Inheritance - mitochondrial

Definition

Mitochondrial DNA (mtDNA) is inherited exclusively through the maternal line - an affected mother transmits mitochondrial disease risk to all her children (of either sex), but an affected father transmits it to none of his children
Mitochondrial disorders collectively affect a meaningful proportion of the population when both mtDNA and nuclear-encoded mitochondrial gene disorders are included, though pure mtDNA-inherited disease is a smaller subset

Sperm mitochondria are essentially eliminated after fertilisation, so only the egg's mitochondria (and therefore only the mother's mtDNA) are passed to offspring - this is the mechanistic basis of strict maternal inheritance, distinct from all Mendelian nuclear gene patterns
Heteroplasmy - a cell/individual can carry a mixture of normal and mutated mtDNA copies, and the proportion mutated (which varies unpredictably between offspring of the same mother, and even between tissues within one individual) determines whether/how severely disease manifests - a key reason mitochondrial disease severity is so variable within a single family

High-energy-demand tissues (brain, muscle, heart, eye) are preferentially affected, since they are most dependent on oxidative phosphorylation - explains the characteristic multisystem pattern (encephalopathy, myopathy, cardiomyopathy, optic atrophy/retinopathy) seen in many mitochondrial disorders
mtDNA sequencing/deletion analysis, alongside nuclear gene testing (since many mitochondrial proteins are actually nuclear-encoded and can follow standard Mendelian inheritance instead), and muscle biopsy (respiratory chain enzyme studies) support diagnosis

No curative treatment exists for most mitochondrial disorders - management is supportive/symptomatic, targeting the specific organs affected
Genetic counselling explains the maternal transmission pattern and the unpredictable heteroplasmy-driven variability in severity between siblings, which makes precise recurrence risk prediction difficult even with strict maternal inheritance established

MELAS, MERRF, Leber hereditary optic neuropathy, mitochondrial myopathies - each covered in more depth elsewhere where relevant

Not every "mitochondrial disease" is mtDNA-inherited - many mitochondrial proteins are encoded by nuclear genes and therefore follow standard Mendelian (usually autosomal recessive) inheritance instead, a frequently confused distinction with real implications for family counselling

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