Presentation
Neuromuscular syndromes are presented clinically either as a case study or as an overview from the literature, accompanied by text presenting molecular defects, and differential diagnosis. [books.google.com]
The book presents detailed information for both basic scientists and for clinicians seeing patients. [books.google.de]
[…] be present as well. [en.wikipedia.org]
Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I) LGMD2I tends to be milder in presentation than MCD1C but has a variable phenotype depending on age of onset. [egl-eurofins.com]
Abstract Background: Congenital muscular dystrophies (CMD) are autosomal recessive disorders that present within the first 6 months of life with hypotonia and a dystrophic muscle biopsy. CNS involvement is present in some forms. [n.neurology.org]
Entire Body System
- Feeding Difficulties
Some infants may experience respiratory and feeding difficulties shortly after birth (neonatal period). Feeding difficulties may result in affected children failing to gain weight and grow at the expected rate (failure to thrive). [rarediseases.org]
MDC1A is characterized by congenital muscle hypotonia, delayed or arrested motor milestones and feeding difficulties. [spandidos-publications.com]
These complications include feeding difficulties leading to poor nutrition; respiratory insufficiency; joint contractures and scoliosis; and, in some subtypes, cardiac involvement. [ncbi.nlm.nih.gov]
The patients show feeding difficulties with failure in sucking and swallowing, facial weakness, and feeble cry. [ijponline.biomedcentral.com]
Difficulties, and Delayed Brain Myelination 1 Neurodevelopmental Disorder with Involuntary Movements 1 Neurodevelopmental Disorder with Microcephaly, Epilepsy, and Brain Atrophy 1 Neuroferritinopathy 1 Neurofibromatosis, Familial Spinal 2 Neurofibromatosis [preventiongenetics.com]
- Difficulty Walking
Clinical features include weakness of the hip and shoulder girdle, difficulty walking, spinal abnormalities including scoliosis, lordosis and kyphosis, and cardiomyopathy. Patients may also experience difficulty breathing. [sema4.com]
Most individuals are able to walk independently although because of progressive spinal rigidity and scoliosis they may experience difficulties walking later during life. [rarediseases.org]
- Hunting
Hunt, Veronica van Heyningen, Michel Michaelides, Andrew R. Webster, Anthony T. [doi.org]
Jaw & Teeth
- Macroglossia
Other clinical features include a normal MRI; a normal IQ (in most cases); hypertrophy of the calves and quadriceps; a myopathic EMG; and macroglossia. Some individuals have dilated cardiomyopathy or impaired left ventricular function. [egl-eurofins.com]
The oldest child in the six individuals was the most severely affected with severe facial weakness, progressive weakness and macroglossia. She underwent surgery for scoliosis and had severe restrictive respiratory insufficiency. [cags.org.ae]
Additional symptoms may occur including overgrowth (hypertrophy) of the muscles of the legs, an abnormally enlarged tongue (macroglossia), weakness and wasting (atrophy) of the muscles of the arms, and contractures, especially of the Achilles tendon, [rarediseases.org]
Additional features include moderate hepatomegaly and macroglossia. [ncbi.nlm.nih.gov]
Skin
Musculoskeletal
- Proximal Muscle Weakness
LGMD 2A (calpain 3) Childhood (8-15) There is mainly proximal muscle weakness. There is slow progression. Muscle atrophy is prominent (notable sparing of the hip abductors). Contractures are common. [patient.info]
Clinical features include proximal muscle weakness, waddling gait, calf hypertrophy, cardiomyopathy and respiratory insufficiency. [abcam.com]
- Lordosis
Clinical features include weakness of the hip and shoulder girdle, difficulty walking, spinal abnormalities including scoliosis, lordosis and kyphosis, and cardiomyopathy. Patients may also experience difficulty breathing. [sema4.com]
The type and location of spinal deformity: Thoracic kyphosis: collagen VI-deficient CMD Thoracic lordosis: laminin alpha-2 deficiency, SELENON -related CMD, and L-CMD; late stage of dystroglycanopathies. [ncbi.nlm.nih.gov]
Psychiatrical
- Suggestibility
Key points for each genetic disease are identified to suggest treatment, when available, or the main clinical exams useful in follow-up of patients. [books.google.com]
These findings suggested that the DAG1 protein is abnormally glycosylated in MDC1C and is central to the pathogenesis of the disorder. [link.springer.com]
A few affected individuals have had mental retardation, suggesting a syndromic form of the condition. Serum creatine kinase (CK) concentration in individuals with LGMD2I and MDC1C is usually markedly increased. [egl-eurofins.com]
Neurologic
- Excitement
This volume deals with brain development malformations of the central nervous system, showcasing a unique approach that furthers research through systematic integration of exciting new developments from fields including molecular genetics, neuroimaging [books.google.de]
[…] thin filament/actin thick filament/myosin elastic filament/titin nebulin Tropomyosin Troponin T C I Connective tissue Epimysium Fascicle Perimysium Endomysium Connective tissue in skeletal muscle General Neuromuscular junction Motor unit Muscle spindle Excitation–contraction [en.wikipedia.org]
MDA-supported scientists are pursuing several exciting strategies in muscular dystrophy research that have implications for LGMD. These strategies include gene therapy, exon skipping, stop codon read through and myostatin blocking. [mda.org]
Muntoni F, Voit T (2004) The congenital muscular dystrophies in 2004: a century of exciting progress. Neuromuscul Disord 14: 635–649. View Article Google Scholar 4. Reed UC (2009) Congenital muscular dystrophy. [journals.plos.org]
The congenital muscular dystrophies in 2004: a century of exciting progress. Neuromuscul Disord. 2004; 14 :635–49. [ PubMed : 15351421 ] Norwood FL, Harling C, Chinnery PF, Eagle M, Bushby K, Straub V. [ncbi.nlm.nih.gov]
Workup
