An Unusual Heart Disease in a Young Old Boy

A 17-year-old boy was referred for a cardiological consultation because of progressive dyspnoea for 1 year. The boy was known to have a learning disability, progerioid features, muscular dystrophy, lipodystrophy, joint contractures, hyperlipidaemia and liver steatosis (Figure 1).

There were no known cardiomyopathies or neuromuscular diseases in his family.

The electrocardiogram (ECG) showed left ventricular hypertrophy and Q-waves in the inferolateral leads (Figure 2). Echocardiography revealed left ventricular dilatation and severe systolic dysfunction (ejection fraction 25%) (Figure 3). On cardiac magnetic resonance imaging (MRI), myocardial transmural late gadolinium enhancement in the inferolateral wall was found (Figure 4). Coronary angiography showed normal coronary arteries (Figure 5). A 24-hour Holter ECG showed about 1000 isolated polymorphic ventricular premature beats. Treatment with a beta-blocker, angiotensin converting-enzyme (ACE) inhibitor and spironolactone was started with symptomatic improvement. Furthermore, we are considering inplantable cardioverter-defibrillator (ICD) implantation as primary prevention for sudden cardiac death.

A genetic test showed a very rare lamin gene mutation: LMNA:NM_005572:exon1:c.C29T:p.T10l.

This rare laminopathy is probably responsible for the whole clinical picture of this young patient.

The lamin gene codes for lamin A/C, which is a structural protein of the nuclear envelope. Laminopathies cause a wide variety of diseases involving skeletal muscles, adipose tissue, peripheral nerves, premature aging and cardiac involvement, including left ventricular dysfunction, atrioventricular block, and atrial and ventricular arrhythmias. The clinical manifestations could involve one or more systems. It has been estimated that LMNA mutations cause up to 10% of familial dilated cardiomyopathies. The cardiac involvement is progressive, with poor prognosis [1,2,3].

Typically, in the LMNA cardiomyopathy, a midventricular septal fibrosis is described on cardiac MRI. In our patient, despite normal coronary arteries, an inferolateral transmural scar was documented, similar to the pattern described in Duchenne and Becker muscular dystrophy [4].

In a young patient with dilated cardiomyopathy, particularly if multisystemic manifestations are present, it is important to suspect a laminopathy, because of the poor prognosis of this disease. In the presence of clinical manifestations that raise suspicion of a laminopathy, a cardiological assessment should be considered.