A 5 y/o boy with a history of muscle weakness starting at 15 months presents progressive weakness of the proximal muscles. On examination, he showed decreased power in his proximal limb muscles, unsteady gait, inability to hop on one feet but intact sensory and cerebellar function.

progressive over what time period. intact dtrs important negative finding

The muscle weakness symptoms and depressed DTR localizes the lesion as one of a lower motor neuron nature. The weakness in the proximal muscles and the child's need to put his hands on his knees to get up from the floor combined with the increased bulk in his calves are distinguishing clinical features in this case and suggests a lesion at the level of the muscle.

true dtrs are depressed but they are not lost; note lmn is the peripheral nerve and its cell body; muscle is not lmn true: proximal weakness of large muscles suggests muscle; however you can get proximal weakness with spinal cord or nerve or NMJ problems.

The clinical course was chronic and progressive indicating a degenerative disease or a metabolic disease of the muscle. The age of the patient suggests a genetic involvement.

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Duchenne's Dystrophy is the likely diagnosis. Becker's Dystrophy is an alternative diagnosis as are other dystrophies (i.e.-FSHD and myotonic dystrophy). Other alternative diagnoses are metabolic myopathy and mitochondrial encephalopathies.

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Muscle biopsy would show variation in fiber size, necrotic, and regenerating fibers, and an increase in connective tissue and fat. Staining of the biopsy(immunoblot analysis) would show the relative abundance of dystrophin and allow differentiation between Duchenne's and Becker's dystrophy.

A myopathic electromyogram would show small amplitude duration and compound action potentials as some of the muscles (muscle cells not muscles) are working. This last test would just support the clinical suspicion.

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The issue of complication in Duchenne's dystrophy is one of continuing progressive weakness that goes on to involved other muscle groups, development of respiratory difficulties and cardiomyopathy. Serum CPK levels is a good ancillary test to monitor progressing disease as the level would increase with muscle necrosis. Respiratory function can be monitored by PFTs.

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Duchenne's dystrophy is the result of a lack of dystrophin, a protein needed to stabilize muscle plasma membranes. The lacking protein results in muscle cell weakness and increasing susceptibility to destruction with use. As the disease is due to a defect at the molecular level, treatment has been to anticipate and treat increasing disability. Splints and braces have been used to help maintain walking as long as possible. Passive stretching exercises are taught to help maintain function. As the back muscles are effected and scoliosis may develop in the growing child, surgery is done to prevent complications with ventilation.

good; also support from organizations such as the MDA, assistance from MDA clinics; also likelihood of replacement therapy with myoblasts or gene therapy in the future as gene has been identified; also early identification of cardiomyopathy and treatment; also genetic counseling.

The patient is a 5-year-old male with a history of progressive weakness resulting in a waddling and unsteady gait, frequent falling and difficulties getting back up. On examination his calves are markedly enlarged, proximal muscles in upper and lower extremities show reduced strength, DTRs are reduced throughout and his spine shows lumbar lordosis.

good; however you don't say over what time period the progression has occurred.

Proximal muscle weakness, dystrophic

you do not indicate where the lesion is. proximal muscle weakness may be found with spinal cord, nmj, occasionally with nerve problems and with muscle problems. The fact that the muscle is dystrophic is not pertinent to the question.

Progressive, suggesting biochemical degenerative process

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Duchenne’s dystrophy Fascioscapulohumeral: although severe cases may involve weakness of distal and proximal leg muscles, more characteristically the disease manifests itself by perioral and periorbital weakness. There is also weakness of the shoulders and proximal arm muscles. Becker’s dystrophy: Slower onset of symptoms, usually retain ability to walk into their 20’s and overall has a longer life expectancy.

which is your one clinical dx?

Muscle biopsy: variation in size of fibers, necrosis and regeneration Serum CPK: patient’s with Duchenne’s usually have elevated levels ( 2000 U/L) Electromyogram: decreased amplitude on stimulation. Genetic testing: abnormalities in dystrophin gene on short arm of chromosome 21

a muscle bx is not as helpful as staining for dystrophin or genetic testing for it.

