Dean John C S
Department of Medical Genetics, NHS Grampian, Argyll House, Foresterhill, Aberdeen, AB25 2ZR, UK.
Eur J Hum Genet. 2007 Jul;15(7):724-33. doi: 10.1038/sj.ejhg.5201851. Epub 2007 May 9.
Marfan syndrome is a multisystem connective tissue disorder usually associated with mutation in fibrillin, and occasionally with mutation in TGFBR1 or 2. The clinical diagnosis is made using the Ghent nosology, which will unequivocally diagnose or exclude Marfan syndrome in 86% of cases. Use of a care pathway can help implementation of the nosology in the clinic. The penetrance of some features is age dependent, so the nosology must be used with caution in children. Molecular testing may be helpful in this context. The nosology cannot be used in families with isolated aortic dissection, or with related conditions such as Loeys-Dietz syndrome, although it may help identify families for further diagnostic evaluation because they do not fulfill the nosology, despite a history of aneurysm. Prophylactic medical (eg beta-blockade) and surgical intervention is important in reducing the cardiovascular complications of Marfan syndrome. Musculoskeletal symptoms are common, although the pathophysiology is less clear--for example, the correlation between dural ectasia and back pain is uncertain. Symptoms in other systems require specialist review such as ophthalmology assessment of refractive errors and ectopia lentis. Pregnancy is a time of increased cardiovascular risk for women with Marfan syndrome, particularly if the aortic root exceeds 4 cm at the start of pregnancy. High-intensity static exercise should be discouraged although low-moderate intensity dynamic exercise may be beneficial. The diagnosis and management of Marfan syndrome requires a multidisciplinary team approach, in view of its multisystem effects and phenotypic variability.
马凡综合征是一种多系统结缔组织疾病,通常与原纤维蛋白突变有关,偶尔也与TGFBR1或2突变有关。临床诊断采用根特分类法,该方法能在86%的病例中明确诊断或排除马凡综合征。使用护理路径有助于在临床中实施该分类法。某些特征的外显率与年龄有关,因此在儿童中使用该分类法时必须谨慎。在这种情况下,分子检测可能会有所帮助。尽管该分类法可能有助于识别那些虽有动脉瘤病史但不符合分类法标准的家庭,以便进行进一步的诊断评估,但它不能用于患有孤立性主动脉夹层或相关疾病(如洛伊迪茨综合征)的家庭。预防性药物治疗(如β受体阻滞剂)和手术干预对于降低马凡综合征的心血管并发症很重要。肌肉骨骼症状很常见,但其病理生理学尚不清楚——例如,硬脊膜膨出与背痛之间的相关性尚不确定。其他系统的症状需要专科检查,如对屈光不正和晶状体异位进行眼科评估。对于患有马凡综合征的女性,怀孕会增加心血管风险,尤其是在怀孕开始时主动脉根部超过4厘米的情况下。应避免高强度的静态运动,不过低至中等强度的动态运动可能有益。鉴于马凡综合征的多系统影响和表型变异性,其诊断和管理需要多学科团队协作。