Aims Filamin-A (FLNA) was identified as the first gene of non-syndromic mitral valve dystrophy (FLNA-MVD). We aimed to assess the phenotype of FLNA-MVD and its impact on prognosis. Methods and results We investigated the disease in 246 subjects (72 mutated) from four FLNA-MVD families harbouring three different FLNA mutations. Phenotype was characterized by a comprehensive echocardiography focusing on mitral valve apparatus in comparison with control relatives. In this X-linked disease valves lesions were severe in men and moderate in women. Most men had classical features of mitral valve prolapse (MVP), but without chordal rupture. By contrast to regular MVP, mitral leaflet motion was clearly restricted in diastole and papillary muscles position was closer to mitral annulus. Valvular abnormalities were similar in the four families, in adults and young patients from early childhood suggestive of a developmental disease. In addition, mitral valve lesions worsened over time as encountered in degenerative conditions. Polyvalvular involvement was frequent in males and non-diagnostic forms frequent in females. Overall survival was moderately impaired in men (P = 0.011). Cardiac surgery rate (mainly valvular) was increased (33.3 ± 9.8 vs. 5.0 ± 4.9%, P < 0.0001; hazard ratio 10.5 [95% confidence interval: 2.9-37.9]) owing mainly to a lifetime increased risk in men (76.8 ± 14.1 vs. 9.1 ± 8.7%, P < 0.0001). Conclusion FLNA-MVD is a developmental and degenerative disease with complex phenotypic expression which can influence patient management. FLNA-MVD has unique features with both MVP and paradoxical restricted motion in diastole, sub-valvular mitral apparatus impairment and polyvalvular lesions in males. FLNA-MVD conveys a substantial lifetime risk of valve surgery in men.

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关于二尖瓣营养不良的新见解：Filamin-A 基因型-表型和结果研究

目的 Filamin-A (FLNA) 被确定为非综合征性二尖瓣营养不良 (FLNA-MVD) 的第一个基因。我们的目的是评估 FLNA-MVD 的表型及其对预后的影响。方法和结果 我们对来自四个 FLNA-MVD 家族（携带三种不同 FLNA 突变）的 246 名受试者（72 名突变）进行了该疾病调查。与对照亲属相比，通过以二尖瓣装置为重点的综合超声心动图来表征表型。在这种 X 连锁疾病中，男性的瓣膜病变为严重，女性为中度。大多数男性具有二尖瓣脱垂（MVP）的典型特征，但没有腱索断裂。与常规 MVP 相比，二尖瓣叶运动在舒张期明显受到限制，并且乳头肌位置更接近二尖瓣环。四个家庭的成人和幼儿患者的瓣膜异常相似，提示存在发育性疾病。此外，二尖瓣病变随着时间的推移而恶化，如在退行性疾病中遇到的那样。多瓣膜受累在男性中常见，而非诊断性形式在女性中常见。男性的总生存率中度受损（P = 0.011）。心脏手术率（主要是瓣膜手术）增加（33.3 ± 9.8 vs. 5.0 ± 4.9%，P < 0.0001；风险比 10.5 [95% 置信区间：2.9-37.9]），主要是由于男性终生风险增加（76.8 ± 14.1 对比 9.1 ± 8.7%，P < 0.0001）。结论 FLNA-MVD 是一种发育退行性疾病，具有复杂的表型表达，可影响患者的治疗。FLNA-MVD 具有独特的特征，包括 MVP 和舒张期反常运动受限、瓣膜下二尖瓣装置损伤和男性多瓣膜病变。FLNA-MVD 表明男性一生中存在瓣膜手术的巨大风险。