Presentation: Patient with a family history of sudden cardiac death

A 44-year-old woman attends an appointment. Her husband has just died, unexpectedly at aged 39 years, of SCD. His brother also died unexpectedly, at 35 years of age, but this happened abroad and no post-mortem was carried out. She has children aged 19, 17 and 15 years (also your patients) and she has been advised that they need genomic testing.

• The most common cause of young SCD is sudden arrhythmic death syndrome (SADS), accounting for 53% of SCD cases. Around 22% of SCD is attributable cardiomyopathies, including arrhythmogenic cardiomyopathy.
• These conditions often follow an autosomal dominant inheritance pattern with variable or age-dependent penetrance.
• Inherited arrhythmia syndromes that can cause young SCD includes long QT syndrome and Brugada syndrome.
• It is crucial that sudden unexpected death should trigger an autopsy, particularly if:
  • one family member is affected below the age of 40 years; or
  • two more family members are affected below the age of 60 years.
• Autopsy would usually include the storage of splenic samples which can then be used subsequently for genomic testing after discussion with family members. This is known as a molecular autopsy.
• If an inherited cardiac condition (ICC) 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 indicated (molecular autopsy).
• Flags for an underlying genetic diagnosis include:
  • SCD at a young age (as above);
  • multiple (particularly young) SCD events in the family; and
  • a family history of inherited cardiac disease.

• Family members, including partners and first degree relatives, should be offered referral to clinical genomics services and/or ICC services as per local pathways. These services facilitate the processes to obtain information and samples regarding a deceased relative.
• Refer family members if:
  • cardiomyopathy is identified at post-mortem at any age, even if this wasn’t a cause of death; or
  • SADS occurs under the age of 50 years.
• Referrals to ICC services should include name, date of birth, date of death and place of death. This enables location of the coronial district and available splenic samples. 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.
• Do not arrange clinical tests (such as an electrocardiogram or an echocardiogram (echo)) prior to referral; these are most appropriately arranged within ICC settings where patients can be informed and counselled prior to any investigation.
• 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 testing).
• If a genetic cause is not identified, ICC services would still make a recommendation as to any recommended surveillance for family members.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.

For clinicians

• NHS England: National Genomic Test Directory

Resources:

• Sheppard MN, Westaby J, Zullo E and others. ‘Sudden arrhythmic death and cardiomyopathy are important causes of sudden cardiac death in the UK: results from a national coronial autopsy database‘. Histopathology 2023: volume 82, issue 7, pages 1,056–1,066. DOI: 10.1111/his.14889

For patients

• British Heart Foundation: Inherited heart conditions
• Cardiac Risk in the Young