Table 1.

Summary of inherited mitochondrial dysfunction mutations.

Inheritance Pattern	Clinical Syndrome	Mutations	Affected Genes/Proteins in Mitochondria	Arrhythmias Involved	Cardiac Manifestations	Other Systems Involved
Maternally Transmitted	Myoclonic epilepsy with ragged red fibers (MERRF) [35,36]	m.8344 A to G, m.8356 T to C, m.8363 G to A, and m.8361 G to A	MT-TK	Pre-excitation	Dilated and histiocytoid cardiomyopathy	Myoclonus, spasticity, myopathy
Maternally Transmitted	Leber hereditary optic neuropathy [37]	m.3460 G to A, m.11778 G to A, and m.14484 T to C	MT-ND1, MT-ND4, MT-ND4L, or MT-ND6	Sudden death	Dilated cardiac myopathy	Loss of vision
Maternally Transmitted/Sporadic	Neuropathy, ataxia, and retinitis pigmentosa (NARP) [38,39]	m.8993 T to G	MT-ATP6	Conduction block	Cardiomyopathy	Psychomotor retardation, epilepsy, ataxia, neuropathy, and myopathy
Maternally Transmitted	Leigh syndrome (Mt DNA associated subtype) [40]	More than 75 monogenic causes	MT-TL-1, MT-TK, MT-TI	Conduction block	Hypertrophic cardiomyopathy	Psychomotor regression, respiratory failure, muscular and movement disorder (death at young age)
Maternally Transmitted/Sporadic	Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) [41]	m.3243 A to G mutation in MT-TL-1	MT-TL1, MT-TK, and MT-TE genes provide instructions for making tRNAs	Pre-excitation, bundle branch block	Dilated/hypertrophic cardiomyopathy	Severe encephalopathy, lactic acidosis, myoclonus
Maternally Transmitted/Sporadic	Kearns–Sayre syndrome [42,43]	4.9 kb Mt DNA deletion (12 genes)/point mutation	Not determined, involved in mitochondrial protein expression and oxidative phosphorylation	Atrioventricular conduction defects	Cardiomyopathy, syncope, Adams–Stokes syndrome, sudden cardiac death	Anemia, myopathy, lactic acidosis, CNS abnormality, endocrine abnormality, renal disease, sensorineural deafness, and retinal involvement
X-Linked Recessive	Barth syndrome [44]	Mutations or deletions of the highly conserved Xq28 tafazzin (TAZ) gene	Tafazzin protein is essential for remodeling of cardiolipin, a principal phospholipid of the inner mitochondrial membrane	Ventricular arrhythmia, sudden cardiac death, prolonged QTc interval	Dilated/hypertrophic cardiomyopathy, endocardial fibroelastosis (EFE), left ventricular non-compaction (LVNC)	Skeletal myopathy, growth delay, neutropenia and increased urinary excretion of 3-methylglutaconic acid (3-MGCA)
Autosomal Recessive	Friedreich’s Ataxia[45]	GAA triplet repeat expansion in the first intron Frataxin (FXN) gene, silencing the gene	Frataxin: expressed in the mitochondria of tissue with high metabolic rates, involved in assembly of iron-sulfur clusters	Conduction block, atrial fibrillation, atrial/ventricular tachycardias, ECG repolarization abnormalities	Hypertrophic cardiomyopathy, heart failure	Gait and limb ataxia, dysarthria, loss of lower limb reflexes, optic neuropathy

Abbreviations: CNS, Central nervous system; ECG, Electrocardiography; MT, Mitochondria.