Kurahashi Hirokazu, Azuma Yoshiteru, Takeuchi Tomoya, Shimada Mayuko, Numoto Shingo, Nishida Mizuki, Ito Yoshinori, Ogi Tomoo, Okumura Akihisa
Department of Pediatrics, Aichi Medical University, Nagakute, Japan.
Department of Pediatrics, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan.
Am J Med Genet A. 2025 Aug;197(8):e64079. doi: 10.1002/ajmg.a.64079. Epub 2025 Apr 1.
Paroxysmal kinesigenic dyskinesia is a rare movement disorder that typically has a genetic basis, with PRRT2 being the primary causative gene. However, TMEM151A mutations have recently emerged as causative factors. Here, we report the cases of two Japanese siblings diagnosed with paroxysmal kinesigenic dyskinesia caused by a novel heterozygous TMEM151A frameshift variant (c.760_761insT). Case 1 was a 17-year-old male who had experienced involuntary movements triggered by sudden actions since the age of 12 years. Carbamazepine alleviated the symptoms but caused side effects, leading to a switch to lacosamide, which was effective. Case 2 was a 14-year-old female who experienced subtle discomfort at the onset of physical activity. Genetic analysis confirmed the presence of the same TMEM151A variant in both siblings. Lacosamide effectively managed the patients' symptoms. TMEM151A-positive paroxysmal kinesigenic dyskinesia differs phenotypically from PRRT2-positive paroxysmal kinesigenic dyskinesia, presenting later onset and shorter-duration dystonia. Case 1 presented with dystonia with a relatively long duration of 15 s. We also found differences in involuntary movements among siblings. This report emphasizes the clinical and genetic diversity of paroxysmal kinesigenic dyskinesia, which may lead to challenges in diagnosing sporadic cases, and finally, reports on the efficacy of lacosamide as a treatment.
发作性运动诱发性运动障碍是一种罕见的运动障碍，通常具有遗传基础，PRRT2是主要致病基因。然而，TMEM151A突变最近已成为致病因素。在此，我们报告了两名日本同胞被诊断为由一种新型杂合TMEM151A移码变异（c.760_761insT）引起的发作性运动诱发性运动障碍的病例。病例1是一名17岁男性，自12岁起就经历了由突然动作触发的不自主运动。卡马西平缓解了症状，但引起了副作用，因此改用拉科酰胺，效果良好。病例2是一名14岁女性，在开始体育活动时会感到轻微不适。基因分析证实两名同胞均存在相同的TMEM151A变异。拉科酰胺有效控制了患者的症状。TMEM151A阳性的发作性运动诱发性运动障碍在表型上与PRRT2阳性的发作性运动诱发性运动障碍不同，表现为起病较晚且肌张力障碍持续时间较短。病例1出现了持续时间相对较长的15秒的肌张力障碍。我们还发现同胞之间的不自主运动存在差异。本报告强调了发作性运动诱发性运动障碍的临床和基因多样性，这可能导致散发性病例诊断面临挑战，最后报告了拉科酰胺作为一种治疗方法的疗效。
