Little is known about children with a rare subset of arrhythmogenic cardiomyopathy called desmoplakin (DSP) cardiomyopathy, but new research led by Teresa M. Lee, M.D., M.S., and Warren A. Zuckerman, M.D., pediatric cardiologists at NewYork-Presbyterian and Columbia, is shedding light on the condition.
In a study published in Circulation: Arrhythmia and Electrophysiology, they reported on a series of 34 pediatric and adolescent patients with pathogenic or likely pathogenic DSP variants. Their findings suggest that children with DSP cardiomyopathy may be at risk for malignant ventricular tachyarrhythmia.
Below, Dr. Lee and Dr. Zuckerman share details of the study and explain why genetic testing is important to guide surveillance and treatment.
The study suggests that DSP cardiomyopathy presents differently in children and adolescents.
Characterizing the Pediatric Population
Dr. Lee: Over the last 20 years, we’ve begun to understand more about different forms of arrhythmogenic cardiomyopathy and we’ve started to routinely perform genetic testing to see how genetic variants influence clinical presentation. But little has been understood about how children may present differently from adults.
We decided to work with five other centers to pool cases of DSP cardiomyopathy and gather as much detailed clinical information as possible, looking at genetics but also echocardiograms, MRIs, EKGs, and electrophysiology studies to try to better understand this disease state in children and adolescents.
— Dr. Teresa M. Lee
Here at NewYork-Presbyterian and Columbia, we had a pediatric patient with the DSP variant and a diagnosis of cardiomyopathy that didn’t exactly fit the symptoms. But when we started looking through our databases, we didn’t have enough patients with DSP cardiomyopathy to draw any conclusions. We decided to work with five other centers to pool cases of DSP cardiomyopathy and gather as much detailed clinical information as possible, looking at genetics but also echocardiograms, MRIs, EKGs, and electrophysiology studies to try to better understand this disease state in children and adolescents.
Key Findings
Dr. Zuckerman: This study was a retrospective case series of 34 pediatric patients with pathogenic or likely pathogenic DSP variants who were treated across six centers between 2000 and 2021. Patients were categorized as either symptomatic gene-positive probands or gene-positive asymptomatic individuals who tested positive for a DSP variant based on family cascade testing or incidentally during genetic testing for another condition. We found that:
- Overall, 10 patients were categorized as probands and about half were initially diagnosed with myocarditis.
- The clinical presentation among the probands was different based on age, with patients under age 13 having symptoms of congestive heart failure such as shortness of breath, as well as severe biventricular dysfunction, and homozygous or compound heterozygous inheritance.
- Older patients in the cohort were more likely to experience chest pain, syncope, and autosomal dominant inheritance.
- Patients who had biventricular involvement and severe left ventricular dysfunction had a higher incidence of malignant ventricular tachyarrhythmia requiring treatment with an implantable cardioverter defibrillator.
We’re often diagnosing patients with myocarditis but if we learn that they have this genetic mutation, our antenna is raised that these could potentially be very sick cardiomyopathic hearts.
— Dr. Warren A. Zuckerman
Importance of Genetic Testing
Dr. Zuckerman: Having the ability to perform genetic testing and identify these patients earlier is critical. We’re often diagnosing patients with myocarditis, but if we learn that they have this genetic mutation, our antenna is raised that these could potentially be very sick cardiomyopathic hearts. This could prompt us to do more aggressive surveillance of the patient and that could end up saving their lives.
Dr. Lee: Cardiologists need to be thinking about genetic testing for all their patients. If you’re working in the community, at least offer patients a genetic consult whether that’s with a geneticist, a genetic counselor, or referring them to a center like ours that specializes in treating cardiomyopathy.
Next Steps
Dr. Zuckerman: An important next step will be to see what happens with the patients have a pathogenic genetic variant but haven’t shown any clinical symptoms yet. Long-term follow up of this patient cohort will be important and we expect that there will also be more gene diagnoses within these families.
Dr. Lee: More broadly, knowing about these genetic variants opens up the possibility for targeted treatment options in the future. It takes this type of basic science understanding to lead to those breakthroughs that are eventually going to improve care for our patients.
