PDF(Pubmed)
Abstract：
Andersen-Tawil syndrome (ATS) is a rare autosomal dominant disorder characterized by a classic symptom triad: periodic paralysis, ventricular arrhythmias associated with prolonged QT interval, and dysmorphic skeletal and facial features. Pathogenic variants of the inwardly rectifying potassium channel subfamily J member 2 (KCNJ2) gene have been linked to the ATS. Herein, we report a novel KCNJ2 causative variant in a proband and her father showing different ATS-associated symptoms. A 15-year-old girl was referred because of episodic weakness and periodic paralysis in both legs for 2-3 months. The symptoms occurred either when she was tired or after strenuous exercise. These attacks made walking or climbing stairs difficult and lasted from one to several days. She had a short stature (142 cm, <3rd percentile) and weighed 40 kg. The proband also showed orbital hypertelorism, dental crowding, mandibular hypoplasia, fifth-digit clinodactyly, and small hands. Scoliosis in the thoracolumbar region was detected by chest X-ray. Since she was 7 years old, she had been treated for arrhythmia-associated long QT interval and underwent periodic echocardiography. Brain MRI revealed cerebrovascular abnormalities indicating absence or hypoplasia of bilateral internal carotid arteries, and compensation of other collateral vessels was observed. There were no specific findings related to intellectual development. The proband\'s father also had a history of periodic paralysis similar to the proband. He did not show any cardiac symptoms. Interestingly, he was diagnosed with hyperthyroidism during an evaluation for paralytic symptoms. Clinical exome sequencing revealed a novel heterozygous missense variant: Chr17(GRCh37):g.68171593A>T, NM_000891.2:c.413A>T, p.(Glu138Val) in KCNJ2 in the proband and the proband\'s father.
摘要：
Andersen-Tawil综合征（ATS）是一种罕见的常染色体显性疾病，其特征是典型的症状三联症：周期性瘫痪，与QT间期延长相关的室性心律失常，和畸形骨骼和面部特征。向内整流钾通道亚家族J成员2（KCNJ2）基因的致病变体已与ATS相关。在这里，我们报道了一个先证者和她父亲的一个新的KCNJ2致病变异,显示出不同的ATS相关症状.一名15岁女孩因间歇性无力和双腿周期性瘫痪2-3个月而被转诊。症状发生在她疲倦或剧烈运动后。这些袭击使步行或爬楼梯变得困难，并持续了一天到几天。她身材矮小（142厘米，<第3百分位数），体重为40公斤。先证者还显示了轨道远距，牙齿拥挤，下颌骨发育不全,五位数斜交，和小手。胸部X线检查发现胸腰段脊柱侧凸。从她7岁开始，她接受过心律失常相关的长QT间期治疗,并接受了定期超声心动图检查.头颅MRI提示脑血管异常，提示双侧颈内动脉缺失或发育不全，并观察到其他侧支血管的补偿。没有与智力发展相关的具体发现。先证者的父亲也有类似于先证者的周期性瘫痪史。他没有表现出任何心脏症状。有趣的是,他在评估麻痹症状时被诊断为甲状腺功能亢进。临床外显子组测序揭示了一种新的杂合错义变异:Chr17(GRCh37):g.68171593A>T,NM_000891.2:c.43A>T,p.(Glu138Val)在KCNJ2中在先证者和先证者的父亲。
