Familial pseudo-Wolff-Parkinson-White syndrome.
BACKGROUND
PRKAG2 plays a role in regulating metabolic pathways, and mutations in this gene are associated with familial ventricular preexcitation, hypertrophic cardiomyopathy, and atrioventricular conduction disturbances. Clinico-pathologic and experimental data suggest the hypothesis of a glycogen storage disease.


OBJECTIVE
To report a unique pattern of clinical features observed in individuals with a mutant PRKAG2 from two unrelated families.


RESULTS
We studied two large families and found a total of 20 affected individuals showing a combination of sinus bradycardia, short PR interval, RBBB, intra and infrahisian conduction disturbances often requiring a pacemaker, and atrial tachyarrhythmias. Three individuals died suddenly at a young age. No patient had the Wolff-Parkinson-White (WPW) syndrome, and only two patients (10%) had myocardial hypertrophy. We performed screening of the exons and exon-intron boundaries of PRKAG2. Genetic analysis revealed a missense mutation (Arg302Gln) in the affected individuals from both families. This mutation had been described before and has been associated with the familial form of the WPW syndrome and with a high prevalence of left ventricular hypertrophy.


CONCLUSIONS
PRKAG2 mutations are responsible for a diverse phenotype and not only the familial form of the WPW syndrome. Familial occurrence of right bundle branch block, sinus bradycardia, and short PR interval should raise suspicion of a mutant PRKAG2 gene.
Sternick
Eduardo Back
EB
Biocor Instituto, Nova Lima, Brazil. eduardosternick@aol.com
Oliva
Antonio
A
Magalhães
Luiz P
LP
Gerken
Luiz M
LM
Hong
Kui
K
Santana
Oto
O
Brugada
Pedro
P
Brugada
Josep
J
Brugada
Ramon
R
D000328:Adult; D000368:Aged; D004562:Electrocardiography; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree