Clinical Guidance

Heterozygous individuals. Although the age of onset of symptoms of SCA6 correlates inversely with the length of the expanded CAG repeat, the same broad range of onset has been noted for individuals with 22 CAG repeats, the most common disease-associated allele . In the few individuals with (CAG)30 or (CAG)33, onset has been later than in individuals with (CAG)22 and (CAG)23 . A recent retrospective study showed even closer correlation of age of onset with the sum of the two allele sizes . Homozygous individuals. Several individuals who are homozygous for an abnormal expansion in CACNA1A have been reported .

Source: GeneReviews — "Spinocerebellar Ataxia Type 6"

Penetrance

Penetrance is nearly 100%, although symptoms may not appear until the seventh decade.

Source: GeneReviews — "Spinocerebellar Ataxia Type 6"

Diagnostic Criteria

Formal diagnostic criteria for spinocerebellar ataxia type 6 (SCA6) have not been established.

Suggestive Findings

SCA6 should be suspected in individuals with the following clinical and imaging findings:

• Clinical findings include adult-onset, slowly progressive cerebellar ataxia; dysarthria; and nystagmus.

• Imaging findings. Atrophy of the cerebellum, most pronounced in the cerebellar vermis, is present in symptomatic individuals with SCA6 .

Establishing the Diagnosis

The diagnosis of SCA6 is established in a proband with a heterozygous CAG repeat expansion in CACNA1A by molecular genetic testing .

Allele sizes

Source: GeneReviews — "Spinocerebellar Ataxia Type 6"

Differential Diagnosis

Individuals with spinocerebellar ataxia type 6 (SCA6) may present with unexplained ataxia that is part of the larger differential diagnosis of hereditary and acquired ataxias (see Hereditary Ataxia Overview). It is difficult and often impossible to distinguish spinocerebellar ataxia type 6 (SCA6) from the other hereditary ataxias (see Hereditary Ataxia Overview). The differential diagnosis should also include Parkinson disease and acquired causes of cerebellar ataxia. SCA6-related CACNA1A pathogenic variants should be in the differential diagnosis of adult-onset sporadic progressive ataxia, multiple system atrophy (MSA). Table 4. Proportion of Individuals with SCA6 Manifesting Phenotypic Features Compared with Individuals with SCA1, SCA3, and SCA2

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with spinocerebellar ataxia type 6 (SCA6), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with Spinocerebellar Ataxia Type 6

Source: GeneReviews — "Spinocerebellar Ataxia Type 6"

Clinical Guidance

Agents with sedative/hypnotic properties such as ethanol or certain medications may produce marked increases in incoordination.

Source: GeneReviews — "Spinocerebellar Ataxia Type 6"

Therapies Under Investigation

suggested gabapentin and pregabalin as potential therapeutic agents. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Spinocerebellar Ataxia Type 6"

Surveillance Guidelines

Table 7.

Recommended Surveillance for Individuals with Spinocerebellar Ataxia Type 6

System/Concern | Evaluation | Frequency

Ataxia

| Neurologic evaluation | Every 6-12 mos

Physiatrist physical /or occupational therapist consultations | Every 12 mos to review need for walking aid(s) home adaptations

Nutrition

| • Nutrition evaluation

• Video esophagram

• Feeding assessment when dysphagia becomes troublesome

| As needed (e.g., w/any change in nutrition/feeding status)

Diplopia

| Evaluation w/ophthalmologist /or optometrist for prisms or surgery | As needed (e.g., when other interventions fail)

Assessment of driving ability by professional | Periodically

Source: GeneReviews — "Spinocerebellar Ataxia Type 6"