Jervell和Lange-Nielsen综合征发病机制与治疗策略

Pathogenesis and Therapeutic Strategies of Jervell and Lange-Nielsen Syndrome

Jervell和Lange-Nielsen综合征(JLNS)是一种伴有耳聋的严重遗传性心律失常综合征。主要临床表现为先天性感觉神经性耳聋,以及包括QT间期延长和室性心律失常引起的晕厥甚至猝死等心脏症状。JLNS是一种隐性遗传疾病,它由位于KCNQ1或KCNE1的纯合突变或复合杂合突变引起,而这种突变会导致缓慢激活延迟整流钾通道IKs通道的功能大部分或完全失活,从而使心脏的复极过程时间延长,即QT间期的延长并引起相应的晕厥等心脏症状;同时,作为维持耳蜗螺旋器兴奋性的重要机制,IKs通道的失活也导致内淋巴液钾离子不足,从而引起感觉神经性耳聋。JLNS是一种预后较差的长QT综合征亚型,目前β受体阻滞剂是治疗JLNS的常规药物,但效果不佳,左心交感神经切除术以及植入式心律转复除颤器被证明能在一定程度上减少猝死率。

The Jervell and Lange-Nielsen syndrome （JLNS） is an autosomal recessive syndrome characterized by profound congenital bilateral sensorineural hearing loss, QT prolongation and syncope or sudden death induced by ventrieular arrhythmias. JLNS has been shown to occur due to homozygous or compound heterozygous mutations in KCNQ1 or KCNE1. The mutations could debase or obliterate the function- al Ix, channel which was encoded by KCNQ1 and KCNE1. As a result, the duration of repolarization prolonged and so the QT interval, which would induce various ventrieular arrhythmias and thusly syncopes or even sudden death ; on the other hand, the decline of Ixs, essential for the preservation of endolymph, would cause sensorineural deafness. JLNS is a major malignant variance of long QT syndrome with poor prog- nosis. B-blocker has been shown to provide limited protection against JLNS, while left cardiac sympathetic denervation and implantable card- ioverter defibrillator could reduce incidences of syncope and sudden death.