Infantile facioscapulohumeral muscular dystrophy: new observations

Clinical, electrodiagnostic, and biopsy findings in a family with infantile facioscapulohumeral muscular dystrophy are reported. Four of eight family members having the disorder, all with onset in infancy, developed severe weakness leading to death in adolescence. The clinical course and prognosis of infantile facioscapulohumeral muscular dystrophy may, therefore, be as devastating as that of Duchenne muscular dystrophy. The unusual infantile presentation and high mortality in our affected family members suggest that the gene coding for this disorder may be different from that responsible for conventional facioscapulohumeral muscular dystrophy.     

Scapulothoracic arthrodesis for patients with facioscapulohumeral muscular dystrophy

Ten scapulothoracic arthrodesis procedures were performed in six patients with facioscapulohumeral muscular dystrophy in order to improve considerably restricted activities of daily living. Four of these procedures were bilateral. The duration of follow-up ranged from 28 to 120 months. All patients reported improved function in activities of daily living. Active shoulder abduction was improved by an average of 44°, and active flexion increased by 56°. There was no deterioration in improved upper limb function with time. Complications included pneumothorax, atelectasis, pleural effusion and re-exploration for a segment of retained drain.     

A scapular onset muscular dystrophy without facial involvement: Possible allelism with facioscapulohumeral muscular dystrophy

A dominantly inherited muscular dystrophy with onset in the shoulder girdle and later progression to the lower limbs is described. The disorder was clinically distinguishable from known facioscapulohumeral, scapulohumeral and limb girdle syndromes. A 38 kb allele detected by probe p13E-11 (D4F104S1) segregated with the disease. Linkage analysis gave a maximum lod score of z = 1.61 at θ = 0.01 with the 4q35 marker D4S184 (affected only analysis z = 1.20 at θ = 0.01) suggesting probable allelism with facioscapulohumeral muscular dystrophy.     

Electrical impedance myography in facioscapulohumeral muscular dystrophy

Introduction: In this study we determined the reliability and validity of electrical impedance myography (EIM) in facioscapulohumeral muscular dystrophy (FSHD). Methods: We performed a prospective study of EIM on 16 bilateral limb and trunk muscles in 35 genetically defined and clinically affected FSHD patients (reliability testing on 18 patients). Summary scores based on body region were derived. Reactance and phase (50 and 100 kHz ) were compared with measures of strength, FSHD disease severity, and functional outcomes. Results: Participants were mostly men, mean age 53.0 years, and included a full range of severity. Limb and trunk muscles showed good to excellent reliability [intraclass correlation coefficients (ICC) 0.72–0.99]. Summary scores for the arm, leg, and trunk showed excellent reliability (ICC 0.89–0.98). Reactance was the most sensitive EIM parameter to a broad range of FSHD disease metrics. Conclusions: EIM is a reliable measure of muscle composition in FSHD that offers the possibility to serially evaluate affected muscles. Muscle Nerve 54 : 696–701, 2016     

Lung and respiratory muscle function in facioscapulohumeral muscular dystrophy

Pulmonary dysfunction is not a well‐recognized feature of facioscapulohumeral muscular dystrophy (FSHD). The aim of this study was to establish the prevalence and type of pulmonary and respiratory muscle dysfunction in FSHD. Sixteen patients with moderately advanced FSHD and 16 healthy controls were evaluated. Standard lung and respiratory muscle function tests were performed. Diaphragm muscle inspiratory action was evaluated with transdiaphragmatic pressure measurements. Lung function tests showed an increased residual volume in five patients. There was a significant difference in global respiratory muscle function in patients versus controls; weakness was mild, and it affected expiratory more than inspiratory muscles. There was no significant difference in the diaphragm inspiratory action of patients versus controls. The dystrophic process that underlies FSHD did not significantly involve the muscles of the diaphragm, but it caused mild global respiratory muscle weakness that affected expiratory more than inspiratory muscles. It is probably not necessary to routinely monitor respiratory muscle function in ambulant FSHD patients who lack symptoms or signs of respiratory impairment. Muscle Nerve, 2009     

