Presentation: Infant with hypertrophic cardiomyopathy

A three-month-old boy is admitted to a paediatric ward for assessment for developmental delay and global low tone. He is noted to have a murmur and an echocardiogram shows significant concentric left ventricular hypertrophy.

• Consider genomic testing in a child if:
  • the cardiomyopathy has an onset of below 12 years old without a non-genetic explanation; or
  • the cardiomyopathy is the primary clinical presentation in an individual of any age and there is also a second condition, dysmorphism or other feature(s) suggestive of a syndromic cause such as a RASopathy (for example, Noonan syndrome).
• Testing should be carried out in parallel with expert phenotypic assessment – for example, in an inherited cardiac conditions (ICC) clinic or specialist paediatric cardiomyopathy service – and with support from clinical genetics where appropriate.

• 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.
• For paediatric cardiomyopathy there are several available clinical indications, including the below.
  • R135 Paediatric or syndromic cardiomyopathy: This indication includes whole genome sequencing (WGS).
  • R131 Hypertrophic cardiomyopathy: This indication investigates single-gene non-syndromic causes of hypertrophic cardiomyopathy. It includes whole exome sequencing or medium gene panel sequencing, as well as multiplex ligation-dependent probe amplification (MLPA) or an equivalent.
• In patients in whom cardiomyopathy is one of multiple features of dysmorphism and/or multiple congenital anomalies, consider referral to clinical genetics for assessment.
• In some patients, a specific disease may be strongly suspected (for example, Barth syndrome), and isolated testing may then be appropriate.
• For WGS-based tests, you will need to:
  • complete an NHS GMS test order form with details of the proband and their parents, including details of the phenotype (refer to human phenotype ontology (HPO) terms and the clinical summary) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support); and
  • complete an NHS GMS record of discussion (ROD) form for each person being tested – for example, if you are undertaking trio testing of an affected child and their parents, you will need three of these forms (see How to complete a record of discussion form for support).
• For tests that do not include WGS, you will need to:
  • complete a test order form and consent (ROD) form, available from your local Genomic Laboratory Hub; and
  • include details of the phenotype (refer to HPO terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
• The tests described above 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: Guidelines for the diagnosis and management of hypertrophic cardiomyopathy (PDF, two pages)
• NHS England: National Genomic Test Directory

References:

• Monda E, Rubino M, Lioncino M and others. ‘Hypertrophic cardiomyopathy in children: Pathophysiology, diagnosis, and treatment of non-sarcomeric causes’. Frontiers in Pediatrics 2021: volume 9, article number 632293. DOI: 10.3389/fped.2021.632293
• Norrish G, Cleary A, Field E and others. ‘Clinical features and natural history of preadolescent nonsyndromic hypertrophic cardiomyopathy’. Journal of the American College of Cardiology 2022: volume 79, issue 20, pages 1,986–1,997. DOI: 10.1016/j.jacc.2022.03.347
• Norrish G, Field E and Kaski JP. ‘Childhood hypertrophic cardiomyopathy: A disease of the cardiac sarcomere’. Frontiers in Pediatrics 2021: volume 9, article number 708679. DOI: 10.3389/fped.2021.708679
• Ommen SR, Mital S, Burke MA and others. ‘AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy’. Circulation 2020: volume 142, issue 25, pages e558–e631. DOI: 10.1161/CIR.0000000000000937

For patients

• British Heart Foundation: Hypertropic cardiomyopathy
• Cardiac Risk in the Young: Hypertrophic cardiomyopathy
• Cardiomyopathy UK: Information for parents, caregivers and families
• myheart: Hypertrophic cardiomyopathy
• NHS Health A to Z: Cardiomyopathy