Arrhythmogenic Right Ventricular Cardiomyopathy
̣̣̣̺ Arrhythmogenic right ventricular dysplasia (ARVD), also called arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), is an inherited heart disease.Wikipedia
ARVD is caused by genetic defects of the parts of heart muscle (also called myocardium or cardiac muscle) known as desmosomes, areas on the surface of heart muscle cells which link the cells together. The desmosomes are composed of several proteins, and many of those proteins can have harmful mutations.
The disease is a type of nonischemic cardiomyopathy that involves primarily the right ventricle. It is characterized by hypokinetic areas involving the free wall of the right ventricle, with fibrofatty replacement of the right ventricular myocardium, with associated arrhythmias originating in the right ventricle.
ARVD can be found in association with diffuse palmoplantar keratoderma, and woolly hair, in a autosomal recessive condition called Naxos disease, because this genetic abnormality can affect also the integrity of the superficial layers of the skin most exposed to pressure stress.
ARVC/D is an important cause of ventricular arrhythmias in children and young adults. It is seen predominantly in males, and 30-50% of cases have a familial distribution.
Genetics[edit]
It is usually inherited in an autosomal dominant pattern, with variable expression. Only 30% to 50% of individuals affected by ARVC will test positive to one of the known genetic mutations.[PMID 21606396
] The penetrance is 20–35% in general, but significantly higher in Italy. Seven gene loci have been implicated in ARVD. It is unclear whether the pathogenesis varies with the different loci involved. Standard genetic screening test are currently tested and evaluated in different state of the art cardiovascular research centers and hospitals. ARVD types include:
| Type | Gene | Locus |
|---|---|---|
| ARVD1 | TGFB3 | 14q23-q24 |
| ARVD2 | RYR2 | 1q42-q43 |
| ARVD3 | ? | 14q12-q22 |
| ARVD4 | ? | 2q32.1-q32.3 |
| ARVD5 | TMEM43 | 3p23 |
| ARVD6 | ? | 10p14-p12 |
| ARVD7 | DES | 10q22.3 |
| ARVD8 | DSP | 6p24 |
| ARVD9 | PKP2 | 12p11 |
| ARVD10 | DSG2 | 18q12.1-q12 |
| ARVD11 | DSC2 | 18q12.1 |
| ARVD12 | JUP | 17q21 |
| ARVD13 | CTNNA3 | 10q21 |
Prevalence[edit]
The prevalence of ARVD is about 1/10,000 in the general population in the United States, although some studies have suggested that it may be as common as 1/1,000. Recently, 1/200 were found to be carriers of mutations that predispose to ARVC.[PMID 21397041] Based on these findings and other evidence, it is thought that in most patients, additional factors such as other genes, athletic lifestyle, exposure to certain viruses, etc. may be required for a patient to eventually develop signs and symptoms of ARVC. ARVD accounts for up to 17% of all sudden cardiac deaths in the young. In Italy, the prevalence is 40/10,000, making it the most common cause of sudden cardiac death in the young population.[PMID 26216213]