Becker and limb-girdle muscular dystrophy associated with pituitary dwarfism

Summary In 1981 a report appeared of a patient with Duchenne muscular dystrophy associated with dwarfism caused by growth hormone deficiency, in whom the muscular disease was unusually benign. The authors suggested that the benign course might be related to the growth hormone deficiency and dwarfism. Other authors later supported this idea, having observed that in dystrophic mice and hamsters with congenital and experimentally induced pituitary dwarfism, respectively, pathological expressions of the dystrophy were markedly reduced. In this paper one case of Becker and one of limb-girdle dystrophy, each associated with short stature and growth hormone deficiency are described. In these cases the disease did not have a particularly benign course. It is concluded that caution is necessary, at least in certain cases, before an association between reduced muscular growth and the dystrophic process can be assumed.     

Becker muscular dystrophy presenting with complete heart block in the sixth decade

Becker muscular dystrophy may be associated with myocardial abnormalities which are usually diagnosed after the onset of weakness. We present a patient who developed complete heart block 6 years before the onset of muscle weakness which occurred unusually late at the age of 62 years.     

Muscle pain as a prominent feature of facioscapulohumeral muscular dystrophy (FSHD): four illustrative case reports

Clinical studies of facioscapulohumeral muscular dystrophy (FSHD) rarely report muscle pain as a significant feature of the condition. We report four adult patients with FSHD in whom muscle pain was a presenting complaint and remains their most disabling symptom. These four patients were investigated using a pain questionnaire and diary. Inflammatory and metabolic causes of muscle pain were sought by muscle biopsy and a range of biochemical investigations. All patients reported between three and seven different pains of varying site and nature. None of the group had more than one painfree day per month and all complained of disturbed sleep. While some pains could potentially be attributed to postural problems, others were clearly myalgic in nature, though most often not specifically exercise-related. These myalgic pains could be particularly difficult to control. Results of metabolic investigations and muscle biopsy revealed no clue to the pathogenesis of these pains and there was no evidence for any exceptional inflammatory response. We believe that pain in FSHD is an under-reported but significant symptom and that further work is necessary to determine its prevalence, understand its cause and provide effective treatment.     

Facioscapulohumeral muscular dystrophy presenting with isolated axial myopathy and bent spine syndrome

Several subtypes of facioscapulohumeral muscular dystrophy (FSHD) with atypical clinical presentation have been described. We report a new, distinct phenotype with progressive bent spine syndrome solely affecting the paraspinal muscles. Magnetic resonance imaging study of the lumbar spine revealed marked atrophy of the paraspinal muscles. The diagnosis was confirmed by DNA testing, which revealed shortened restriction fragments of the D4Z4 repeat on haplotype A in connection with a positive family history. Muscle Nerve 42:273–275, 2010     

Evaluation of the cardiomyopathy in becker muscular dystrophy

To evaluate the features and the course of cardiomyopathy in Becker muscular dystrophy, 68 patients–identified by clinical assessment and by reduced dystrophin labeling and/or DNA analysis–were followed in the years 1976–1993, for periods ranging from 3 to 18 years (mean 8). Patients periodically underwent clinical, electrocardiographic, echocardiographic, nuclear, and radiological assessments. Preclinical cardiac involvement was found in 67.4% of patients under 16 years of age, decreasing to 30% in patients older than 40. Clinically evident cardiomyopathy was found in 15% of patients under 16 years of age, increasing to 73% in patients older than 40. A real, dilated cardiomyopathy is the most frequent type of myocardial involvement after the age of 20. Results show that the severity of cardiac involvement can be unrelated to the severity of skeletal muscle damage and confirm that cardiac dysfunction is a primary feature of Becker muscular dystrophy.© 1995 John Wiley &Sons, Inc.     

