Cases Of Becker Muscular Dystrophy Research Articles

Comprehensive analysis of 2097 patients with dystrophinopathy based on a database from 2011 to 2021

BackgroundAn increasing number of clinical trials for new therapeutic strategies are underway or being considered for dystrophinopathy. Having detailed data on the natural progression of this condition is crucial for assessing the effectiveness of new drugs. However, there’s a lack of data regarding the long-term data on the natural course and how it’s managed in China. In this study, we offer a comprehensive overview of clinical and molecular findings, as well as treatment outcomes in the Chinese population.MethodsInstitutional data on all patients with dystrophinopathy from August 2011 to August 2021 were retrospectively reviewed. The data included geographic distribution, age at diagnosis, molecular findings, and treatment options, such as corticosteroids, cardiac interventions, and clinical outcomes.ResultsIn total, 2097 patients with dystrophinopathy, including 1703 cases of Duchenne muscular dystrophy (DMD), 311 cases of Becker muscular dystrophy (BMD), 46 cases of intermediate muscular dystrophy (IMD), and 37 cases categorized as “pending” (individuals with an undetermined phenotype), were registered in the Children’s Hospital of Fudan University database for dystrophinopathy from August 2011 to August 2021. The spectrum of identified variants included exonic deletions (66.6%), exonic duplications (10.7%), nonsense variants (10.3%), splice-site variants (4.5%), small deletions (3.5%), small insertions/duplications (1.8%), and missense variants (0.9%). Four deep intronic variants and two inversion variants were identified. Regarding treatment, glucocorticoids were administered to 54.4% of DMD patients and 39.1% of IMD patients. The median age at loss of ambulation was 2.5 years later in DMD patients who received glucocorticoid treatment. Overall, one cardiac medicine at least was prescribed to 7.4% of DMD patients, 8.3% of IMD patients, and 2.6% of BMD patients. Additionally, ventilator support was required by four DMD patients. Eligibility for exon skipping therapy was found in 55.3% of DMD patients, with 12.9%, 10%, and 9.6% of these patients being eligible for skipping exons 51, 53, and 45, respectively.ConclusionsThis is one of the largest studies to have evaluated the natural history of dystrophinopathy in China, which is particularly conducive to the recruitment of eligible patients for clinical trials and the provision of real-world data to support drug development.

A case of Becker muscular dystrophy with developmental dyslexia diagnosed as a result of school refusal

A case of Becker muscular dystrophy with developmental dyslexia diagnosed as a result of school refusal

A case report of COVID-19 positive Becker Muscular Dystrophy

Background: 
 Becker and Duchenne muscular dystrophies constitute the most common inherited dystrophinopathies. The chronic steroid treatment predisposes them to any infection, hence, we sought to determine the current COVID-19 infection in them. We conducted an analysis on a real-world database to identify the effect of COVID-19 infection and identified a case of Becker muscular dystrophy who tested positive for COVID-19. For our analysis, we utilized Cerner Real-World DataTM that was provided through Cerner's HealtheDataLab research tool.
 Case report:
 A 63-year-old Caucasian male with Becker muscular dystrophy, hyperlipidemia, and atrial fibrillation, was hospitalized with COVID-19 infection. Our search revealed June 22, 2020, as the patient's COVID-19 service date when tested positive. The patient received antibiotics and supportive therapy during hospitalization. Intricate details like oxygen requirement, blood gas analysis, and mechanical ventilation could not be retrieved if used. The patient developed complications like sepsis, pneumonia, acute respiratory failure that resulted in prolonged hospitalization. Our data reported that the patient was alive during discharge.
 Conclusion:
 Although patient developed complications during hospitalization, no death from the COVID-19 infection was observed in our analysis.

