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Neurology(R) Neuroimmunology &... Jul 2021To report on a cohort of patients diagnosed with brachio-cervical inflammatory myopathy (BCIM), with specific focus on muscle MRI and follow-up data.
OBJECTIVE
To report on a cohort of patients diagnosed with brachio-cervical inflammatory myopathy (BCIM), with specific focus on muscle MRI and follow-up data.
METHODS
Clinical, histopathologic, serologic, and pre- and post-treatment MRI findings of patients diagnosed with BCIM were retrospectively evaluated.
RESULTS
Six patients, all females with a mean age at onset of 53 years (range 37-62 years), were identified. Mean diagnostic delay was 17 months, and mean follow-up was 35 months. Most common clinical features encompassed predominant involvement of neck and proximal upper limb muscles, followed by distal upper limb, facial, and bulbar muscle weakness with different severity. Lower limb involvement was rare, although present in severe cases. Muscle biopsies showed a heterogeneous degree of perivascular and endomysial inflammatory changes. Myositis-specific antibodies were absent in all patients, whereas all resulted positive for antinuclear antibodies; half of the patients had anti-acetylcholine receptor antibodies without evidence of muscle fatigability. MRI showed disproportionate involvement of upper girdle and neck muscles compared with lower limbs, with frequent hyperintensities on short-tau inversion recovery sequences. Partial clinical and radiologic improvement with steroid and immunosuppressant therapy was obtained in most patients, especially in proximal upper limb muscles, whereas neck weakness persisted.
CONCLUSION
BCIM is an inflammatory myopathy with a peculiar clinical and radiologic presentation and a relatively broad spectrum of severity. Long-term follow-up data suggest that appropriate and early treatment can prevent chronic muscle function impairment. MRI characterization can be helpful in reducing diagnostic and treatment delay with positive consequence on clinical outcome.
Topics: Adult; Autoantibodies; Autoimmune Diseases; Delayed Diagnosis; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Muscle, Skeletal; Myositis; Neck Muscles; Retrospective Studies; Upper Extremity
PubMed: 34011678
DOI: 10.1212/NXI.0000000000001016 -
Journal of Ayurveda and Integrative... 2022Limb girdle muscular dystrophy (LGMD) is a type of Muscular dystrophy (MD), heterogeneous devastating complex genetic disorders causing progressive weakness and...
Limb girdle muscular dystrophy (LGMD) is a type of Muscular dystrophy (MD), heterogeneous devastating complex genetic disorders causing progressive weakness and degeneration of muscles. LGMD is hereditary autosomal diseases characterized by weak and wasteful limb girdle muscles. The available management of LGMD in biomedicine is unsatisfactory. Here we present a case of LGMD managed with combinations of Ayurvedic oral medicines and Panchakarma procedures. The Ayurvedic diagnosis of the condition was considered as Mansagata Vata (∼neuromuscular diseases), a type of Vatavyadhi (∼neuromusculo skeleton disorders). The patient was treated with Shalishashtika Pinda Swedana and Mustadi Yapana Basti for the duration of 16 days along with following Ayurvedic oral medicines: Yograj Guggulu 500 mg with 40 ml Dashamoola Kwatha, Ekangaveera Rasa 125 mg with honey, a combination of Ashwagandha Churna -2g, Satavari Churna - 2g, and Sankha Bhasma 500 mg with milk, Narsinha Churna- 3g and Ashwagandhavleha- 5g with milk. All medicines were given twice a day. Patient's condition was assessed for symptoms of pain, walking distance, power and reflexes of both upper and lower limb and psedohypertrophy of both calf muscles. Serum Creatine Phoshphokinase (S.CPK) level and electromyography (EMG) were also measured. There was symptomatic improvement in the patient's condition and reduction in S.CPK level. The study suggests that LGMD can be satisfactorily managed with Ayurvedic oral medicines and Panchakarma therapy.
PubMed: 34961685
DOI: 10.1016/j.jaim.2021.07.002 -
Phenotypic and genetic spectrum of patients with limb-girdle muscular dystrophy type 2A from Serbia.Acta Myologica : Myopathies and... Sep 2019Limb-girdle muscular dystrophy (LGMD) type 2A (calpainopathy) is an autosomal recessive disease caused by mutation in the gene. The aim of this study was to examine...
