Myotonic muscular dystrophy

ShoU JS, Hughey MJ, Hrrschmann RA. Myotonic muscular dystrophy associated with ritodrine tocolysis. Am J Obstet Gynecol 1985 151(l) 83-6. 

Enteric Myopathies. The familial types include the dominant type 1 [150], the recessive type 2 with ophthalmoplegia [151] and the recessive type 3 [116]. The sporadic types include muscular dystrophies [152] including myotonic dystrophy [153] and Duchenne s dystrophy. Dysmotility has been associated with all these diseases. 

Pain, muscular weakness, cramps and ease of fatigue are the most usual symptoms of muscular disease. In most cases, it is diseases of the vascular or nervous system or problems with the processes providing energy within the muscle that are responsible for clinical problems with muscles. Other clinical problems include the muscular dystrophies, myotonic disorders, inflammatory myopathies and disorders of neuromuscular transmission (see Walton, 1996). The best known is Duchenne muscular dystrophy. 

FSHD is the third most common hereditary muscular dystrophy after Duchenne muscular dystrophy and myotonic dystrophy. As its name represents, the disease predominantly affects the face, the scapulae, and the proximal arm muscles. In... 

Muscular dystrophy itself, however, is strictly defined as a genetically determined degenerative primary myopathy (W4). The condition is progressive, painless, almost always widespread, and frequently disastrous to the sufferer. The three main clinical forms are now described, together with the myotonic syndrome, but omitting those rare varieties mentioned elsewhere (W4). 

W5. Walton, J. N., and Gardner-Medwin, D., Progressive muscular dystrophy and the myotonic disorders. In Disorders of Voluntary Muscle (J. N. Walton, ed.), pp. 455-499. Churchill, London, 1969. 

Pathogenic effects may be caused by mutant mRNA. In the case of myotonic dystrophy (MD, prevalence 1 in 7400 live buths), is the most common form of muscular dystrophy in adult humans and results from the expansion of a CTG repeat in the 3 untranslated region of the DMPK gene. The mutant DMPK mRNA contains an expanded CUG repeat and is retained in the nucleus. An untranslated CUG repeat was expressed in an unrelated mRNA... 

Muscle E ovides form, support, stability, and capability of directed movement to the body Becker muscular dystrophy Duchenne muscular dystrophy Emery-Dreifuss muscular dystrophy Facioscapulohumeral muscular dystrophy Limb-girdle muscular dystrophy Myotoniacongenita Myotonic dystrophy Biodegradable polymers such as poly (lactide-co-glycolide), poly (caprolac-tone), polyphosphazenes, and conposites of diese polymers with each odier and various inorganic conpounds AVI-4658, Eteplirsen... 

The implication of these findings is that VCP plays some role in regulating the activity of RNA-binding proteins and mutations in VCP impair this function. Thus, there may be mechanistic overlap between the pathogenesis of IBM and the vast array of diseases that are characterized by defects in RNA metabolism, including myotonic dystrophy, oculopharyngeal muscular dystrophy, spinal muscular atrophy, and many others [51]. 

Musculoskeletal disorders (NMD and TRD) are relatively uncommon, but when present are often complicated by respiratory failure (20). Data on the burden of patients with CRF from musculoskeletal disorders are quite heterogeneous. Of the 79 patients who received HMV for CRF in a rehabilitation facility in California, 64% had poliomyelitis with bulbar and respiratory involvement (21), the next most common being Duchenne s muscular dystrophy. Other studies have reported CRF in scoliosis, kyphosis, and post-thoracoplasty TRD, as well as in myopathies such as Ducheime s muscular dystrophy, myotonic dystrophy, postpoliomyelitis, and amyotrophic lateral sclerosis (22). 

Approximately 15% of patients receiving PMV or LTMV have NMD (37,64). NMD can be grouped into disorders involving the central nervous system, such as multiple sclerosis and amyotrophic lateral sclerosis the motor neuron, such as postpolio syndrome and amyotrophic lateral sclerosis the peripheral nerves, such as Guillain-Barre syndrome the neuromuscular junction, such as botulism and myasthenia gravis and the peripheral muscles, such as inflammatory myopathies, myotonic dystrophy type 1, and Duchenne s muscular dystrophy (40). 

At 27 national hospitals, 1092 (51%) of the 2147 inpatients with muscular dystrophy (MD) were receiving LTV and 61% of the patients receiving LTV were undergoing NIPPV in 2005 (Table 1) (10). NIPPV was used for 71% in Duchenne muscular dystrophy, 66% in limb-girdle dystrophy, 61% in myotonic dystrophy, 53% in Becker s MD, and 50% in Fukuyama congenital progressive MD (10). Sixty percent of the patients, on either NIPPV or TIPPV, required 24-hour ventilation. 

A decreased ability of the sarcoplasmic reticulum to accumulate calcium has been reported in muscular dystrophy in both human [108] and mouse [109] and in some other human muscle diseases [108], although not in myotonic dystrophy [110] the slow relaxation rate in the latter condition appears, therefore, to be due to other causes. After experimental denervation in the rat an increase in calcium-accumulating ability has been reported [111] both in fast and slow muscle, particularly the latter. 

Generally a much more limited increase in serum creatine kinase is encountered in the adult form of muscular dystrophy and in myotonic dystrophy. It is normally raised in untreated cases of polymyositis, and the level may be very high. Typical data are provided by Pearce et al [113] and other workers. It was at one time considered that little or no rise in serum creatine kinase occurred in muscle diseases of recognized neurogenic origin, but modest increases have been recorded in Kugelberg-Welander disease and spastic spinal paralysis [115] and in motor neurone disease [116]. Elevated values may occur also in hyperkalaemic and hypokalaemic myopathies [117, 118]. 

Trinucleotide sequences that increase in number (microsateUite instability) can cause disease. The unstable p(CGG) repeat sequence is associated with the fragile X syndrome. Other trinucleotide repeats that undergo dynamic mutation (usually an increase) are associated with Huntington s chorea (CAG), myotonic dystrophy (CTG), spinobulbar muscular atrophy (CAG), and Kennedy s disease (CAG). 

Myotonic dystrophy is a generalized adult-onset disorder with muscular spasms, weakness, and many other symptoms.11 It is one of the triple-repeat diseases (Table 26-4). The affected gene encodes a protein kinase of unknown function. The corresponding mRNA transcript has -2400 nucleotides. The gene has a CTG repeat (CTG) near the 3 -end with n< 30 normally. For persons with the mildest cases of myotonic dystrophy n may be over 50 while in severe cases it may be as high as 2000. As in other triple-repeat diseases the repeat number tends to increase in successive generations of people as does the severity of the diseased... 

Seznec, H., Agbulut, O., Sergeant, N., Savouret, C., Ghestem, A., Tabti, N., et al. (2001) Mice transgenic for the human myotonic dystrophy region with expanded CTG repeats display muscular and brain abnormalities. Hum Mol Genet 10, 2717-2726. 

Keywords Cerebellar ataxias Dentatorubral pallidoluysian atrophy Fragile X syndrome Friedreich ataxia Huntington disease Myotonic dystrophy Spinobulbar muscular atrophy Trinucleotide expansion diseases... 

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