This may simplify the diagnostic workup at least for some patients. [jmg.bmj.com]
PMID 20301468. update 2012 a b c "Congenital Muscular Dystrophy Workup: Laboratory Studies, Imaging Studies, Other Tests". emedicine.medscape.com. Retrieved 2016-04-28. a b c "Congenital muscular dystrophy". [en.wikipedia.org]
Treatment
Sections dedicated to management and treatment are also included in an effort to aid clinicians in their goal of providing better care for individuals affected by these types of malformations. * A single source that encompasses the various aspects of [books.google.de]
Key points for each genetic disease are identified to suggest treatment, when available, or the main clinical exams useful in follow-up of patients. [books.google.com]
There is currently no treatment for these conditions; though optimizing and standardizing care and care delivery can promote significant gains in quality of life and survival. [clinicaltrials.gov]
Coverage includes major updates on genetics of diseases, new diagnostic techniques, and the newest treatment options. [books.google.ro]
Prognosis
If you or your child has been told the diagnosis is SMA but it’s not the chromosome 5-related type, talk with your doctor and perhaps a genetic counselor to find out more about the genetics and prognosis for the particular SMA involved. [mda.org]
Genetic counselling provides information on the inheritance pattern, risks to other family members, and the ‘prognosis’ (likely outcome of the disorder). [mda.org.au]
Chronic pain can occur, and pain management should be part of care. [ 19 ] Prognosis This depends on the type of LGMD and whether there is cardiac or respiratory involvement. In general, all types of LGMD progress with time. [patient.info]
To date, data for all CMD subtypes are insufficient to make any firm genotype / phenotype correlations or to provide definitive prognosis or anticipatory guidance based on CMD subtype. [ncbi.nlm.nih.gov]
Performing clinical and molecular diagnosis is extremely important for genetic counseling, prognosis, and anticipatory treatment and also for prospective treatment. [ijponline.biomedcentral.com]
Etiology
The low call percentage or mutation detection rate for individual gene tests is due mostly to incorrect presumption of genetic etiology and suspicion of the incorrect gene. [journals.plos.org]
Integrin alpha 7 beta 1 in muscular dystrophy/myopathy of unknown etiology. [ncbi.nlm.nih.gov]
Clinical diagnosis of infantile hypotonia is particularly difficult considering the different etiologic factors causing the lesions, the difficulty in localizing the involved CNS area (central vs. peripheral) and the limited role of the diagnostic procedures [ijponline.biomedcentral.com]
Epidemiology
[…] girdle muscular dystrophy type 2A Synonym(s): - LGMD2B - Limb-girdle muscular dystrophy due to dysferlin deficiency Classification (Orphanet): - Rare genetic disease - Rare neurologic disease Classification (ICD10): - Diseases of the nervous system - Epidemiological [csbg.cnb.csic.es]
Relevant External Links for FKRP Genetic Association Database (GAD) FKRP Human Genome Epidemiology (HuGE) Navigator FKRP Atlas of Genetics and Cytogenetics in Oncology and Haematology: FKRP No data available for Genatlas for FKRP Gene New FKRP mutations [genecards.org]
Internationale statistische Klassifikation der Krankheiten und verwandter Gesundheitsprobleme – The International Classification of Diseases is the international standard diagnostic tool for epidemiology, health management and clinical purposes. [wikivisually.com]
Other proteins involved include dystroglycan, fukutin-related protein, calpain, dysferlin and telethonin. [ 5 ] Epidemiology [ 2 ] The LGMDs individually are rare, with some forms reported in only a few families. [patient.info]
Accordingly, a prevalence for LGMD2I could be estimated that is within the range of other, more frequent muscular dystrophies. 15 However, epidemiological studies are warranted to prove this hypothesis. [jmg.bmj.com]
Pathophysiology
This new set of data explains, at least in part, why many of these disorders are interconnected, though the primary pathophysiological events, such as gene mutations, may be different for each disorder. [books.google.de]
Mechanism [ edit ] In terms of the mechanism of congenital muscular dystrophy, one finds that though there are many types of CMD the glycosylation of α-dystroglycan and alterations in those genes that are involved are an important part of this conditions pathophysiology [en.wikipedia.org]
Pathophysiology The pathophysiology of the congenital muscular dystrophies depends on the specific genetic defect for each of the dystrophies and is discussed with each of the congenital muscular dystrophies below. [emedicine.medscape.com]
Although the pathophysiology of the white matter changes has not been completely elucidated, the majority of investigators postulate that disruption of the blood-brain barrier associated with laminin α-2 leads to increased water content, which results [spandidos-publications.com]
Prevention
Protein coding - M0QYV8 - 3' truncation in transcript evidence prevents annotation of the end of the CDS. CDS 3' incomplete Transcript Support Level 4, for transcripts supported by an EST flagged as suspect. [ensembl.org]
Thus, overexpressing Smad7 suppresses Smad2/3 signaling, promotes muscle hypertrophy and prevents muscle wasting. [aavogen.com]
A shortage of FKRP prevents the normal glycosylation of α-dystroglycan. As a result, α-dystroglycan can no longer effectively anchor cells to the proteins and other molecules that surround them. [ghr.nlm.nih.gov]
[…] such as laxatives to prevent constipation, medication for gastroesophageal reflux (GER), and oral caloric supplements as required Trunk bracing in those with severe axial or cervical hypotonia with spinal collapse to prevent severe spinal deformities [ncbi.nlm.nih.gov]
People with MD have incorrect or missing information in their genes, which prevents them from making the proteins they need for healthy muscles. [kidshealth.org]