Quadriceps Myopathy Research Articles

Genotype-phenotype correlation in Becker muscular dystrophy in Chinese patients.

Large deletions and duplications are the most frequent causative mutations in Becker muscular dystrophy (BMD), but genetic profile varied greatly among reports. We performed a comprehensive molecular investigation in 95 Chinese BMD patients. All patients were divided into three subtypes: normal muscle strength (type 1) in 18 cases, quadriceps myopathy (type 2) in 20 cases, and limb-girdle weakness (type 3) in 57 cases. Nineteen cases (20.0%) had small mutations and 76 cases (80.0%) had major rearrangements, including 67 cases (70.5%) of exonic deletions and 9 cases (9.5%) of exonic duplications. We identified 50 cases (65.8%) of in-frame mutations, and 26 cases (34.2%) of frame-shift mutations. The frequency of deletion in exons 13-19 was 30.6% in type 1 patients, 9.7% in type 2 patients, and 10.4% in type 3 patients. The frequency of deletion in exons 45-55 was 28.6% in type 1 patients, 40.8% in type 2, and 50.0% in type 3 patients. All major rearrangements of DMD gene in type 1 patients were also observed in type 3 patients. Our study suggested that frame-shift mutation was not rare in Chinese BMD patients. Although no difference was observed on the forms of DMD gene mutations among the three types of patients, the mutation in proximal region of DMD gene has higher frequency for patients without weakness. Effect of exon skipping for DMD depends on the size and location of the mutation. Additional studies are required to determine whether exon-skipping strategies in proximal region of DMD gene could yield more functional dystrophin.

Current concepts in dystrophinopathies.

Dystrophinopathies comprise a group of hereditary muscle disorders characterized by progressive wasting and weakness of skeletal muscle, as a result of degeneration of muscle fibers, and can be distinguished by the mode of transmission, age at onset and pattern of muscle weakness. The range of phenotypes associated with the region Xp21 has been expanding since identification of the gene in 1987. The mild end of the spectrum includes the phenotype of the muscle cramps with myoglobinuria and isolated quadriceps myopathy, while at the severe end, there are progressive muscle diseases that are classified as Duchenne / Becker muscular dystrophy (DMD/BMD).

Quadriceps myopathy caused by skeletal muscle-specific ablation of βcyto-actin

Quadriceps myopathy (QM) is a rare form of muscle disease characterized by pathological changes predominately localized to the quadriceps. Although numerous inheritance patterns have been implicated in QM, several QM patients harbor deletions in dystrophin. Two defined deletions predicted loss of functional spectrin-like repeats 17 and 18. Spectrin-like repeat 17 participates in actin-filament binding, and thus we hypothesized that disruption of a dystrophin-cytoplasmic actin interaction might be one of the mechanisms underlying QM. To test this hypothesis, we generated mice deficient for β(cyto)-actin in skeletal muscles (Actb-msKO). Actb-msKO mice presented with a progressive increase in the proportion of centrally nucleated fibers in the quadriceps, an approximately 50% decrease in dystrophin protein expression without alteration in transcript levels, deficits in repeated maximal treadmill tests, and heightened sensitivity to eccentric contractions. Collectively, these results suggest that perturbing a dystrophin-β(cyto)-actin linkage decreases dystrophin stability, which results in a QM, and implicates β(cyto)-actin as a possible candidate gene in QM pathology.

Autosomal dominant Late-onset Quadriceps Myopathy: Three Patients of a Taiwanese Kindred

Primary quadriceps weakness/atrophy is a rare disorder with variable etiologies; therefore, this disorder has been regarded as a clinical syndrome rather than a distinct entity. However, three affected patients of a Taiwanese family demonstrate a uniform pattern of quadriceps weakness and atrophy, their clinical manifestations and pattern of inheritance may suggest a new disease entity. Three patients in a Taiwanese kindred with selective quadriceps weakness and atrophy, which began after age 40 years, were examined. To disclose the confines of this disorder, muscle CT scans, electromyography, nerve conduction studies and muscle biopsies were performed; and to unravel and better understand the nature of this disorder, histopathological, ultrastructural, immunocytochemical and genetic studies were carried out. In two patients with long-standing disease, muscle imaging showed marked atrophy and fat replacement of the anterior thigh muscles and electromyography showed a mixture of myopathic and neuropathic changes. Muscle histopathology on the mildly affected tibialis anterior showed myopathic changes with myofibrillar degeneration and secondary neurogenic alterations. Immunocytochemical staining was not diagnostic but excluded the dystrophinopathies and other well-known muscular dystrophies. All previously identified diseases resulting in quadriceps weakness and atrophy have been ruled out and the present disorder appears to be a new disease entity of autosomal dominant late onset quadriceps myopathy.