A child case of Becker muscular dystrophy with left hydronephrosis and giant ureter discovered by macroscopic hematuria

A child case of Becker muscular dystrophy with left hydronephrosis and giant ureter discovered by macroscopic hematuria

E-POSTERS – MITOCHONDRIAL / METABOLIC DISEASES –CASE REPORTS: EP.01Becker muscular dystrophy with acid α-glucosidase pseudodeficiency

Diagnosis of Pompe disease is sometimes challenging because it exhibits clinical similarities to muscular dystrophy. We describe a case of Becker muscular dystrophy (BMD) with a remarkable reduction in activity of the acid α-glucosidase (GAA) enzyme, caused by a combination of pathogenic mutation and polymorphism variants resulting in pseudodeficiency in GAA. The three-year-old boy demonstrated asymptomatic creatinine kinase elevation. Neither exon deletion nor duplication was detected on multiplex ligation-dependent probe amplification (MLPA) of dystrophin. GAA enzyme activity in both dried blood spots and lymphocytes was low, at 11.7% and 7.7% of normal, respectively. However, genetic analysis of GAA detected only heterozygosity for a nonsense mutation (c.118C>T, p.Arg40*). Muscle pathology showed no glycogen deposits and no high acid phosphatase activity. Hematoxylin-eosin staining detected scattered regenerating fibers; the fibers were faint and patchy on immunochemistry staining of dystrophin. The amount of dystrophin protein was reduced to 11.8% of normal, on Western blotting analysis. Direct sequencing analysis of dystrophin revealed hemizygosity for a nonsense mutation (c.72G>A, p.Trp24*). The boy was diagnosed with BMD, despite remarkable reduction in GAA activity; further, he demonstrated heterozygosity for [p.Gly576Ser; p.Glu689Lys] polymorphism variants that indicated pseudodeficiency on another allele in GAA. Pseudodeficiency alleles are detected in approximately 4% of the Asian population; these demonstrate low activity of acid α-glucosidase (GAA), similar to levels found in Pompe disease. Clinicians should be careful in their interpretations of pseudodeficiency alleles that complicate diagnosis in cases of elevated creatinine kinase.

Motor clinical progression in a series of pediatric Duchenne and Becker muscular dystrophy cases

Muscular dystrophy is a neuromuscular disorder that begins with muscle weakness and impaired motor function. Duchenne muscular dystrophy (DMD) is more severe and destructive than Becker muscular dystrophy (BMD), and both are progressive in nature. These 2 types of muscular dystrophy are caused by mutations in related to X-chromosome genes.1 The mutations that occur in DMD are nonsense mutations. Deletion is present in 60% of DMD cases, while duplication occurs in 10% of DMD cases, resulting in loss of dystrophin protein. Mutations in BMD are missense mutations, so dystrophin is still formed, but in decreased amounts and quality.2,3
 The prevalence of DMD was reported to be three times greater than that of BMD, with a prevalence of 1.02 per 10,000 male births vs. 0.36 per 10,000 male infants, respectiveley.4 Anatomical pathology examination revealed loss of dystrophin in the examination of muscle biopsy without the presence of evidence leading to other neuromuscular diseases. Clinical DMD symptoms begin to appear at the age of 2-4 years. The child is observed to fall often and has difficulty climbing stairs. Muscle weakness worsens, especially in the upper limbs, continuing with heart and respiratory problems. The main causes of death in DMD are respiratory failure and heart failure.5 The BMD has varied clinical symptoms, beginning with the appearance of myalgia, muscle cramps, and arm weakness progressing towards myopathy. Some patients are asymptomatic until the age of 15, but 50% of patients show symptoms at age 10, and almost all by age 20.6

Medical Attitudes Survey for Female Dystrophinopathy Carriers in Japan.

Objective This study attempted to clarify the current status of female dystrophinopathy carriers, including the numbers of patients, the status of genetic screening, the status of counseling, physicians' understanding, and barriers to registration. Methods We sent out questionnaires to 402 physicians registered in the Remudy dystrophinopathy registry. The total number of responses received was 130 (response rate: 32%). Result In total, 1,212 cases of Duchenne muscular dystrophy, 365 cases of Becker muscular dystrophy, and 132 cases of female dystrophinopathy with a confirmed genetic mutation were encountered, and genetic testing was performed in the mother in 137, 23, and 12 cases, respectively. With respect to the risk of the onset of health problems, 25% of physicians always explained, 29% usually explained, 29% sometimes explained, and 13% never explained the risk to the mothers and female siblings of dystrophinopathy patients. The most common reason for not explaining the risk was a lack of knowledge/information. Thirty-five percent were familiar with the guidelines for testing the heart function of carriers. Conclusion Fewer mothers of dystrophinopathy patients have undergone genetic testing in Japan than in other countries. A significant portion of doctors did not explain the risks of health problems due to a lack of knowledge. We hope this survey will lead to an increased discussion of female dystrophinopathy patients.