Limb-girdle muscular dystrophy (LGMD) type 2A (calpainopathy) is an autosomal recessive disease caused by mutation in the gene. The aim of this study was to examine genetic and phenotypic features of Serbian patients with calpainopathy. The study comprised 19 patients with genetically confirmed calpainopathy diagnosed at the Neurology Clinic, Clinical Center of Serbia and the Clinic for Neurology and Psychiatry for Children and Youth in Belgrade, Serbia during a ten-year period. Eighteen patients in this cohort had c.550delA mutation, with nine of them being homozygous. In majority of the patients, disease started in childhood or early adulthood. The disease affected shoulder girdle - upper arm and pelvic girdle - thigh muscles with similar frequency, with muscles of lower extremities being more severely impaired. Facial and bulbar muscles were spared. All patients in this cohort, except two, remained ambulant. None of the patients had cardiomyopathy, while 21% showed mild conduction defects. Respiratory function was mildly impaired in 21% of patients. Standard muscle histopathology showed myopathic and dystrophic pattern. In conclusion, the majority of Serbian LGMD2A patients have the same mutation and similar phenotype.
Topics: Adolescent; Adult; Age of Onset; Alleles; Biopsy; Calpain; Child; Female; Genotype; Humans; Magnetic Resonance Imaging; Male; Muscle Proteins; Muscular Dystrophies, Limb-Girdle; Mutation; Phenotype; Serbia
PubMed: 31788660
DOI: No ID Found -
Zhongguo Dang Dai Er Ke Za Zhi =... Aug 2019Limb-girdle muscular dystrophy (LGMD) is a group of muscular dystrophies with predominantly proximal muscular weakness, and some genes associated with this disease have... (Review)
Review
Limb-girdle muscular dystrophy (LGMD) is a group of muscular dystrophies with predominantly proximal muscular weakness, and some genes associated with this disease have been identified at present. LGMD type 2Q (LGMD2Q) is a subtype of LGMD and is associated with PLEC gene mutation. Major phenotypes of PLEC gene mutation include epidermolysis bullosa with late-onset muscular dystrophy and epidermolysis bullosa with other lesions. LGMD2Q without skin lesions is rarely reported. This article reviews the pathogenic gene PLEC and clinical manifestations of LGMD2Q, so as to deepen the understanding of the pathogenic gene and phenotype of LGMD2Q.
Topics: Humans; Muscular Dystrophies, Limb-Girdle; Mutation; Phenotype
PubMed: 31416513
DOI: 10.7499/j.issn.1008-8830.2019.08.019 -
Molecular Medicine (Cambridge, Mass.) 2011Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene, encoding the dysferlin protein. DYSF mutations lead to a wide range... (Review)
Review
Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene, encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B) and the second most common being LGMD. Symptoms generally appear at the end of childhood and, although disease progression is typically slow, walking impairments eventually result. Dysferlin is a modular type II transmembrane protein for which numerous binding partners have been identified. Although dysferlin function is only partially elucidated, this large protein contains seven calcium sensor C2 domains, shown to play a key role in muscle membrane repair. On the basis of this major function, along with detailed clinical observations, it has been possible to design various therapeutic approaches for dysferlin-deficient patients. Among them, exon-skipping and minigene transfer strategies have been evaluated at the preclinical level and, to date, represent promising approaches for clinical trials. This review aims to summarize the pathophysiology of dysferlinopathies and to evaluate the therapeutic potential for treatments currently under development.
Topics: Animals; Dysferlin; Genetic Therapy; Humans; Membrane Proteins; Muscle Proteins; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle; Mutation; Translational Research, Biomedical
PubMed: 21556485
DOI: 10.2119/molmed.2011.00084 -
BMC Neurology Jan 2017Cleidocranial dysplasia (CCD) is a rare hereditary disorder that arises from heterozygous loss of function mutations in the runt-related transcription factor 2 (RUNX2)... (Review)
Review
BACKGROUND
Cleidocranial dysplasia (CCD) is a rare hereditary disorder that arises from heterozygous loss of function mutations in the runt-related transcription factor 2 (RUNX2) gene. As RUNX2 is mainly expressed in osteoblasts, CCD typically affects the skeletal and dental systems. Few studies have investigated RUNX2 mutation effects on non-skeletal systems. Here, we describe limb-girdle myopathy, an uncommon phenotype of CCD, in a patient with a heterozygous missense mutation (p.R225Q) in the RUNX2 gene.
