Presentation: Child with supravalvular aortic stenosis

An 11-year-old girl is reviewed in the paediatric cardiology clinic after her GP reports hearing a murmur. She is doing well at school and has no additional health concerns. On questioning, it becomes apparent that her mother and maternal grandfather have been diagnosed with supravalvular aortic stenosis (SVAS).

• You should consider testing if the patients is:
  • non-syndromic but there is a presence of congenital heart disease of a type associated with elastin variants, with an autosomal dominant pattern of inheritance in at least three family members; or
  • presenting with SVAS characteristic of elastin variants.
• SVAS may also arise as part of Williams syndrome due to a deletion on chromosome 7. If this is the case, the presentation will be syndromic, with associated learning disability and dysmorphic features.
  • See Clinical suspicion of Williams syndrome for more information.
• Testing should be carried out in parallel with expert phenotypic assessment – for example in an inherited cardiac conditions (ICC) clinic or a specialist paediatric cardiology service – and with support from clinical genetics. Note that testing may occasionally be appropriate outside these criteria following discussion in an ICC 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 the relevant eligibility criteria are met, discuss the case with or refer it to your local 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 indication for familial SVAS is:
  • R140 Elastin-related phenotypes: This indication includes a single gene sequencing test that looks for small variations in the ELN gene.
• For tests that do not include whole genome sequencing, you will need to:
  • complete a test order form and consent (record of discussion) form, available from your local Genomic Laboratory Hub; and
  • include on the test order form details of the phenotype (human phenotype ontology (HPO) terms or the clinical summary) and the appropriate panel name(s) with associated R number.
• This test is 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

• Genetic and Rare Diseases Information Center: Supravalvular aortic stenosis
• MedlinePlus: Supravalvular aortic stenosis
• NHS England: National Genomic Test Directory

References:

• Merla G, Brunetti-Pierri N, Piccolo P and others. ‘Supravalvular aortic stenosis: Elastin arteriopathy’. Circulation: Genomic and Precision Medicine 2012: volume 5, issue 6, pages 692–696. DOI: 10.1161/CIRCGENETICS.112.962860

For patients

• Children’s Heart Federation: Aortic stenosis