Aneurysm syndromes caused by mutations in the TGF-beta receptor.
Aneurysm syndromes caused by mutations in the TGF-beta receptor.
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DOI：
10.1016/j.jvs.2006.10.011
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发表时间：
2006-12
期刊：
影响因子：
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通讯作者：
B. Loeys;U. Schwarze;Tammy M. Holm;B. Callewaert;G. Thomas;H. Pannu;J. De Backer;Gretchen L. Oswald;S. Symoens;S. Manouvrier;A. Roberts;F. Faravelli;M. Greco;R. Pyeritz;D. Milewicz;P. Coucke;D. Cameron;A. Braverman;P. Byers;A. De Paepe;H. Dietz
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文献类型：
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作者：
B. Loeys;U. Schwarze;Tammy M. Holm;B. Callewaert;G. Thomas;H. Pannu;J. De Backer;Gretchen L. Oswald;S. Symoens;S. Manouvrier;A. Roberts;F. Faravelli;M. Greco;R. Pyeritz;D. Milewicz;P. Coucke;D. Cameron;A. Braverman;P. Byers;A. De Paepe;H. Dietz
背景Loeys-Dietz综合征是一种近年来发现的常染色体显性遗传性动脉瘤综合征。该疾病的特点是由三联体的动脉迂曲和动脉瘤，间距过宽，双悬雍垂或腭裂，是由编码转化生长因子β受体1和2（TGFBR 1和TGFBR 2，分别）的基因杂合突变引起的。40例先证者表现为Loeys-Dietz综合征的典型表现。鉴于该综合征与血管性Ehlers-Danlos综合征之间的表型重叠，我们筛选了另外一组40名患有血管性Ehlers-Danlos综合征的患者，这些患者没有典型的III型胶原异常或Loeys-Dietz综合征的颅面特征。Danlos综合征（Loeys-Dietz综合征II型）。这两种类型的自然病史的特征是侵袭性动脉瘤（死亡时平均年龄为26.0岁）和妊娠相关并发症的高发生率（12名女性中有6名）。与II型患者相比，I型Loeys-Dietz综合征患者接受心血管手术的时间更早（平均年龄，16.9岁vs. 26.9岁），死亡时间更早（22.6岁vs. 31.8岁）。队列中有59例血管手术，其中1例在手术过程中死亡。这种低手术死亡率区分Loeys-Dietz综合征血管Ehlers-Danlos syndrome.ConclusionsMutations in eitherTGFBR 1 or TGFBR 2 predispose patients to aggressive and widely vascular disease.临床表现的严重程度可预测结局。对出现血管性Ehlers-Danlos综合征等症状的患者进行基因分型可用于指导治疗，包括预防性血管手术的使用和时机。
BackgroundThe Loeys–Dietz syndrome is a recently described autosomal dominant aortic-aneurysm syndrome with widespread systemic involvement. The disease is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate and is caused by heterozygous mutations in the genes encoding transforming growth factor β receptors 1 and 2 (TGFBR1andTGFBR2,respectively).MethodsWe undertook the clinical and molecular characterization of 52 affected families. Forty probands presented with typical manifestations of the Loeys–Dietz syndrome. In view of the phenotypic overlap between this syndrome and vascular Ehlers–Danlos syndrome, we screened an additional cohort of 40 patients who had vascular Ehlers–Danlos syndrome without the characteristic type III collagen abnormalities or the craniofacial features of the Loeys–Dietz syndrome.ResultsWe found a mutation inTGFBR1orTGFBR2in all probands with typical Loeys–Dietz syndrome (type I) and in 12 probands presenting with vascular Ehlers–Danlos syndrome (Loeys–Dietz syndrome type II). The natural history of both types was characterized by aggressive arterial aneurysms (mean age at death, 26.0 years) and a high incidence of pregnancy-related complications (in 6 of 12 women). Patients with Loeys–Dietz syndrome type I, as compared with those with type II, underwent cardiovascular surgery earlier (mean age, 16.9 years vs. 26.9 years) and died earlier (22.6 years vs. 31.8 years). There were 59 vascular surgeries in the cohort, with one death during the procedure. This low rate of intraoperative mortality distinguishes the Loeys–Dietz syndrome from vascular Ehlers–Danlos syndrome.ConclusionsMutations in eitherTGFBR1orTGFBR2predispose patients to aggressive and widespread vascular disease. The severity of the clinical presentation is predictive of the outcome. Genotyping of patients presenting with symptoms like those of vascular Ehlers–Danlos syndrome may be used to guide therapy, including the use and timing of prophylactic vascular surgery.