The Role of Genetic Testing in the Prevention, Diagnosis and Prognosis of Sudden Cardiac Death in Children

Background: Determining the pathogenesis of sudden cardiac death (SCD) in children is crucial for management and prognosis. Our aim was to analyze the effectiveness of genetic testing.

Methods: Among 104 families with at least 1 index case of SCD (resuscitated or not), 29 cases were in children younger than 18 years, age 11± 5 years. Survivors were studied with ECG, 12 lead holter, exercise testing, cardiac imaging, familial study and genetic testing. Families with deceased probands were studied using the ECG before, postmortem findings, family study and genetic testing.

Results: After a thorough clinical and genetic evaluation in a specialized clinic, a positive diagnosis was reached in 24/29 (82%). Inherited Channelopathies (long QT syndrome and catecholaminergic polymorphic ventricular tachycardia) were the most prevalent diagnosis 20/29 (69%). Cardiomyopathy was in 3 (10%). In 1 patient (3%) the cause of SCD was acute myocarditis and was not genetic. Genetic testing (large panel, using next generation sequencing) was performed in 24/29 (82%) of families and was positive in 16/24 cases (67%). Genetic testing (p=0.002) and family screening (p=0.05) were statistically significant contributors to the diagnosis. In 5 cases (17%) genetic testing was the only positive test available. In multivariate logistic regression model, genetic testing among patients age ≤18 years had high diagnostic value (p=0.05, OR 8.8, CI 0.96-83). Of 155 family members who underwent clinical evaluation, 73 (47%) had abnormal results. Sixty four family members (41%) carried a pathogenic mutation. Forty eight family members are followed in the clinic and medically treated. During 6± 4.8 years, 4 family members experienced appropriate ICD shock, from 9 implanted.

Conclusion: The major cause for sudden cardiac death among children is of genetic etiology. Genetic testing has a high yield in this group. Family screening has a major role both in the diagnosis and in preventing SCD.