Challenges and Applications of Genetic Testing in Dilated Cardiomyopathy: Genotype, Phenotype and Clinical Implications

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorFURQUIM, Silas Ramos
dc.contributor.authorLINNENKAMP, Bianca
dc.contributor.authorSANGIORGI, Natalia Quintella
dc.contributor.authorGIUGNI, Fernando Rabioglio
dc.contributor.authorLIPARI, Layara Fernanda Vicente Pereira
dc.contributor.authorANDRADE, Fernanda Almeida
dc.contributor.authorKRIEGER, Jose Eduardo
dc.date.accessioned2024-02-15T14:40:13Z
dc.date.available2024-02-15T14:40:13Z
dc.date.issued2023
dc.description.abstractGenetic tests for dilated cardiomyopathy (DCM) have a diagnostic yield of up to 40%, but there is significant genetic heterogeneity and other challenges, such as variable expressivity and incomplete penetrance. Pedigree analysis is essential for distinguishing between sporadic and familial DCM cases by assessing family history. Familial DCM yields higher results in genetic testing, but sporadic DCM does not rule out the possibility of a genetic cause. Some genes have specific phenotypes, with the Lamin gene (LMNA) being associated with a phenotype of malignant arrhythmias and advanced heart failure (HF). The presence of a causal genetic variant can also aid in prognostic evaluation, identifying more severe cases with lower rates of reverse remodeling (RR) compared to individuals with a negative genotype. Current guidelines recommend genetic evaluation and counseling for individuals with DCM, along with cascade screening in first-degree relatives in cases where one or more variants are identified, offering an opportunity for early diagnosis and treatment. Relatives with a positive genotype and negative phenotype are candidates for serial evaluation, with frequency varying by age. Genotype also assists in individualized recommendations for implantable cardioverter-defibrillator (ICD) placement and advice regarding physical activity and family planning. Ongoing studies are progressively elucidating the details of genotype/ phenotype relationships for a large number of variants, making molecular genetics increasingly integrated into clinical practice.eng
dc.description.abstractOs testes genéticos para cardiomiopatia dilatada (CMD) apresentam uma positividade de até 40%, mas há uma grande heterogeneidade genética e outros desafios decorrentes de expressividade variável e penetrância incompleta. O heredograma é fundamental para diferenciar os casos de CMD esporádica e familiar, por meio da avaliação do histórico familiar. A CMD familiar apresenta um rendimento maior nos testes genéticos, mas a CMD esporádica não exclui a possibilidade de causa genética. Alguns genes têm fenótipos específicos, sendo o gene da Lamina ( LMNA ) o mais fortemente associado a um fenótipo de arritmias malignas e quadros de insuficiência cardíaca (IC) avançada. A presença de uma variante genética causal também pode ajudar na avaliação prognóstica, identificando quadros mais graves e com menores taxas de remodelamento reverso em comparação com indivíduos com genótipo negativo. As diretrizes atuais recomendam a avaliação e aconselhamento genético em indivíduos com CMD, além do rastreamento em cascata nos familiares de primeiro grau nos casos em que há uma ou mais variantes identificadas, sendo uma oportunidade para o diagnóstico e tratamento precoces. Familiares com genótipo positivo e fenótipo negativo são candidatos à avaliação seriada, com periodicidade que varia conforme a idade. O genótipo também auxilia na indicação individualizada de cardiodesfibrilador implantável e em recomendações quanto à atividade física e planejamento familiar. Estudos em curso esclarecem progressivamente os detalhes das relações genótipo/fenótipo de um grande número de variantes e fazem com que a genética molecular esteja cada vez mais presente na prática clínica.
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.identifier.citationARQUIVOS BRASILEIROS DE CARDIOLOGIA, v.120, n.10, article ID e20230174, 8p, 2023
dc.identifier.doi10.36660/abc.20230174
dc.identifier.eissn1678-4170
dc.identifier.issn0066-782X
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/57887
dc.language.isoeng
dc.publisherARQUIVOS BRASILEIROS CARDIOLOGIAeng
dc.relation.ispartofArquivos Brasileiros de Cardiologia
dc.rightsopenAccesseng
dc.rights.holderCopyright ARQUIVOS BRASILEIROS CARDIOLOGIAeng
dc.subjectCardiomyopathy, Dilatedeng
dc.subjectGeneticseng
dc.subjectGenetic Testingeng
dc.subjectCardiomiopatia Dilatada
dc.subjectGenética
dc.subjectTestes Genéticos
dc.subject.othercardiology working groupeng
dc.subject.otherposition statementeng
dc.subject.othereuropean-societyeng
dc.subject.otherassociationeng
dc.subject.otherguidelineseng
dc.subject.othermutationseng
dc.subject.otherdiagnosiseng
dc.subject.othervariantseng
dc.subject.wosCardiac & Cardiovascular Systemseng
dc.titleChallenges and Applications of Genetic Testing in Dilated Cardiomyopathy: Genotype, Phenotype and Clinical Implicationseng
dc.title.alternativeDesafios e Aplicações dos Testes Genéticos na Cardiomiopatia Dilatada: Genótipo, Fenótipo e Implicações Clínicas
dc.typearticleeng
dc.type.categoryrevieweng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.citation.scopus1
hcfmusp.contributor.author-fmusphcSILAS RAMOS FURQUIM
hcfmusp.contributor.author-fmusphcBIANCA DOMIT WERNER LINNENKAMP
hcfmusp.contributor.author-fmusphcNATALIA QUINTELLA SANGIORGI OLIVETTI
hcfmusp.contributor.author-fmusphcFERNANDO RABIOGLIO GIUGNI
hcfmusp.contributor.author-fmusphcLAYARA FERNANDA LIPARI DINARDI
hcfmusp.contributor.author-fmusphcFERNANDA ALMEIDA ANDRADE
hcfmusp.contributor.author-fmusphcJOSE EDUARDO KRIEGER
hcfmusp.description.articlenumbere20230174
hcfmusp.description.issue10
hcfmusp.description.volume120
hcfmusp.origemWOS
hcfmusp.origem.pubmed38055534
hcfmusp.origem.scopus2-s2.0-85178266197
hcfmusp.origem.wosWOS:001123851100001
hcfmusp.publisher.cityRIO DE JANEIROeng
hcfmusp.publisher.countryBRAZILeng
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hcfmusp.scopus.lastupdate2024-05-17
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