Cardiac involvement in Becker's muscular dystrophy, necessitating heart transplantation, 6 years before apparent skeletal muscle involvement

doi:10.1016/S0960-8966(99)00045-0

Neuromuscular Disorders

Volume 9, Issue 8, 1 December 1999, Pages 598-600

https://doi.org/10.1016/S0960-8966(99)00045-0 Get rights and content

Abstract

In Becker's muscular dystrophy cardiac abnormalities usually occur after onset of neuromuscular symptoms. We describe a Becker muscular dystrophy patient in whom chronic heart failure, necessitating cardiac transplantation, was the initial manifestation. Neuromuscular symptoms occurred not earlier than 6 years after the initial cardiac symptoms and 5 years after heart transplantation. In conclusion, severe heart failure due to dilated cardiomyopathy may be the initial manifestation of Becker's muscular dystrophy and may predate neuromuscular symptoms for years.

Introduction

Becker's muscular dystrophy is an X-linked skeletal muscle disorder due to in-frame mutations in the 2400 kb large dystrophin gene. In the majority of the Becker muscular dystrophy patients the myocardium is affected by the myopathic process [1], [2], [3], [4], [5], [6], [7]. Myocardial affection (cardiac involvement) may manifest as electrocardiographic abnormalities [4], non-compaction [8], dilated cardiomyopathy [2], [5], [9] or heart failure [2], [10]. Severe cardiac involvement may even necessitate heart transplantation [1], [2], [3], [5], [6], [10], [11]. No association between the type of dystrophin gene mutation and cardiac involvement has been demonstrated so far [5], [7], [12]. Usually, onset of neuromuscular symptoms precedes cardiac involvement, but in rare cases cardiac involvement pre-dates the affection of the skeletal muscle [6], [7], [9], [10]. If cardiac involvement necessitates heart transplantation in a patient who carries a Becker muscular dystrophy mutation but has no neuromuscular symptoms, Becker's muscular dystrophy might be diagnosed only years after surgery.

Section snippets

Case report

A 33-year old man was referred in November 1995 suffering from progressive fatigability, tiredness and weakness of both legs since June 1994. From November 1994 he also observed slowly progressive wasting of the thighs. In October 1989 he underwent orthotopic heart transplantation without major postoperative complications. Heart transplantation was indicated because of end-stage dilated cardiomyopathy of unknown aetiology, diagnosed according to the WHO criteria [5] in March 1988.

Discussion

This case shows, that dilated cardiomyopathy, necessitating heart transplantation, may be the initial manifestation of Becker's muscular dystrophy, even years before the skeletal muscle affection is clinically evident and that such patients start to produce antibodies against the deleted dystrophin sequence even years after heart transplantation.

It is well known that various myopathies, including Becker's muscular dystrophy, manifest not only in the skeletal muscle but also in the myocardium (

