Clinical Guidance

Heterozygotes

Clinical features. The length of the CAG/CAA repeat in TBP correlates with the clinical features based on data available from 52 individuals (50 from the literature and 2 unreported) (, ). As the information reported in the literature was incomplete, the frequencies listed for symptom occurrence may be underestimated [, , , , , , , , , , , ]. Of note is the high proportion of individuals with psychiatric symptoms and chorea.

Source: GeneReviews — "Spinocerebellar Ataxia Type 17"

Penetrance

The penetrance of alleles of 41-44 repeats is estimated at 50% and the penetrance of alleles of 45-48 repeats is estimated at greater than 80% .

Source: GeneReviews — "Spinocerebellar Ataxia Type 17"

Diagnostic Criteria

Suggestive Findings

Spinocerebellar ataxia type 17 (SCA17) should be suspected in individuals with the following:

• Ataxia

• Dementia

• Involuntary movements – e.g., chorea and dystonia (blepharospasm, torticollis, writer's cramp, foot dystonia)

• Psychiatric symptoms

Establishing the Diagnosis

The diagnosis of SCA17 is established in a proband by identification of a heterozygous pathogenic variant of CAG (and sometimes CAA) repeats in TBP by molecular genetic testing . Because both codons CAA and CAG encode glutamine residues, the resulting proteins will have variable tracts of glutamine residues. Allele sizes. The structure of the repeat sequence in a normal, stably transmitted allele is variable but typically consists of series of CAG repeats interrupted by CAA repeats – e.g.

Source: GeneReviews — "Spinocerebellar Ataxia Type 17"

Differential Diagnosis

Table 3.

Inherited Conditions to Consider in the Differential Diagnosis of Spinocerebellar Ataxia Type 17 (SCA17)

DiffDx Disorder | Gene(s) | MOI | Clinical Features of the DiffDx Disorder

Overlapping w/SCA17 | Distinguishing from SCA17

Hereditary cerebellar ataxia (See Hereditary Ataxia Overview.) | Many | ADARXL | Cerebellar ataxia | Hereditary cerebellar ataxia assoc w/prominent cerebellar long tract signs

DRPLA (dentatorubral-pallidoluysian atrophy) | ATN1 | AD | Progressive ataxia dementia; psychiatric disturbances | Ataxia myoclonus are prominent mvmt disorders.

Huntington disease (HD) | HTT | AD | Progressive movement disorders dementia; psychiatric disturbances | Progressive chorea is prominent.

C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia

| C9orf72 | AD | Mvmt...

Source: GeneReviews — "Spinocerebellar Ataxia Type 17"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with spinocerebellar ataxia type 17 (SCA17), the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Neuropsychological testing to evaluate for dementia and/or psychiatric disturbance

• Brain MRI to evaluate areas and degree of atrophy

• Neurology consultation, if not completed prior to initial diagnosis

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Table 4.

Treatment of Manifestations in Individuals with Spinocerebellar Ataxia Type 17

Manifestation/Concern | Treatment

Psychiatric symptoms | Psychotropic medications

Seizures | Anti-seizure medication(ASM)

Dystonia | Local injections of botulinum toxin

Dementia | Adaptation of environment

Prevention of Secondary Complications

The side effects of psychotropic medications and ASMs (e.g., depression, sedation, nausea, restlessness, headache, neutropenia, and tardive dyskinesia) can be major secondary complications in persons with SCA17. For some individuals, the side effects of certain therapeutics may be worse than the symptoms of the disease; such individuals may benefit from total or intermittent discontinuation of the treatment or reduction in dose.

Surveillance

Affected individuals should be followed annually or semiannually by a neurologist or more frequently if symptoms are progressing rapidly, as may happen in the advanced sta...

Source: GeneReviews — "Spinocerebellar Ataxia Type 17"

Clinical Guidance

Agents with sedative/hypnotic properties, such as ethanol or certain medications, may markedly increase incoordination.

Source: GeneReviews — "Spinocerebellar Ataxia Type 17"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for 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 17"

Surveillance Guidelines

Affected individuals should be followed annually or semiannually by a neurologist or more frequently if symptoms are progressing rapidly, as may happen in the advanced stages .

Source: GeneReviews — "Spinocerebellar Ataxia Type 17"