Becker muscular dystrophy: detection of unusual disease courses by combined approach to dystrophin analysis.

The rapid progress of research on the structure of the dystrophin gene has enormously increased our understanding of the molecular basis of Duchenne (DMD) and Becker (BMD) muscular dystrophy. Apart from "classical" clinical presentations, asymptomatic or only mildly affected individuals with deletions in the dystrophin gene have now been reported. We describe two families which were initially classified as metabolic myopathies, until the diagnosis of atypical BMD was established after dystrophin analysis at the protein and DNA level. A modern diagnostic approach to myopathies should, therefore, not only include morphological and biochemical investigations, but also be extended to the analysis of the dystrophin gene.     

Heterogeneity of dystrophin expression in patients with Duchenne and Becker muscular dystrophy

Summary This report documents the results of an integrated biochemical and immunocytochemical investigation into the expression of dystrophin (the protein product of the Duchenne muscular dystrophy gene) in muscle biopsies from 226 patients. It is the first study in which dystrophin has been analysed on blots and on tissue sections in such a large number of patients using the same (monoclonal) antibody. The 140 patients with Xp21 muscular dystrophy who were included in this study represent a continuous spectrum of disease severity and this range was reflected in the heterogeneity of dystrophin expression which was observed with respect to abundance, size and the pattern of tissue localisation. Approximately 40% of biopsies obtained from patients diagnosed as having Duchenne muscular, dystrophy (DMD) contained isolated clearly positive fibres and a further 20% had very weak labelling on a large number of fibres. Biopsies from patients with Becker muscular dystrophy (BMD) showed labelling patterns which varied from weak labelling on the majority of fibres to clear labelling on all fibres. Typically, however, there was inter-and intra-fibre variation in labelling intensity. Approximately 85% of the 52 BMD and 54 DMD patients who had unequivocal labelling on blots demonstrated a protein of abnormal size. The remaining 15% had a protein of normal size but reduced abundance. Overall, the estimated abundance of dystrophin correlated well with clinical assessments of the disease severity expressed in patients: We conclude that dystrophin analysis is an essential and dependable technique for the differential diagnosis of patients with Xp21 muscular dystrophy.Supported by the University of Newcastle-upon-Tyne Research Committee, the Muscular Dystropy Group of Great Britain and the Medical Research Council     

Muscle histology in Becker muscular dystrophy.

Twenty patients with Becker muscular dystrophy (BMD), confirmed by dystrophin tests, were studied histologically. There were several morphological differences between younger (less than or equal to 15-year-old) and older (greater than 15-year-old) patients. In the younger patients, active muscle fiber necrosis followed by a regenerating process was conspicuous. In the older patients, the active degenerative changes appeared less prominent and, instead, more chronic myopathic changes such as moth-eaten fibers, fiber splitting, and hypertrophic fibers were evident. These age-dependent differences in the pathology of BMD were irrespective of the duration of clinical symptoms, i.e., BMD patients of a similar age showed a similar morphological feature regardless of age at onset. Although the presence of mild fiber type grouping and some small angulated atrophic fibers suggested a certain degree of neurogenic involvement, none of biopsies showed significant grouped atrophy as seen in neuropathic disorders. There was no correlation between the histological changes and the specific dystrophin abnormality.     

First familial Becker muscular dystrophy in Tanzania: Clinical and genetic features,

In African neurological practice, muscle disorders are either underdiagnosed or underrepresented. This may in part be due to the large burden of other more common neurological disorders. In this report we describe the first Tanzanian patient with genetically confirmed Becker muscular dystrophy. His phenotype and genotype were compatible with elsewhere in the world. Remarkably, this patient reported his progressive weakness of the legs with difficulty in walking only after a fall. We demonstrate that muscular dystrophies occur in sub-Saharan Africa. Neurologists must however be aware that patients are likely to delay seeking medical care for muscle disorders.     

