Journal of the Practice of Cardiovascular Sciences

: 2016  |  Volume : 2  |  Issue : 2  |  Page : 128--130

Desmin-related cardiomyopathy presenting as restrictive cardiomyopathy: A case report with review of literature

Kalpana Kumari1, Sudheer Arava1, TC Nag2, Ruma Ray1,  
1 Department of Pathology, All Institute of Medical Sciences, New Delhi, India
2 Department of Anatomy, All Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Sudheer Arava
Department of Pathology, All India Institute of Medical Sciences, Academic Building, Ansari Nagar, New Delhi - 110 029


Isolated cardiac involvement due to deposition of desmin is a rare cause of restrictive cardiomyopathy due to pathogenic mutation in desmin related genes. A 25 year female presented with clinical diagnosis of restrictive cardiomyopathy for which an endomyocardial biopsy was performed. Histology including ultrastructural examination showed features of desmin cardiomyopathy.

How to cite this article:
Kumari K, Arava S, Nag T C, Ray R. Desmin-related cardiomyopathy presenting as restrictive cardiomyopathy: A case report with review of literature.J Pract Cardiovasc Sci 2016;2:128-130

How to cite this URL:
Kumari K, Arava S, Nag T C, Ray R. Desmin-related cardiomyopathy presenting as restrictive cardiomyopathy: A case report with review of literature. J Pract Cardiovasc Sci [serial online] 2016 [cited 2022 Dec 6 ];2:128-130
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Desmin-related myopathy is morphologically characterized by abnormal accumulation of desmin within muscle fibers and skeletal muscle.[1] Occasional involvement of the smooth muscles with visceral manifestations affecting the urinary bladder and intestine has also been documented.[2] Restrictive cardiomyopathies have different etiologies, of which storage disease in the form of deposition of desmin is a rare genetic cause.[3] To date, many of these cardiomyopathies remain undiagnosed due to their diverse clinical picture. We report a rare case of clinically diagnosed restrictive cardiomyopathy due to deposition of desmin in a patient who did not have any clinical manifestation of peripheral muscle weakness.

 Case Report

A 25-year-old female, 7 months postpartum, presented with a history of palpitation, easy fatigability, and polyarthralgia. She also had history of fever, shortness of breath, and pedal edema. However, she had no family history of heart disease, diabetes, or hypertension. Her symptoms subsided on intake of antibiotics and diuretics. Echocardiography showed altered echotexture of septum, poor biventricular function (left ventricular ejection fraction 20%), and mild pericardial effusion. Computed tomography (CT) showed thickened calcified pericardium and dilated atria [Figure 1]. Magnetic resonance imaging showed mild myocardial thickening in the basal inferior portion of the left ventricle and left ventricle hypertrophy more than the right ventricle [Figure 2]. Late gadolinium enhancement was seen in mid myocardial location in mid-cavity apical and along the right ventricular side of septum superiorly. Based on imaging findings, sarcoidosis and amyloidosis were kept as differential diagnoses. Thereafter, the patient underwent endomyocardial biopsy (EMB). Microscopic sections showed myocyte hypertrophy with nucleomegaly and degenerative changes in the sarcoplasm. A single myocyte revealed the presence of an intracytoplasmic butterfly-shaped eosinophilic aggregate [Figure 3]a and [Figure 3]b. Immunohistochemistry for antibodies against desmin showed irregular distribution pattern of desmin within the sarcoplasm of individual cardiac myocytes [Figure 4]a. Masson trichrome stain revealed perimyocytic fibrosis. For electron microscopy (EM), tissue was retrieved from paraffin block and processed and embedded in epoxy resin. Ultrathin sections were stained with lead citrate and uranyl acetate, following staining with anti-desmin antibody. Ultrastructural evaluation showed myofibrillar disruption and deposition of amorphous desmin-positive dense material [Figure 4]b. Based on histomorphological, immunohistochemical, and EM findings, a final diagnosis of desmin-related cardiomyopathy was made. The patient was further investigated and showed raised creatine phosphokinase levels (400 IU/L). Electromyography showed myopathic pattern, indicative of subclinical myopathy.{Figure 1}{Figure 2}{Figure 3}{Figure 4}


