Makindo Medical Notes

🧠 Dentatorubral Pallidoluysian Atrophy (DRPLA) is a rare, autosomal dominant neurodegenerative trinucleotide repeat disorder. It is caused by expanded CAG repeats in the ATN1 gene (chromosome 12p13.31). Clinically it presents with combinations of ataxia, chorea, myoclonus, seizures, and dementia.

📖 About

• Rare cause of chorea and ataxia.
• Seen predominantly in Japanese populations.
• Autosomal dominant inheritance.
• Mutant gene located on chromosome 12p13.31.

📊 The number of CAG repeats correlates with severity and age of onset:

🧬 Genetics

• Normal: <35 CAG repeats.
• Intermediate: 35–48 repeats (may or may not cause symptoms).
• Pathogenic: >48 repeats → DRPLA develops.

🤒 Clinical Features

Presentation varies by age of onset:

• Childhood-Onset:
  • Seizures (often myoclonic epilepsy).
  • Progressive intellectual disability.
  • Ataxia (loss of coordination).
  • Behavioral changes.
  • Rapid progression.
• Adult-Onset:
  • Ataxia and progressive gait disturbance.
  • Choreoathetosis (involuntary writhing movements).
  • Dementia / cognitive decline.
  • Myoclonus.
  • Psychiatric symptoms (e.g., depression, anxiety).

🔍 Investigations

• MRI: Cerebellar and brainstem atrophy ± cerebral changes.
• EEG: Abnormalities in seizure patients.
• Neuropsychological testing: To track cognitive and behavioural decline.
• Genetic testing: Definitive diagnosis (CAG repeat expansion).

🩺 Management

❌ No disease-modifying cure. Treatment is supportive and aimed at improving quality of life.

• 💊 Anticonvulsants: Control seizures (esp. myoclonic epilepsy).
• 🏃 Physiotherapy: Helps with mobility and balance.
• 🛠️ Occupational therapy: Adaptations for daily living and independence.
• 🗣️ Speech therapy: Supports communication and swallowing difficulties.
• 🧑‍⚕️ Psychiatric care: Manage depression, anxiety, and behavioural issues.
• 👪 Genetic counselling: Essential for families to understand inheritance risk.