Spinocerebellar Ataxia Type 8

Excerpt

Clinical characteristics: SCA8 is a slowly progressive ataxia with onset typically in the third to fifth decade but with a range from before age one year to after age 60 years. Common initial manifestations are scanning dysarthria with a characteristic drawn-out slowness of speech and gait instability. Over the disease course other findings can include eye movement abnormalities (nystagmus, abnormal pursuit and abnormal saccades, and, rarely, ophthalmoplegia); upper motor neuron involvement; extrapyramidal signs; brain stem signs (dysphagia and poor cough reflex); sensory neuropathy; and cognitive impairment (e.g., executive dysfunction, psychomotor slowing and other features of cerebellar cognitive-affective disorder in some). Life span is typically not shortened.

Diagnosis/testing: The diagnosis of SCA8 is established in a proband with suggestive findings and a heterozygous abnormal (CTG·CAG)_n repeat expansion in the two overlapping genes ATXN8OS/ATXN8 identified by molecular genetic testing.

Management: Treatment of manifestations: Canes and walkers to help prevent falls; modification of the home (e.g., grab bars, raised toilet seats, ramps for motorized chairs) as needed; speech therapy and communication devices for those with dysarthria; weighted eating utensils and dressing hooks to maintain some independence; feeding evaluations to reduce risk of aspiration from dysphagia; physical activity to maintain muscular and cardiopulmonary conditioning.

Surveillance: Routine follow up by the multidisciplinary care team including neurology to assess disease progression; physiatry and occupational and physical therapy to assess mobility and self-help skills; speech and language specialists to assess need for alternative communication method or speech therapy; feeding team to assess nutrition, aspiration risk, and feeding methods; and mental health professionals.

Agents/circumstances to avoid: Alcohol can exacerbate incoordination.

Genetic counseling: SCA8 is inherited in an autosomal dominant manner with reduced penetrance. To date, all individuals diagnosed with SCA8 whose parents have been evaluated with molecular genetic testing have one parent with an ATXN8OS/ATXN8 (CTG·CAG)_n repeat expansion. The transmitting parent may or may not have clinical manifestations of SCA8. If a parent of the proband is known to have a (CTG·CAG)_n repeat expansion, the risk to each sib of inheriting the repeat expansion is 50%. The (CTG·CAG)_n repeat expansion is highly unstable and almost always changes in size on transmission: the repeat expansion is more likely to become larger when maternally transmitted and more likely to contract with paternal transmission. Sibs who inherit a (CTG·CAG)_n repeat expansion may or may not develop clinical manifestations of SCA8. Once an SCA8 (CTG·CAG)_n repeat expansion has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.