Spinocerebellar Ataxia Type 36 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

Excerpt

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: Spinocerebellar ataxia type 36 (SCA36) is characterized by a late-onset, slowly progressive cerebellar syndrome typically associated with sensorineural hearing loss. Other common features are muscle atrophy and denervation, especially of the tongue, as well as pyramidal signs, thus overlapping with motor neuron disorders. Mild frontal-subcortical affective and cognitive decline may be present as the disease progresses. Brain MRI shows atrophy of the cerebellar vermis in initial stages, later evolving to a pattern of olivopontocerebellar atrophy.

Diagnosis/testing: The diagnosis is suspected based on clinical findings in the absence of primary causes of cerebellar dysfunction. It is supported by a family history consistent with autosomal dominant inheritance, which can include simplex cases (i.e., a single occurrence in a family). Confirmation of the diagnosis relies on detection of an abnormal hexanucleotide GGCCTG repeat expansion in NOP56. Affected individuals typically have alleles with 650 or more repeats. Such testing detects virtually 100% of affected individuals.

Management: Treatment of manifestations: Treatment of SCA36 involves multidisciplinary specialists and focuses on routine exercise and physical therapy with attention to gait and balance, weight control, and walking aids to facilitate ambulation and mobility. Occupational therapy aids fine movement coordination; speech therapy and communication devices for those with dysarthria. Hearing loss may require hearing aids or cochlear implants, together with audiologic rehabilitation. Emotional and cognitive decline can be addressed in cognitive therapy, treatment of depression, and psychological support. Living space may need to be adapted to help with accessibility.

Prevention of secondary complications: Dietary assessment and feeding therapy programs can improve dysphagia and reduce the risk of aspiration.

Surveillance: At least annual evaluation by a neurologist or more frequently if manifestations are progressing. Annual or biannual evaluation by an otolaryngologist to monitor possible hearing loss. Surveillance of speech and ambulation.

Agents/circumstances to avoid: Alcohol and medications known to affect cerebellar function, as well as those affecting the inner auditory function. Avoidance of acoustic trauma (e.g., use of headphones, noisy environments).

Genetic counseling: SCA36 is inherited in an autosomal dominant manner. Penetrance is complete, although age-dependent. Offspring of affected individuals have a 50% chance of inheriting the NOP56 pathogenic variant. Prenatal testing is possible for pregnancies at increased risk if the pathogenic variant has been identified in an affected family member.