Spinocerebellar ataxia type 6 (ORPHA:98758)
An autosomal dominant cerebellar ataxia type III that is characterized by late-onset and slowly progressive gait ataxia and other cerebellar signs such as impaired muscle coordination and nystagmus.
Epidemiology
Spinocerebellar ataxia type 6 (SCA6) estimated worldwide prevalence is less than 1/100,000. It is most commonly seen in Japan, Korea, the Netherlands and Germany.
Clinical description
The mean age of onset is 45 years but can range from the ages of 16 to 72 years. It usually presents with the cerebellar signs of ataxia, dysarthria and dysphagia. Some patients also have episodic vertigo and diplopia. Eye movement abnormalities such as gaze evoked and downbeat nystagmus, impaired smooth pursuit and abnormal vestibulo-ocular reflex are commonly seen in SCA6 patients. Less common presentations include pyramidal tract signs and peripheral neuropathy. Parkinsonism, dystonia, myoclonus, tremor and cognitive impairment have been reported in rare cases. Depression and fatigue have been associated with SCA6. Disease severity seems to increase during pregnancy. SCA6 progresses very slowly with a disease duration that can last over 25 years.
Etiology
SCA6 is caused by small expansions of the trinucleotide (CAG) repeat in the CACNA1A gene (19p13) which encodes an alpha 1 subunit of a P/Q-type voltage-gated calcium channel, necessary for proper neural communication in the brain. The expansions in SCA6 patients are usually of 21-29 CAG repeats.
Diagnostic methods
Diagnosis is based on the characteristic clinical findings and molecular genetic testing. As the manifestations of SCA6 are not specific, diagnosis is only confirmed with the finding of a mutation in the CACNA1A gene.
Differential diagnosis
Differential diagnosis includes other types of autosomal dominant cerebellar ataxia, familial or sporadic hemiplegic migraine and episodic ataxia type 2.
Antenatal diagnosis
Antenatal diagnosis is possible in families with a known mutation.
Genetic counseling
SCA6 is inherited autosomal dominantly and genetic counseling is possible. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the mutation to offspring.
Management and treatment
There is no cure for SCA6 and treatment is supportive. Acetazolamide may help with episodes of ataxia but does not halt the progression of the disease. Physical therapy, as well as the use of canes and walkers, should be offered in order to maximize strength and maintain activity. Wheelchairs are eventually necessary. Speech therapy and communication devices may be useful to those with dysarthria. Dysphagia should be monitored to decrease the risk of aspiration pneumonia. In those with vertigo, vestibular suppressants may be beneficial. Annual neurological examinations are recommended to monitor disease progression.
Prognosis
Life expectancy is not reduced but the quality of life can be significantly affected. Mean age when aid walking needed is about 53 years, and mean age when wheelchair needed is approximately 60 years.

                            Last update: 
                            January 2020


                            - Expert reviewer(s): 
                            Dr Shinsuke FUJIOKA  - Dr Yoshio TSUBOI  - Dr Zbigniew WSZOLEK