Juvenile sudden death in a family with polymorphic ventricular arrhythmias caused by a novel RyR2 gene mutation: evidence of specific morphological substrates.
We report on a family with a history of sudden death and effort-induced polymorphic ventricular arrhythmias. The index case was a 17-year-old boy who died suddenly and at postmortem had evidence of fibrofatty replacement in the right ventricular free wall, consistent with arrhythmogenic right ventricular cardiomyopathy, as well as calcium phosphate deposits within the myocytes. A molecular genetics investigation carried out in the paraffin-embedded myocardium of the subject and in blood samples of family members disclosed a missense mutation in exon 3 (230C-->T; A77V) of the cardiac ryanodine receptor type 2 gene. The carriers showed effort-induced polymorphic ventricular tachycardia in the setting of normal resting electrocardiogram and trivial echocardiographic abnormalities, consistent with catecholaminergic polymorphic ventricular tachycardia. The observation of both arrhythmogenic right ventricular cardiomyopathy type 2 and catecholaminergic polymorphic ventricular tachycardia in the same family suggests that the two entities might correspond to different degrees of phenotypic expression of the same disease. This experience underscores the importance of a precise autopsy diagnosis in the case of sudden cardiac death, including molecular genetics, and the mission of pathologists to guide further clinical investigation of family members.
d'Amati
Giulia
G
Department of Experimental Medicine and Pathology, La Sapienza University, Rome 00161, Italy.
Bagattin
Alessia
A
Bauce
Barbara
B
Rampazzo
Alessandra
A
Autore
Camillo
C
Basso
Cristina
C
King
Kathy
K
Romeo
Maria Daniela
MD
Gallo
Pietro
P
Thiene
Gaetano
G
Danieli
Gian Antonio
GA
Nava
Andrea
A
D000293:Adolescent; D000328:Adult; D002114:Calcinosis / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D016757:Death, Sudden, Cardiac / Q000209:etiology* / Q000473:pathology; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics* / Q000378:metabolism; D017180:Tachycardia, Ventricular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D019837:Ryanodine Receptor Calcium Release Channel