Presentation: Adult with progressive cardiac conduction disease

A 25-year-old female is admitted to the cardiology ward for assessment after two episodes of syncope. An electrocardiogram (ECG) shows high-degree atrioventricular block and subsequent imaging confirms normal bi-ventricular function.

• Genomic testing should be considered if your patient has progressive cardiac conduction anomalies with an onset before 50 years of age, a structurally normal heart and no skeletal myopathy.
• Appropriate investigations should be completed to exclude coronary artery disease or cardiomyopathy.
• Cardiac sarcoidosis should be excluded with either cardiac magnetic resonance imaging or positron emission tomography-flurodeoxyglucose imaging (PET-FDG).
• 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 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 indication for a presentation of young-onset idiopathic cardiac conduction disease is:
  • R328 Progressive cardiac conduction disease: This indication includes whole exome sequencing or small gene panel sequencing and multiplex ligation-dependent probe amplification (MLPA) or an equivalent.
• For tests that do not include WGS, you will need to:
  • complete a test order form and 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.
• 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

• NHS England: National Genomic Test Directory

References:

• Wilde AAM, Semsarian C, Márquez MF and others. ‘European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases’. EP Europace 2022: volume 24, issue 8, pages 1,307–1,367. DOI: 10.1093/europace/euac030

For patients

• British Heart Foundation: Progressive cardiac conduction defect
• British Heart Foundation: Life with sudden arrhythmic death syndrome
• Cardiac Risk in the Young
• myheart: Progressive cardiac conduction defect