Case

An 8-year-old girl with a normal family history, normal psychomotor development, and no significant past medical history was referred to our hospital because of nausea, cough, and generalised body swelling. At presentation, her characteristics were as follows: temperature, 36.4°C; pulse rate, 110 beats/min; respiratory rate, 30 cycles/min; and blood pressure, 90/70 mmHg. She had a gallop rhythm, a grade 3/6 parasystolic murmur at the cardiac apex, bibasal crepitation, and hepatomegaly. Chest radiography showed cardiac enlargement (cardio-thoracic ratio, 60%). Echocardiography showed reduced left ventricular systolic function (left ventricular ejection, 25%) with marked ventricular dilation and severe mitral regurgitation. Her laboratory data showed that the troponin T and brain natriuretic peptide levels were 104.4 (upper limit: 26.2 pg/mL) and 2431 pg/mL (upper limit: 18.4 pg/mL), respectively. Cardiac catheterisation on hospitalisation day 9 showed no abnormalities in coronary artery blood flow, and myocardial biopsy showed no evidence of fibrosis other than a mild infiltration by inflammatory cells, which was diagnosed as acute myocarditis. She initiated catecholamine administration for heart failure, but her cardiac contractility and mitral regurgitation were not improved; thus, she was referred to our hospital.

On admission, the patient was stable. Her height was 123 cm (-0.8 SD) and her weight was 17.2 kg (-3.3 SD). A chest radiograph showed mild cardiac enlargement, and a 12-lead electrocardiogram showed reduced amplitude of the P wave and mildly prolonged PR interval, but not atrial or ventricular tachycardia (Fig 1). Holter electrocardiogram showed no arrhythmias. Laboratory data showed mildly increased creatinine kinase (338 U/L) and creatinine kinase-MB levels (26 U/L). Echocardiography showed diffusely decreased cardiac contractility (left ventricular ejection fraction, 40%) and severe mitral regurgitation. Despite heart failure management, cardiac function was not improved; therefore, she underwent mitral valvuloplasty for functional mitral regurgitation. The patient’s condition initially improved and the brain natriuretic peptide levels decreased to 375 pg/mL, but later deteriorated, and she was repeatedly admitted and discharged. Because of the lack of improvement in the course of acute myocarditis, myocardial biopsy was repeated, but there was no fibrosis of the myocardium. Cardiac MRI findings showed delayed enhancement in the ventricular septum to the posterior inferior wall.

Figure 1.

Twelve-lead electrocardiography shows reduced amplitude of the Pwave and a mildly prolonged PR interval.

Neurological examination due to prolonged hyperCKemia revealed posterior neck joint contracture and proximal muscle weakness (deltoid manual muscle test; MMT 4-/4-, biceps MMT 4/4). We suspected that the patient may have had a form of skeletal muscle disease, but the dystrophin multiplex-ligation-dependent probe amplification test results and the skeletal muscle MRI findings were normal. Skeletal muscle biopsy showed no abnormal findings, and immunostaining was normal. Genetic testing using next-generation sequencing revealed a mutation in the LMNA gene (c.182T>C:p. Leu6Pro) (Fig 2). We confirmed that the mutation was a de novo mutation, which was not observed in either parent, and she was diagnosed with Emery-Dreifuss muscular dystrophy caused by an LMNA mutation, consistent with the clinical history. She was listed for heart transplantation, as it was difficult to manage her condition with medical treatment alone. Informed consent was obtained from the patient’s parents for publication of this case report.

Figure 2.

Sequence analysis of the LMNA gene. A mutation (c.182T>C:p. Leu6Pro) is observed in the proband.