Clinical Guidance

Heterozygotes. In general, an inverse correlation exists between the age at onset and the size of the expanded ATN1 CAG repeat . Note: ATN1 CAG repeat ranges overlap and the distinctions are not clearly defined.

Table 2.

Correlation between Age at Onset and Size of ATN1 Repeat

Age at Onset | ATN1 CAG Repeat Range

21 years | 63-79

21-40 years | 61-69

40 years | 48-67

Adapted from ,

Source: GeneReviews — "DRPLA"

Penetrance

Pathogenic (full-penetrance) CAG repeats (i.e., 48-93 CAG repeats) are fully penetrant, except for one individual with 51 CAG repeats who was asymptomatic at age 81 years .

Source: GeneReviews — "DRPLA"

Diagnostic Criteria

No consensus clinical diagnostic criteria for DRPLA (dentatorubral-pallidoluysian atrophy) have been published.

Suggestive Findings

DRPLA should be suspected in a proband with the following clinical features by age, brain MRI findings, and family history. Clinical features (by age)

• Juvenile onset (before age 20 years). Ataxia, myoclonus, seizures, progressive intellectual deterioration

• Adult onset (after age 20 years). Ataxia, choreoathetosis, dementia, psychiatric disturbance

Brain MRI findings. Cerebellar and brain stem atrophy; white matter lesions

Family history is consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations) and Japanese familial origin. DRPLA is extremely rare outside of Japanese populations .

Source: GeneReviews — "DRPLA"

Differential Diagnosis

Adult onset. For individuals with adult-onset DRPLA (dentatorubral-pallidoluysian atrophy) who exhibit ataxia, dementia, or choreoathetosis (the non-PME phenotype), the differential diagnosis includes the autosomal dominant disorders summarized in . Table 3. Selected Genes in the Differential Diagnosis of Adult-Onset DRPLA

Management Guidelines

No clinical practice guidelines for DRPLA (dentatorubral-pallidoluysian atrophy) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with DRPLA, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. DRPLA: Recommended Evaluations Following Initial Diagnosis by Age of Onset

Source: GeneReviews — "DRPLA"

Clinical Guidance

General anesthesia can increase the risk of intra- and postoperative seizures .

Source: GeneReviews — "DRPLA"

Therapies Under Investigation

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 — "DRPLA"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized (for individuals with juvenile onset) and (for individuals with adult onset) are recommended. Table 8. Juvenile-Onset DRPLA: Recommended Surveillance

Source: GeneReviews — "DRPLA"