A novel autosomal recessive limb-girdle muscular dystrophy with quadriceps atrophy maps to 11p13-p12

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of pathologies. We have identified a cohort of 14 French-Canadian patients from eight different families displaying a novel form of LGMD with an autosomal recessive inheritance. These patients share some features with previously described cases of 'quadriceps myopathy' that evolved into an LGMD. All demonstrate quadriceps femoris asymmetrical atrophy. Creatine kinase values were variable from normal to 6000 U/l. Clinical evaluations and MRI studies demonstrate a variable intrafamilial and interfamilial phenotype. Asymmetrical muscle involvement was clinically observed and confirmed by imaging. MRI studies suggest that the hamstrings and the adductor magnus are the first limb muscles to demonstrate fatty infiltration. Muscle pathology shows no sign of active inflammation but increased endomysial connective tissue associated with basal lamina duplication and collagen disorganization. A genome-wide scan using the two largest families uncovered linkage to marker D11S1360 on chromosome 11p12 [multipoint logarithm of the odds (LOD) score of 2.78]. Further genotyping for the eight families confirmed linkage to this new LGMD locus (multipoint LOD score of 4.56). Fine mapping subsequently defined a less than 3.3 cM candidate interval on 11p13-p12. Haplotype analysis of carrier chromosomes suggests that the most frequent mutation may account for up to 81.3% of French-Canadian mutations. In this study, we describe the chromosomal locus of a new form of recessive LGMD with prominent quadriceps femoris atrophy.

Severe dilated cardiomyopathy and quadriceps myopathy due to lamin A/C gene mutation: A phenotypic study

This study reports a family affected by a new phenotype associated with dilated cardiomyopathy and quadriceps myopathy. 29 family members underwent a physical and neurological examination, including an electromyogram and biopsy of muscle abnormalities. A cardiac examination was performed in all subjects. The family pedigree (n=72) demonstrated that transmission was autosomal dominant. Eleven subjects had cardiac involvement, only four had quadriceps muscle involvement. Cardiac impairment preceded neurological involvement. The mean age for neurological involvement was 44+/-0.8 years (range 43-45) and cardiac involvement was 37+/-7.9 years (range: 24-45). Cardiac involvement consisted of: hypokinetic dilated cardiomyopathy (64%); atrial fibrillation (100%); ventricular arrhythmias (64%); impaired conduction with bundle branch or complete atrio ventricular block (73%). Four patients required pacemakers and anti arrhythmic therapies. Four patients died: two of refractory heart failure and two of sudden death; two patients were resuscitated following cardiac arrest. Three patients required a prophylactic implantable cardiac defibrillator (ICD). Muscle morphological abnormalities were characterized by a variable number of fibers with rimmed vacuoles. The quadriceps deteriorated progressively without impairment of other muscles. Genotypic study showed a lamin A/C gene mutation. This family was affected by a new phenotype composed of an autosomal dominant severe dilated cardiomyopathy with conduction defects or arrhythmias and quadriceps myopathy. Cardiac abnormalities preceded neuromuscular disorders and defined the prognosis of this disease.

Attacking the disease spiral in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is the commonest respiratory cause of mortality and morbidity in adults in the UK. Although the condition is initially a pulmonary one, data exist to support the concept that factors associated with COPD, including immobility, gives rise to secondary effects, including a quadriceps myopathy, which in turn cause anaerobic metabolism at low work rates. This, through bicarbonate buffering, leads to CO2 retention which, because of constraints imposed by pulmonary mechanics, cause acidosis and dyspnoea. Various therapeutic strategies to reverse this spiral may be employed including pulmonary rehabilitation, quadriceps strength training and surgical or bronchoscopic lung volume reduction.

Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations

Aims: Mutations in the lamin A/C gene (LMNA) have been reported to be involved in dilated cardiomyopathy (DCM) associated with conduction system disease and/or skeletal myopathy. The aim of this...

Quadriceps myopathy: Forme fruste of Becker muscular dystrophy

AbstractWe examined dystrophin, the protein product of the Duchenne muscular dystrophy gene, in muscle biopsy specimens from 4 male patients with quadriceps myopathy, all of whom showed a mild and slowly progressive myopathy confined to the quadriceps muscles. All 4 patients had clear abnormalities of dystrophin, and were diagnosed as having Becker muscular dystrophy by both immunofluorescence and immunoblot examinations; that is, dystrophin of an abnormal molecular mass was visualized in muscle cryosections as “patchy” or discontinuous immunostaining at the surface membrane of the muscle fibers. One patient had a brother who showed widespread myopathic changes consistent with typical Becker muscular dystrophy. We conclude that the syndrome called quadriceps myopathy includes a group of forme fruste Becker muscular dystrophy.

?Quadriceps myopathy?: a clinical variant form of becker muscular dystrophy

A 26-year-old male with "quadriceps myopathy" is presented. He had a family history and only the bilateral quadriceps were wasted, without symptomatic weakness. The specimen of the muscle biopsy showed typical myopathic features without inflammatory reactions. The patchy defect of muscular dystrophin was proved by immunohistochemical study. Dystrophin analysis revealed abnormal 380 kDa dystrophin. Gene deletion was proved at exon 45-48 of Xp21 without frameshift. This case was considered to be a clinical variant form of Becker muscular dystrophy.

Quadriceps myopathy: a variant of the limb-girdle dystrophy syndrome

The clinical and pathological features in a patient with quadriceps myopathy are presented. The pattern of progression of the disorder, during a period of 18 years observation, suggests that it represents an unusual and perhaps specific syndrome within the clinical spectrum of the limb-girdle muscular dystophies.