CASE PRESENTATION
A 58 year-old man presented with progressive back pain and six months of weakness in the proximal parts of all four limbs. Physical examinations showed that he was short in stature (height, 164.4 cm; weight, 79.1 kg) with a dysmorphic face, including hypertelorism, midface hypoplasia, and chin protrusion. At a young age, he had received orthodontic surgery, due to dental abnormalities. Neurological examinations revealed sloping shoulders, weakness, and atrophy in the proximal areas of the arms, shoulder girdle muscles, and legs. The deep tendon reflex and sensory system were normal. Radiological examinations revealed mild scoliosis, shortened clavicles, and a depressed skull bone, which were consistent with a clinical diagnosis of CCD. Electromyography (EMG) studies showed myogenic polyphasic waves in the deltoid, biceps brachii, and rectus femoris muscles. Instead, the EMG findings were normal in the first dorsal interosseous, tibialis anterior and facial muscles. The EMG findings were compatible with a limb-girdle pattern with facial sparing. The patient's family history showed his father and eldest daughter with similar dysmorphic faces, skeletal disorders and proximal upper extremity weakness. We sequenced the RUNX2 gene and discovered a heterozygous missense mutation (c.G674A, p.R225Q), which altered the C-terminal end of the RUNX2 protein. This mutation was predicted to inactivate the protein and might affect its interactions with other proteins. This mutation co-segregated with the disease phenotypes in the family.
CONCLUSIONS
We described limb-girdle myopathy in a patient with CCD that carried a heterozygous RUNX2 missense mutation. This uncommon phenotype expanded the phenotypic spectrum of the RUNX2 p.R225Q mutation. The role of RUNX2 in myogenic development merits future studies. Our findings remind clinicians that myopathic patients with myopathies combined with facial dysmorphism and shortened clavicles should consider the diagnosis of CCD.
Topics: Cleidocranial Dysplasia; Core Binding Factor Alpha 1 Subunit; Humans; Male; Middle Aged; Muscular Dystrophies, Limb-Girdle; Mutation, Missense; Phenotype
PubMed: 28056872
DOI: 10.1186/s12883-016-0781-2 -
Neurology(R) Neuroimmunology &... Jan 2019To determine the prevalence and clinical features of anti-HMGCR myopathy among patients with presumed limb-girdle muscular dystrophy (LGMD) in whom genetic testing has...
OBJECTIVE
To determine the prevalence and clinical features of anti-HMGCR myopathy among patients with presumed limb-girdle muscular dystrophy (LGMD) in whom genetic testing has failed to elucidate causative mutations.
METHODS
Patients with presumed LGMD and unrevealing genetic testing were selected based on a few clinico-pathologic features and tested for anti-HMGCR autoantibodies (n = 11). These clinico-pathologic features are peak creatine kinase (CK) greater than 1,000 IU/L and at least 3 of the following features: (1) limb-girdle pattern of weakness, (2) selective involvement of posterior thigh on clinical examination or muscle imaging, (3) dystrophic changes on muscle biopsy, and (4) no family history of muscular dystrophy.
RESULTS
Six patients tested positive for anti-HMGCR autoantibodies. In 4, there was a presymptomatic phase, lasting as long as 10 years, characterized by elevated CK levels without weakness. Muscle biopsies revealed variable degrees of a dystrophic pathology without prominent inflammation. In an independent cohort of patients with anti-HMGCR myopathy, 17 of 51 (∼33%) patients were initially presumed to have a form of LGMD based on clinico-pathologic features but were ultimately found to have anti-HMGCR myopathy. Most of these patients responded favorably to immunomodulatory therapies, evidenced by reduction of CK levels and improved strength.
CONCLUSIONS
Anti-HMGCR myopathy can resemble LGMD. Diagnosis of patients with a LGMD-like presentation of anti-HMGCR myopathy is critical because these patients may respond favorably to immunotherapy, especially those with shorter disease duration.
Topics: Adolescent; Adult; Autoantibodies; Child; Cohort Studies; Female; Humans; Hydroxymethylglutaryl CoA Reductases; Male; Middle Aged; Muscular Diseases; Muscular Dystrophies, Limb-Girdle
PubMed: 30588482
DOI: 10.1212/NXI.0000000000000523 -
Neurotherapeutics : the Journal of the... Oct 2008Fourteen years ago, the first disease-causing mutation in a form of autosomal recessive limb-girdle muscular dystrophy was reported. Since then the number of genes has... (Review)
Review
Fourteen years ago, the first disease-causing mutation in a form of autosomal recessive limb-girdle muscular dystrophy was reported. Since then the number of genes has been extended to at least 14 and the phenotypic spectrum has been broadened. The generation of mouse models helped to improve our understanding of the pathogenesis of the disease and also served to study therapeutic possibilities. All autosomal recessive limb-girdle muscular dystrophies are rare diseases, which is one reason why there have been so very few controlled clinical trials. Other reasons are insufficient natural history data and the lack of standardized assessment criteria and validated outcome measures. Currently, therapeutic possibilities are mainly restricted to symptomatic treatment and the treatment of disease complications. On the other hand, new efforts in translational research and the development of molecular therapeutic approaches suggest that more promising clinical trials will be carried out in autosomal recessive limb-girdle muscular dystrophy in the next several years.
