Clinical Guidance

A correlation between CAG repeat sizes and disease severity exists: the longer the CAG repeat, the earlier the age of onset and the more severe and rapidly progressive the disease.

• Infantile onset may be associated with CAG repeat sizes ranging from 200 to 400; however, technical limitations of genetic testing utilizing PCR amplification of the ATXN7CAG repeat region that often underestimate the repeat expansion size may report a CAG repeat size of fewer than 150.

• Childhood onset is usually associated with CAG repeat sizes greater than 100.

• Juvenile onset is often associated with CAG repeat sizes 60-100.

A correlation between CAG repeat size and initial clinical manifestation exists :

Source: GeneReviews — "Spinocerebellar Ataxia Type 7"

Penetrance

See for CAG repeat sizes associated with age-related reduced penetrance.

Source: GeneReviews — "Spinocerebellar Ataxia Type 7"

Diagnostic Criteria

Suggestive Findings

Spinocerebellar ataxia type 7 (SCA7) should be suspected in individuals with the following (by age) and .

Clinical Findings

Adult onset

• Progressive incoordination caused by cerebellar ataxia, including dysarthria/dysphagia, dysmetria, and dysdiadochokinesia.

• Cone-rod retinal dystrophy with the following:

• Loss of central vision

• A tritan-axis (blue/yellow) defect on detailed color vision testing

• Macular changes on fundoscopic examination

• Paracentral scotoma on visual field testing

• On electroretinogram (ERG), abnormalities of cone function initially, followed by abnormalities of rod function

Infantile or early-childhood onset

• Failure to thrive and loss of motor milestones (may be the earliest findings)

• Rapid deterioration with early death

• Ataxia and visual loss not obvious

Source: GeneReviews — "Spinocerebellar Ataxia Type 7"

Differential Diagnosis

While many of the neurologic and pathologic findings of the other spinocerebellar ataxias (SCAs) overlap with SCA7, retinal degeneration is the distinguishing feature of SCA7 (see Hereditary Ataxia Overview). Table 3. Disorders with Retinal Degeneration in the Differential Diagnosis of Spinocerebellar Ataxia Type 7

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with spinocerebellar ataxia type 7 (SCA7) of adolescent or adult onset, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

Recommended Evaluations Following Initial Diagnosis of SCA7: Adolescent or Adult Onset

System/Concern | Evaluation | Comment

Neurologic

| Neurologist assessment for cerebellar motor dysfunction (gait postural ataxia, dysmetria, dysdiadochokinesis, tremor, dysarthria, nystagmus, saccades smooth pursuit) | Use standardized scale to establish baseline for ataxia (SARA, ICARS, or BARS).1

UMN /or LMN dysfunction (weakness, spasticity, Babinski signs, hyperreflexia, amyotrophy, fasciculations) | Since most exhibit some corticospinal tract involvement, comprehensive assessment of motor sensory function recommended for all affected persons

Refer to neuromuscular clinic (OT/PT / rehab specialist). | Assess gross motor fine motor skills, gait, ambulation, need for adaptive devices, PT, OT.

Ophthalmologic

involvement | Complete eye exam | Incl:

• BCVA

• Extraocular movement

• Refractive error

• Color vision testing

• Full-field ERG

• Spectral-domain OCT

Speech

| For those w/dysarthria: speech/language eval | Consider involving certified practitioner of speech/language pathology.

Feeding

| For those w/frequent choking or severe dysphagia, assess:

• Nutritional status;

• Aspiration risk.

Source: GeneReviews — "Spinocerebellar Ataxia Type 7"

Clinical Guidance

Avoid drinking alcoholic beverages, as alcohol intake can further impair cerebellar function, especially if excessive. Avoid foods identified by a registered dietician as potentially causing dizziness or disorientation.

Source: GeneReviews — "Spinocerebellar Ataxia Type 7"

Therapies Under Investigation

Ongoing clinical trials for SCA7 include a study of:

• Troriluzole in adults as a treatment for ataxia in the United States (ClinicalTrials.gov: NCT03701399);

• Riluzole in adults as a treatment for ataxia in Italy (ClinicalTrials.gov: NCT03660917).

Ionis Pharmaceuticals is developing an antisense oligonucleotide for dosage reduction of ataxin-7 in the retina and brain, as a preclinical trial of this strategy was found to be an effective treatment for retinal degeneration in an SCA7 mouse model . 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.

Source: GeneReviews — "Spinocerebellar Ataxia Type 7"

Surveillance Guidelines

Table 6.

Recommended Surveillance for Individuals with SCA7

System/Concern | Evaluation | Frequency

Neurologic

|

• Neurologic assessment for progression of ataxia; UMN or LMN signs; dystonia parkinsonism; autonomic dysfunction

• Monitor ataxia progression w/standardized scale (SARA, ICARS, or BARS).1

| Annually; more often for an acute exacerbation

Physiatry; OT/PT assessment of mobility; self-help skills as they relate to ataxia, spasticity, weakness

Dysarthria

| Assess need for alternative communication method or speech therapy. | Per symptom progression

Dysphagia

| Assess aspiration risk feeding methods.

Retinopathy

| Exam by ophthalmologist for evidence of cone-rod dystrophy: BCVA, color vision testing, visual field testing, ERG | Every 3-5 yrs or as needed based on concerns re visual acuity, visual field deficits, /or color vision (as an indicator of cone function)

Cognitive/

Psychiatric

| Evaluate mood, signs of psychosis, cognitive complaints to identify need for pharmacologic psychotherapeutic interventions. | Per symptom progression development of psychiatric symptoms

Family support/

resources | Provide various options for affected persons their families, ranging from joining patient support groups (e.g., National Ataxia Foundation, which has local chapters throughout the US) to social work consultation. | Per symptom progression

Source: GeneReviews — "Spinocerebellar Ataxia Type 7"