Clinical profile of four families with arrhythmogenic right ventricular cardiomyopathy caused by dominant desmoplakin mutations
Clinical profile of four families with arrhythmogenic right ventricular cardiomyopathy caused by dominant desmoplakin mutations
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DOI：
10.1093/eurheartj/ehi341
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发表时间：
2005-08-01
影响因子：
39.3
通讯作者：
Nava, A
中科院分区：
文献类型：
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作者：
Bauce, B;Basso, C;Nava, A
目的描述常染色体显性遗传性致瘤性右心室心肌病（ARVC）家族患者的临床特征，ARVC家族患者是由于编码细胞间粘附蛋白桥连蛋白（DSP）的基因突变所致。（3例错义，1例位于内含子-外显子剪接区）进行了临床和遗传学研究，包括每年12导联ECG、信号平均ECG、24 h Hotter ECG和二维超声心动图。26名家庭成员（11名配偶和15名女性）被发现携带DSP突变。随访1-24年后，中位6例，14例（54%）符合（诊断时平均年龄33 ± 15岁），12例（末次随访时平均年龄43 ± 24岁）不符合ARVC的既定诊断标准，尽管其中5例有一些心脏异常。临床表现为心悸6例，猝死（SD）3例，晕厥1例，胸痛伴心肌酶升高2例。15例（58%）出现异常12导联ECG结果，12例（46%）出现室性心律失常，11例（42%）出现晚电位。14例（54%）超声心动图异常，其中7例左心室受累。6例受试者发生SD，3例为疾病的首发症状;此外，1例受试者死于心力衰竭。结论DSP突变引起的ARVC家族性疾病以SD为首发症状的发生率较高，且以SD为主要临床表现。左心室受累并不罕见，应用目前可用的标准经常逃避临床诊断。基因筛查是强制性的早期识别无症状携带者和预防策略在一个家庭与基因分型索引案件。
Aims To characterize the clinical profile of patients belonging to families affected with autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) due to mutations of the gene encoding for the cell-to-cell adhesion protein desmoptakin (DSP).Methods and results Thirty-eight subjects belonging to four families showing different DSP mutations (three missense and one in the intron-exon splicing region) underwent clinical and genetic investigation, including annual 12-lead ECG, signal averaged ECG, 24 h Hotter ECG, and two-dimensional echocardiography. Twenty-six family members (11 mates and 15 females) were found to carry a DSP mutation. After a follow-up of 1-24 years, median 6, 14 (54%) fulfilled (mean age at diagnosis 33 +/- 15 years) and 12 (mean age 43 +/- 24 years at the last follow-up) did not fulfil the established diagnostic criteria of ARVC, although five of them had some cardiac abnormalities. Clinical presentations were palpitations in six, sudden death (SD) in three, syncope in one, and chest pain with increased myocardial enzymes in two. Abnormal 12-lead ECG findings were present in 15 cases (58%), ventricular arrhythmias in 12 (46%), and late potentials in 11 (42%). Fourteen (54%) had abnormal echocardiographic findings, with left ventricular involvement in seven of them. SD occurred in six subjects and in three it was the first symptom of the disease; moreover, one subject died due to heart failure. The annual disease-related death and SD/aborted SD were 0.028 and 0.023 patient/year, respectively.Conclusion Familial ARVC caused by DSP mutations is characterized by a high occurrence of SD even as first clinical manifestation. Left ventricular involvement is not a rare feature of the disease, which frequently escapes clinical diagnosis by applying the currently available criteria. Genetic screening is mandatory for early identification of asymptomatic carriers and preventive strategies within a family with a genotyped index case.