Age-related penetrance of phospholamban p.Arg14del cardiomyopathy
PLN p.(Arg14del) and heart disease
Some people carry a change (or variant) in a gene called PLN, short for phospholamban. One specific variant, called p.(Arg14del) and located on a specific section of the PLN gene, has been linked to heart problems like heart failure and dangerous irregular heartbeats (arrhythmias). But not all carriers of this gene variant get sick, and symptoms can show up at very different ages—even in the same family.
A new study looked at 868 people with this gene variant to better understand:
- How likely they are to develop heart problems
- At what age symptoms tend to appear
- How to manage their care over time
What did the study find?
- Most carriers develop some heart problem during their life
By age 70, up to:
- 70% of carriers had experienced a major heart event, such as heart failure or a life-threatening arrhythmia.
- Nearly all (84–100%) showed early warning signs, like reduced pumping function of the heart , abnormal ECGs, scars in the heart visible on MRI, or frequent extra heartbeats.
This means that even if someone feels healthy, most carriers of the gene variant will eventually show some signs of heart involvement.
- Heart rhythm issues often happen first
Irregular or fast heartbeats, called arrhythmias, usually showed up about 10 years earlier than heart failure (reduced pumping function of the heart). These arrhythmias can be serious and may cause fainting or sudden cardiac arrest if untreated.
What does this mean for carriers?
- Lifelong heart monitoring is essential
Because problems can appear from adolescence, heart checkups should begin in adolescence and continue for life. This may include ECGs, heart ultrasounds or MRIs, and rhythm monitoring.
- Even healthy carriers need follow-up
About 1 in 4 healthy carriers developed a major event within 10 years. So even if all tests are normal now, regular monitoring is still important.
3.Treatment can prevent serious events
Some carriers may need medications or even an implantable defibrillator (ICD) to prevent sudden death and treat heart failure.
Takeaway
The PLN p.(Arg14del) gene variant increases the risk of serious heart problems, often without early warning. But with regular checkups, early treatment, and family screening, several complications including sudden cardiac death can be prevented or symptoms managed.
Tom Verstraelen et al. European Journal of Heart Failure (2025), doi:10.1002/ejhf.3672
Translated by Arthur Wilde and Ruth Biller