Background: Spinocerebellar ataxia type 21 (SCA21) is a rare inherited neurological disorder characterized by motor, cognitive, and behavioral disturbances, caused by autosomal dominant TMEM240 variants.
Objectives: To identify the genetic cause of a dystonic tremor with autosomal dominant inheritance.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: autism spectrum; dystonia; psychomotor delay; spinocerebellar ataxia; tremor.
© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.