Arrhythmogenic right ventricular dysplasia classification: Difference between revisions

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==Overview==
==Overview==
Variants of arrhythmogenic right ventricular dysplasia can be classified based upon the genetic abnormality involved. So far, 12 variants have been identified.
Variants of arrythmogenic right ventricular dysplasia can be classified based on the the genetic abnormality involved; So far, 12 variants have been identified. Another classification was based on the clinical manifestation which was first developed by Fontaine et al. and lead to the identification of 3 clinical forms (based on a 9-year observation of 4 patients with different clinical course of ARVC). Later on, another variant of the ARVC classification was proposed, in which the RV and left ventricular forms were distinguished and a total of eleven different clinical forms were identified. However, these classifications did not define prognosis and approaches to treatment and hence, none was widely used in clinical practice. So, The development of clinical classification is considered an important task and an ultimate challenge.
== Classification ==


The first classification was developed by Fontaine et al., based on a 9-year observation of 4 patients with different clinical course of ARVC. 3 clinical forms were identified. Three years later another variant of the ARVC classification was proposed, in which the RV and left ventricular forms were distinguished and a total of eleven different clinical forms were identified. None of these classifications was widely used in clinical practice, as they did not define prognosis and approaches to treatment. Thus, the development of clinical classification seems to us an important task and an ultimate challenge.
 
