Spinocerebellar Ataxia Type 17

CLINICAL CHARACTERISTICS

Spinocerebellar ataxia type 17 (SCA17) is characterized by ataxia, dementia, and involuntary movements, including chorea and dystonia. Psychiatric symptoms, pyramidal signs, and rigidity are common. The age of onset ranges from three to 55 years. Individuals with full-penetrance alleles develop neurologic and/or psychiatric symptoms by age 50 years. Ataxia and psychiatric abnormalities are frequently the initial findings, followed by involuntary movement, parkinsonism, dementia, and pyramidal signs. Brain MRI shows variable atrophy of the cerebrum, brain stem, and cerebellum. The clinical features correlate with the length of the polyglutamine expansion but are not absolutely predictive of the clinical course.

DIAGNOSIS/TESTING: The diagnosis of SCA17 is established in a proband by identification of an abnormal CAG/CAA repeat expansion in . Affected individuals usually have more than 41 repeats. The CAA and CAG codons both encode glutamine residues resulting in a pathogenic polyglutamine expansion.

MANAGEMENT

Psychotropic medications for psychiatric issues, anti-seizure medication for seizures (ASM); botulinum toxin injections for dystonia; adaptation of the environment to accommodate dementia. Side effects of psychotropic medications and ASMs may require total or intermittent discontinuation of the treatment or reduction in dose. Annual or semiannual evaluation by a neurologist or more frequently if symptoms are progressing rapidly. Sedative/hypnotic agents, such as ethanol or certain medications, may exacerbate incoordination.

GENETIC COUNSELING

SCA17 is inherited in an autosomal dominant manner. Offspring of affected individuals are at a 50% risk of inheriting the expanded allele. The age of onset, severity, specific symptoms, and progression of the disease are variable and cannot be precisely predicted by family history or size of expansion. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible if the diagnosis has been established in an affected family member by molecular genetic testing.