Cardiomyopathy: EKG and Echocardiogram. Respiratory difficulties: auscultation of chest on physical examination Scoliosis: physical examination and x-ray if necessary

ok: also contractures, respiratory tract infections,

Absent or significantly decreased levels of dystrophin, a protein involved in membrane stabilization, results in unstable and leaky muscle cell membranes.

The repetitive trauma that occurs with contraction of muscles may allow Calcium to enter the cells in a unregulated fashion leading to necrosis and subsequently an increase in the serum CPK level. It is therefore helpful to measure the serum CPK level if DM is suspected. Confirmation relies on findings of a muscle biopsy. The pseduohypertrophy that is observed results from replacement of muscle fibers with fat.

As we are born with all the muscle cells we will ever have, there is currently no way to rescue the dead or dying muscle cells. Treatment involves surgically lengthening of Achilles tendon when contracture is evident. Prednisone is given to curtail fibrosis that may occur in conjunction with the necrosis that is taking place

. Gene counseling for prospective parents may predict that possibility of having a child with the illness.

Finally, gene therapy may hold promise for the future.

ok, don't forget prevention of complications eg contractures, role of physical therapy, assistive devices, family support groups eg MDA and services.

Our patient is a 5 year old boy displaying signs of progressive motor weakness, most notably in proximal muscles, with intact sensory, cerebellar, and cognitive modalities. Significant history and PE findings include delayed walking (15 mo), unsteady gait, never learning to run, Achilles tendon contractures and Gower's sign (using arms to help himself up).

good; progressive over what time period; also what was the onset>

On the basis of our patient's alert and attentive mental status, fluent speech and intact cranial nerves, we feel the lesion is below the brainstem. In fact, slightly diminished DTR's (1+ throughout) as well as completely intact sensory modalities suggest there has been no interruption of the spinal tracts, i.e. this is not an upper motor neuron disease. Since we see intact sensory function we also do not believe that this is a peripheral nerve problem since most peripheral neuropathies involve both motor and sensory modalities. The fact that we see bilateral weakness at various locations throughout the body leads us to believe that this is a problem involving either the muscle itself (a myopathy) or the neural-muscular junction. To further localize the lesion, the finding of weakness in the larger proximal muscle groups is suggestive of a myopathy rather than a NMJ problem, as NMJ dysfunction tends to involve distal muscle groups and present with fatigue.

very good thought process; just too long

The fact that the disease has presented extremely early in life suggests it may be congenital. The slowly progressive, chronic nature suggests an underlying molecular/biochemical nature.

congenital means presence in the neonatal period (acquired or hereditary); It is not clear from the history that this was indeed the case; however you are right it may have been.

Duchenne's Muscular Dystrophy

Other possibilities in our ddx: Becker's MD, Myotonic Dystrophy, Anterior horn cell problems (Werdig-Hoffman, Kugelberg-Welander ) NMJ problems (myasthenia gravis, Eaton-Lambert).

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Staining for dystrophin can confirm our diagnosis of Duchenne's, refute it, and it can confirm Becker's MD. We can also do molecular testing with PCR to detect a deletion mutation in the dystrophin gene. With Duchenne's we should see no gene product because of the nature of the mutation. With Becker's, we should see an defective gene product.

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Pulmonary function tests can help us determine the prognosis of these patients since they typically die from the failure of respiratory musculature in the late teens or early twenties. In addition, EMG can give us an idea of the progression of the muscular degeneration.

good; also contractures, inability to walk, pneumonia in advanced disease

The defect in Duchenne's is found at the genetic level, with a lack of production of dystrophin, a protein critical to the integrity of the myocytes throughout the body. Thus much research has looked at the efficacy of either delivering either normal myocytes or a normal gene to abnormal myocytes in individuals who lack the critical gene product. With the progressive weakness of muscles that result from dying myocytes, contractures develop in understretched tendons. Thus stretching excercises can help. Splints and braces help in keeping patients walking. If weakness in the back muscles leads to scoliosis, surgery can sometimes help maintain optimum ventilation, for as we said before, this is the number one cause of death.

good; the identification of the abnormal protein and gene product has led to research in gene therapy in this disease.