AN74.1-4 | Patterns of Inheritance — Summary & Reflection

REFLECT

Consider how your understanding of inheritance patterns would change your approach to a family history. When you next take a patient history, can you identify whether a clustering of disease in the family follows an AD, AR, XLR, or multifactorial pattern? Think about the practical implications: if you suspect an AR condition in a consanguineous family, what screening would you recommend for the extended family? If a patient with neurofibromatosis asks about the risk to their children, can you explain why all children have a 50% risk regardless of how many siblings are already affected? Reflect on why India's burden of genetic disease is shaped by social practices like consanguinity and how genetic counselling must be culturally sensitive while remaining scientifically accurate.

KEY TAKEAWAYS

This guide covered the major patterns of inheritance mandated by NMC competencies AN74.1-74.4. Autosomal dominant conditions require only one mutant allele, show vertical transmission, and are modified by penetrance, expressivity, and anticipation; achondroplasia (FGFR3 G380R mutation) is the prototype with 80% arising de novo. Autosomal recessive conditions require two mutant alleles, show horizontal transmission, and are more common with consanguinity; cystic fibrosis (CFTR gene, ΔF508 mutation) illustrates multi-system involvement from a single gene defect. X-linked recessive conditions predominantly affect males with no male-to-male transmission; haemophilia and G6PD deficiency are clinically important in India. X-linked dominant conditions affect both sexes but may be male-lethal; vitamin D-resistant rickets (PHEX gene) is the key example in the NMC curriculum. Mitochondrial inheritance is strictly maternal. Multifactorial inheritance involves polygenic and environmental components; the threshold model explains all-or-none disease outcomes from continuous liability distributions. Pedigree construction and analysis is the foundational tool for clinical genetics, and Hardy-Weinberg equilibrium enables carrier frequency calculations essential for genetic counselling.