Elsevier

Brain and Development

Volume 25, Issue 1, January 2003, Pages 62-66
Brain and Development

Case report
Centronuclear myopathy and cardiomyopathy requiring heart transplant

https://doi.org/10.1016/s0387-7604(02)00151-1Get rights and content

Abstract

Centronuclear myopathy has been extremely rarely associated with cardiomyopathy, which can lead to heart failure and premature death. We report the case of a 3.5-year-old girl with early-onset dilated cardiomyopathy, biventricular hypertrophy and histologic features suggestive of centronuclear myopathy. After unsuccessful medical treatment for heart failure, she underwent cardiac transplantation at the age of 4.5 years. Results of a skeletal muscle biopsy showed increased central nuclei and perinuclear vacuolations with aggregates of mitochondria. Examination of the heart at the time of transplantation confirmed a diagnosis of dilated cardiomyopathy. Histologic results revealed hypertrophic myocardiocytes, focal areas of infarction and endocardial fibroelastosis, most prominently in the left ventricle. Although cardiomyopathy is commonly associated with other childhood myopathies, to our knowledge, this is the youngest patient reported with centronuclear myopathy presenting with heart failure caused by cardiomyopathy, and the first patient to successfully undergo cardiac transplantation. One year after the heart transplant, there were no signs of rejection. We recommend detailed cardiac assessment with regular follow-up for children with histologic features consistent with centronuclear myopathy.

Introduction

Centronuclear myopathy (CNM) is a congenital myopathy, first described by Spiro et al. [1] in 1966. It is clinically characterized by generalized hypotonia, ptosis, ophthalmoplegia, and facial and limb weakness [2]. CNM has great clinical variability, ranging from a severe, fatal disorder (the neonatal X-linked form) to mild weakness with normal life expectancy (the autosomal recessive form). Classification is based on the age of onset, mode of inheritance, severity of involvement and rapidity of progress [3]. Three major patterns of inheritance have been described: the X-linked recessive form, called by some authors myotubular myopathy is linked to the Xq28 gene; the autosomal recessive form with childhood onset; and the autosomal dominant form, which has a milder course with adult onset [3], [4], [5], [6].

Diagnosis of the disease is based on clinical suspicion and the results of appropriate muscle histopathological and electron microscopic studies, and exclusion of other causes of centrally nucleated muscle fibers [3], [5]. CNM is suspected if the percentage of central nuclei in the muscle biopsy samples is increased (normal range ≤3%). This suspicion is supported by clinical evidence of facial and limb weakness and exclusion of other causes of muscular disorders associated with central nuclei [6].

The pathological features of CNM are an increased number of centrally nucleated muscle fibers, variation in the diameter of the muscle fibers, type I fiber predominance or atrophy, and a central area of the muscle cell devoid of activity on reaction with adenosinetriphosphatase (ATPase) [6], [7].

We report a case of CNM in a young girl with a rare presentation of severe dilated cardiomyopathy that necessitated heart transplantation. To the best of our knowledge, this is the first reported patient with CNM to successfully undergo heart transplantation.

Section snippets

Case report

A 3.5-year-old girl, who presented with early-onset dilated cardiomyopathy, biventricular hypertrophy and CNM, was born at term; her birth weight was 3.4 kg. The pregnancy was uncomplicated; fetal movements were perceived to be normal; the postnatal period was uneventful; and her developmental history was normal.

At age 30 months, the patient presented with fever, cough, shortness of breath and lethargy. Subsequently, she developed acute congestive heart failure. After being diagnosed with

Discussion

Although cardiomyopathy is commonly associated with other childhood myopathies, our patient is the youngest reported with CNM presenting with heart failure caused by cardiomyopathy. CNM is rarely associated with cardiomyopathy: only three reports [2], [7], [9] have indicated this association. Almost all reported patients with CNM and cardiac manifestations die because of congestive heart failure. Our patient was the first patient with CNM and congestive heart failure to successfully undergo

Acknowledgements

This manuscript was prepared with the assistance of Editorial Services, The Hospital for Sick Children, Toronto, Canada.

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