DIFFERENT VARITIES :
*DUCHENNES MUSCULAR DYSTROPHY
* MYOTONIC MUSCULAR DYSTROPHY
* LIMB-GIRDLE DYSTROPHY
* FACIOSCAPULOHUMERAL DYSTROPHY
* FRIEDREICHS ATAXIA
* EMERY-DREIFUSS & ASSOCIATED DISORDERS
* BECKER MUSCULAR DYSTROPHY
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CAUSES
1. CMD
. Primary merosin deficiency: Chromosome 6q2. Laminin alpha2 gene mutation
2. Myotonic dystrophy
. Chromosome 19. CTG expansion affecting a protein kinase. Repeat size ranges from 50 to > 2000. The larger the repeat, the earlier the presentation.
. Anticipation in successive generations may occur
3. Dystrophinopathies
. DMD: 96% with frame-shift mutation. 30% with new mutation
. BMD: 70% with in-frame mutation
4. LGMD
. The most common LGMD in childhood are due to disruption of sarcolemmal proteins: part of a complex linking extracellular collagen with intracellular matrix proteins
5. EDMD
. EDMD 1: Chromosome Xq28. Most are nonsense mutations causing complete loss of emerin (nuclear membrane protein).
. EDMD 2: Chromosome 1q21. Encodes laminin A/C (nuclear membrane protein). (Mutations within laminin A/C gene can also present as LGMD 1B, and
cardiomyopathy with conduction block.)
6. FSHD
. Primary mechanism unknown. All patients have a reduction in the number of tandem repeats, of a tandem sequence termed D4Z4. Normal patients have more than 10 copies of this repeat. Patients with FSHD have 1-8 copies. Links to chromosome 4q35.
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DIFFERENTIAL DIAGNOSIS
1. Onset from birth to early infancy:
. Encephalopathy, spinal muscular atrophy, infantile botulism, myasthenia gravis, congenital myopathies, metabolic myopathies, chromosomal disorders, paroxysmal disorders, neonatal spinal cord injury
2. Onset from infancy to early childhood:
. Mitochondrial myopathies, carnitine deficiency, acid maltase deficiency, spinal muscular atrophy, channelopathies
3. Onset from childhood to adolescence:
. Inflammatory myopathies, mitochondrial myopathies, spinal muscular atrophy, congenital and metabolic myopathies, channelopathies, myasthenia gravis
OTHER TESTS -
ECG - DUCHENNES MUSCULAR DYSTROPHY HAS UNIQUE ECG ABNORMALITY - TALL R WAVE IN RT. CHEST LEADS WITH R/S RATIO > 1.0, OFTEN ASSOCIATED WITH DEEP Q-WAVE IN LIMB & LAT CHEST LEADS WITH VARIETY OF SUPRAVENTRICULAR OR VENTRICULAR ARRHYTHMIAS.
* CPK - ELEVATED
* CPK-MB - ELEVATED IF CARDIAC INVOLVEMENT IS PRESENT
* X-RAY CHEST - MAY SHOW CARDIAC ENLARGEMENT
* EMG: . Very helpful in workup to exclude neuropathies and disorders of the neuromuscular junction
. In myotonic dystrophy high frequency repetitive, waxing and waning discharges (Dive-bomber effect).
IMAGING: Brain MRI in merosin deficient CMD shows diffuse white matter changes resembling a leukodystrophy (represents a dysmyelinating process)
DIAGNOSTIC PROCEDURES:
. Muscle biopsy
. Biopsy moderately weak muscle (vastus lateralis, triceps, supraspinatus) not studied by needle EMG
. Immunostaining: determines where the protein is present or absent. Useful in DMD, BMD, LGMD, CMD.
. Western blot analysis allows the size and abundance of the protein to be determined. In DMD dystrophin content is <3% of normal; in BMD dystrophin content is <20% of normal.
. Prenatal diagnosis:
- DMD/BMD: Dystrophin studies in chorionic villous sampling and amniocytes; analysis of fetal RBC in maternal blood
- CMD: direct mutation analysis of chorionic villous material or direct trophoblast staining for laminin alpha2 chain
. Commercially available DNA testing: DMD/BMD, EDMD, FSHD, myotonic dystrophy