A 66-year-old man presented with episodic limb weakness beginning at 2 years of age, sometimes in both lower extremities and sometimes in both the upper and lower limbs. Prolonged walking was often the predisposing factor, with seizure frequency occurring once or twice a month. With age, he appeared to have permanent muscle weakness, manifested by difficulty in running, squatting, standing up, and lifting the upper limbs. During this period, he visited many hospitals to check his creatine kinase (CK) levels, which ranged from approximately 600-1,000 U/L. Muscle biopsies of his calf, shoulder, and back were performed at the ages of 13, 20, and 26 at two hospitals. The examination results showed no abnormalities, leading to a suspicion of muscular dystrophy as a possible cause. He underwent genetic testing at the age of 26, but the diagnosis was still inconclusive. Twenty-five years ago, an electrophysiologic concentric needle examination of the iliopsoas muscle, the gluteus maximus, and the lumbar paraspinal muscles indicated the presence of myopathy in the patient. There was a suspicion of limb-type muscle malnutrition, but treatment with coenzyme Q10 was found to be ineffective. It is worth noting that he had all his teeth extracted due to difficulties during intubation during vocal cord polyp surgery and was found quadriplegic after general anesthesia 10 years ago. The doctor conducted a cervical spine magnetic resonance imaging (MRI) on the patient, but the results showed no abnormalities. The patient complained of limb weakness, which progressively worsened in the morning before admission. He fell to the ground, could not stand up, and was brought to the emergency department of our hospital. Physical examination of the patient's proximal part of the extremities presented amyotrophy (Medical Research Council Grade 4) and decreased tendon reflexes, and negative bilateral pathological signs. The electrocardiogram of our patient showed a U-wave inversion (Figure 1), and the 24-h dynamic electrocardiogram showed 245 premature ventricular contractions (PVCs) in a total of 91,847 heartbeats. The EMG examination revealed narrow and irregular waves during the needle examination, with no pronouncement of the fibrillation. A long-term exercise test indicated a significant decrease in the compound muscle action potential (CMAP) amplitude of the right little finger abductor muscle, measuring 74.4% lower than the baseline and a 66% reduction in the area (Figure 2).
The blood test results showed a potassium level of 2.9 mmol/L (normal value: 3.5-5.5 mmol/L). Additionally, the CK (creatine kinase) level was measured at 1,600 U/L, lactic acid level at 2.8, and lactate dehydrogenase (LDH) at 224 U/L. We considered the possibility of ATS given the patient's characteristic physical features, including short stature, small hands and feet, clinodactyly of the fifth toe, hypoplastic mandible, and low-set ears (Figure 3). An electrocardiogram revealed slightly inverted U waves. Further genetic analysis using the sequencing system (Amplicon Gene, Inc.) identified a heterozygous c.220A > G mutation in the exon 2 region of chromosome 17 of the KCNJ2 gene. This mutation resulted in the substitution of alanine with threonine at amino acid 74 (p.T74A) (Figure 1), which was reported to be a pathogenic mutation for ATS. Our patient had special physical characteristics. Based on the positive results of the long-term exercise test, muscle symptoms, and the genetic testing outcome, it was determined that he was not affected by the myopathic condition but rather ATS.