Presentation: Child with syndromic cardiomyopathy

A 13-year-old boy with a background of mild global developmental delay is referred to paediatric cardiology with a murmur. He has some dysmorphic features and is found to have an atrial septal defect and hypertrophic cardiomyopathy.

• You should consider genomic testing in a child with cardiomyopathy if:
  • the cardiomyopathy has an onset of under 12 years of age without a non-genetic explanation; or
  • cardiomyopathy is the primary clinical presentation in an individual of any age and there is also a second condition, such as dysmorphism, or other feature(s) suggestive of a syndromic cause such as a RASopathy.
• Testing should be carried out in parallel with expert phenotypic assessment – for example, in an inherited cardiac conditions (ICC) clinic or specialist paediatric cardiology service – and with support from clinical genetics. Note that testing may occasionally be appropriate outside these criteria following a 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 the case to an ICC clinic for further assessment.
• The relevant clinical indications for paediatric cardiomyopathy include:
  • R135 Paediatric or syndromic cardiomyopathy: This indication includes whole genome sequencing (WGS) and whole exome sequencing; and
  • R27 Paediatric disorders: Consider this indication if cardiomyopathy is one of multiple features of a likely multi-system condition (the test comprises WGS and microarray).
• For WGS-based tests, you will need to:
  • complete an NHS GMS test order form with details of the child (proband) and their parents, including details of the phenotype (refer to human phenotype ontology (HPO) terms or clinical summary) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support);
  • complete an NHS GMS record of discussion 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); and
  • submit parental samples alongside the child’s sample (this is trio testing) to aid interpretation, especially for the larger WGS panels (where this is not possible, for example because the child is in care or the parents are unavailable for testing, the child’s sample may be submitted as a singleton).
• The tests outlined 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

• 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

For patients

• British Heart Foundation: Hypertropic cardiomyopathy
• Cardiomyopathy UK: Cardiomyopathy for parents and carers (PDF, 44 pages)
• Cardiomyopathy UK: Information for parents, caregivers and families
• NHS Health A to Z: Cardiomyopathy