Objective: To describe a patient belonging to a SCA1 family, who presented with action tremor and dysmetria but with a different genetic etiology.

Background: Spino-Cerebellar Ataxias (SCAs) are a large group of neurodegenerative diseases characterized by progressive ataxia and cerebellar signs, associated with extrapyramidal, pyramidal signs or peripheral neuropathy. Tremor has been mainly reported in SCA2, SCA3 and SCA12; postural tremor is present in 6% of SCA1 cases¹. Intention tremor is a core feature of Fragile X-associated tremor/ataxia syndrome (FXTAS), a rare cause of ataxia caused by a CGG expansion in the FMR1 gene (55-200 CGG repeats).

Method: Clinical evaluation, MRI imaging and genetic testing.

Results: A 65-year-old Italian man came to our attention complaining of upper limb tremor since age 56. On examination, he showed a position-dependent postural tremor and intention tremor of the right upper limb associated with dysmetria. Over time the tremor gradually spread to the contralateral upper limb. He also developed head and voice tremor without dysarthria. Tandem gait was possible although the patient subjectively reported postural instability. The remainder of neurological examination was unremarkable. Brain MRI showed cerebellar atrophy of both hemispheres and vermis, whereas DaT-Scan showed mildly reduced tracer uptake in posterior putamina. The patient had a family history of SCA1 on the paternal side, but his father was not reported to be affected. Treatable causes of cerebellar ataxia (Vitamin E and B12 deficiency) were ruled out. Genetic tests for SCA1, SCA2, SCA3, SCA6, SCA8, SCA12, SCA17 were negative; a panel for recessive ataxias only revealed found a heterozygous VUS in SYNE1 gene.

Further family history investigation revealed the presence of a nephew with intellectual disability and behavioral disturbances. This clue prompted us to investigate FMR1 gene CGG expansion, revealing 93 CGG repeats. The patient was therefore diagnosed with FXTAS. His nephew later tested positive for full FMR1 CGG expansion, being diagnosed with Fragile-X syndrome.

Conclusion: FXTAS and SCA1 share some clinical features, including ataxia and parkinsonism. Deep investigation of patients’ family history can be an essential clue to hypothesize alternative diagnoses even in families with a known multi-generational genetic disorder. Dystonic tremor can be the presenting symptom of FXTAS².

References: 1. Gan SR, Wang J, Figueroa KP, et al. Postural Tremor and Ataxia Progression in Spinocerebellar Ataxias. Tremor Other Hyperkinet Mov (N Y). 2017;7:492. Published 2017 Oct 9. doi:10.7916/D8GM8KRH
2. Maureen A. Leehey, M.D. Fragile X-associated Tremor/Ataxia Syndrome (FXTAS): Clinical Phenotype, Diagnosis and Treatment. J Investig Med. 2009 December; 57(8): 830–836. doi:10.231/JIM.0b013e3181af59c4

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MDS Abstracts - https://www.mdsabstracts.org/abstract/double-trouble-dystonic-tremor-due-to-fxtas-in-a-sca1-family/