Presentation: Patient with a family history of sudden cardiac death
Sudden cardiac death at a young age can be caused by inherited cardiac conditions, such as cardiomyopathies and inherited arrhythmia syndromes. If an underlying genetic cause is identified in an autopsy, family members should be referred for predictive genomic testing.
At a glance:
- Sudden cardiac death (SCD) at a young age may be caused by inherited cardiac conditions, including cardiomyopathies and inherited arrhythmia syndromes.
- Post-mortem testing of individuals who have suffered SCD should include an autopsy and may include genetic analysis, which will help identify the cause.
- Identifying a pathogenic variant within a family can guide clinical management and plays a crucial part in providing access to genomic testing for unaffected family members (cascade genomic testing).
- If the autopsy shows a normal heart, this is known as sudden arrhythmic death syndrome (SADS). Most SADS deaths are caused by inherited arrhythmia syndromes (for example, Brugada syndrome).
- Alert! If a genetic cause of SCD is identified, lifestyle modifications, medications and implantable defibrillators can save lives.
Example clinical scenario
A 44-year-old woman attends an appointment. Her husband has just died unexpectedly aged 39 of SCD. His brother also died unexpectedly aged 35, but this happened abroad and no post-mortem was carried out. She has children aged 19, 17 and 15 (also your patients) and she has been advised that they need genomic testing.
Identifying those at risk of a genetic condition
- The most common cause of young SCD is hypertrophic cardiomyopathy, which has an autosomal dominant inheritance pattern with variable penetrance.
- Another important cause is arrhythmogenic right ventricular cardiomyopathy, which has an autosomal dominant inheritance pattern with age-dependent penetrance.
- Inherited arrhythmia syndromes that can cause young SCD include long QT syndrome and Brugada syndrome.
- Sudden unexpected death in a young person should trigger an autopsy.
- Some SCD victims may be suitable for post-mortem genomic testing.
- If an inherited cardiac condition has been identified at autopsy, genomic testing will be targeted to that condition. See the National Genomic Test Directory for further details.
- If no underlying cause of death is found at autopsy and the SCD remains unexplained, broader genomic testing may be considered in the form of a molecular autopsy.
- Flags for an underlying genetic diagnosis include:
- SCD at a young age;
- multiple (particularly young) SCD events in the family; and
- a family history of inherited cardiac disease.
What should you do next?
- If young SCD occurs in a family (particularly if the autopsy shows an inherited cardiac condition or if the SCD remains unexplained after autopsy), first-degree relatives (parents, siblings and children) should be referred to an inherited cardiac conditions service for clinical screening.
- Referrals to inherited cardiac conditions services should include as much information as possible, and first-degree relatives should be asked to take a copy of their relative’s death certificate and post-mortem report (if a post-mortem was performed) to their appointment.
- There is no need to arrange clinical tests prior to referral, although a 12-lead electrocardiogram (ECG) can be helpful.
- If the SCD remains unexplained after autopsy, the National Genomic Test Directory has further referral criteria for genomic testing.
- If an underlying genetic cause is identified, family members should be referred to clinical genetics services for cascade genomic testing of family members (this is called predictive genomic testing).
- For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
- Information about patient eligibility and test indications were 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.
Resources
For clinicians
- NHS England: National Genomic Test Directory
For patients
- British Heart Foundation: Inherited heart conditions
- Cardiac Risk in the Young