BabyScreen+ newborn screening

Gene: RYR2

Green List (high evidence)

ClinGen has assessed as 'strong actionability' in paediatric patients. Part of the ACMG list.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review

Treatment with beta blockers is associated with a reduction in adverse cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Agents to avoid:
The following lifestyle changes are recommended in patients with a diagnosis of CPVT, especially in those presenting with syncope of suspected arrhythmic etiology: avoidance of competitive sports, strenuous exercise, and stressful environments. Emotional situations, dehydration, electrolyte disturbances, and hyperthermia should be avoided. Digitalis should also be avoided in all individuals with CPVT, as it may provoke the onset of cardiac arrhythmias.

Created: 13 Dec 2022, 7:53 a.m. | Last Modified: 13 Dec 2022, 7:53 a.m.

Panel Version: 0.1367

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Ventricular tachycardia, catecholaminergic polymorphic, 1, MIM# 604772