Dissections or ruptures of aortic aneurysms annually account for approximately 4 deaths per 100,000 in the United States [1]. Identifying an underlying genetic or nongenetic cause can prevent a sudden death in an asymptomatic individual by initiating early medical management. The strength of genetic contributions is dependent on the aortic aneurysm's location. Low penetrance variants combined with environmental factors (e.g. atherosclerosis, infection, or injury) are more likely to cause abdominal aortic dissections or ruptures; however, autosomal dominant monogenic disorders, such as Marfan syndrome and Loeys-Dietz syndrome, often present as thoracic aortic dissections or ruptures (TADR) [2]. The same genes responsible for syndromic TADR may also have highly penetrant TADR variants that present without other syndromic features [3]. Ultimately, up to 25 percent of individuals with thoracic aortic disease harbor a detectable underlying Mendelian pathogenic variant [4].

An aortic aneurysm may present with no or minor symptoms prior to a dissection or rupture [5]. When a sudden death occurs from TADR, genetic testing can inform the family of recurrence risk as well as screening and intervention options to prevent another fatal outcome in the family. Eleven genes with definitive or strong roles in TADR are classified by Clinical Genome Resource (ClinGen), which include ACTA2, COL3A1, FBN1, LOX, MYH11, MYLK, SMAD3, TGFB2, TGFBR1, TGFBR2, and PRKG1 [4]. Moderate or limited roles of additional genes have also been reported [4].

Sudden deaths due to TADR often occur outside hospitals and are therefore investigated by medical examiner or coroner offices in the United States. At New York City Office of Chief Medical Examiner (NYC-OCME), TADR cases routinely receive molecular testing by the in-house Molecular Genetics Laboratory. The purpose of this retrospective study is to report molecular testing results of TADR cases investigated by the NYC-OCME, the largest medical examiner's office in the United States.