Harvey's Garden

Modes of inheritance

2 min read

Autosomal Dominant (AD)

  • Inheritance Pattern
    • Affected individuals in every generation (vertical transmission)
  • Key Features
    • Often structural proteins, receptors, or transcription factors
    • Variable expressivity (severity varies among affected individuals)
    • Incomplete penetrance (not all with mutation show disease)
    • New mutations common (especially if reduced reproductive fitness)
  • Classic Examples
    • Familial hypercholesterolemia (LDL receptor defect)
    • Huntington disease (CAG repeat expansion, chromosome 4)
    • Marfan syndrome (fibrillin-1 defect)
    • Neurofibromatosis type 1 (NF1 gene)
    • Achondroplasia (FGFR3 mutation)
    • ADPKD (PKD1/PKD2)
    • Hereditary spherocytosis (spectrin/ankyrin defects)

Autosomal Recessive (AR)

  • Inheritance Pattern
    • Skips generations (horizontal transmission)
  • Key Features
    • Often enzyme deficiencies
    • Carriers asymptomatic (heterozygotes)
    • More common in isolated populations
  • Classic Examples
    • Cystic fibrosis (CFTR, ΔF508 most common)
    • Sickle cell disease (β-globin mutation)
    • Thalassemias (α or β-globin defects)
    • Phenylketonuria (phenylalanine hydroxylase deficiency)
    • Albinism (tyrosinase deficiency)
    • Glycogen storage diseases (most types)
    • Lysosomal storage diseases (Tay-Sachs, Gaucher, Niemann-Pick)
    • Hemochromatosis (HFE gene, C282Y mutation)

X-Linked Recessive (XLR)

  • Inheritance Pattern
    • Affects mostly males
    • Transmitted through carrier females
    • No male-to-male transmission
    • Affected males have unaffected parents
    • 50% of male offspring of carrier females affected
  • Key Features
    • Males hemizygous (only one X chromosome)
    • Females usually carriers (lyonization may cause mild symptoms)
  • Classic Examples
    • Duchenne/Becker muscular dystrophy (dystrophin gene)
    • Hemophilia A (Factor VIII deficiency)
    • Hemophilia B (Factor IX deficiency)
    • G6PD deficiency
    • Fabry disease (α-galactosidase A deficiency)
    • Hunter syndrome (iduronate sulfatase deficiency)
    • Lesch-Nyhan syndrome (HGPRT deficiency)
    • Bruton agammaglobulinemia (BTK gene)
    • Wiskott-Aldrich syndrome (WAS gene)

X-Linked Dominant (XLD)

  • Inheritance Pattern
    • Affects both sexes, but females > males
    • No male-to-male transmission
    • Affected males have all affected daughters
    • Often lethal in males (in utero)
  • Classic Examples
    • Fragile X syndrome (CGG repeat expansion in FMR1)
    • Vitamin D-resistant rickets (hypophosphatemic rickets)
    • Rett syndrome (MECP2 mutation, lethal in males)
    • Incontinentia pigmenti (NEMO gene, lethal in males)

Mitochondrial Inheritance

  • Inheritance Pattern
    • Maternal inheritance only (mitochondria from oocyte)
    • Affects both sexes equally
    • All offspring of affected mother may be affected
    • Affected fathers do NOT pass to offspring
  • Key Features
    • Heteroplasmy (variable % of mutant mitochondria in cells)
    • Affects high-energy tissues (muscle, brain, heart)
    • Variable expressivity due to heteroplasmy
  • Classic Examples
    • Leber hereditary optic neuropathy (acute vision loss in young males)
    • MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, Stroke-like episodes)
    • MERRF (Myoclonic Epilepsy with Ragged Red Fibers)
    • Kearns-Sayre syndrome (ophthalmoplegia, retinopathy, cardiomyopathy)

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