Centre for Inherited Cardiovascular Diseases, IRCCS Foundation University Hospital Policlinico San Matteo, Pavia, Italy.
Centre for Inherited Cardiovascular Diseases, IRCCS Foundation University Hospital Policlinico San Matteo, Pavia, Italy.
Int J Cardiol. 2018 Apr 15;257:358-365. doi: 10.1016/j.ijcard.2018.01.003.
The concept "common presentation of rare diseases" implies that rare diseases are masked by common phenotypic manifestations. This concept applies to both aneurysmal and valvular diseases that can be syndromic and non-syndromic. Syndromic disorders include genetic connective tissue diseases and chromosomal disorders that are diagnosed independently from the aneurysm or valve disease. Non-syndromic diseases, on the other hand, are defined by the presence of aneurysm or valve disease or both. The reasons for suspecting these rare diseases include young age, the absence of risk factors, a positive family history for aortic or valvular disease/event, and extra-cardiovascular traits for syndromes. The probands should receive genetic counseling, genetic testing [single gene in case of precise phenotyping addressing the gene to be tested, or multigene panels, in case of diseases with genetic heterogeneity], post-test counseling, clinical family screening and cascade genetic testing in relatives after the identification of a causative mutation. Segregation studies are essential in case of novel mutations, in particular non-truncation predicting variants. Clinical family screening of syndromic diseases is facilitated by the evaluation of non-cardiovascular traits; this supports early diagnosis and geno-phenotype correlation. Vice versa, family screening studies in non-syndromic aneurysmal and valvular diseases exclusively relies on CV imaging screening of relatives. In this context, conditions such as BAV and related aortopathy are easy to diagnose because BAV is present at birth while aortopathy usually develops during the life course.
“罕见病的常见表现”这一概念意味着，罕见病可能被常见的表型表现所掩盖。这一概念既适用于有综合征和无综合征表现的动脉瘤性疾病和瓣膜性疾病。综合征性疾病包括遗传性结缔组织疾病和染色体疾病，这些疾病是独立于动脉瘤或瓣膜疾病而诊断的。另一方面，非综合征性疾病是由动脉瘤或瓣膜疾病或两者共同存在所定义的。怀疑这些罕见病的原因包括年龄较小、不存在风险因素、主动脉或瓣膜疾病/事件的阳性家族史，以及综合征的心血管外特征。先证者应接受遗传咨询、基因检测（在明确表型的情况下，针对要检测的基因进行单基因检测，或在遗传异质性疾病的情况下进行多基因检测）、检测后咨询、临床家族筛查和亲属的级联遗传检测，以确定致病突变。在出现新突变时，特别是非截断预测变异时，分离研究至关重要。对于综合征性疾病，非心血管特征的评估有助于临床家族筛查，从而支持早期诊断和基因表型相关性。相反，在非综合征性动脉瘤性和瓣膜性疾病的家族筛查研究中，仅依赖于对亲属的心血管成像筛查。在这种情况下，BAV 和相关的主动脉病变等情况很容易诊断，因为 BAV 在出生时就存在，而主动脉病变通常在生命过程中发展。
