Cardiac Involvement in Patients With Limb-Girdle Muscular Dystrophy Type 2 and Becker Muscular Dystrophy

Sveen, Marie-Louise; Thune, Jens Jakob; Køber, Lars; Vissing, John

doi:10.1001/archneur.65.9.1196

Cited by 61 publications

(66 citation statements)

References 21 publications

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“…Cardiac involvement has also been reported in several other muscular dystrophies such as Duchenne and Becker, mainly revealing dilated cardiomyopathy [40,41]. A beneficial effect of the combination of an ACE-inhibitor and a beta-blocker on long-term survival of Duchenne muscular dystrophy has previously been reported.…”

Section: Discussionmentioning

confidence: 89%

Cardiac manifestations of myotonic dystrophy type 1

Petri

Vissing

Witting

et al. 2012

International Journal of Cardiology

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135

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Section: Discussionmentioning

confidence: 89%

Cardiac manifestations of myotonic dystrophy type 1

Petri

Vissing

Witting

et al. 2012

International Journal of Cardiology

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135

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“…Cardiac involvement affects more than 50% of patients with LGMD2E [22][23][24]28 independently from skeletal muscle phenotype and may occur at all stages of the disease, even before skeletal muscle involvement. This discrepancy is surprising, but has been reported for related muscular dystrophies with cardiac involvement.…”

Section: Study Design and Patient Cohort All Patients Diagnosed Withmentioning

confidence: 99%

“…[14][15][16][17][18][19] LGMD2E is a rare cause of sarcoglycanopathy, with an estimated prevalence of 0.86 3 10 26 cases, 20 and it has generally been considered a severe muscular dystrophy often associated with cardiomyopathy. [21][22][23][24][25][26][27][28] Knowledge about the specific features of this disease is scarce, because no large cohort has been reported. The aim of this study was to detail clinical, biochemical, and molecular data from a large population of patients with LGMD2E, to evaluate the specific clinical pattern of the disease, and to identify possible correlations among phenotype, genotype, and protein expression levels to recognize prognostic factors.…”

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confidence: 99%

Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E

et al. 2015

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Objective: To determine the clinical spectrum of limb-girdle muscular dystrophy 2E (LGMD2E) and to investigate whether genetic or biochemical features can predict the phenotype of the disease.Methods: All LGMD2E patients followed in participating centers were included. A specific clinical protocol was created, including quantitative evaluation of motor, respiratory, and cardiac function. Phenotype was defined as severe or mild if the age at loss of ambulation occurred before or after 18 years. Molecular analysis of SGCB gene and biochemical features of muscle biopsies were reviewed.Results: Thirty-two patients were included (16 male, 16 female; age 7-67 years; 15 severe, 12 mild, and 5 unknown). Neurologic examination showed proximal muscle weakness in all patients, but distal involvement was also observed in patients with severe disease early in the disease course. Cardiac involvement was observed in 20 patients (63%) even before overt muscle involvement. Six patients had restrictive respiratory insufficiency requiring assisted ventilation (19%). Seventeen different mutations were identified, and 3 were recurrent. The c.377_384dup (13 alleles) was associated with the severe form, the c.-22_10dup (10) with the milder form, and the c.341C.T (9) with both. The entire sarcoglycan complex was undetectable by muscle immunohistochemistry or Western blot in 9/10 severe cases and reduced in 7/7 mild cases. The residual amount of sarcoglycan in muscle resulted a predictor of age at loss of ambulation.Conclusions: This study expands the spectrum of phenotype in b-sarcoglycanopathy and provides strong evidence that severity of clinical involvement may be predicted by SGCB gene mutation and sarcoglycan protein expression. Sarcoglycanopathies are recessive limb-girdle muscular dystrophies (LGMDs) and represent 20%-25% of all LGMDs and 40%-65% of LGMD cases with infantile onset.1,2 Sarcoglycanopathies are caused by mutations in genes encoding 4 transmembrane glycoproteins, a-, b-, g-, and d-sarcoglycan, that form a tetrameric complex at the cell membrane of skeletal and cardiac muscle and play an important role in stabilizing the dystrophin-associated glycoprotein complex localized in the sarcolemma of muscle fibers. [3][4][5][6][7] Mutations in individual sarcoglycan genes are responsible for LGMD2C (g-sarcoglycan, SGCC gene q12 8 ), LGMD2D (a-sarcoglycan, SGCA 9,10 ), LGMD2E (b-sarcoglycan, SGCB 11,12 ), and LGMD2F (d-sarcoglycan, SGCD 13 ).LGMD2C and 2D are the most frequent and extensively studied of the 4 sarcoglycanopathies, with a clinical phenotype characterized by progressive skeletal muscle weakness ranging from a severe Duchenne-like dystrophy to a *These authors contributed equally to this work.

