Spinocerebellar Ataxia Type 10

Excerpt

Clinical characteristics: Spinocerebellar ataxia type 10 (SCA10) is characterized by slowly progressive cerebellar ataxia that usually starts as poor balance and unsteady gait, followed by upper-limb ataxia, scanning dysarthria, and dysphagia. Abnormal tracking eye movements are common. Recurrent seizures after the onset of gait ataxia have been reported with variable frequencies among different families. Some individuals have cognitive dysfunction, behavioral disturbances, mood disorders, mild pyramidal signs, and peripheral neuropathy. Age of onset ranges from 12 to 48 years.

Diagnosis/testing: Diagnosis of SCA10 is established in a proband by identification of a heterozygous ATTCT pentanucleotide-repeat expansion in ATXN10. Affected individuals have expanded alleles with up to 4,500 ATTCT pentanucleotide repeats; intermediate alleles (280 to 850 repeats) may show reduced penetrance.

Management: Treatment of manifestations: Treatment is primarily focused on control of seizures, as uncontrolled seizures may lead to potentially fatal status epilepticus. Conventional anticonvulsants such as levetiracetam, phenytoin, carbamazepine, and valproic acid achieve reasonable control, although occasional breakthrough seizures may occur. Treatment measures for ataxia: canes / walkers / mobilized chairs; standard home modifications; exercise and physical therapy; and weight control to avoid difficulty with ambulation and mobility. For dysphagia: percutaneous placement of a gastrostomy tube for both prevention of aspiration and maintenance of nutritional intake; vitamin supplementation. For dysarthria: speech therapy and speech/communication assistive devices. Weighted utensils and dressing hooks for upper-limb coordination issues. Mild tranquilizers may be helpful for those with anxiety.

Surveillance: Clinical neurology evaluation every four to six months; video esophagrams to evaluate those with dysphagia.

Agents/circumstances to avoid: Alcohol and drugs that are known to adversely affect cerebellar functions; falls, which may compromise motor function; activities that are potentially dangerous to individuals with ataxia or epilepsy.

Genetic counseling: SCA10 is inherited in an autosomal dominant manner. Offspring of an affected individual have a 50% chance of inheriting the repeat expansion. The risk of developing the SCA10 phenotype in individuals with expanded alleles in the intermediate range (280-850) is uncertain because of the apparently reduced penetrance. Anticipation has been observed in some families with paternal (but not maternal) transmission of the pentanucleotide repeat expansion. Prenatal testing for pregnancies at increased risk is possible if the diagnosis has been established by molecular genetic testing in an affected family member.