A Case of Refractory Heart Failure in Becker Muscular Dystrophy Improved With Corticosteroid Therapy

The patient was a 26 year-old man who was referred to our hospital in June 2011 because of severe heart failure. At age 24 years, he was found to have Becker muscular dystrophy. He received enalapril for cardiac dysfunction; however, he had worsening heart failure and was thus referred to our hospital. Echocardiography showed enlargement of the left ventricle, with a diastolic dimension of 77 mm and ejection fraction of 19%. His condition improved temporarily after an infusion of dobutamine and milrinone. He was then administered amiodarone for ventricular tachycardia; however, he subsequently developed hemoptysis. Amiodarone was discontinued and corticosteroid pulse therapy was administered followed by oral prednisolone (PSL). His creatinine phosphokinase (CPK) level and cardiomegaly improved after the corticosteroid therapy. The PSL dose was reduced gradually, bisoprolol was introduced, and the catecholamine infusion was tapered. A cardiac resynchronization device was implanted; however, the patient's condition gradually worsened, which necessitated dobutamine infusion for heart failure. We readministered 30 mg PSL, which decreased the CPK level and improved the cardiomegaly. The dobutamine infusion was discontinued, and the patient was discharged. He was given 7.5 mg PSL as an outpatient, and he returned to normal life without exacerbation of the heart failure. There are similar reports showing that corticosteroids are effective for skeletal muscle improvement in Duchenne muscular dystrophy; however, their effectiveness for heart failure has been rarely reported. We experienced a case of Becker muscular dystrophy in which corticosteroid therapy was effective for refractory heart failure.

A case of Becker muscular dystrophy with rimmed vacuoles

A case of Becker muscular dystrophy with rimmed vacuoles

Reliability and accuracy of skeletal muscle imaging in limb-girdle muscular dystrophies

To evaluate the reliability and accuracy of skeletal muscle CT to correctly identify different muscular dystrophies manifesting with limb-girdle weakness. Four evaluators assessed scans from 118 patients with limb-girdle muscular dystrophy (LGMD) caused by mutations in 7 different genes and from 32 controls. The conditions studied were scans of genetically confirmed cases of Becker muscular dystrophy (BMD) (n = 28), LGMD2C-F (sarcoglycanopathies) (n = 11), LGMD2I (n = 4), LGMD1B (n = 26), LGMD2A (n = 24), Bethlem myopathy (n = 14), and LGMD2L (n = 11). The control group (n = 32) consisted of patients with neuromuscular disorders manifesting with limb-girdle weakness in which the aforementioned muscular dystrophies were excluded. The scans were compared with the characteristic patterns described in literature. The overall interobserver agreement was poor (κ = 0.27), with markedly higher scores for BMD (κ = 0.51) and Bethlem myopathy (κ = 0.59). The sensitivity to detect selective patterns in relation to the genetic diagnosis was 40% if all LGMDs were taken together. The specificity was 58%, positive predictive value (PPV) 77%, and 1 - negative predictive value (NPV) 79%. Markedly better scores were observed for BMD (sensitivity 91%, PPV 66%, 1 - NPV 3%) and Bethlem myopathy (sensitivity 90%, PPV 69%, 1 - NPV 1%). Our findings suggest that muscle CT might be an adjunct to the clinical diagnosis of BMD and Bethlem myopathy. However, pattern recognition was cumbersome in the other LGMDs.

