Common presentation of rare diseases: Aortic aneurysms & valves. (15th April 2018) - Arbustini, Eloisa
Abstract: 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. Highlights: Rare aneurysmal diseases can be syndromic and non-syndromic. The diagnosis of syndromic aneurysms benefits from the presence of extra-vascular traits. Non-syndromic aneurysmal diseases are only diagnosed with cardiovascular imaging. Rare valvular diseases also occur in syndromic or non-syndromic combinations. The origin of rare aneurysmal and valvular diseases is genetic in most cases.