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At a glance

Very rare syndrome characterized by extensive aortic calcifications, dental anomalies, and abnormal ossification of the distal limbs.

Synonym

Merten-Singleton Syndrome.

Incidence

Extremely rare. Described in three affected families.

Genetic inheritance

Autosomal dominant with variable expression.

Pathophysiology

Mutation in IFIH1 (interferon induced with helicase C domain 1) gene on 2q24.2, which encodes MDA5 (melanoma differentiation-associated protein 5) resulting in an enhanced interferon response in affected families. These mutations have also been linked to the ☞Aicardi-Goutières Syndrome with only limited overlap. A second mutation has been reported in Dead-box polypeptide 58 gene which has been dubbed “Type 2” but has similar phenotype to “Type 1” without dental anomalies. Linear calcification of the ascending aorta and severe calcific mixed aortic valve disease (stenotic and regurgitant). Histology shows extensive medial necrosis of the proximal aorta and its branches with secondary plaques of calcium confined to those areas. No evidence of previous inflammation or destructive/reparative processes.

Diagnosis

Clinical findings consistent with aortic stenosis, possibly associated with mild regurgitation and left ventricular hypertrophy. ECG may show left ventricular hypertrophy, left axis deviation, or left bundle branch block. Radiographic examination characteristically shows severe tubular calcification of the ascending aorta and aortic valve. Cases described have not shown aortic dilatation. Echocardiographic and cardiac catheter studies may reveal the aortic stenosis and regurgitation across a tricuspid aortic valve. History, examination, and investigations must exclude other causes of aortitis and aortic calcification, for example, syphilis, arthrosclerosis, rheumatoid arthritis, and ankylosing spondylitis. The Singleton-Merten Syndrome is also described as showing ascending aortic calcification and aortic valve disease developing in childhood, but is characterized by dental dysplasia and osteoporosis.

Clinical aspects

Cardiac murmur detected in first or second decades of life. The clinical features include aortic stenosis and radiographic evidence of calcification seen from second decade. The progressive course leads to an eventual need for aortic valve replacement.

Precautions before anesthesia

Obtain full cardiac history, particularly with regard to heart failure, syncope, and chest pain. Evaluate ECG for evidence of left ventricular hypertrophy and bundle branch block. Review chest radiograph for evidence of aortic calcification, ventricular dilatation, and pulmonary congestion. Echocardiography to assess aortic valve gradient and left ventricular function. Review cardiac catheter studies if available.

Anesthetic considerations

Those pertinent to aortic stenosis and/or regurgitation. Bacterial endocarditis prophylaxis necessary.

Pharmacological implications

Caution with use of intravenous induction agents in presence of decreased cardiac output. Circulation time may be prolonged. Avoid excessive decreases in systemic vascular resistance in presence of relatively fixed cardiac output across a stenotic valve.

Other conditions to be considered

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