Genomics in general practice

Disease specific topics

Sudden arrhythmic death syndrome

Sudden arrhythmic death syndrome


Genetic heart disorders are an important cause of sudden arrhythmic death syndrome (SADS) in people <40 years of age. In many cases, the death of a young person in the family can often be the first sign of a genetic heart disease within that family. Identifying a genetic basis of sudden cardiac death is vital in being able to accurately manage families.

What do I need to know?

SADS is an umbrella term to describe unexpected deaths in young people (usually <40 years of age), whose cause of death following post-mortem examination is ‘undetermined’ or ‘unascertained’.

The most common SADS conditions include genetic arrhythmia syndromes such as long QT syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT) and Brugada syndrome.

These conditions follow an autosomal dominant inheritance Autosomal recessive conditions affect either sex, and often occur in the absence of any family history. Recessive conditions or traits appear when an individual inherits two copies of pathogenic variants in the same (one from each parent). Parents of a child with an autosomal recessive condition are usually asymptomatic carriers. The affected child has two copies of the particular gene change. The recurrence risk of autosomal recessive conditions is one in four for each pregnancy. Wide variability in clinical expression is common in many autosomal recessive conditions. Autosomal recessive conditions are more common when the parents are consanguineous. pattern. Therefore, first-degree relatives (ie parents, siblings, children) of an individual who has a genetic arrhythmogenic disorder are at a 50% risk of also having a gene variant Gene variants are small DNA sequence changes (ie additions, duplications, deletions, substitutions). These variants can have a range of effects: some may cause disease (pathogenic variant), while others do not cause disease but may modify an individual’s risk of disease (i.e may increase risk or provide a protective effect). The vast majority of gene variants are benign and do not result in disease but rather contribute to the differences between people. for the condition, and thus, at risk of sudden arrhythmic death. All these conditions show considerable clinical variability within families and have incomplete penetrance Penetrance refers to the proportion of people with a particular genetic variant who will go on to develop the condition. For example, people carrying an autosomal dominant variant may not always develop the condition – this is called ‘incomplete penetrance’. If a condition is 100% penetrant, an individual will definitely develop the condition. If penetrance is 80%, most but not all individuals will develop the condition. Other genes and lifestyle factors, such as diet, exercise and smoker status, may affect the penetrance of some conditions. For more information, refer to MedlinePlus’ ‘What are reduced penetrance and variable expressivity?’ .

Important clinical features are:

  • any first-degree relatives with unexplained sudden cardiac death <40 years of age
  • episodes of unexplained syncope
  • syncope or seizures during exercise, excitement or startle

Collect a comprehensive family history (three generations), noting any relatives with the features above.

Genetic testing

Genetic testing can be arranged through a genetics clinic if appropriate. There is currently no Medicare Benefits Schedule (MBS) rebate for testing.

When should I refer?

Refer those with relevant clinical or family history to cardiology for cardiac screening tests, and to a cardiac genetics clinic for risk assessment.

Other considerations

Familial screening is vital when a genetic heart condition has been confirmed in an index case.

Emotional and psychological support is vital for families where sudden cardiac death has occurred and referrals for grief counselling should be offered.

Further reading

Resource for general practitioners

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