Objective To evaluate the prevalence and phenotype of smooth muscle alpha-actin (ACTA2) mutations in non-syndromic thoracic aortic aneurysms and dissections (TAAD).
Design Observational study of ACTA2 mutations in TAAD.
Setting Centre for Inherited Cardiovascular Diseases.
Patients A consecutive series of 100 patients with TAAD. Exclusion criteria included genetically confirmed Marfan syndrome, Loeys–Dietz type 2, familial bicuspid aortic valve and Ehlers–Danlos type IV syndromes.
Interventions Multidisciplinary clinical and imaging evaluation, genetic counselling and testing of ACTA2, and family screening.
Main outcome measures Prevalence of ACTA2 mutations and corresponding phenotypes.
Results TAAD was familial in 43 cases and sporadic in 57 cases. Five mutations in the familial TAAD group (12%) were identified that were absent in controls. The known p.Arg149Cys and the novel p.Asp82Glu, p.Glu243Lys and p.Val45Leu mutations affected evolutionarily conserved residues. The IVS4+1G>A mutation was novel. Of 14 affected relatives, 13 were carriers of the mutation identified in the corresponding proband while one deceased relative had no genetic test. Type A dissection was the first manifestation of aortic aneurysm in four probands and occurred unexpectedly in five relatives. The aortic aneurysm was age dependent and absent in mutated children. Of nine patients who had acute dissection, five died following surgery. At dissection, the size of the aortic aneurysm ranged from 40 mm to 95 mm. Extravascular, ocular, skeletal, nervous and pulmonary traits were variably associated with TAAD, with iris flocculi being most common.
Conclusions Timely diagnosis of TAAD in the probands, genetic counselling and family screening identify predisposed relatives and prevent catastrophic aortic dissections.
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Funding This study was funded by the National Ministry of Health ‘RC, 2007–2010, IRCCS Policlinico San Matteo, Pavia, Italy; ‘Marfan Syndrome’, Fondazione Banca Regionale Europea, Milan, Italy; Project on Loeys-Dietz Syndrome, National Institute of Health (ISS), Roma, Italy.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the IRCCS San Matteo Ethical Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
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