Makindo Medical Notes

Related Subjects: |Dementias |Abbreviated Mental Test Score (AMTS)

Dentatorubral Pallidoluysian Atrophy (DRPLA) is a rare, hereditary neurodegenerative disorder characterized by progressive ataxia, choreoathetosis, myoclonus, seizures, and dementia. It is classified as a trinucleotide repeat disorder, specifically involving an expanded CAG repeat in the ATN1 gene on chromosome 12.

About

• Rare cause of chorea
• Seen in Japanese
• Autosomal dominant pattern
• Mutant gene on 12p13.31

The number of CAG repeats in the ATN1 gene correlates with the severity and age of onset of the disease:

Genetics

• Normal allele: Fewer than 35 CAG repeats.
• Intermediate allele: 35-48 CAG repeats, which may not always result in symptoms.
• Pathogenic allele: Greater than 48 CAG repeats, leading to DRPLA.

Clinical: typically appearing in childhood, adolescence, or adulthood:

• Childhood-Onset:
  • Seizures (often myoclonic epilepsy)
  • Progressive intellectual disability
  • Ataxia (loss of coordination)
  • Behavioral changes
  • Rapidly progressive course
• Adult-Onset:
  • Ataxia
  • Choreoathetosis (involuntary, writhing movements)
  • Dementia
  • Myoclonus
  • Psychiatric symptoms (e.g., depression, anxiety)

Investigations

• MRI: Shows characteristic brain atrophy, particularly in the cerebellum and brainstem.
• Electroencephalography (EEG): May reveal abnormalities in patients with seizures.
• Neuropsychological Testing: Used to assess cognitive and behavioral changes.

Management

• Currently, there is no cure for DRPLA, and treatment is primarily symptomatic and supportive:
• Anticonvulsants: Used to manage seizures.
• Physical therapy: Helps maintain mobility and manage ataxia.
• Occupational therapy: Assists with daily living activities and adapts the home environment.
• Speech therapy: Helps with communication difficulties and swallowing issues.
• Psychiatric care: Manages psychiatric symptoms like depression and anxiety.
• Genetic counseling: Recommended for affected families to understand the inheritance pattern and risks.