Presentation: Patient with a thoracic aortic aneurysm or dissection

A 44-year-old woman is evaluated with clinical screening due to the death of her brother at 39 years of age from a ruptured thoracic aortic aneurysm. No samples of his DNA are available from autopsy. The patient’s echocardiogram identifies dilatation measuring 44mm at the sinus of Valsalva. She is tall but has no other features of an aortopathy syndrome. Her blood pressure is normal. A thoracic aneurysm is confirmed on cross-sectional imaging and she is referred to a specialist in aortopathy.

• Consider genomic testing if the patient:
  • has a thoracic aortic aneurysm or dissection with onset before the age of 50;
  • has a thoracic aortic aneurysm or dissection with onset before the age of 60, with a first-degree relative with either a thoracic aortic aneurysm or dissection;
  • has a thoracic aortic aneurysm or dissection before the age of 60 with no classical cardiovascular risk factors;
  • has a thoracic aortic aneurysm or dissection before the age of 60 with features suggestive of aortopathy, such as arterial tortuosity;
  • displays clinical features suggestive of Loeys-Dietz syndrome;
  • displays clinical features suggestive of Marfan syndrome with a systemic Ghent score of seven or less, following assessment by a clinical geneticist or specialist with expertise in aortopathy;
  • displays features causing a high clinical suspicion of a condition predisposing to aortic or arterial disease, where diagnostic testing for other conditions such as Ehlers-Danlos syndrome (where indicated) has not identified a causative variant; or
  • is deceased, with a thoracic aortic aneurysm or dissection detected at autopsy, meets one of the above criteria and has relatives who would benefit from cascade testing if a genetic diagnosis is found during post-mortem testing.

• Note that a thoracic aortic aneurysm is defined in adults as a dilatation higher than 38mm and in children as having a z-score (defined as the number of standard deviations from the population mean) greater than two for body surface area.
• Testing should be carried out following assessment by a clinician specialising in management of patients with aortopathy, with support from clinical genetics services. Note that testing may occasionally be appropriate outside these criteria, following discussion in an aortic genetics multidisciplinary team meeting.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• If eligibility criteria are met, discuss the case with or refer it to your local inherited cardiac conditions (ICC) clinical service for genomic testing and family screening. You will need to provide details confirming that the patient fulfils the criteria.
• If the patient fulfils diagnostic criteria as detailed in published guidelines that differ from the eligibility criteria in the test directory, it is appropriate to refer to an ICC clinic for further assessment.
• The relevant clinical indication for thoracic aortic aneurysm or dissection is:
  • R125 Thoracic aortic aneurysm or dissection: This panel uses whole exome sequencing and multiplex ligation-dependent probe amplification (MLPA) or equivalent.
• The majority of genomic tests for ICCs are currently undertaken on a singleton basis, though samples may be needed from additional family members in order to interpret results.
• For tests that do not include WGS, you will need to:
  • complete a test order form and a consent (record of discussion) form, available from your local Genomic Laboratory Hub; and
  • include details of the phenotype in the test order form (refer to human phenotype ontology (HPO) terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
• These tests are DNA based, and an EDTA sample (purple-topped tube) is required.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• European Society of Cardiology: Aortic disease guidelines
• NHS England: National Genomic Test Directory

For patients

• British Heart Foundation: Thoracic aortic aneurysm
• The Aortic Dissection Charitable Trust