== Classification ==
 
Variants of arrhythmogenic right ventricular dysplasia can be classified based upon the genetic abnormality involved into 12 variants:
=== '''Genetic-Based classification''' ===
<br />
Arhythmogenic right ventricular dysplasia can be classified based upon the genetic abnormality involved into 12 variants:☂<ref>Basso C, Corrado D, Marcus FI et-al. Arrhythmogenic right ventricular cardiomyopathy. Lancet. 2009;373 (9671): 1289-300. {{doi|10.1016/S0140-6736%2809%2960256-7}} - [http://www.ncbi.nlm.nih.gov/pubmed/19362677 Pubmed citation]</ref><ref>Rampazzo A, Nava A, Erne P et-al. A new locus for arrhythmogenic right ventricular cardiomyopathy (ARVD2) maps to chromosome 1q42-q43. Hum. Mol. Genet. 1995;4 (11): 2151-4. Hum. Mol. Genet. (link) - Pubmed citation</ref><ref>Severini GM, Krajinovic M, Pinamonti B et-al. A new locus for arrhythmogenic right ventricular dysplasia on the long arm of chromosome 14. Genomics. 1996;31 (2): 193-200. [http://linkinghub.elsevier.com/retrieve/pii/S0888754396900312 Genomics (link)] - [http://www.ncbi.nlm.nih.gov/pubmed/8824801 Pubmed citation]</ref><ref>Rampazzo A, Nava A, Miorin M et-al. ARVD4, a new locus for arrhythmogenic right ventricular cardiomyopathy, maps to chromosome 2 long arm. Genomics. 1997;45 (2): 259-63. {{doi|10.1006/geno.1997.4927}} - [http://www.ncbi.nlm.nih.gov/pubmed/9344647 Pubmed citation]</ref><ref>Ahmad F, Li D, Karibe A et-al. Localization of a gene responsible for arrhythmogenic right ventricular dysplasia to chromosome 3p23. Circulation. 98 (25): 2791-5. [http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=9860777 Circulation (link)] - [http://www.ncbi.nlm.nih.gov/pubmed/9860777 Pubmed citation]</ref><ref>Li D, Ahmad F, Gardner MJ et-al. The locus of a novel gene responsible for arrhythmogenic right-ventricular dysplasia characterized by early onset and high penetrance maps to chromosome 10p12-p14. Am. J. Hum. Genet. 2000;66 (1): 148-56. {{doi|10.1086/302713}} - [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288320 Free text at pubmed] - [http://www.ncbi.nlm.nih.gov/pubmed/10631146 Pubmed citation]</ref><ref>Kuhl A, Melberg A, Meinl E et-al. Myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7: corroboration and narrowing of the critical region on 10q22.3. Eur. J. Hum. Genet. 2008;16 (3): 367-73. {{doi|10.1038/sj.ejhg.5201980}} - [http://www.ncbi.nlm.nih.gov/pubmed/18197198 Pubmed citation]</ref><ref>Rampazzo A, Nava A, Malacrida S et-al. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am. J. Hum. Genet. 2002;71 (5): 1200-6. {{doi|10.1086/344208}} - [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC385098 Free text at pubmed] - [http://www.ncbi.nlm.nih.gov/pubmed/12373648 Pubmed citation]</ref><ref>Grossmann KS, Grund C, Huelsken J et-al. Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation. J. Cell Biol. 2004;167 (1): 149-60. {{doi|10.1083/jcb.200402096}} - [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172504 Free text at pubmed] - [http://www.ncbi.nlm.nih.gov/pubmed/15479741 Pubmed citation]</ref><ref>Pilichou K, Nava A, Basso C et-al. Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy. Circulation. 2006;113 (9): 1171-9. {{doi|10.1161/CIRCULATIONAHA.105.583674}} - [http://www.ncbi.nlm.nih.gov/pubmed/16505173 Pubmed citation]</ref><ref>Syrris P, Ward D, Evans A et-al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am. J. Hum. Genet. 2006;79 (5): 978-84. {{doi|10.1086/509122}} - [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1698574 Free text at pubmed] - [http://www.ncbi.nlm.nih.gov/pubmed/17033975 Pubmed citation]</ref><ref>Asimaki A, Syrris P, Wichter T et-al. A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy. Am. J. Hum. Genet. 2007;81 (5): 964-73. {{doi|10.1086/521633}} - [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265660 Free text at pubmed] - [http://www.ncbi.nlm.nih.gov/pubmed/17924338 Pubmed citation]</ref><br />
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
! style="background: #4479BA; padding: 5px 5px;" rowspan=1 | {{fontcolor|#FFFFFF|Variant}}
! style="background: #4479BA; padding: 5px 5px;" rowspan=1 | {{fontcolor|#FFFFFF|Variant}}
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|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="1;"|[[ARVD10]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="1;"|[[ARVD10]]
| style="padding: 5px 5px; background: #F5F5F5;" |Associated with a mutation in the [[DSG2]] gene  on chromosome 18q12.1-q12
| style="padding: 5px 5px; background: #F5F5F5;" |Associated with a mutation in the [[DSG2]] gene  on chromosome 18q12.1-q12 [http://omim.org/entry/610193 610193], [http://omim.org/entry/125671 125671]
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="1;"|[[ARVD11]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="1;"|[[ARVD11]]
| style="padding: 5px 5px; background: #F5F5F5;" |Associated with a mutation in the [[DSC2]] gene on chromosome 18q12.1
| style="padding: 5px 5px; background: #F5F5F5;" |Associated with a mutation in the [[DSC2]] gene on chromosome 18q12.1 [http://omim.org/entry/610476 610476], [http://omim.org/entry/125645 125645]
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="1;"|[[ARVD12]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="1;"|[[ARVD12]]
| style="padding: 5px 5px; background: #F5F5F5;" |Associated with a mutation in the [[JUP]] gene  on chromosome 17q21
| style="padding: 5px 5px; background: #F5F5F5;" |Associated with a mutation in the [[JUP]] gene  on chromosome 17q21 [http://omim.org/entry/611528 611528], [http://omim.org/entry/173325 173325]
|-
|-
|}
|}
Clinical classification:<ref name="pmid7487328">{{cite journal| author=Fontaine G, Brestescher C, Fontaliran F, Himbert C, Tonet J, Frank R| title=[Outcome of arrhythmogenic right ventricular dysplasia. Apropos of 4 cases]. | journal=Arch Mal Coeur Vaiss | year= 1995 | volume= 88 | issue= 7 | pages= 973-9 | pmid=7487328 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7487328  }}</ref><ref name="pmid9593556">{{cite journal| author=Fontaine G, Fontaliran F, Frank R| title=Arrhythmogenic right ventricular cardiomyopathies: clinical forms and main differential diagnoses. | journal=Circulation | year= 1998 | volume= 97 | issue= 16 | pages= 1532-5 | pmid=9593556 | doi=10.1161/01.cir.97.16.1532 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9593556  }}</ref><ref name="pmid28874384">{{cite journal| author=Gilotra NA, Bhonsale A, James CA, Te Riele ASJ, Murray B, Tichnell C | display-authors=etal| title=Heart Failure Is Common and Under-Recognized in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia. | journal=Circ Heart Fail | year= 2017 | volume= 10 | issue= 9 | pages=  | pmid=28874384 | doi=10.1161/CIRCHEARTFAILURE.116.003819 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28874384  }}</ref><ref name="pmid10506390">{{cite journal| author=Norman MW, McKenna WJ| title=Arrhythmogenic right ventricular cardiomyopathy: perspectives on disease. | journal=Z Kardiol | year= 1999 | volume= 88 | issue= 8 | pages= 550-4 | pmid=10506390 | doi=10.1007/s003920050324 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10506390  }}</ref>


