Open AccessMitochondrial DNA mutation “m.3243A>G”—Heterogeneous clinical picture for cardiologists (“m.3243A>G”: A phenotypic chameleon)
Author(s) -
Niedermayr Katharina,
Pölzl Gerhard,
SchollBürgi Sabine,
Fauth Christine,
Schweigmann Ulrich,
Haberlandt Edda,
Albrecht Ursula,
Zlamy Manuela,
Sperl Wolfgang,
Mayr Johannes A.,
Karall Daniela
Publication year - 2018
Publication title -
congenital heart disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.828
H-Index - 42
eISSN - 1747-0803
pISSN - 1747-079X
DOI - 10.1111/chd.12634
Subject(s) - medicine , mitochondrial encephalomyopathy , melas syndrome , heteroplasmy , mitochondrial disease , hypertrophic cardiomyopathy , cardiomyopathy , mitochondrial dna , cardiology , lactic acidosis , sick sinus syndrome , context (archaeology) , mitochondrial myopathy , pediatrics , genetics , heart failure , biology , paleontology , gene
Objective 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 M itochondrial E ncephalomyopathy, L actic A cidosis, and at least one S troke‐like episode. We here present various phenotypic characteristics of the mitochondrial mutation m.3243A>G with particular focus on cardiac manifestations. Methods and Results 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. Conclusion 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.