Sudden Death Associated With Danon Disease in Women
Sudden Death Associated With Danon Disease in Women
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DOI：
10.1016/j.amjcard.2011.09.024
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发表时间：
2012-02-01
影响因子：
2.8
通讯作者：
Proclemer, Alessandro
中科院分区：
文献类型：
--
作者：
Miani, Daniela;Taylor, Matthew;Proclemer, Alessandro
Danon病是一种X连锁的全身性疾病，其特征是影响年轻男性的左心室肥大、精神发育迟滞和骨骼肌病变。心电图通常显示沃尔夫帕金森白色预激模式。关于女性表型的报道较少，尽管有晚发型心脏症状的报道。本研究的目的是扩大知识的表型Danon病的妇女。我们临床随访并评价超声心动图，心脏磁共振成像（cMRI），和遗传检测受Danon病，其中2名男性和6名女性表现出严重的致瘤表型的家庭。受影响的家族成员在外显子3的294位进行核苷酸替换（c.294 G -> A），将溶酶体相关膜蛋白2（LAMP 2）基因中的色氨酸残基变为W 98 X位的终止密码子。4名妇女在37至54岁时突然死亡（1人流产）。6例中2例出现Wolff Parkinson白色征伴房室传导阻滞。其中四人成功怀孕，没有心力衰竭的症状。cMRI显示在临床上健康的女性谁是突变携带者迟钆增强区。两名患者接受心脏移植;组织学检查显示，移植心脏严重的间质纤维化，肥大的心肌细胞胞浆空泡，和肌原纤维紊乱。总之，LAMP 2突变可导致女性出现严重的致突变表型，包括猝死的高风险。cMRI可能对携带LAMP 2突变的女性有用，可以早期检测心脏受累，并指导及时考虑植入式心律转复除颤器治疗。由于疾病进展迅速，心脏移植应在出现心力衰竭症状时考虑。(C)2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109：406-411）
Danon disease is an X-linked systemic disorder characterized by left ventricular hypertrophy, mental retardation, and skeletal myopathy affecting young men. Electrocardiogram usually displays a Wolff Parkinson White preexcitation pattern. Less has been reported about the phenotype in women, although later-onset cardiac symptoms have been described. The aim of this study was to expand the knowledge of the phenotype of Danon disease in women. We clinically followed and evaluated with echocardiography, cardiac magnetic resonance imaging (cMRI), and genetic testing a family affected by Danon disease in which 2 men and 6 women showed a severe arrhythmogenic phenotype. Affected family members carried a nucleotide substitution at position 294 in exon 3 (c.294 G -> A) that changed a tryptophan residue to a stop codon at position W98X in the lysosome-associated membrane protein 2 (LAMP2) gene. Four women died suddenly (1 aborted) at 37 to 54 years of age. Wolff Parkinson White pattern with atrioventricular block was detected in 2 of 6 women. Four had successful pregnancies without symptoms of heart failure. cMRI showed late gadolinium enhancement areas in a clinically healthy woman who was a mutation carrier. Two patients underwent heart transplantation; histology of explanted hearts demonstrated severe interstitial fibrosis, hypertrophic cardiomyocytes with cytoplasmic vacuoles, and myofibrillar disarray. In conclusion, LAMP2 mutation can cause a severe arrhythmogenic phenotype in women that includes a high risk of sudden death. cMRI may be useful in women harboring LAMP2 mutations to permit early detection of cardiac involvement and guide timely considerations of implantable cardioverter defibrillator therapy. Heart transplantation should be considered at onset of heart failure symptoms owing to rapid progression of the disease. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:406-411)