U01.01.055 Autosomal dominant diseases

Written by

in

 

Learning Objectives

  • Identify the classic Autosomal Dominant (AD) disorders tested on the USMLE.
  • Understand the characteristic phenotypic features of each condition.
  • Recognize key gene associations and pathognomonic clinical signs.

1. Structural and Growth Disorders

  • Achondroplasia: Failure of longitudinal bone growth (enchondral ossification) leading to short limbs. Associated with advanced paternal age.
  • Marfan Syndrome: FBN1 gene mutation (fibrillin-1). Features include tall stature, ectopia lentis (upward lens subluxation), and aortic root dilation.
  • Hereditary Spherocytosis: defect in spectrin or ankyrin; results in sphere-shaped RBCs and hemolytic anemia.

2. Neuro-Cutaneous & Neurodegenerative

  • Huntington’s disease: CAG repeat disease. Findings: chorea, dementia, and caudate atrophy.
  • Neurofibromatosis Type 1 (NF1): Café-au-lait spots, Lisch nodules (iris hamartomas), and cutaneous neurofibromas.
  • Neurofibromatosis Type 2 (NF2): Characterized by bilateral acoustic neuromas.
  • Tuberous Sclerosis: Ash-leaf spots, facial angiofibromas, and “shagreen patches.”

3. Cancer Predisposition & Organ Systems

Disease Key Clinical Finding
ADPKD Bilateral, massive cystic kidneys; associated with berry aneurysms.
FAP Thousands of polyps after puberty; 100% progress to colon cancer.
Li-Fraumeni p53 mutation; SBLA syndrome (Sarcoma, Breast, Leukemia, Adrenal).
VHL Disease Hemangioblastomas (retina/cerebellum) and renal cell carcinoma.
MEN (1, 2A, 2B) Multiple endocrine tumors (e.g., parathyroid, pituitary, pancreas).

4. Metabolic & Vascular

  • Familial Hypercholesterolemia: Defective LDL receptor; leads to severe atherosclerosis and tendon xanthomas.
  • Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu): Telangiectasias and recurrent epistaxis.
  • Myotonic Muscular Dystrophy: CTG repeat; “can’t let go” of a handshake (myotonia) and cataracts.

 

Activity