Dominant appears in every generation; recessive skips; X-linked spares father to son
Mnemonic
“Dominant goes down the generations; recessive skips them”:
- Autosomal dominant - vertical transmission, every generation affected, males and females equally, and male to male transmission is possible. Structural proteins. Examples: Huntington’s, Marfan’s, polycystic kidney disease, familial hypercholesterolaemia, neurofibromatosis
- Autosomal recessive - horizontal, siblings affected, parents are carriers, associated with consanguinity. Enzyme deficiencies. Examples: cystic fibrosis, sickle cell, thalassaemia, haemochromatosis, phenylketonuria
- X-linked recessive - males affected, females carriers, no male to male transmission, transmitted through carrier mothers. Examples: haemophilia A and B, Duchenne, G6PD, red-green colour blindness
- X-linked dominant - affected fathers pass it to all daughters and no sons. Examples: vitamin D resistant rickets, Alport’s
- Mitochondrial - maternal transmission only, affecting both sexes. Examples: MELAS, Leber’s hereditary optic neuropathy
“Dominant is structural, recessive is enzymatic” and “no father to son in X-linked” are the two rules that solve most pedigree questions.
Expansion
| Pattern | Features | Examples |
|---|---|---|
| Autosomal dominant | Every generation, male to male transmission occurs, 50 per cent risk | Huntington, Marfan, familial hypercholesterolaemia, neurofibromatosis, polycystic kidney disease |
| Autosomal recessive | Skips generations, consanguinity, 25 per cent risk from carrier parents | Cystic fibrosis, sickle cell, thalassaemia, most inborn errors |
| X-linked recessive | Mainly males, no male to male, transmitted through carrier mothers | Haemophilia A and B, Duchenne, G6PD, colour blindness |
| X-linked dominant | Affected males more severely; no male to male | Vitamin D resistant rickets, Rett syndrome |
| Mitochondrial | Maternal transmission only, affects both sexes | Leber optic neuropathy, MELAS |
Useful generalisations: structural protein defects tend to be dominant, while enzyme deficiencies tend to be recessive, because 50 per cent of normal enzyme activity is usually sufficient.
Complicating features to recognise: incomplete penetrance (not all carriers affected), variable expressivity, anticipation in trinucleotide repeat disorders, mosaicism, and imprinting.
Mitochondrial disorders show heteroplasmy, which is why severity varies so widely within a family.