D.P.21 Reliability and accuracy of skeletal muscle imaging in limb girdle muscular dystrophies

Objective: To evaluate the reliability and accuracy of skeletal muscle computed tomography to correctly identify different muscular dystrophies manifesting with limb girdle weakness. Four evaluators assessed scans from 118 patients with limb girdle muscular dystrophy caused by mutations in seven different genes and from 32 controls. The conditions studied were scans of genetically confirmed cases of Becker muscular dystrophy (BMD) [n=28], LGMD2C-F (Sarcoglycanopathies) [n=11], LGMD2I [n=4], LGMD1B [n=26], LGMD2A [n=24], Bethlem myopathy [n=14] and LGMD2L [n=11]. The control group [n=32] consisted of patients affected by muscular dystrophies manifesting with limb girdle weakness in which the aforementioned muscular dystrophies were excluded. The scans were compared with the characteristic patterns described in literature. The overall interobserver agreement was poor (κ=0,27), with markedly higher scores for Becker muscular dystrophy (κ=0,51) and Bethlem myopathy (κ=0,59). The sensitivity to detect selective patterns in relation to the genetic diagnosis was 40% if all limb girdle muscular dystrophies were taken together. The specificity was 58%, positive predictive value (PPV) 77% and 1-negative predictive value (1-NPV) 79%. Markedly better scores were observed for Becker muscular dystrophy (sensitivity 91%, PPV 66%, 1-NPV 3%) and Bethlem myopathy (sensitivity 90%, PPV 69%, 1-NPV 1%). Our findings suggest that muscle computed tomography might be an adjunct to the clinical diagnosis of Becker muscular dystrophy and Bethlem myopathy. However, pattern recognition was cumbersome in the other limb-girdle muscular dystrophies.

A case of Becker muscular dystrophy with early manifestation of cardiomyopathy

A case of Becker muscular dystrophy with early manifestation of cardiomyopathy

A case of Becker muscular dystrophy with early manifestation of cardiomyopathy

An 18-year-old boy was admitted with chest discomfort, nausea, and dyspnea at rest. At the age of 3 years, he underwent muscle biopsy and dystrophin gene analysis owing to an enlarged calf muscle and elevated serum kinase level (6,378 U/L) without overt weakness; based on the results, Becker muscular dystrophy (BMD) was diagnosed. The dystrophin gene showed deletion of exons 45 to 49. He remained ambulant and could step upstairs without significant difficulties. A chest roentgenogram showed cardiomegaly (cardiothoracic ratio, 54%), and his electrocardiogram (ECG) showed abnormal ST-T wave, biatrial enlargement, and left ventricular hypertrophy. The 2-dimensional and M-mode ECGs showed a severely dilated left ventricular cavity with diffuse hypokinesis. The systolic indices were reduced, including fractional shortening (9%) and ejection fraction (19%). Despite receiving intensive medical treatment, he died from congestive heart failure 5 months after the initial cardiac symptoms. We report a case of BMD with early-onset dilated cardiomyopathy associated with deletion of exons 45 to 49. Early cardiomyopathy can occur in BMD patients with certain genotypes; therefore, careful follow-up is required even in patients with mild phenotypes of BMD.

Becker muscular dystrophy due to an inversion of exons 23 and 24 of the DMD gene

The use of hybridization-based methods for Duchenne muscular dystrophy (DMD) mutation analysis is increasingly common. We report a case of Becker muscular dystrophy in which discrepant results between a polymerase chain reaction (PCR)-based single-condition amplification/internal primer (SCAIP) and a comparative genomic hybridization assay incompletely characterized the mutation (an inversion of exons 23 and 24). These results demonstrate the limits of sensitivity and specificity of both tests, and highlight the need for more detailed analysis when intronic deletions are detected by comparative genome hybridization methods.

Immobility reduces muscle fiber necrosis in dystrophin deficient muscular dystrophy

Duchenne/Becker muscular dystrophy is a progressive muscle disease, which is caused by the abnormality of dystrophin. Spina bifida is characterized by paralysis of the feet, with most of the upper extremities not being affected. We report here on the first case of Becker muscular dystrophy coinciding with spina bifida. The muscle biopsy specimens of the patient showed dystrophic changes in upper extremities, but clearly less in lower extremities. The results show that the restriction of excessive exercise is important for dystrophin deficiency disease.