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Dystrophinopathies result from mutations of the DMD gene that primarily affect skeletal muscle but also affect heart, brain, and smooth muscle. Advances in the genetic analysis of these disorders have improved diagnosis and genetic counseling and are leading to effective therapies. This chapter details the genetic factors underlying the etiology and pathogenesis of the dystrophinopathies, and discusses the heterogeneous clinical presentations seen in both males and females. The differential diagnosis and appropriate diagnostic testing strategies are also itemized.
Cardiovascular manifestations of neurologic disease
2014, Handbook of Clinical Neurology
Citation Excerpt :
Cardiac involvement typically becomes clinically apparent in the third decade of life, and is associated with ECG abnormalities, arrhythmias, and myocardial abnormalities that are similar to, but less severe than, those seen with DMD (Yilmaz et al., 2008). In a rare subset of patients, cardiac disease may be more severe than skeletal muscle weakness, or even the presenting symptom of BMD (Finsterer et al., 1999; Yokota et al., 2004). In pediatric patients, the occurrence of cardiomyopathy is less frequent than those with DMD but may be more severe.
Cardiac manifestations of neurologic diseases are common in clinical practice. There are numerous anatomic and pathophysiologic links between the normal and abnormal function of both systems. There are a number of brain–heart interactions which affect the care of patients as well as help guide therapeutic development. This is exemplified in the area of vascular neurology where knowledge of the brain–heart connection is essential not only for bedside management but where collaborative efforts between neurology and cardiology are key in developing new strategies for ischemic stroke prevention and treatment, atrial fibrillation, and interventional techniques. This chapter will focus on cardiac manifestations of neurologic disease, with special emphasis on vascular and intensive care neurology, epilepsy, and neurodegenerative and peripheral nervous system diseases.
Prognosis of Duchenne/Becker muscular dystrophy with noncompaction is worse than without noncompaction
2013, International Journal of Cardiology
Cardiomyopathy in neurological disorders
2013, Cardiovascular Pathology
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In most of these cases DCM is found already at onset of the neurological manifestations. Occasionally, DCM may precede the neurological manifestations for years [106]. Frequently, DCM leads to heart failure, which usually responds to established drug treatment.
According to the American Heart Association, cardiomyopathies are classified as primary (solely or predominantly confined to heart muscle), secondary (those showing pathological myocardial involvement as part of a neuromuscular disorder) and those in which cardiomyopathy is the first/predominant manifestation of a neuromuscular disorder. Cardiomyopathies may be further classified as hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, or unclassified cardiomyopathy (noncompaction, Takotsubo-cardiomyopathy). This review focuses on secondary cardiomyopathies and those in which cardiomyopathy is the predominant manifestation of a myopathy. Any of them may cause neurological disease, and any of them may be a manifestation of a neurological disorder. Neurological disease most frequently caused by cardiomyopathies is ischemic stroke, followed by transitory ischemic attack, syncope, or vertigo. Neurological disease, which most frequently manifests with cardiomyopathies are the neuromuscular disorders. Most commonly associated with cardiomyopathies are muscular dystrophies, myofibrillar myopathies, congenital myopathies and metabolic myopathies. Management of neurological disease caused by cardiomyopathies is not at variance from the same neurological disorders due to other causes. Management of secondary cardiomyopathies is not different from that of cardiomyopathies due to other causes either. Patients with neuromuscular disorders require early cardiologic investigations and close follow-ups, patients with cardiomyopathies require neurological investigation and avoidance of muscle toxic medication if a neuromuscular disorder is diagnosed. Which patients with cardiomyopathy profit most from primary stroke prevention is unsolved and requires further investigations.
Thematic review series: Genetics of human lipid diseases: Delineating the role of alterations in lipid metabolism to the pathogenesis of inherited skeletal and cardiac muscle disorders
2012, Journal of Lipid Research
As the specific composition of lipids is essential for the maintenance of membrane integrity, enzyme function, ion channels, and membrane receptors, an alteration in lipid composition or metabolism may be one of the crucial changes occurring during skeletal and cardiac myopathies. Although the inheritance (autosomal dominant, autosomal recessive, and X-linked traits) and underlying/defining mutations causing these myopathies are known, the contribution of lipid homeostasis in the progression of these diseases needs to be established. The purpose of this review is to present the current knowledge relating to lipid changes in inherited skeletal muscle disorders, such as Duchenne/Becker muscular dystrophy, myotonic muscular dystrophy, limb-girdle myopathic dystrophies, desminopathies, rostrocaudal muscular dystrophy, and Dunnigan-type familial lipodystrophy. The lipid modifications in familial hypertrophic and dilated cardiomyopathies, as well as Barth syndrome and several other cardiac disorders associated with abnormal lipid storage, are discussed. Information on lipid alterations occurring in these myopathies will aid in the design of improved methods of screening and therapy in children and young adults with or without a family history of genetic diseases.
Diagnostic work-up and risk stratification in X-linked dilated cardiomyopathies caused by dystrophin defects
2011, Journal of the American College of Cardiology
Citation Excerpt :
The effect of single deletion of exon 48 has been elegantly investigated in 5 male members of a single family by Morrone et al. (27), who documented the abnormal junction of exons 47 to 49 as well as the loss of exon 48 at the messenger ribonucleic acid level; of the 5 patients, 4 adults showed “sub-clinical DCM,” whereas an 8-year-old boy had normal echocardiogram. The long-term prognosis after transplantation seems to be excellent, confirming prior observations in solitary case reports or small series (28,29), with no impact of skeletal muscle involvement on the outcome. Therefore, patients with X-linked DCM associated with DYS defects confirm as good candidates for transplantation similar to other DCM patients.
We sought to describe the diagnostic work-up, phenotype, and long-term evolution of dilated cardiomyopathy (DCM) associated with Dystrophin (DYS) defects.
X-linked DCM associated with DYS defects can be clinically indistinguishable from other types of DCM.
The series comprises 436 consecutive male patients diagnosed with DCM. Patients underwent endomyocardial biopsy (EMB). Genetic testing employed multiplex polymerase chain reaction and multiple ligation dependent probe assay for deletions and direct sequencing of the 79 exons and flanking regions of the gene for point mutations or small rearrangements.
We identified DYS defects in 34 of 436 patients (7.8%) (onset age 34 ± 11 years, age range 17 to 54 years); 30 had proven X-linked inheritance. The 2 phenotypes included DCM with mild skeletal myopathy and/or increased serum creatine phosphokinase (n = 28) or DCM only (n = 6). The EMB showed defective dystrophin immunostain. The DYS defects consisted of 21 in-frame deletions and 11 out-of-frame deletions as well as 1 stop and 1 splice-site mutation. During a median follow-up of 60 months (interquartile range: 11.25 to 101.34 months) we observed 17 events, all related to heart failure (HF) (median event-free survival: 83.5 months). Eight patients (23%) underwent transplantation, and 9 (26%) died of HF while waiting for transplantation. Eight patients received an implantable cardioverter-defibrillator, although none had device intervention during a median follow-up of 14 months (interquartile range: 5 to 25 months). No patient died suddenly, suffered syncope, or developed life-threatening ventricular arrhythmias.
DYS-related DCM should be suspected in male patients with increased serum creatine phosphokinase (82%) and X-linked inheritance. The disease shows a high risk of end-stage HF but a lower risk of life-threatening arrhythmias.

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Short case reportCardiac involvement in Becker's muscular dystrophy, necessitating heart transplantation, 6 years before apparent skeletal muscle involvement

Abstract

Introduction

Section snippets

Case report

Discussion

Neuromusc Disord

Neuromusc Disord

J Neurol Sci

Am Heart J

Serum antibodies to the deleted dystrophin sequence after cardiac transplantation in a patient with Becker's muscular dystrophy

N Engl J Med

Acute pulmonary edema as the inaugural symptom of Becker's muscular dystrophy in a 19-year-old patient

Clin Cardiol

Short case report
Cardiac involvement in Becker's muscular dystrophy, necessitating heart transplantation, 6 years before apparent skeletal muscle involvement