Aritmojenik Sağ Ventrikül Kardiyomiyopatisi ve Kutanöz Bulgular: DSP Geni İlişkili Fenotip
Özet
Bu bölüm, Desmoplakin (DSP) geni mutasyonu zemininde gelişen Aritmojenik Kardiyomiyopati (AK) ve eşlik eden kutanöz bulguları (kardiyokutanöz sendrom) detaylı bir klinik olgu üzerinden incelemektedir. Klasik sağ ventrikül tutulumunun ötesinde, DSP mutasyonlarında sol veya biventriküler etkilenimin çok daha erken ve baskın görülebileceği vurgulanmaktadır. Bölümde, halı sahada ani kardiyak ölüm ile kaybedilen genç bir hastanın aile taraması sonucunda; palmar keratoderma, elektrokardiyografik sol prekordiyal (V5-V6) T dalga negatifliği, sağ ventrikül diskinezisi ve miyokardiyal fibrozis (LGE) saptanan iki kardeşin tıbbi değerlendirmesi sunulmaktadır. 2024 Avrupa Görev Gücü (ETF) kriterleri ışığında teşhis edilen bu özgün fenotipin patofizyolojisi, genetik mimarisi ve klinik gidişatı belirleyen inflamatuar "hot phase" (miyokardit benzeri) atakları güncel literatür eşliğinde tartışılmaktadır. Ayrıca, ani kardiyak ölümün önlenmesinde spor kısıtlamasının, farmakoterapinin, primer koruma amaçlı İmplante Edilebilir Kardiyoverter Defibrilatör (ICD) kullanımının ve kaskad aile taramasının hayati önemi çizilmektedir.
This chapter examines Arrhythmogenic Cardiomyopathy (AC) and its associated cutaneous manifestations (cardiocutaneous syndrome) driven by Desmoplakin (DSP) gene mutations, presented through a detailed clinical case. Beyond classic right ventricular involvement, the text highlights that DSP mutations frequently present with early and dominant left or biventricular disease. It details the familial cascade screening of a young patient who suffered sudden cardiac death during sports, revealing palmar keratoderma, left precordial (V5-V6) T-wave inversions, right ventricular dyskinesia, and myocardial fibrosis (LGE) in his siblings. Evaluated according to the 2024 European Task Force (ETF) diagnostic criteria, the pathophysiology, genetic architecture, and "hot phase" (myocarditis-like) inflammatory episodes of this unique phenotype are discussed alongside current literature. Furthermore, the chapter underscores the critical importance of exercise restriction, pharmacotherapy, Implantable Cardioverter Defibrillators (ICD) for primary prevention, and genetic screening in preventing sudden cardiac death.
Referanslar
Corrado D, Link MS, Calkins H. Arrhythmogenic Right Ventricular Cardiomyopathy. N Engl J Med. 2017 Jan 5;376(1):61-72. doi: 10.1056/NEJMra1509267. PMID: 28052233.
Corrado D, Anastasakis A, Basso C, et al. Proposed diagnostic criteria for arrhythmogenic cardiomyopathy: European Task Force consensus report. Int J Cardiol. 2024 Jan 15;395:131447. doi: 10.1016/j.ijcard.2023.131447. Epub 2023 Oct 14. PMID: 37844667.
Patel V, Asatryan B, Siripanthong B, et al. State of the Art Review on Genetics and Precision Medicine in Arrhythmogenic Cardiomyopathy. Int J Mol Sci. 2020 Sep 10;21(18):6615. doi: 10.3390/ijms21186615. PMID: 32927679; PMCID: PMC7554944.
Protonotarios N, Tsatsopoulou A. Naxos disease and Carvajal syndrome: cardiocutaneous disorders that highlight the pathogenesis and broaden the spectrum of arrhythmogenic right ventricular cardiomyopathy. Cardiovasc Pathol. 2004 Jul-Aug;13(4):185-94. doi: 10.1016/j.carpath.2004.03.609. PMID: 15210133.
Norgett EE, Hatsell SJ, Carvajal-Huerta L, et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet. 2000 Nov 1;9(18):2761-6. doi: 10.1093/hmg/9.18.2761. PMID: 11063735.
Corrado D, Thiene G. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: clinical impact of molecular genetic studies. Circulation. 2006 Apr 4;113(13):1634-7. doi: 10.1161/CIRCULATIONAHA.105.616490. PMID: 16585401.
Hoorntje ET, Te Rijdt WP, James CA, et al. Arrhythmogenic cardiomyopathy: pathology, genetics, and concepts in pathogenesis. Cardiovasc Res. 2017 Oct 1;113(12):1521-1531. doi: 10.1093/cvr/cvx150. PMID: 28957532.
Smith ED, Lakdawala NK, Papoutsidakis N, et al. Desmoplakin Cardiomyopathy, a Fibrotic and Inflammatory Form of Cardiomyopathy Distinct From Typical Dilated or Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation. 2020 Jun 9;141(23):1872-1884. doi: 10.1161/CIRCULATIONAHA.119.044934. Epub 2020 May 6. PMID: 32372669; PMCID: PMC7286080.
Perazzolo Marra M, Cipriani A, Rizzo S, et al. Myocardial Tissue Characterization in Arrhythmogenic Cardiomyopathy: Comparison Between Endomyocardial Biopsy and Cardiac Magnetic Resonance. JACC Cardiovasc Imaging. 2021 Aug;14(8):1675-1678. doi: 10.1016/j.jcmg.2021.02.015. Epub 2021 Apr 14. PMID: 33865777.
Gasperetti A, James CA, Cerrone M, et al. Arrhythmogenic right ventricular cardiomyopathy and sports activity: from molecular pathways in diseased hearts to new insights into the athletic heart mimicry. Eur Heart J. 2021 Mar 31;42(13):1231-1243. doi: 10.1093/eurheartj/ehaa821. Erratum in: Eur Heart J. 2021 Mar 31;42(13):1272. doi: 10.1093/eurheartj/ehaa985. PMID: 33200174.
Cipriani A, Bauce B, De Lazzari M, et al. Arrhythmogenic Right Ventricular Cardiomyopathy: Characterization of Left Ventricular Phenotype and Differential Diagnosis With Dilated Cardiomyopathy. J Am Heart Assoc. 2020 Mar 3;9(5):e014628. doi: 10.1161/JAHA.119.014628. Epub 2020 Mar 2. PMID: 32114891; PMCID: PMC7335583.
Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur Heart J. 2010 Apr;31(7):806-14. doi: 10.1093/eurheartj/ehq025. Epub 2010 Feb 19. PMID: 20172912; PMCID: PMC2848326.
Corrado D, Perazzolo Marra M, Zorzi A, et al. Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria. Int J Cardiol. 2020 Nov 15;319:106-114. doi: 10.1016/j.ijcard.2020.06.005. Epub 2020 Jun 16. PMID: 32561223.
Towbin JA, McKenna WJ, Abrams DJ, et al. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm. 2019 Nov;16(11):e301-e372. doi: 10.1016/j.hrthm.2019.05.007. Epub 2019 May 9. PMID: 31078652.