Diagnosis of desmin-related myopathy can be difficult due to heterogeneity of clinical features and lack of suspicion due to nonspecificity of the histological findings.[4] Desmin is a 53-kDa and constitutes chief intermediate filament of cardiac and skeletal muscles.[5] Desminopathy may manifest with a variety of phenotypes, depending on the type of mutation and/or location of mutation within the structurally complex desmin molecule.[6] Age of disease onset and rate of progression of disease also are quite variable and depend on the type of inheritance and location of mutation. Review of literature has shown that isolated cases of cardiac involvement typically manifests in the 2nd to 3rd decades of life,[7] but rare reports affecting pediatric age group with exclusive cardiac involvement have also been published.[8] In literature, there is evidence suggesting that different mutations result in distinct clinical phenotypes.[2] Clinical heterogeneity may also result from different modes of inheritance, i.e. dominant, recessive, and de novo mutations, or due to different distribution patterns of desmin within skeletal, cardiac, and smooth muscles.[9] Patients with autosomal recessive inheritance present with early onset and most severe form of disease while patients with de novo desmin mutations are also symptomatic with varied presentations.[9] Autosomal dominant mode of inheritance can present with either isolated progressive skeletal myopathy, skeletal myopathy, followed by cardiomyopathy or respiratory insufficiency, cardiomyopathy, followed by skeletal myopathy or mere isolated cardiomyopathy.[7] The index case presented with cardiac dysfunction, manifesting clinically as restrictive cardiomyopathy, without any complaint of muscle weakness or respiratory symptoms. Mutations in desmin gene may result in loss of desmin protein function or accumulation of misfolded desmin into insoluble aggregates within the myocytes.[3] Myopathic changes and widespread aggregation of desmin-reactive deposits are hallmark of desmin myopathy. These are also known as sarcoplasmic bodies, cytoplasmic bodies, or spheroid bodies depending on shape and location.[10] Commonly, electron-dense granulofilamentous deposits are present in subsarcolemmal location. However, it is also possible that in some cases muscle protein study may not be sufficient for establishing the diagnosis since other proteins such as dystrophin, γ-sarcoglycan, fragment of Aβ, αB-crystallin, and N-terminal epitopes of amyloid precursor protein may be present in the deposit.[11],[12] In the present case, ultrastructural examination with immunogold labeling revealed deposition of desmin-positive material establishing the diagnosis of desmin-related cardiomyopathy. Studies have demonstrated that misfolded protein is unable to form filaments and escapes proteolytic breakdown forming insoluble aggregates compromising contractile ability of individual muscle fibers.[10] Electrocardiography is to be done to rule out arrhythmia and conduction defects and echocardiogram to diagnose or exclude dilated cardiomyopathy.[13] This investigations should be done routinely and on serial follow-up to diagnose later manifestations of symptoms particularly for cardiac disorder succeeding skeletal involvement.

Even after diagnosis, currently, there is no available specific treatment for desmin-associated myopathy.[13] Since proportion of affected patients have insidious onset, early detection and treating cardiac complications can prolong survival. Pathologists play an important role since etiological diagnosis of cause of cardiomyopathy will enable cardiologist for timely treatment of heart failure. Hence, combined use of immunohistochemistry, EM, in the background of a strong clinical suspicion of restrictive cardiomyopathy might help in difficult cases.

In summary, restrictive cardiomyopathy should no longer be termed as idiopathic unless and until extensive search or complete work up is done before final diagnosis. Even in the cases with nonspecific histological finding, EM is recommended since ultrastructural appearance is diagnostic for desmin-related myopathies. Awareness of this rare entity on EMB is of utmost importance as otherwise such cases may be misdiagnosed as idiopathic restrictive cardiomyopathy. In future, genetic testing including mutation analysis might become imperative in establishing the final diagnosis.

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