Clinical Guidance

SCA8 is a slowly progressive ataxia with onset typically in adulthood (range: neonatal period to age 73 years) [, , , , , , ]. Disease progression is typically over decades regardless of the age of onset. Common initial manifestations are dysarthria and gait instability; life span is typically not shortened . Persons with adult onset typically exhibit cerebellar signs (e.g., nystagmus, abnormal pursuit and saccadic eye movement) and gait and limb ataxia indicated by a broad-based gait and abnormal finger-to-nose, finger-chase, and heel-to-shin maneuvers. These are often associated with additional neurologic signs [unpublished data and ]. Dysphagia can be a significant complication .

Table 2.

Select Features of Spinocerebellar Ataxia Type 8

Feature | Prevalence of Feature1

Gait ataxia | +++

Source: GeneReviews — "Spinocerebellar Ataxia Type 8"

Penetrance

The true penetrance of the combined (CTATAG)n(CTGCAG)n repeat lengths is not understood, as interfamilial differences in penetrance for the same size repeat expansion can be seen. Nevertheless, the following have been observed:

• A number of independent studies have shown that greater than 90 combined (CTATAG)n(CTGCAG)n repeats are more often found in individuals with ataxia than in unaffected controls .

• In a large family (MN-A ) with SCA8, individuals with ataxia had longer combined (CTATAG)n(CTGCAG)n repeat lengths (mean size: 117) compared to 21 asymptomatic relatives with shorter combined repeat lengths (mean size: 92), demonstrating that repeat length plays a role in disease penetrance .

Source: GeneReviews — "Spinocerebellar Ataxia Type 8"

Clinical Guidance

Alcohol should be avoided because it can exacerbate problems with incoordination.

Source: GeneReviews — "Spinocerebellar Ataxia Type 8"

Therapies Under Investigation

Troriluzole is in a Phase III clinical trial (NCT03701399) for a number of SCAs including SCA8. Ongoing preclinical studies are being performed in SCA8 animal models to assess possible benefits of therapies that target the pathogenic (CTATAG)n(CTGCAG)n repeat expansions or the RNA or proteins produced from the pathogenic repeat expansion. Because it is possible that therapeutic strategies successful for one spinocerebellar ataxia caused by an abnormal nucleotide repeat expansion could apply to other SCAs, it is important to prepare for eventual clinical trial studies by establishing key outcome measures for affected individuals. Search ClinicalTrials.

Source: GeneReviews — "Spinocerebellar Ataxia Type 8"