AUTHOR=MacGowan Taylor , McClinchey Taylor , Parcha Vibhu , Vatta Matteo , Litovsky Silvio , Arora Pankaj , Benson Paul V. TITLE=De novo heterozygous pathogenic FBN1 variant in an autopsy case of multiple aneurysms and right renal artery dissection: a case report JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=10 YEAR=2023 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1170460 DOI=10.3389/fcvm.2023.1170460 ISSN=2297-055X ABSTRACT=Background

Marfan syndrome is a potentially fatal inherited autosomal dominant condition impacting the cardiovascular and the skeletal system with an estimated 25% cases caused by sporadic genetic variations. Given the genetic inheritance pattern, an autopsy of probands with Marfan syndrome–associated mortality is critical to establish the phenotypic expression and clinical implications of the particular genetic variant, especially for first-degree relatives. We present the findings of a Marfan syndrome proband decedent presenting with sudden onset abdominal pain and unexplained retroperitoneal abdominal hemorrhage.

Methods

An autopsy was performed to inform the blood relatives of the phenotypic expression and penetrance of the potentially heritable condition. A clinical laboratory improvement amendment (CLIA)-certified clinical grade genetic sequencing was performed to identify pathogenic variants in genes associated with aortopathy.

Results

The autopsy showed intra-abdominal and retroperitoneal hemorrhage due to infarction of the right kidney caused by dissection of the right renal artery. Genetic testing identified a heterozygous pathogenic FBN1 gene variant. The specific variant is FBN1 NM_000138.4 c.2953G > A p.(Gly985Arg).

Conclusions

We report a case of a previously undiagnosed Marfan syndrome death due to a de novo FBN1 variant, c.2953G > A.