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Romanian Journal of Internal Medicine =... 2015Limb-girdle muscular dystrophies (LGMD) are an extremely heterogeneous and rapidly expanding group of diseases characterized by progressive weakness of pelvic, scapular... (Review)
Review
Limb-girdle muscular dystrophies (LGMD) are an extremely heterogeneous and rapidly expanding group of diseases characterized by progressive weakness of pelvic, scapular and trunk muscles with sparing of facial and distal musculature in most of the subtypes, onset in childhood or in adults of both sexes, very variable clinical severity ranging from mild to severe phenotypes, some associated with cardio-pulmonary and extraskeletal impairment and high serum creatine-kinase (CK) levels. In the past years, huge advances have been recorded in the various identification methods and new distinct entities were discovered. However, it is not yet clear why some muscle groups are affected and others spared in a specific subtype of LGMD, why similar clinical pictures are associated with different genes and mutations, while the same gene or mutation may present with very various clinical phenotypes. In this review we summarize the main aspects of positive and differential diagnosis in LGMD.
Topics: Humans; Muscular Dystrophies, Limb-Girdle
PubMed: 26076556
DOI: 10.1515/rjim-2015-0002 -
Current Neurology and Neuroscience... Jul 2010The muscular dystrophies show muscle degeneration and regeneration (necrotizing myopathy) on muscle biopsy, typically associated with elevated serum creatine kinase, and... (Review)
Review
The muscular dystrophies show muscle degeneration and regeneration (necrotizing myopathy) on muscle biopsy, typically associated with elevated serum creatine kinase, and muscle weakness. In 1986, the first causative gene was identified for the most prevalent and best-characterized form of muscular dystrophy, Duchenne muscular dystrophy. Over the past 25 years, the number of other genes determined to cause different subtypes has grown rapidly. This review gives a synopsis of the 45 genetically defined types of muscular dystrophies and describes the clinical, pathologic, and molecular aspects of each disease. DNA diagnosis remains the most sensitive and specific method for differential diagnosis, but molecular diagnostics can be expensive and complex (because of multiple genes at multiple testing facilities) and reimbursement may be challenging to obtain. However, emerging DNA sequencing technologies (eg, single-molecule third-generation sequencing units) promise to dramatically reduce the complexity and costs of DNA diagnostics. Treatment for nearly all forms remains supportive and is aimed at preventing complications. However, several promising approaches have entered clinical trials, providing tangible hope that quality of life will improve for many patients in the near future.
Topics: Humans; Muscular Dystrophies, Limb-Girdle; Sequence Analysis, DNA
PubMed: 20467841
DOI: 10.1007/s11910-010-0119-1 -
Neurology India 2008The recent years have seen remarkable progress in the field of limb girdle muscular dystrophies (LGMDs) with the advances in immunocytochemistry and genetics. Based on... (Review)
Review
The recent years have seen remarkable progress in the field of limb girdle muscular dystrophies (LGMDs) with the advances in immunocytochemistry and genetics. Based on this, many subgroups have emerged. Protein products and genes are getting defined and newer mechanisms of disease are being recognized. Limb girdle muscular dystrophies are common in India. The clinical material is plentiful, and from various centers in the country, phenotypes have been studied. With the help of immunocytochemistry, sarcoglycanopathies and dysferlinopathies have been studied. Genetic information on these subgroups is now beginning to emerge. The laboratory facilities are limited and available in select centers in large institutes. Establishment of genetic laboratories and sophisticated muscle pathology techniques will further elucidate the LGMDs in India.
Topics: Animals; Humans; India; Mice; Muscle, Skeletal; Muscular Dystrophies, Limb-Girdle; Phenotype; Prevalence
PubMed: 18974554
DOI: 10.4103/0028-3886.43446 -
Acta Myologica : Myopathies and... Dec 2020The term 'limb girdle muscular dystrophy' (LGMD) was first used in the seminal paper by Walton and Nattrass in 1954, were they identified LGMD as a separate clinical...
The term 'limb girdle muscular dystrophy' (LGMD) was first used in the seminal paper by Walton and Nattrass in 1954, were they identified LGMD as a separate clinical entity In LGMD description it is pointed out that the category of LGMD most likely comprises a heterogeneous group of disorders. After that the clinical entity was discussed but the LMGD nosography reached a permanent classification during two ENMC workshops held in 1995 and 2017, in the last one an operating definition of LGMD was agreed. This last classification included dystrophies with proximal or distal-proximal presentation with evidence at biopsy of fibre degeneration and splitting, high CK, MRI imaging consistent with degenerative changes, fibro-fatty infiltration present in individuals that reached independent walking ability. To be considered in this group at least two unrelated families should be identified. A review is done of the first genetic characterisation of a number of LGMDs during the late twentieth century and a historical summary is given regarding how these conditions were clinically described and identified, the progresses done from identification of genetic loci, to protein and gene discoveries are reported. The LGMD described on which such historical progresses were done are the recessive calpainopathy (LGMD 2A/R1), dysferlinopathy (LGMD 2B/R2), sarcoglycanopathy (LGMD 2C-2F/R3-R6) types and the dominant type due to TPNO3 variants named transportinopathy (LGMD 1F/D2). Because of new diagnostic techniques such as exome and genome sequencing, it is likely that many other subtypes of LGMD might be identified in the future, however the lesson from the past discoveries can be useful for scientists and clinicians.
