Makindo Medical Notes

Autosomal dominant inheritance is a genetic pattern where only one copy of a defective gene (inherited from either parent) is enough to cause expression of a trait or disorder. These conditions often appear in every generation of a family pedigree.

📌 Key Characteristics

• 👨‍👩‍👧 Affected Individuals :
  • Only one mutated copy of the gene is required for an individual to be affected.
  • Each child of an affected parent has a 50% chance of inheriting the condition.
  • Disorders are typically visible in successive generations.
• ⚖️ Equal Gender Distribution :
  • Males and females are affected equally (not sex-linked).
• 🎭 Variable Expressivity :
  • Symptoms and severity vary between affected individuals, even in the same family.
• 🕵️ Reduced Penetrance :
  • Some carriers of the mutation may show no clinical signs at all.
• ⏳ Anticipation :
  • Seen in disorders like Huntington’s — symptoms appear earlier and more severely in successive generations due to trinucleotide repeat expansion.
• ✨ New Mutations :
  • Some cases arise de novo without a family history (e.g. achondroplasia).

🧪 Examples of Autosomal Dominant Disorders

• 🧠 Huntington's Disease :
  • HTT gene mutation → abnormal CAG repeat expansion.
  • Progressive neurodegeneration: movement disorder, cognitive decline, psychiatric symptoms.
• 📏 Marfan Syndrome :
  • FBN1 gene mutation → defective fibrillin.
  • Connective tissue disorder: tall stature, long fingers, lens dislocation, aortic root dilatation.
• 🦴 Achondroplasia :
  • FGFR3 gene mutation.
  • Short stature with disproportionately short limbs.
• 💉 Familial Hypercholesterolemia :
  • LDLR gene mutation (sometimes APOB or PCSK9).
  • Very high LDL cholesterol → premature cardiovascular disease, tendon xanthomas.

🧾 Genetic Counseling and Testing

• 🔍 Predictive Testing :
  • Detects at-risk individuals before symptoms (e.g. Huntington’s testing).
• 👶 Prenatal Testing :
  • Amniocentesis or chorionic villus sampling (CVS) can diagnose certain mutations before birth.
• 🧫 Preimplantation Genetic Diagnosis (PGD) :
  • Embryo selection during IVF to avoid transmission.
• 🧑‍⚕️ Genetic Counseling :
  • Supports families, explains inheritance, risks, and reproductive options.

⚕️ Management and Treatment

• 💊 Symptomatic Treatment :
  • Focus on managing complications (e.g. physiotherapy in Marfan, psychiatric care in Huntington’s).
• 🔧 Surgical Interventions :
  • For example, aortic root repair in Marfan syndrome.
• 🥗 Lifestyle Modifications :
  • Diet and exercise crucial in familial hypercholesterolemia.
• 🧬 Gene Therapy :
  • Emerging therapies may correct or silence defective genes in the future.

📝 Summary

Autosomal dominant inheritance means one mutated gene = disease. It shows vertical transmission in pedigrees, affects both sexes equally, and may vary in severity due to expressivity and penetrance. Examples include Huntington’s disease, Marfan syndrome, achondroplasia, and familial hypercholesterolemia. Early recognition, genetic counseling, and tailored management are key in supporting patients and families.