Based on the clinical manifistations and course of the disease, four clinical forms of ARVC have been identified
 
 
=== '''Clinical-based Classification''' ===
Another classification is based on the clinical manifestations and course of the disease, six clinical forms of ARVC have been identified:<ref name="pmid7487328">{{cite journal| author=Fontaine G, Brestescher C, Fontaliran F, Himbert C, Tonet J, Frank R| title=[Outcome of arrhythmogenic right ventricular dysplasia. Apropos of 4 cases]. | journal=Arch Mal Coeur Vaiss | year= 1995 | volume= 88 | issue= 7 | pages= 973-9 | pmid=7487328 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7487328  }}</ref><ref name="pmid9593556">{{cite journal| author=Fontaine G, Fontaliran F, Frank R| title=Arrhythmogenic right ventricular cardiomyopathies: clinical forms and main differential diagnoses. | journal=Circulation | year= 1998 | volume= 97 | issue= 16 | pages= 1532-5 | pmid=9593556 | doi=10.1161/01.cir.97.16.1532 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9593556  }}</ref><ref name="pmid28874384">{{cite journal| author=Gilotra NA, Bhonsale A, James CA, Te Riele ASJ, Murray B, Tichnell C | display-authors=etal| title=Heart Failure Is Common and Under-Recognized in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia. | journal=Circ Heart Fail | year= 2017 | volume= 10 | issue= 9 | pages=  | pmid=28874384 | doi=10.1161/CIRCHEARTFAILURE.116.003819 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28874384  }}</ref><ref name="pmid10506390">{{cite journal| author=Norman MW, McKenna WJ| title=Arrhythmogenic right ventricular cardiomyopathy: perspectives on disease. | journal=Z Kardiol | year= 1999 | volume= 88 | issue= 8 | pages= 550-4 | pmid=10506390 | doi=10.1007/s003920050324 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10506390  }}</ref>


{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
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| rowspan="1;" style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" |Nonarrhythmic form of ARVC
| rowspan="1;" style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" |Nonarrhythmic form of ARVC
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*
*Asymptomatic ARVC
|-
|
|}<br />
|}


===[[ARVD1]]===
This variant is due to a heterozygous mutation in the [[TGFB3]] gene ([http://omim.org/entry/190230 190230]) on chromosome 14q24.


===[[ARVD2]]===
<br />
This variant ([http://omim.org/entry/600996 600996]) is associated with a mutation in the [[RYR2 gene]] ([http://omim.org/entry/180902 180902]) on chromosome 1q42-q43.
 
===[[ARVD3]]===
This variant ([http://omim.org/entry/602086 602086]) is associated with a mutation in the chromosome 14q12-q22 region.
 
===[[ARVD4]]===
This variant ([http://omim.org/entry/602087 602087]) is associated with a mutation in the chromosome 2q32.1-q32.3 region.
 
===[[ARVD5]]===
This variant ([http://omim.org/entry/604400 604400]) is associated with a mutation in the TMEM43 gene ([http://omim.org/entry/612048 612048]) on chromosome 3p23 region.
 
===[[ARVD6]]===
This variant ([http://omim.org/entry/604401 604401]), is associated with a mutation in the chromosome 10p14-p12 region.
 
===[[ARVD7]]===
This variant [http://omim.org/entry/609160 609160]) is associated with a mutation in the chromosome 10q22.3 region.
 
