RESUMO
INTRODUCTION AND OBJECTIVES: Genetic testing is becoming increasingly important for diagnosis and personalized treatments in aortopathies. Here, we aimed to genetically diagnose a group of acute aortic syndrome (AAS) patients consecutively admitted to an intensive care unit and to explore the clinical usefulness of AAS-associated variants during treatment decision-making and family traceability. METHODS: We applied targeted next-generation sequencing, covering 42 aortic diseases genes in AAS patients with no signs consistent with syndromic conditions. Detected variants were segregated by Sanger sequencing in available family members. Demographic features, risk factors and clinical symptoms were statistically analyzed by Fisher or Fisher-Freeman-Halton Exact tests, to assess their relationship with genetic results. RESULTS: Analysis of next-generation sequencing data in 73 AAS patients led to the detection of 34 heterozygous candidate variants in 14 different genes in 32 patients. Family screening was performed in 31 relatives belonging to 9 families. We found 13 relatives harboring the family variant, of which 10 showed a genotype compatible with the occurrence of AAS. Statistical tests revealed that the factors associated with a positive genetic diagnosis were the absence of hypertension, lower age, family history of AAS and absence of pain. CONCLUSIONS: Our findings broaden the spectrum of the genetic background for AAS. In addition, both index patients and studied relatives benefited from the results obtained, establishing the most appropriate level of surveillance for each group. Finally, this strategy could be reinforced by the use of stastistically significant clinical features as a predictive tool for the hereditary character of AAS. CLINICALTRIALS: gov (Identifier: NCT04751058).
