A case report of a rare genetic mutation (LMNA-C.185G>C, p.Arg62Pro) associated with dilated cardiomyopathy in a Han Chinese child

Abstract

Dilated cardiomyopathy (DCM) remains an enigmatic myocardial disorder characterized either by enlargement of either the left or right ventricle or both and reduced contractility, posing a significant burden on pediatric populations as a leading cause of cardiac-related mortality and morbidity. This paper presents a compelling case of DCM in a Han Chinese child whose genomic analysis unveiled a novel LMNA-C.185G>C (p.Arg62Pro) variant. Over a meticulous 3-year clinical follow-up, spanning ten outpatient consultations and hospital admissions since the initial diagnosis, the patient exhibited a progressive emergence of various cardiac conduction anomalies closely mirroring LMNA-associated phenotypes. Delving into a comprehensive review of the patient's 14-year medical journey and familial history, antecedent signs of muscular dystrophy (MD) predated DCM onset. Familial scrutiny revealed a lineage marred by muscular atrophy, with the patient's maternal grandmother having a history of muscular dystrophy and an episode of DCM, necessitating cardiac transplantation in the patient's uncle at age 37. This scenario illuminates the intricate interplay between LMNA-associated diseases and genetic predisposition. Timely identification of etiological triggers stands paramount in DCM management. Beyond conventional genetic scrutiny, leveraging novel serum biomarkers such as anti-heart muscle antibodies (AHA) remarkably enhanced diagnostic precision. Notably, personalized therapeutic interventions comprising prednisolone regimens and intravenous immunoglobulin infusions precipitated marked amelioration in heart failure symptoms and serum biomarker profiles. It is noteworthy to identify this novel genetic locus within the Han Chinese populace, underscoring the imperative of expanding the LMNA mutation repository within this demographic cohort. Early recognition of clinical manifestations and etiological cues in pediatric DCM heralds a paradigm shift in risk prognostication and individualized therapeutic interventions, underscoring the profound significance of precision medicine in combating rare familial cardiomyopathies.

Keywords: LMNA gene mutation; dilated cardiomyopathy; heart failure; muscular dystrophy; pediatric.

Figure 1

The patient's NT-proBNP level from 2021/9/24 to 2023/8/23.

Figure 2

The patient's CK level from 2021/9/24 to 2023/8/23.

Figure 3

The patient's CK-MB level from 2021/9/24 to 2023/8/23.

Figure 4

ECG on September 28, 2021.

Figure 5

ECG on September 29, 2022.

Figure 6

Echocardiogram results on October 14, 2021. (A) Four-chamber view showing global enlargement of the heart. (B) Long-axis view of the left ventricle indicating a left ventricular end-diastolic diameter of 51.60 mm. (C) Increased number of trabeculations in the mid to lower segments of the left ventricular lateral wall, with a trabecular height of 8.5 mm at the lateral wall. (D) Moderate regurgitation of both the mitral and tricuspid valves. (E) Indirect estimation of pulmonary artery systolic pressure of 40 mmHg. (F) Reduced cardiac function with an ejection fraction (EF) of 33%.

Figure 7

LVEF results from September 17, 2021, to February 22, 2023.

Figure 8

Chest x-ray on September 23, 2021.

Figure 9

Cardiac MRI on September 23, 2021. (A,B) Show short-axis and four-chamber cine images that suggest left ventricular enlargement, reduced wall motion, and increased free wall thickness. (C) Showed delayed enhancement imaging in the short-axis view, which revealed linear enhancement between the mid-septal myocardium and the mid-lateral left ventricular wall.

Figure 10

LMNA gene mutation DCM disease family chart.