Novel CMR findings in megaconial congenital muscular dystrophy

A 27-year-old male presented with acute heart failure, who had mental retardation and muscle weakness from his childhood. He was born to consanguineous parents. Physical examination revealed Gower's sign, jugular vein distention, and severe peripheral edema. Laboratory tests showed elevated N-terminal pro-brain natriuretic peptide of 13,371 ng/ml (normal < 88 ng/ml), troponin-T at 93.9 ng/L (normal < 14 ng/L), and creatine kinase (CK) of 2624 IU/L (normal < 226 IU/L). Electrocardiogram displayed atrial flutter and right bundle-branch block. A normal left ventricle (LV) chamber size with a reduced ejection fraction of 34% and an enlarged right ventricle (RV) with decreased systole were identified by echocardiography. Further investigation by cardiac magnetic resonance (CMR) detected RV dilation, biventricular hypokinesis, and trace pericardial effusion. Although late gadolinium enhancement (LGE) was confined to the basal to mid anteroseptal wall (Figure 1A,B), markedly increased extracellular volume fraction (ECV; Figure 1C) and native T1 (Figure 1D) indicated diffuse myocardial fibrosis of the LV. Despite normal brain magnetic resonance imaging, Montreal Cognitive Assessment and Mini-Mental State Examination confirmed a severe cognitive impairment. Despite decreased proximal muscle strength and a 10-time higher serum CK level, the electromyography was negative. Muscle biopsy of the left deltoid suggested chronic myogenic myopathy, but the dystrophin N, C; dysferlin; and sarcoglycan α, β, γ, and δ were not absent. Therefore, the high-throughput sequencing was performed, which detected a homozygous nonsense mutation of c.319G > T (p.G107X) on exon 2 and concluded the diagnosis of megaconial congenital muscular dystrophy (MCMD). Unfortunately, the patient died of pump failure 9 months after the diagnosis. Congenital muscular dystrophy is a heterogeneous group of inherited disorders, in which MCMD is a less common subtype1 and a rare autosomal recessive disorder caused by mutations in choline kinase beta—a key enzyme for de novo biosynthesis of phospholipid on mitochondrial membrane.2 Apart from hypotonia and muscle weakness that occurred early in childhood, later onset of dilated cardiomyopathy and other cardiac anomalies were affected in some patients1 but remained poorly described. It is characterized by global developmental delay, proximal muscle weakness, and nonexpressive language with intact brain structure. Cardiac involvement, predominantly presented as dilated/hypokinetic cardiomyopathy, occurs in half of the patients and is the major cause of death.2 The current report first described the CMR findings of MCMD and was distinct from other mitochondrial myopathies that showed the intramural pattern of LGE in the basal inferolateral wall or the overt concentric hypertrophy with a rather unique, focally accentuated, and diffusely distributed LGE.3 Of note, using LGE alone might underestimate the extent of myocardial damage, whereas native T1 and ECV help uncover diffuse fibrosis that strongly predicts poor prognosis.4 The authors declare no conflict of interest.