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Congenit Heart Dis. 2018 Sep;13(5):671-677. doi: 10.1111/chd.12634. Epub 2018 Aug 21.

Mitochondrial DNA mutation "m.3243A>G"-Heterogeneous clinical picture for cardiologists ("m.3243A>G": A phenotypic chameleon).

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Department of Child and Adolescent Health, Pediatrics I/III, Medical University of Innsbruck, Innsbruck, Austria.
University Hospital for Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Innsbruck, Austria.
Department of Medical Genetics, Molecular and Clinical Pharmacology, Human Genetics Division, Medical University of Innsbruck, Innsbruck, Austria.
University Children's Hospital, Paracelsus Medical University Salzburg, Salzburg, Austria.



In general, a mitochondrial disorder is diagnosed on the basis of symptom combinations and confirmed by genetic findings. However, patients carrying the m.3243A>G mutation in the mitochondrial tRNA leucine 1 (MT-TL1) do not always meet all the proposed criteria for the most frequently encountered mitochondrial syndrome "MELAS," an acronym for Mitochondrial Encephalomyopathy, Lactic Acidosis, and at least one Stroke-like episode. We here present various phenotypic characteristics of the mitochondrial mutation m.3243A>G with particular focus on cardiac manifestations.


We followed nine patients (1 month to 68 years old; median 42 years; four female and five male) from nine different families with this m.3243A>G mutation in the MT-TL1. The classical "MELAS" criteria are met by only three of these patients. Electrocardiography (ECG) shows preexcitation pattern with short PR intervals and delta waves (Wolff-Parkinson-White) in three patients and sick sinus syndrome plus atrioventricular block I in one patient. Hypertrophic cardiomyopathy was found in eight patients with moderate to severe regurgitation of various valves.


Cardiac manifestation can encompass hypertrophic or dilated cardiomyopathy, as well as preexcitation syndromes or conduction delay. In general, the clinical presentation to meet the "MELAS" criteria varies due to heteroplasmy. Thus, cardiologists should screen patients with unexplained cardiac features in the context of deafness, short stature and learning disabilities for mtDNA mutations, especially the m.3243A>G mutation. A clear diagnosis is essential as a basis for prognostic advice concerning the disease course and clinical impact on family testing.


MELAS; adults; cardiomyopathy; children; m.3243A>G; mitochondrial disease

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