Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Arrhythmogenic Right Ventricular Dysplasia (ARVD) [I42.80]

OMIM-Nummer: 607450, 125647 (DSP), 609040, 602861 (PKP2), 610193, 125671 (DSG2)

Dr. rer. nat. Christoph Marschall

Scientific Background

Arrhythmogenic right ventricular dysplasia (ARVD) is a mostly autosomal dominant inherited disorder of the heart muscle in which the myocardium is progressively replaced by fat and connective tissue. This fibrofatty remodeling mainly affects the right ventricle and leads to impaired conduction resulting in ventricular arrhythmias, palpitations or syncopes. ECG typically shows epsilon waves as well as an inverted T wave with broadened QRS complex in the right precordial leads. Usually the arrhythmias that can lead to sudden cardiac death are triggered by physical activity. Around one third of index patients suddenly die in the age of 14–20. This age seems to constitute a vulnerable period for fatal arrhythmia. However, 50% of all carriers develop clinical symptoms not until > 50 years of age and one third even does not present symptoms in old age. Prevalence of ARVD is estimated to be 1 in 5,000. A family history of ARVD is present in about 50% of all cases. So far, more than 10 different types of ARVD have been described.

The most common types are caused by mutations in genes that code for components of desmosomes (cell-cell adhesions). In 50–60% of patients mutations in the genes for desmoplakin (DSP), plakophilin-2 (PKP2) and desmoglein-2 (DSG2) can be detected by molecular genetic analysis. Furthermore, in 5% of all hereditary ARVD/C cases mutations in other desmosomal proteins such as plakoglobin (JUP) and desmocollin-2 (DSC2) or in other genes such as transmembrane protein 43 (TMEM43) and transforming growth factor beta-3 (TGFB3) can be found. In approximately 40% of ARVD/C cases no genetic cause can be identified so far.