Topics: History, 20th Century; History, 21st Century; Humans; Muscular Dystrophies, Limb-Girdle
PubMed: 33458576
DOI: 10.36185/2532-1900-024 -
Skeletal Radiology May 2023Ultrasound guidance is valuable for performing precise joint interventions. Joint interventions may be requested for therapeutic and diagnostic pain injections, joint... (Review)
Review
Ultrasound guidance is valuable for performing precise joint interventions. Joint interventions may be requested for therapeutic and diagnostic pain injections, joint aspiration in the setting of suspected infection, or contrast injection for arthrography. In practice, interventions of the shoulder girdle, elbow, and hand/wrist joints may be performed without any imaging guidance. However, imaging guidance results in more accurate interventions and better patient outcomes than those performed by palpation alone. When compared to other modalities used for imaging guidance, ultrasound has many potential advantages. Radiologists should be prepared to perform ultrasound-guided upper extremity joint interventions utilizing recommended techniques to optimize clinical practice and patient outcomes. KEY POINTS: 1. Ultrasound-guided injections of the glenohumeral, acromioclavicular, sternoclavicular, elbow, and hand/wrist joints have higher accuracy than injections performed without imaging guidance. 2. Ultrasound-guided aspirations of upper extremity joints have advantages to fluoroscopic-guided aspirations because of the potential to identify effusions, soft tissue abscess, or bursitis. 3. Ultrasound-guided contrast injection prior to MR arthrography is as accurate as fluoroscopic-guided injection for upper extremity joints.
Topics: Humans; Injections, Intra-Articular; Ultrasonography, Interventional; Joints; Ultrasonography; Contrast Media; Upper Extremity
PubMed: 35962837
DOI: 10.1007/s00256-022-04148-9 -
Folia Neuropathologica 2022This study aims to demonstrate the effectiveness of rehabilitation in patients with limb-girdle disease, who were given a home exercise program and called for follow-up...
This study aims to demonstrate the effectiveness of rehabilitation in patients with limb-girdle disease, who were given a home exercise program and called for follow-up in certain periods by observing the functional areas of the shoulder and pelvic groups every six months. Suitable statistical methods were conducted. Descriptive findings and continuous variables regarding the patients were presented. As a result of the analyses, no statistically significant difference was found only in pre-treatment and post-treatment wrist strength and trunk extension variables, but a statistically significant difference was found between the pre-treatment and post-treatment scores of all other types of strength. Significant differences were found between the pre-treatment and post-treatment cervical flexion strength in terms of general weakness and inability to walk, joint limitation and walking status. It is believed that the rehabilitation method to be applied to patients with limb-girdle muscular dystrophy (LGMD) detected in the early period will provide effective results and may form the basis for referring them to physicians and health professionals. It has been concluded that rehabilitation will help them lead a comfortable life.
Topics: Cohort Studies; Exercise Therapy; Humans; Muscular Dystrophies, Limb-Girdle; Time Factors
PubMed: 35359145
DOI: 10.5114/fn.2022.114149 -
Acta Myologica : Myopathies and... May 2014Limb-girdle muscular dystrophies (LGMD) are a highly heterogeneous group of muscle disorders, which first affect the voluntary muscles of the hip and shoulder areas. The... (Review)
Review
Limb-girdle muscular dystrophies (LGMD) are a highly heterogeneous group of muscle disorders, which first affect the voluntary muscles of the hip and shoulder areas. The definition is highly descriptive and less ambiguous by exclusion: non-Xlinked, non-FSH, non-myotonic, non-distal, nonsyndromic, and non-congenital. At present, the genetic classification is becoming too complex, since the acronym LGMD has also been used for a number of other myopathic disorders with overlapping phenotypes. Today, the list of genes to be screened is too large for the gene-by-gene approach and it is well suited for targeted next generation sequencing (NGS) panels that should include any gene that has been so far associated with a clinical picture of LGMD. The present review has the aim of recapitulating the genetic basis of LGMD ordering and of proposing a nomenclature for the orphan forms. This is useful given the pace of new discoveries. Thity-one loci have been identified so far, eight autosomal dominant and 23 autosomal recessive. The dominant forms (LGMD1) are: LGMD1A (myotilin), LGMD1B (lamin A/C), LGMD1C (caveolin 3), LGMD1D (DNAJB6), LGMD1E (desmin), LGMD1F (transportin 3), LGMD1G (HNRPDL), LGMD1H (chr. 3). The autosomal recessive forms (LGMD2) are: LGMD2A (calpain 3), LGMD2B (dysferlin), LGMD2C (γ sarcoglycan), LGMD2D (α sarcoglycan), LGMD2E (β sarcoglycan), LGMD2F (δ sarcoglycan), LGMD2G (telethonin), LGMD2H (TRIM32), LGMD2I (FKRP), LGMD2J (titin), LGMD2K (POMT1), LGMD2L (anoctamin 5), LGMD2M (fukutin), LGMD2N (POMT2), LGMD2O (POMTnG1), LGMD2P (dystroglycan), LGMD2Q (plectin), LGMD2R (desmin), LGMD2S (TRAPPC11), LGMD2T (GMPPB), LGMD2U (ISPD), LGMD2V (Glucosidase, alpha ), LGMD2W (PINCH2).