===[[ARVD8]]===
This variant [http://omim.org/entry/607450 607450]) is associated with a mutation in the DSP gene ([http://omim.org/entry/125647 125647]) on chromosome 6p24.
 
===[[ARVD9]]===
This variant ([http://omim.org/entry/609040 609040]) is associated with a mutation in the [[PKP2]] gene ([http://omim.org/entry/602861 602861]) on chromosome 12p11.
 
===[[ARVD10]]===
This variant [http://omim.org/entry/610193 (610193]) is associated with a mutation in the [[DSG2]] gene  ([http://omim.org/entry/125671 125671]) on chromosome 18q12.1-q12.
 
===[[ARVD11]]===
This variant ([http://omim.org/entry/610476 610476]) is associated with a mutation in the [[DSC2]] gene ([http://omim.org/entry/125645 125645]) on chromosome 18q12.1.
 
===[[ARVD12]]===
This variant ([http://omim.org/entry/611528 611528]) is associated with a mutation in the [[JUP]] gene ([http://omim.org/entry/173325 173325]) on chromosome 17q21.


==References==
==References==

Latest revision as of 20:36, 15 May 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Variants of arrythmogenic right ventricular dysplasia can be classified based on the the genetic abnormality involved; So far, 12 variants have been identified. Another classification was based on the clinical manifestation which was first developed by Fontaine et al. and lead to the identification of 3 clinical forms (based on a 9-year observation of 4 patients with different clinical course of ARVC). Later on, another variant of the ARVC classification was proposed, in which the RV and left ventricular forms were distinguished and a total of eleven different clinical forms were identified. However, these classifications did not define prognosis and approaches to treatment and hence, none was widely used in clinical practice. So, The development of clinical classification is considered an important task and an ultimate challenge.

Classification

Genetic-Based classification

Arhythmogenic right ventricular dysplasia can be classified based upon the genetic abnormality involved into 12 variants:☂[1][2][3][4][5][6][7][8][9][10][11][12]

Variant Associated mutation
ARVD1 This variant is due to a heterozygous mutation in the TGFB3 gene on chromosome 14q24 190230
ARVD2 Associated with a mutation in the RYR2 gene on chromosome 1q42-q43 180902
ARVD3 Associated with a mutation in the chromosome 14q12-q22 region 602086
ARVD4 Associated with a mutation in the chromosome 2q32.1-q32.3 region 602087
ARVD5 Associated with a mutation in the TMEM43 gene on chromosome 3p23 region 604400
ARVD6 Associated with a mutation in the chromosome 10p14-p12 region 604401
ARVD7 Associated with a mutation in the chromosome 10q22.3 region 609160
ARVD8 Associated with a mutation in the DSP gene on chromosome 6p24 607450, 125647
ARVD9 Associated with a mutation in the PKP2 gene on chromosome 12p11 609040, 125647
ARVD10 Associated with a mutation in the DSG2 gene on chromosome 18q12.1-q12 610193, 125671
ARVD11 Associated with a mutation in the DSC2 gene on chromosome 18q12.1 610476, 125645
ARVD12 Associated with a mutation in the JUP gene on chromosome 17q21 611528, 173325


Clinical-based Classification

Another classification is based on the clinical manifestations and course of the disease, six clinical forms of ARVC have been identified:[13][14][15][16]

Type Characterestics
Sudden arrhythmic death
  • Presents as the only clinical manifestation
Latent arrhythmic form
  • Frequent PVCs and/or nonsustained VT in the absence of sustained VT and syncope
  • Isolated RV PVCs;
  • RV PVCs with episodes of nonsustained VT
The manifested arrhythmic form
  • Sustained VT/ventricular fibrillation (VF)
ARVC with a progressive CHF
  • The main manifestation of the disease is CHF:
  • Predominantly right heart failure
  • Biventricular heart failure
ARVC in combination with LVNC
  • Arrhythmic form without CHF
  • Biventricular heart failure
Nonarrhythmic form of ARVC
  • Asymptomatic ARVC



