DISEASE: Arrhythmogenic right ventricular cardiomyopathy
Entry
H00293 Disease
Name
Arrhythmogenic right ventricular cardiomyopathy
Description
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are progressive myocyte loss and fibrofatty replacement, with a predilection for the right ventricle. A number of genetic studies have identified mutations in various components of the cardiac desmosome that have important roles in the pathogenesis of ARVC. Disruption of desmosomal function by defective proteins might lead to death of myocytes under mechanical stress. The myocardial injury may be accompanied by inflammation. Since regeneration of cardiac myocytes is limited, repair by fibrofatty replacement occurs. Several studies have implicated that desmosome dysfunction results in the delocalization and nuclear translocation of plakoglobin. As a result, competition between plakoglobin and beta-catenin will lead to the inhibition of Wnt/beta-catenin signaling, resulting in a shift from a myocyte fate towards an adipocyte fate of cells. The ryanodine receptor plays a crucial part in electromechanical coupling by control of release of calcium from the sarcoplasmic reticulum into the cytosol. Therefore, defects in this receptor could result in an imbalance of calcium homeostasis that might trigger cell death.
Category
Cardiovascular disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
11 Diseases of the circulatory system
Diseases of the myocardium or cardiac chambers
BC43 Cardiomyopathy
H00293 Arrhythmogenic right ventricular cardiomyopathy
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06528 Calcium signaling
H00293 Arrhythmogenic right ventricular cardiomyopathy
Cellular process
nt06539 Cytoskeleton in muscle cells
H00293 Arrhythmogenic right ventricular cardiomyopathy
Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F, Larderet G, Brahmbhatt B, Brown K, Bauce B, Muriago M, Basso C, Thiene G, Danieli GA, Rampazzo A
Title
Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2).
Merner ND, Hodgkinson KA, Haywood AF, Connors S, French VM, Drenckhahn JD, Kupprion C, Ramadanova K, Thierfelder L, McKenna W, Gallagher B, Morris-Larkin L, Bassett AS, Parfrey PS, Young TL
Title
Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene.
van Hengel J, Calore M, Bauce B, Dazzo E, Mazzotti E, De Bortoli M, Lorenzon A, Li Mura IE, Beffagna G, Rigato I, Vleeschouwers M, Tyberghein K, Hulpiau P, van Hamme E, Zaglia T, Corrado D, Basso C, Thiene G, Daliento L, Nava A, van Roy F, Rampazzo A
Title
Mutations in the area composita protein alphaT-catenin are associated with arrhythmogenic right ventricular cardiomyopathy.
Mayosi BM, Fish M, Shaboodien G, Mastantuono E, Kraus S, Wieland T, Kotta MC, Chin A, Laing N, Ntusi NB, Chong M, Horsfall C, Pimstone SN, Gentilini D, Parati G, Strom TM, Meitinger T, Pare G, Schwartz PJ, Crotti L
Title
Identification of Cadherin 2 (CDH2) Mutations in Arrhythmogenic Right Ventricular Cardiomyopathy.
Striate palmoplantar keratoderma (SPPK) is an autosomal dominant genodermatosis characterized by linear hyperkeratosis of volar aspects of the fingers and on the palm as well as by focal hyperkeratosis on the soles. SPPK is a heterogenous group of disorders caused by mutations in either desmoglein 1 (DSG1), desmoplakin (DSP), or keratin 1 (KRT1).
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
14 Diseases of the skin
Genetic and developmental disorders affecting the skin
EC20 Genetic disorders of keratinisation
H00717 Striate palmoplantar keratoderma
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H00717 Striate palmoplantar keratoderma
Inherited epidermolysis bullosa (EB) is a diverse group of disorders that encompass dozens of clinically and genotypically distinct diseases. It is characterized by mechanically fragile skin that readily blister. Most of the more severe subtypes are associated with clinically significant extracutaneous complications. Some subtypes may lead to death, even in early infancy. There are four major types of EB: EB simplex, junctional EB, dystrophic EB, and Kindler syndrome.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
14 Diseases of the skin
Genetic and developmental disorders affecting the skin
Genetically-determined epidermolysis bullosa
EC3Z Epidermolysis bullosa
H01737 Epidermolysis bullosa
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H01737 Epidermolysis bullosa
Bolling MC, Veenstra MJ, Jonkman MF, Diercks GF, Curry CJ, Fisher J, Pas HH, Bruckner AL
Title
Lethal acantholytic epidermolysis bullosa due to a novel homozygous deletion in DSP: expanding the phenotype and implications for desmoplakin function in skin and heart.
Carvajal syndrome is an autosomal recessive disorder, manifesting with dilated left ventricular cardiomyopathy, woolly hair, and palmoplantar keratoma. Carvajal syndrome is considered as a variant of Naxos disease. It is caused by homozygous mutation in the gene coding for desmoplakin. Recently, the autosomal dominant phenotype associated with leukonychia and oligodontia was reported (DCWHKTA).
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
11 Diseases of the circulatory system
Diseases of the myocardium or cardiac chambers
BC43 Cardiomyopathy
H02094 Carvajal syndrome
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H02094 Carvajal syndrome
Naxos disease and Carvajal syndrome: cardiocutaneous disorders that highlight the pathogenesis and broaden the spectrum of arrhythmogenic right ventricular cardiomyopathy.