Topics: Disease Progression; Genetic Predisposition to Disease; Humans; Muscular Dystrophies, Limb-Girdle
PubMed: 24843229
DOI: No ID Found -
Neurology India 2008The increasing knowledge about limb girdle muscular dystrophy (LGMD) has clarified many aspects of this extensive group of neuromuscular conditions and has moreover... (Review)
Review
The increasing knowledge about limb girdle muscular dystrophy (LGMD) has clarified many aspects of this extensive group of neuromuscular conditions and has moreover proven their wide clinical and genetic heterogeneity. For these reasons, achieving a precise diagnosis of a particular type of LGMD may be still difficult and requires a comprehensive approach, which includes epidemiology, medical history, clinical examination, laboratory and genetic tests. All of the LGMDs are individually rare and their population frequency is highly variable. The prevalence of the different forms of LGMD in different populations has to be considered for the differential diagnosis. Some characteristic clinical features may help to distinguish subtypes of LGMD however protein analysis on muscle biopsy and genetic testing still represent the gold standard in the diagnosis of these muscular dystrophies. Reaching a precise diagnosis in all patients is important to allow genetic counseling to be properly applied and to direct appropriate medical management with a potential positive impact on the length and quality of life. Moreover, new specific therapeutic approaches, including limited local gene therapy, have been emerging over the last few years and require a precise genetic definition of the conditions. This article will concentrate on the diagnostic process by which these disorders can be defined and the implications of making these diagnoses.
Topics: Humans; Muscular Dystrophies, Limb-Girdle
PubMed: 18974553
DOI: 10.4103/0028-3886.43445 -
Developmental Dynamics : An Official... May 2011Limb development has long provided an excellent model for understanding the genetic principles driving embryogenesis. Studies utilizing chick and mouse have led to new... (Review)
Review
Limb development has long provided an excellent model for understanding the genetic principles driving embryogenesis. Studies utilizing chick and mouse have led to new insights into limb patterning and morphogenesis. Recent research has centered on the regulatory networks underlying limb development. Here, we discuss the hierarchical, overlapping, and iterative roles of Pbx family members in appendicular development that have emerged from genetic analyses in the mouse. Pbx genes are essential in determining limb bud positioning, early bud formation, limb axes establishment and coordination, and patterning and morphogenesis of most elements of the limb and girdle. Pbx proteins directly regulate critical effectors of limb and girdle development, including morphogen-encoding genes like Shh in limb posterior mesoderm, and transcription factor-encoding genes like Alx1 in pre-scapular domains. Interestingly, at least in limb buds, Pbx appear to act not only as Hox cofactors, but also in the upstream control of 5' HoxA/D gene expression.
Topics: Animals; Extremities; Gene Expression Regulation, Developmental; Homeodomain Proteins; Humans; Mesoderm; Morphogenesis; Protein Binding
PubMed: 21416555
DOI: 10.1002/dvdy.22605 -
Acta Myologica : Myopathies and... Dec 2014Muscle fatigability and atrophy are frequent clinical signs in limb girdle muscular dystrophy (LGMD), but their pathogenetic mechanisms are still poorly understood. We... (Review)
Review
Muscle fatigability and atrophy are frequent clinical signs in limb girdle muscular dystrophy (LGMD), but their pathogenetic mechanisms are still poorly understood. We review a series of different factors that may be connected in causing fatigue and atrophy, particularly considering the role of neuronal nitric oxide synthase (nNOS) and additional factors such as gender in different forms of LGMD (both recessive and dominant) underlying different pathogenetic mechanisms. In sarcoglycanopathies, the sarcolemmal nNOS reactivity varied from absent to reduced, depending on the residual level of sarcoglycan complex: in cases with complete sarcoglycan complex deficiency (mostly in beta-sarcoglycanopathy), the sarcolemmal nNOS reaction was absent and it was always associated with early severe clinical phenotype and cardiomyopathy. Calpainopathy, dysferlinopathy, and caveolinopathy present gradual onset of fatigability and had normal sarcolemmal nNOS reactivity. Notably, as compared with caveolinopathy and sarcoglycanopathies, calpainopathy and dysferlinopathy showed a higher degree of muscle fiber atrophy. Males with calpainopathy and dysferlinopathy showed significantly higher fiber atrophy than control males, whereas female patients have similar values than female controls, suggesting a gender difference in muscle fiber atrophy with a relative protection in females. In female patients, the smaller initial muscle fiber size associated to endocrine factors and less physical effort might attenuate gender-specific muscle loss and atrophy.
Topics: Atrophy; Female; Humans; Male; Muscle Fatigue; Muscle, Skeletal; Muscular Dystrophies, Limb-Girdle; Nitric Oxide Synthase Type I; Sex Factors
PubMed: 25873780
DOI: No ID Found