Age-related penetrance of phospholamban p.Arg14del cardiomyopathy
The pathogenic (disease causing) p.Arg14del variant in the phospholamban (PLN) gene is a widespread variant in the Netherlands (and several other countries in the world where Dutch citizens settled over the years) and associates with a severe form of dilated cardiomyopathy (widening of the heart leading to diminished pumping function) and potentially life-threatening arrhythmias. There is not too much known about the percentage of patients that suffer from these symptoms. And this information is of importance because it determines the earliest age at which patients should be seen and how the follow-up should be arranged.
In order to achieve information about thus we collected clinical data from 868 PLN p.(Arg14del) carriers (mainly from the Netherlands and a few from Spain). In particular data on cardiac symptoms or signs of the disease were collected and these were either defined as a major event or as a risk factor. A major event consisted of malignant (i.e. life-threatening) ventricular arrhythmias or symptomatic heart failure (reduction of the heart´s pumping function). Risk factors were specific abnormalities on the ECG, decreased cardiac function or cardiac fibrosis on magnetic resonance imaging (MRI) which means that there are scars in the heart muscle.
During a medium of 5.3 years 207 (23.8%) carriers had a major event, at a mean age of 51 years. The onset of symptoms or the appearance of a risk factor was age-related, with new cardiac manifestations emerging from adolescence to senior age. At age 70, up to 70% of carriers had experienced a major event and the presence of a risk factor was even higher at that age. If only family members are studied (i.e. an analysis without involvement of the first individual diagnosed in a new family) ±30% of patients had suffered from a major event at age 70.
It should therefore be concluded that the likelihood of developing disease is high in individuals with the PLN p.(Arg14del) variant and that life-long cardiac follow-up is needed, starting from adolescence (± age 15).
Tom Verstraelen et al. European Journal of Heart Failure (2025), doi:10.1002/ejhf.3672
Translated by Arthur Wilde and Ruth Biller