Trinucleotide Repeats Lecture by Dirty Medicine

Overview

• Focus on four diseases with trinucleotide repeats relevant for USMLE and COMLEX exams.
• Importance due to rarity of trinucleotide expansions and frequent testing on these conditions.

Diseases Covered

1. Huntington's Disease
2. Fragile X Syndrome
3. Friedreich's Ataxia
4. Myotonic Dystrophy Type 1

Huntington's Disease

• Trinucleotide Repeat: CAG
• Inheritance: Autosomal dominant
• Symptoms: Aggression, psychosis, chorea, dementia
• Findings:
  • Increased dopamine
  • Decreased acetylcholine
  • Decreased GABA
  • Atrophy of caudate nucleus
• Mnemonic: "Can't Aim Great when you Hunt for an animal"
  • CAG - Trinucleotide
  • Hunt - Huntington's Disease
  • Chromosome 4 involvement
  • Anticipation - Earlier onset in subsequent generations

Fragile X Syndrome

• Trinucleotide Repeat: CGG
• Inheritance: X-linked dominant
• Symptoms: Macroorchidism, intellectual disability, long face, large ears
• Mnemonic: "Congenitally Giant Gonads"
  • CGG - Trinucleotide
  • Macroorchidism as key symptom

Friedreich's Ataxia

• Trinucleotide Repeat: GAA
• Inheritance: Autosomal recessive
• Symptoms: Ataxia, staggering gait, hammertoes, pes cavus, scoliosis
• Complications: Hypertrophic cardiomyopathy (common cause of death)
• Pathophysiology:
  • Defect in frataxin gene
  • Abnormal iron accumulation in cells
  • Mitochondrial damage
• Mnemonic: "Lady Gaga was ataxic and fell"
  • GAA - Trinucleotide
  • Associated with neurologic symptoms and structural deformities

Myotonic Dystrophy Type 1

• Trinucleotide Repeat: CTG
• Inheritance: Autosomal dominant
• Symptoms: Distal extremity weakness, particularly difficulty releasing grip
• Findings: Cataracts, testicular atrophy, hypogammaglobulinemia
• Mnemonic: "Can't Terminate Grip"
  • CTG - Trinucleotide
  • Associated findings: Cataracts, testicular atrophy, gamma globulinemia

Summary Chart

• Huntington's Disease: CAG, Autosomal dominant, "Can't Aim Great"
• Fragile X Syndrome: CGG, X-linked dominant, "Congenitally Giant Gonads"
• Friedreich's Ataxia: GAA, Autosomal recessive, "Lady Gaga"
• Myotonic Dystrophy Type 1: CTG, Autosomal dominant, "Can't Terminate Grip"

• Use mnemonics for easier memorization of trinucleotide repeats and associated symptoms.
• Recommended for students to familiarize themselves with disease presentations and inheritance patterns for exam preparation.
• Good luck with your studies!