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

ObjectiveIn 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. Methods and ResultsWe followed nine patients (1month to 68years old; median 42years; 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. ConclusionCardiac 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.