Paroxysmal Kinesigenic Dyskinesia in Two Siblings With Novel Heterozygous TMEM151A Frameshift Variant: The First Case...

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.