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DISEASES OF SPINAL CORD, PERIPHERAL NERVE, AND MUSCLE
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clinical presentations and has necessitated a revision of the older conventional classi cation
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somal recessive mutation causing a limb-girdle dystrophy as discussed further on Clinical Features Duchenne muscular dystrophy is usually recognized by the third year of life and almost always before the sixth year Nearly half of the patients show evidence of disease before beginning to walk Many of them are slightly backward in other ways (psychomotor retardation), and the muscle weakness may at rst be overlooked A greatly elevated creatine kinase (CK) may be the rst clue In another group of young children, an indisposition to walk or run normally at the expected time brings them to medical attention; or, having achieved these motor milestones, they appear to be less active than usual and are prone to falls Increasing dif culty in walking, running, and climbing stairs, swayback, and waddling gait become ever more obvious as time passes The iliopsoas, quadriceps, and gluteal muscles are involved initially; then the pretibial muscles weaken (foot drop and toe walking) Muscles of the pectoral girdle and upper limbs are affected after the pelvicrural ones; the serrati, lower parts of pectorals, latissimus dorsi, biceps, and brachioradialis muscles are affected, more or less in the order mentioned Enlargement of the calves and certain other muscles is progressive in the early stages of the disease, but most of the muscles, even the ones that are originally enlarged, eventually decrease in size; only the gastrocnemii, and to a lesser extent the lateral vasti and deltoids, are consistently large, and this peculiarity may attract attention before the weakness becomes evident The enlarged muscles have a rm, resilient ( rubbery ) feel and as a rule are slightly
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Duchenne Muscular Dystrophy (Severe Generalized Muscular Dystrophy of Childhood) (See Table 50-1)
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This is the most frequent and best known of the muscular dystrophies It begins in early childhood and runs a relatively rapid, progressive course The incidence rate is in the range of 13 to 33 per 100,000 yearly or about one in 3300 live male births in every part of the world There is a strong familial liability since the disease is transmitted as an X-linked recessive trait, occurring predominantly in males However, careful examination of their mothers will show slight involvement in as many as half of the so-called mutant cases, as pointed out by Roses and coworkers Approximately 30 percent of patients have no family history of the disease and represent spontaneous mutations Very occasionally, a severe proximal muscular dystrophy occurs in young girls This may have several explanations: The female may have only one X chromosome, as occurs in the Turner (XO) syndrome and that chromosome carries the Duchenne gene, or the so-called Lyon principle may be operative; ie, there is inactivation of the unaffected paternal X chromosome allowing expression of the mutated Duchenne protein from the maternal chromosome in a large proportion of embryonic cells It so happens that most childhood dystrophies in girls prove to be of an entirely different type that is not X-linked and is instead due to an auto-
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Table 50-1 Duchenne/Becker, Emery-Dreifuss, limb-girdle, and related major muscular dystrophies
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ONSET INHERITANCE TYPE GENE OR CHROMOSOME DECADE CK ELEVATION REGIONS AFFECTED
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X-linked recessive Duchenne/Becker Emery-Dreifuss Autosomal dominant LGMD 1A LGMD 1B LGMD 1C LGMD 1D LGMD 1E Autosomal recessive LGMD 2A LGMD 2B LGMD 2C F LGMD 2G LGMD 2H LGMD 2I LGMD 2J
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Dystrophin Emerin
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1st 2nd 3rd
10 50 x 5x
Proximal, then distal muscles Cardiac muscle Proximal muscles, joint contractures Life-threatening cardiac arryhthmias Distal greater than proximal weakness, vocal cords, pharynx Resembles Emery-Dreifuss disease Proximal muscles and heart, joint contractures Proximal muscles Proximal muscles; cardiomyopathy Proximal muscles Proximal and distal muscles Proximal and distal muscles Allelic to Miyoshi myopathy Phenotype of Becker dystrophy Proximal greater than distal muscles Proximal greater than distal muscles Proximal greater than distal muscles FKRP defects also cause CMD Proximal and sometimes distal muscles
Myotilin Lamin A/C Caveolin-3 6p 7q Calpain-3 Dysferlin , , , -sarcoglycans Telethonin TRIM32 Fukutin-related protein (FKRP) Titin
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