Dystrophin associated glycoprotein complex in a particular case of Becker muscular dystrophy

Dystrophin associated glycoprotein complex in a particular case of Becker muscular dystrophy

A case of Becker muscular dystrophy presenting cardiac failure as an initial symptom

A case of Becker muscular dystrophy presenting cardiac failure as an initial symptom

The heart in Becker muscular dystrophy, facioscapulohumeral dystrophy, and Bethlem myopathy.

We report a study, assessing involvement of the heart in 33 familial cases of Becker muscular dystrophy (BMD), 31 familiar cases of facioscapulohumeral (FSH) dystrophy, and 27 familial cases of Bethlem myopathy. In the patients with BMD, correlations of myocardial involvement with age and extent of musculoskeletal involvement were made. We performed physical examination, chest x-ray, electrocardiographic (EKG), and echocardiographic examination on all patients, and continuous EKG Holter-monitoring in the patients with FSH dystrophy. Thirteen patients with BMD (45%) showed EKG changes similar to those found in Duchenne muscular dystrophy. Only 1 of the 13 individuals with cardiac involvement was wheelchair-bound. We found no evidence of cardiac changes in the patients with FSH dystrophy. In Bethlem myopathy, only 1 patient had a form of hypertrophic cardiomyopathy (asymmetrical septal hypertrophy).

Identification of duchenne muscular dystrophy genomic probe P20 constant Taq1 fragment corresponding to the EcoRV and Msp1 polymorphisms

The majority of Duchenne and Becker muscular dystrophy cases are caused by deletions observable in Southern blots with cDNA probes for the gene. When the deletion includes polymorphic probes, they may be used to determine carrier status by deletion segregation analysis: non-inheritance of parental alleles, or heterozygosity. The polymorphic genomic probe P20 is deleted in a large percentage of probands. P20 hybridizes with two constant fragments of 6.7 and 0.8 kb in Taql digests. In a number of probands, only the larger P20 Taql fragment is deleted. This study demonstrates that this fragment corresponds with the polymorphic EcoRV and Mspl fragments of P20. Families in which the upper Taql fragment is deleted may be screened for carrier status using non-inheritance of parental alleles or heterozygosity of P20 in EcoRV or Mspl digests.

Immunocytochemical localisation of complement components C8 and C9 in human diseased muscle the role of complement in muscle fibre damage

The localisation of the complement components C8 and C9 was studied immunocytochemically in human diseased muscle to determine the role of complement in muscle fibre damage. Monoclonal antibodies to 2 epitopes of C9 and a monoclonal antibody to the α subunit of C8 were applied to frozen sections of muscle biopsies from 9 cases of dermatomyositis, 5 cases of polymyositis, 7 cases of Duchenne muscular dystrophy and 4 cases of Becker muscular dystrophy. These were compared with 6 control biopsies which were morphologically normal. In all cases of inflammatory myopathies several non-necrotic fibres showed discrete peripheral patches of C9 and to a lesser extent C8. In the muscular dystrophies peripheral C9 was observed on a few non-necrotic fibres and basophilic fibres showed C9 between the fibres as well as at the periphery. In all cases necrotic fibres labelled intensely with C9 and C8 but intensities varied with the different monoclonal antibodies. This was thought to result from differences in the polymerisation of the C9 molecule in the membrane attack complex. Complement C8 and C9 were also localised to blood vessels in 3 cases of muscular dystrophy, 2 cases of polymyositis and all cases of juvenile dermatomyositis. No complement was observed in the control samples. Our results provide evidence for the sublytic formation of the membrane attack complex (MAC) on non-necrotic fibres in inflammatory myopathies and muscular dystrophy. This sublytic formation of the MAC may induce sublethal metabolic damage, mediated by calcium, and suggests a primary role of complement in muscle damage not only in inflammatory disorders but also muscular dystrophy.