Topics: Animals; Calpain; Dysferlin; Dystroglycans; Humans; Membrane Proteins; Muscle Proteins; Muscular Dystrophies, Limb-Girdle; Sarcoglycans
PubMed: 19019315
DOI: 10.1016/j.nurt.2008.08.003 -
Anatomical Record (Hoboken, N.J. : 2007) Jul 2022The upper extremity posture is characteristic of each Carnegie stage (CS), particularly between CS18 and CS23. Morphogenesis of the shoulder joint complex largely...
The upper extremity posture is characteristic of each Carnegie stage (CS), particularly between CS18 and CS23. Morphogenesis of the shoulder joint complex largely contributes to posture, although the exact position of the shoulder joints has not been described. In the present study, the position of the upper arm was first quantitatively measured, and the contribution of the position of the shoulder girdle, including the scapula and glenohumeral (GH) joint, was then evaluated. Twenty-nine human fetal specimens from the Kyoto Collection were used in this study. The morphogenesis and three-dimensional position of the shoulder girdle and humerus were analyzed using phase-contrast X-ray computed tomography and magnetic resonance imaging. Both abduction and flexion of the upper arm displayed a local maximum at CS20. Abduction gradually decreased until the middle fetal period, which was a prominent feature. Flexion was less than 90° at the local maximum, which was discrepant between appearance and measurement value in our study. The scapular body exhibited a unique position, being oriented internally and in the upward direction, with the glenoid cavity oriented cranially and ventrally. However, this unique scapular position had little effect on the upper arm posture because the angle of the scapula on the thorax was canceled as the angle of the GH joint had changed to a mirror image of that angle. Our present study suggested that measuring the angle of the scapula on the thorax and that of the GH joint using sonography leads to improved staging of the human embryo.
Topics: Arm; Biomechanical Phenomena; Fetal Development; Humans; Posture; Range of Motion, Articular; Scapula; Shoulder Joint; Upper Extremity
PubMed: 34605199
DOI: 10.1002/ar.24796 -
Arquivos de Neuro-psiquiatria Oct 2023Limb-girdle muscular dystrophy (LGMD) is a group of myopathies that lead to progressive muscle weakness, predominantly involving the shoulder and pelvic girdles; it has... (Review)
Review
Limb-girdle muscular dystrophy (LGMD) is a group of myopathies that lead to progressive muscle weakness, predominantly involving the shoulder and pelvic girdles; it has a heterogeneous genetic etiology, with variation in the prevalence of subtypes according to the ethnic backgrounds and geographic origins of the populations. The aim of the present study was to analyze a series of patients with autosomal recessive LGMD (LGMD-R) to contribute to a better characterization of the disease and to find the relative proportion of the different subtypes in a Southern Brazil cohort. The sample population consisted of 36 patients with LGMD-R. A 9-gene targeted next-generation sequencing panel revealed variants in 23 patients with LGMD (64%), and it identified calpainopathy (LGMD-R1) in 26%, dysferlinopathy (LGMD-R2) in 26%, sarcoglycanopathies (LGMD-R3-R5) in 13%, telethoninopathy (LGMD-R7) in 18%, dystroglicanopathy (LGMD-R9) in 13%, and anoctaminopathy (LGMD-R12) in 4% of the patients. In these 23 patients with LGMD, there were 27 different disease-related variants in the , , , , , , , and genes. There were different causal variants in different exons of these genes, except for the gene, for which all patients carried the p.Gln53* variant, and the gene, which showed recurrence of the p.Leu276Ile variant. We analyzed the phenotypic, genotypic and muscle immunohistochemical features of this Southern Brazilian cohort.
Topics: Humans; Anoctamins; Brazil; Muscle Weakness; Muscular Dystrophies, Limb-Girdle; Pentosyltransferases
PubMed: 37852290
DOI: 10.1055/s-0043-1772833