Predictors of severe aortic involvement in Marfan syndrome
Stengl Roland
Szív-és Érgyógyászati Tagozat
Dr. Merkely Béla
SE Városmajori Szív- és Érgyógyászati Klinika Nagy előadóterem
2025-01-16 14:00:00
Szív és érrendszeri betegségek élettana és klinikuma
Dr. Merkely Béla
Dr. Benke Kálmán, Dr. Szabolcs Zoltán
Dr. Gál Anikó
Dr. Bari Gábor
Dr. Tory Kálmán
Dr. Buzás Edit
Dr. Székely László
Marfan syndrome belongs to the syndromic heritable thoracic aortic diseases and it is caused by mutations of the FBN1 gene. Aortic aneurysm and dissection are the main causes of morbidity and mortality of the syndrome. A prophylactic aortic surgery to prevent acute aortic events is mainly indicated based on aortic diameters. However, aortic dissection may occur by normal or mildly dilated aortas, and on the other hand, patients with dilated aorta may never experience acute aortic events. Furthermore, a prophylactic surgery has lower mortality and short- and long-term postoperative morbidity rate than the operation of an acute aortic dissection. Thus, predictors of severe aortic involvement in Marfan syndrome patients need to be identified to optimize the indications and timing of prophylactic aortic operation.
We assessed the role of genotype-phenotype correlations and arterial tortuosity in the prediction of more severe aortic involvement in patients with Marfan syndrome.
Genetic testing of patients with Marfan syndrome and Marfanoid habitus was carried out with single-gene-, gene-panel- and copy number variation (CNV) analyses.
We could differentiate between FBN1 variant types based on their aortic involvement severity. Haploinsufficient (HI) variants and dominant negative mutations with cysteine elimination (DN Cys) led to more severe aortic involvement than dominant negative mutations without the elimination of cysteine (DN non-Cys). Furthermore, DN Cys variants appeared more deleterious than HI ones. We also demonstrated the relevance of CNV screening and the use of a multi-gene panel in this patient population.
We evaluated the visceral arterial tortuosity of Marfan syndrome patients with different aortic involvement severity and control individuals. CT angiography images were analyzed with dedicated software tools and various tortuosity metrics. The renal arteries and the splenic artery were examined as their geometry is not influenced by the common skeletal abnormalities of the syndrome. All three vessels showed increased tortuosity in Marfan syndrome compared to the general population and more tortuous renal arteries were associated with more severe aortic phenotype.
In conclusion, the type of genetic variant and the degree of renal artery tortuosity could be predictors of severe aortic involvement, thereby could potentially be used for optimizing the indication and timing of prophylactic aortic surgery in Marfan syndrome patients.
