Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Mov Disord Clin Pract. 2024 Nov;11(11):1445-1450. doi: 10.1002/mdc3.14220. Epub 2024 Sep 28.
Spinocerebellar ataxia type 21 (SCA21) is a rare inherited neurological disorder characterized by motor, cognitive, and behavioral disturbances, caused by autosomal dominant TMEM240 variants.
To identify the genetic cause of a dystonic tremor with autosomal dominant inheritance.
Six subjects of a multi-generational French family affected by tremor and dystonia were studied. Each patient underwent a comprehensive clinical assessment and a whole-exome sequencing analysis.
All six subjects presented with early-onset prominent hand dystonic tremor and multifocal/generalized dystonia, secondarily developing mild cerebellar ataxia. The younger generation showed more pronounced cognitive and behavioral impairment. The known pathogenic TMEM240 c.509C>T (p.P170L) variant was found in heterozygosis in all subjects.
Dystonic tremor can represent the core clinical feature of SCA21, even in absence of overt cerebellar ataxia. Therefore, TMEM240 pathogenic variants should be considered disease-causing in subjects displaying dystonic tremor, variably associated with ataxia, parkinsonism, neurodevelopmental disorders, and cognitive impairment.
脊髓小脑性共济失调 21 型（SCA21）是一种罕见的遗传性神经疾病，其特征为运动、认知和行为障碍，由常染色体显性 TMEM240 变异引起。
确定具有常染色体显性遗传的肌张力障碍性震颤的遗传原因。
研究了一个受震颤和肌张力障碍影响的多代法国家庭的 6 名受试者。每位患者均接受了全面的临床评估和全外显子组测序分析。
所有 6 名受试者均表现为早发性手部显著肌张力障碍性震颤和多灶/全身性肌张力障碍，随后出现轻度小脑共济失调。年轻一代表现出更明显的认知和行为障碍。在所有受试者中均发现已知致病性 TMEM240 c.509C>T（p.P170L）变异杂合。
即使没有明显的小脑共济失调，肌张力障碍性震颤也可以代表 SCA21 的核心临床特征。因此，在表现出肌张力障碍性震颤、伴有共济失调、帕金森病、神经发育障碍和认知障碍的患者中，应考虑 TMEM240 致病变异引起疾病。
