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.