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“…One postulation to explain this finding is that, despite CAPN3 transcripts being present, there is a lack of calpain 3 expression in adult cardiomyocytes. 3 Our patient clearly exhibits CAPN3 sequencing alteration on genetic testing and is now diagnosed with new ventricular dysfunction of no other clear pathogenesis, at the age of 23 years. He was also noted to have findings suggestive of left ventricular noncompaction that has also been linked to genetic mutations responsible for various neuromuscular disorders, including the LMNA gene giving rise to limb girdle muscular dystrophy.…”

Section: Discussionmentioning

confidence: 74%

A Cardiomyopathy in a Patient With Limb Girdle Muscular Dystrophy Type 2A

Okere

Reddy

Gupta

et al. 2013

Circ: Heart Failure

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L imb girdle muscular dystrophy (LGMD) is a muscular dystrophy with predominantly proximal distribution of weakness that spares the distal, facial, and extraocular muscles early in the course of the disease. Cardiac muscle may be affected, which may manifest as hypertrophic/dilated cardiomyopathy and cardiac dysrhythmias. Significant cardiac involvement has been documented frequently in LGMD2C-F, 2I, and LGMD1B forms of the disease, rarely in the LGMD1C and 2B subtypes, and thus far have not been reported in type 2A. We report a presentation of severe cardiomyopathy in an adult with muscular dystrophy type 2A.A 23-year-old black man was seen in hospital with complaints of decreased exercise tolerance, dyspnea on exertion, orthopnea, and some presycopal episodes for several weeks.The patient's LGMD was diagnosed at the age of 21 years. No family history of similar problems was noted. Physical examination at the time revealed decreased strength in the shoulder girdle area, with inability to raise the arm over the head. Laboratory data at the time showed a creatinine kinase of 4263 U/L and serum troponin of 0.77 ng/mL. ECG revealed sinus rhythm with bifascicular block. The patient's blood was then sent for genetic testing, which demonstrated CAPN3 sequencing alteration (Athena Diagnostics, Inc).When seen by cardiology, he was noted to be alert and oriented, afebrile, and normotensive. On physical examination he was noted to have jugular venous distension, with cardiac examination significant for a grade III/VI holosystolic murmur at the left lower sternal border, with a displaced point of maximal impulse. ECG revealed normal sinus rhythm, right bundle-branch block, and left anterior fascicular block. Laboratory tests revealed a BNP of 541 pg/mL, with negative cardiac enzymes. His other laboratory tests were found to be within normal limits. An echocardiogram was notable for severely reduced right and left ventricular systolic function, left ventricular ejection fraction of 15%, severe tricuspid regurgitation, and findings suggestive of left ventricular noncompaction (Figure). The patient was treated with ACE inhibitors, β blockers, and diuretics, with no improvement in his cardiac function on subsequent echocardiography. He had few evidence to suggest possible secondary causes of his cardiomyopathy, including myocarditis and ischemic disease, although he refused more extensive testing. DiscussionSignificant cardiac involvement has been rarely documented in LGMD1C, 2A, and 2B, whereas it is relatively common in LGMD2C, 2D, 2E, 2F, 2I, and LGMD1B. This may manifest as hypertrophic/dilated cardiomyopathy and cardiac dysrhythmias.LGMD1B patients often exhibit findings of both cardiomyopathy and dysrhythmia. 1LGMD2A (calpainopathy) is found as a result of a mutation of chromosome 15 in the CAPN3 gene encoding the proteolytic enzyme calpain-3.2 Calpain-3 (p94) belongs to the calpain family of soluble intracellular cysteine proteases, the majority of which are activated by a calcium-dependent mechanism. Calpain-3 is not, ...

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Cardiac Involvement in Patients With Limb-Girdle Muscular Dystrophy Type 2 and Becker Muscular Dystrophy

Abstract: To investigate the extent of cardiac involvement in patients with 1 of the 12 groups of recessively inherited limb-girdle muscular dystrophy type 2 (LGMD2A-L) and Becker muscular dystrophy (BMD).

Cited by 61 publications

References 21 publications

Cardiac manifestations of myotonic dystrophy type 1

Cardiac manifestations of myotonic dystrophy type 1

Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E

A Cardiomyopathy in a Patient With Limb Girdle Muscular Dystrophy Type 2A

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