{
  "abstract": "Background Genetic testing plays an increasingly important role in the evaluation and management of thoracic aortic aneurysm and dissection (TAAD). National guidance via the NHS Genomic Test Directory (R125 criteria) aims to target testing to individuals at higher likelihood of heritable thoracic aortic disease. However, real-world diagnostic yield and its impact on clinical outcomes, including timing of surgery, remain less well-defined.Methods We conducted a retrospective audit of all patients referred for genetic testing through a tertiary aortopathy clinic between May 2020 and June 2025. Clinical, imaging, genetic, and surgical data were collected. Indications for testing were mapped to NHS Genomic Test Directory R125 criteria. Genetic results were analysed in relation to family history, presence and type of aortic dissection, variant distribution, and surgical outcomes (elective versus emergency).Results Of 408 patients reviewed, 144 underwent genetic testing (52.1% male; median age 52.3 years), predominantly using the R125 panel (98.6%). The most common indication was thoracic aortic aneurysm or dissection before age 50 (35.5%; median age 44.8 years), followed by syndromic features suggestive of Loeys–Dietz syndrome (19.9%) and family history of aortic aneurysm or dissection (14.5%). Overall diagnostic yield was 21% (n=30), comprising 25 pathogenic/likely pathogenic variants and 5 variants of uncertain significance; 79% of tests were negative.Aortic dissection occurred in 53 patients (36.8%). Diagnostic yield was higher in those with a positive family history (27% vs 17%). The prevalence of detected variants was similar in patients with and without dissection (18.9% vs 20.2%). Among dissection cases, Type A was more common (62.3%), however, variants were proportionally more frequent in Type B dissections (58.3% vs 31.7%). Variant-positive patients were more likely to undergo elective surgery compared with variant-negative patients (75.0% vs 41.1%), whereas emergency surgery occurred more frequently in variant-negative patients (58.9% vs 25.0%), despite similar dissection rates. The most frequently implicated genes were FBN1, SMAD3, ACTA2, and TGFBR2. One death occurred in the variant-negative group.Conclusions In this real-world cohort, genetic testing yield was modest but higher in patients with family history or syndromic features. While variant status was not associated with increased dissection incidence, it was associated with differences in clinical pathways, with variant-positive patients more likely to undergo planned elective surgery. These findings support the role of genetic testing in risk stratification, surveillance, and proactive management of thoracic aortopathy, while highlighting the need for broader inclusion of fatal dissection cases in future analyses.",
  "authors": [
    {
      "affiliations": [
        "Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom"
      ],
      "name": "Wen Hui The"
    },
    {
      "affiliations": [
        "Clinical Genetics Department, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom"
      ],
      "name": "Deborah Osio"
    },
    {
      "affiliations": [
        "Clinical Genetics Department, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom"
      ],
      "name": "Marie O’Donnell"
    },
    {
      "affiliations": [
        "Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom"
      ],
      "name": "Paul Clift"
    }
  ],
  "title": "238 Clinical utility of genetic testing in thoracic aortopathy: a five-year single-centre audit",
  "uid": "e770d038-66ec-569f-8f83-a092872c71a4"
}