Cardiac transplantation in becker muscular dystrophy

Summary A 23-year-old man with X-linked Becker type muscular dystrophy underwent cardiac transplantation because of dilated cardiomyopathy which was complicated by terminal heart failure. Impairment of muscle function was mild and slowly progressive, whereas the cardiac disease was severe and rapidly progressive. All four chambers of the removed heart were grossly dilated; microscopically, the myocardial fibres were hypertrophic and pale; the nuclei exhibited pleomorphism with variability in nuclear size, shape, and depth of staining.     

Plasma pyruvate kinase and creatine kinase activity in Becker muscular dystrophy

Plasma creatine kinase (CK) and pyruvate kinase (PK) were measured in 31 obligate carriers of Becker muscular dystrophy (BMD), 36 BMD patients and appropriate controls. Mean plasma CK was 108 U/l in obligate carriers and 62 U/l in 43 age- and sex-matched controls (P less than 0.001 carriers vs controls). Control CK reference range was 31-125 U/l (mean +/- 2 SD of log transformed values). Mean plasma PK was 40 U/l in obligate carriers and 34 U/l in 56 controls (P less than 0.02 carriers vs controls). Control PK reference range was 18-61 U/l. Values of CK above the reference range upper limit were found in 13 of 31 BMD obligate carriers but only 2 showed elevated PK values. The sensitivity of CK in determining BMD carrier status, although only 42%, was markedly better than PK at 6.5%. Mean plasma CK in BMD patients was 2366 U/l, a 19-fold increase over the control value of 127 U/l (P less than 0.001 patients vs controls). Control CK reference range was 40-316 U/l. In contrast, mean plasma PK in BMD patients was 353 U/l, only 7-fold higher than the mean control value of 57 U/l (P less than 0.001 patients vs controls). Control PK reference range was 22-126 U/l. Clearly, the estimation of plasma PK as a means of determining BMD carrier status is markedly inferior to CK. Previous reports of increased sensitivity of PK compared with CK may have been due to artefactually elevated PK levels produced during sample preparation.     

Becker muscular dystrophy: carrier detection by real-time ultrasound

Summary The applicability was tested of real-time ultrasound imaging to the thigh musculature for the carrier detection of Becker muscular dystrophy (BMD). A total of 17 obligate carriers were examined. Ultrasound images in 3 patients, aged between 46 and 59 years, showed moderate differences compared with the controls. In 3 other obligate carriers, aged between 46 and 71 years, only doubtfully abnormal findings could be made; ultrasound images showed no differences in 11 BMD carriers aged between 10 and 47 years. In women aged over 40 years, compared with adequate controls of the same body type, real-time ultrasound imaging may provide additional evidence and thus help in the detection of BMD carriers.     

Leg muscle involvement in facioscapulohumeral muscular dystrophy assessed by MRI

Using MRI, we evaluated the degree of involvement of muscles in the lower extremities of 18 unselected patients with facioscapulohumeral muscular dystrophy (FSHD). Findings were correlated with fragment size of the mutated gene, age, disease duration and muscle power. Most affected muscles were the hamstrings followed by the tibialis anterior and the medial gastrocnemius. The vastus-, gluteal- and peroneal muscles were the most unaffected, and the psoas muscle did not show evidence of involvement in any of the investigated subjects. Asymmetric involvement was evident in 15% of the investigated muscles on MRI and 6% on manual muscle strength testing. MRI findings in muscle tended to correlate with disease duration (r = 0.49; p < 0.05), but not with gene fragment size or age. MRI disclosed involvement of muscles performing hip flexion and ankle dorsal flexion that could not be detected by manual muscle strength testing. Otherwise, there was a close correlation (≈ r = 0.75; p < 0.0001) between muscle strength and MRI severity score for other muscle groups. The present study shows that MRI may disclose muscle involvement in FSHD that is not apparent on manual muscle testing, and suggests that MRI of muscle may be an important assessment tool in clinical trials involving patients with FSHD. Received in revised form: 10 March 2006