risk than females, whereas TGFBR2 males and females had a similar aortic risk. Additionally, aortic root diameter prior to or at the time of type A aortic dissection tended to be smaller in patients carrying a TGFBR2 mutation and was ≤45 mm in 6 women with TGFBR2 mutations, presenting with marked systemic features and low body surface area. Aortic dissection was observed in 1.6% of pregnancies.
Patients with TGFBR1 or TGFBR2 mutations show the same prevalence of systemic features and the same global survival. Preventive aortic surgery at a diameter of 45 mm, lowered toward 40 in females with low body surface area, TGFBR2 mutation, and severe extra-aortic features may be considered.
不同研究者报道的转化生长因子β受体1（TGFBR1）或转化生长因子β受体2（TGFBR2）突变患者的主动脉疾病自然史差异很大。特别是，目前关于主动脉根部动脉瘤手术修复时机的建议可能过于激进。
蒙塔尔奇诺主动脉联盟由全球15个专门研究遗传性胸主动脉疾病的中心组成，用于收集来自228个家庭的441例患者的数据，其中176例携带TGBR1突变，265例携带TGFBR2突变。与携带TGFBR2突变的患者相比，携带TGFBR1突变的患者具有相似的生存率（60岁时80%存活）、主动脉风险（23%主动脉夹层和18%预防性主动脉手术）以及主动脉外特征的患病率（29%眼距增宽、53%颈动脉硬化和27%宽瘢痕）。然而，携带TGFBR1突变的男性主动脉风险高于女性，而携带TGFBR2突变的男性和女性主动脉风险相似。此外，A型主动脉夹层发生前或发生时，携带TGFBR2突变的患者主动脉根部直径往往较小，6例携带TGFBR2突变的女性患者主动脉根部直径≤45mm，这些患者具有明显的全身特征和低体表面积。1.6%的孕妇发生了主动脉夹层。
携带TGFBR1或TGFBR2突变的患者全身特征患病率和总体生存率相同。对于体表面积低、携带TGFBR2突变且具有严重主动脉外特征的女性，可考虑在主动脉直径为45mm时进行预防性主动脉手术，对于此类女性可将手术阈值降至40mm。
