title: Juvenile sudden death in a family with polymorphic ventricular arrhythmias caused by a novel RyR2 gene mutation: evidence of specific morphological substrates.
abstract: 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.
authors.affiliation: Department of Experimental Medicine and Pathology, La Sapienza University, Rome 00161, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: d'Amati
authors.forename: Alessia
authors.initials: A
authors.lastname: Bagattin
authors.forename: Barbara
authors.initials: B
authors.lastname: Bauce
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rampazzo
authors.forename: Camillo
authors.initials: C
authors.lastname: Autore
authors.forename: Cristina
authors.initials: C
authors.lastname: Basso
authors.forename: Kathy
authors.initials: K
authors.lastname: King
authors.forename: Maria Daniela
authors.initials: MD
authors.lastname: Romeo
authors.forename: Pietro
authors.initials: P
authors.lastname: Gallo
authors.forename: Gaetano
authors.initials: G
authors.lastname: Thiene
authors.forename: Gian Antonio
authors.initials: GA
authors.lastname: Danieli
authors.forename: Andrea
authors.initials: A
authors.lastname: Nava
mesh_terms: 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
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel