Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death: early diagnosis of asymptomatic carriers.
OBJECTIVE
We sought to establish the role of genetic screening for ryanodine receptor type 2 (RyR2) gene mutations in families with effort-induced polymorphic ventricular arrhythmia (PVA), syncope and juvenile sudden death.


BACKGROUND
The RyR2 mutations have been associated with PVA, syncope and sudden death in response to physical or emotional stress.


METHODS
We studied 81 subjects (39 males and 42 females; mean age 31 +/- 20 years) belonging to eight families with pathogenic RyR2 mutations. All subjects underwent screening for RyR2 mutations, electrocardiography (ECG), 24-h Holter monitoring, signal-averaged electrocardiography (SAECG), two-dimensional echocardiography and exercise stress testing. Electrophysiologic (EP) study was performed in nine patients.


RESULTS
Six different RyR2 mutations were found in eight families. Forty-three family members carried the gene mutation. Of these, 28 (65%) showed effort-induced arrhythmic symptoms or signs and one died suddenly during follow-up. Family history revealed 19 juvenile cases of sudden death during effort or emotion. In two families sharing the same mutation, no subject presented with PVA during the stress test; thus, sudden death and syncope were the only clinical manifestations. The 12-lead ECG was normal in all but two subjects, whereas five patients showed positive late potentials on the SAECG. In 17 (39.5%) of 43 subjects, the two-dimensional echocardiogram revealed localized kinetic abnormalities and mild structural alterations of the right ventricle. The EP study was not able to induce PVA.


CONCLUSIONS
The absence of symptoms and PVA on the stress test in more than one-third of carriers of RyR2 mutations, as well as the lack of PVA inducibility by the EP study, underlies the importance of genetic screening for the early diagnosis of asymptomatic carriers and prevention of sudden death.
Bauce
Barbara
B
Department of Cardiology, University of Padua Medical School, Via A. Gabelli, 86-35121 Padua, Italy.
Rampazzo
Alessandra
A
Basso
Cristina
C
Bagattin
Alessia
A
Daliento
Luciano
L
Tiso
Natascia
N
Turrini
Pietro
P
Thiene
Gaetano
G
Danieli
Gian Antonio
GA
Nava
Andrea
A
D000293:Adolescent; D000328:Adult; D002648:Child; D004452:Echocardiography; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D005260:Female; D005820:Genetic Testing; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D012815:Signal Processing, Computer-Assisted; D013575:Syncope / Q000235:genetics; D017180:Tachycardia, Ventricular / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology
D019837:Ryanodine Receptor Calcium Release Channel