References

  1. ↑ Basso C, Corrado D, Marcus FI et-al. Arrhythmogenic right ventricular cardiomyopathy. Lancet. 2009;373 (9671): 1289-300. doi:10.1016/S0140-6736%2809%2960256-7 - Pubmed citation
  2. ↑ Rampazzo A, Nava A, Erne P et-al. A new locus for arrhythmogenic right ventricular cardiomyopathy (ARVD2) maps to chromosome 1q42-q43. Hum. Mol. Genet. 1995;4 (11): 2151-4. Hum. Mol. Genet. (link) - Pubmed citation
  3. ↑ Severini GM, Krajinovic M, Pinamonti B et-al. A new locus for arrhythmogenic right ventricular dysplasia on the long arm of chromosome 14. Genomics. 1996;31 (2): 193-200. Genomics (link) - Pubmed citation
  4. ↑ Rampazzo A, Nava A, Miorin M et-al. ARVD4, a new locus for arrhythmogenic right ventricular cardiomyopathy, maps to chromosome 2 long arm. Genomics. 1997;45 (2): 259-63. doi:10.1006/geno.1997.4927 - Pubmed citation
  5. ↑ Ahmad F, Li D, Karibe A et-al. Localization of a gene responsible for arrhythmogenic right ventricular dysplasia to chromosome 3p23. Circulation. 98 (25): 2791-5. Circulation (link) - Pubmed citation
  6. ↑ Li D, Ahmad F, Gardner MJ et-al. The locus of a novel gene responsible for arrhythmogenic right-ventricular dysplasia characterized by early onset and high penetrance maps to chromosome 10p12-p14. Am. J. Hum. Genet. 2000;66 (1): 148-56. doi:10.1086/302713 - Free text at pubmed - Pubmed citation
  7. ↑ Kuhl A, Melberg A, Meinl E et-al. Myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7: corroboration and narrowing of the critical region on 10q22.3. Eur. J. Hum. Genet. 2008;16 (3): 367-73. doi:10.1038/sj.ejhg.5201980 - Pubmed citation
  8. ↑ Rampazzo A, Nava A, Malacrida S et-al. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am. J. Hum. Genet. 2002;71 (5): 1200-6. doi:10.1086/344208 - Free text at pubmed - Pubmed citation
  9. ↑ Grossmann KS, Grund C, Huelsken J et-al. Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation. J. Cell Biol. 2004;167 (1): 149-60. doi:10.1083/jcb.200402096 - Free text at pubmed - Pubmed citation
  10. ↑ Pilichou K, Nava A, Basso C et-al. Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy. Circulation. 2006;113 (9): 1171-9. doi:10.1161/CIRCULATIONAHA.105.583674 - Pubmed citation
  11. ↑ Syrris P, Ward D, Evans A et-al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am. J. Hum. Genet. 2006;79 (5): 978-84. doi:10.1086/509122 - Free text at pubmed - Pubmed citation
  12. ↑ Asimaki A, Syrris P, Wichter T et-al. A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy. Am. J. Hum. Genet. 2007;81 (5): 964-73. doi:10.1086/521633 - Free text at pubmed - Pubmed citation
  13. ↑ Fontaine G, Brestescher C, Fontaliran F, Himbert C, Tonet J, Frank R (1995). "[Outcome of arrhythmogenic right ventricular dysplasia. Apropos of 4 cases]". Arch Mal Coeur Vaiss. 88 (7): 973–9. PMID 7487328.
  14. ↑ Fontaine G, Fontaliran F, Frank R (1998). "Arrhythmogenic right ventricular cardiomyopathies: clinical forms and main differential diagnoses". Circulation. 97 (16): 1532–5. doi:10.1161/01.cir.97.16.1532. PMID 9593556.
  15. ↑ Gilotra NA, Bhonsale A, James CA, Te Riele ASJ, Murray B, Tichnell C; et al. (2017). "Heart Failure Is Common and Under-Recognized in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia". Circ Heart Fail. 10 (9). doi:10.1161/CIRCHEARTFAILURE.116.003819. PMID 28874384.
  16. ↑ Norman MW, McKenna WJ (1999). "Arrhythmogenic right ventricular cardiomyopathy: perspectives on disease". Z Kardiol. 88 (8): 550–4. doi:10.1007/s003920050324. PMID 10506390.
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