1. Dystrophies, Inflammatory myopathies & endocrine myopathies

2. Classification of Myopathies
A. Hereditary
Muscular dystrophies
Congenital myopathies
Myotonias and channelopathies
Metabolic myopathies
Mitochondrial myopathies
B. Acquired
Inflammatory myopathies
Endocrine myopathies
Drug induced/ toxic myopathies
Myopathies associated with systemic illness

3. Muscular Dystrophies
Definition: Group of genetically determined, progressive degenerative disorders of muscle
History: Distinction between myopathic and neuropathic disease was made only in the later half of the 19th century.
Duchenne in 1855 first described a progressive muscular atrophy of childhood and was termed “hypertrophic paraplegia of infancy”.
Erb in 1891 was the first to recognize the group of diseases due to primary degeneration of muscle and called it “muscular dystrophies”.

4. Classification of Muscular dystrophies
Age of onset:
A. Early childhood: Duchenne muscular dystrophy
B. Childhood/ adolescence: Becker
Landouzy-Dejerine (FSH)
Emery-Dreifuss
Limb-girdle (Erb)
C. Adult: Oculopharyngeal, myotonic dystrophy (Steinert)

5. Classification of Muscular dystrophies
Genetic: Chromosome Protein
A. Sex linked: (X-linked)
Duchenne (Xp21) Dystrophin
Becker (Xp21) Dystrophin
Emery-Dreifuss (Xq28) Emerin
B. Autosomal dominant :
Facioscapulohumeral (4q35) ? oculopharyngeal (14q11) Protein 2
myotonic dystrophy (19) DMPK
C. Variable inheritance: Limb-girdle type (Erb)

6. Dystrophinopathies -Duchenne’s and Becker
Duchenne’s Muscular dystrophy (DMD)
X linked recessive
1:3500 male newborns
Usual onset between 3 and 5 years
Clinical features
Proximal muscles and neck flexors involved early
Calf hypertrophy, Gower’s sign
Contractures in tendoachilles, scoliosis, cardiomyopathy
Slow progression and wheelchair bound by age 12
Death common by age 20 due to respiratory cause
Lab features: CPK elevated, EMG, Biopsy
Identifiable Xp21 mutation with absence of dystrophin

8. Duchenne’s…pathology
Scattered groups of necrotic and regenerating fibres
Hypertrophied fibres
Small round fibres
Perimysial and endomysial proliferation
Muscle fibre loss and fat replacement
Dystrophin deficiency demonstrated by immunohistochemical staining

10. Duchenne’s…molecular pathology
Duchenne’s dystrophy is caused by the absence or deficiency of dystrophin protein which is the product of Xp21 gene locus
It is part of the dystrophin-glycoprotein complex (DGC) which is a group of membrane-associated proteins that span the muscle sarcolemma and provide linkage and stability between the intracellular and cytoskeleton and the extracellular matrix
The postulate is that absence of this protein results in tears in the membrane due to weakening of the sarcolemma with a resulting calcium leak into the muscle fibre initiating a cascade of events leading to muscle fibre necrosis

11. Duchenne’s Treatment
Supportive care: Use of leg braces, passive exercises, scoliosis if more than 35 degrees treated surgically
Corticosteroids: Prednisolone and deflazocort found to be useful
Prednisolone at a dose of 0.75mg/kg prolongs ambulation by 3 to 4 years
Gene replacement therapy in the future

12. Inflammatory myopathies
Definition: Heterogenous group of disorders characterised by inflammation in the skeletal muscles with resultant muscle fiber damage and subsequent clinical weakness
These are relatively uncommon about 1 in

13. Classification of Inflammatory myopathies
Idiopathic:
Dermatomyositis
Polymyositis
Connective tissue disease: Scleroderma, SLE, RA
Inclusion body myositis
Miscellaneous: Eosinophilic myositis, Sarcoid myopathy
Infectious:
Viral myositides: Influenza, HIV and other
Parasitic myositis: Trichinosis, toxoplasmosis, cysticercosis
Bacterial myositis
Fungal mysositis

14. Inflammatory myopathies
Clinical features:
Weakness affects neck flexors, pectoral and pelvic girdle muscles in dermatomyositis (DM) and polymyositis (PM). Distal muscles involved in inclusion body myositis (IBM)
Cardiac and smooth muscle may be involved. Dysphagia is a common symptom in DM, PM and IBM
Diagnosis confirmed by elevated CPK and biopsy. DM is humorally mediated whereas PM is cell mediated muscle injury
Treatment with steroids, immuno suppresants and I.V immunoglobulins in PM and DM.

16. Endocrine myopathies
Hyperthyroidism: Proximal weakness; periodic paralysis. CPK is usually normal. Type 1 and 2 fibre atrophy
Hypothyroidism: Proximal weakness, muscle hypertrophy, cramps, myalgia. Ankle jerks may demonstrate delayed relaxation. Myoedema which is a painless mounding of the muscle when it is percussed. CPK usually elevated.
Hyperparathyroidism: Proximal weakness and atrophy
Hypoparathyroidism: mild weakness, tetany

17. Endocrine myopathy…contd
Hypercortisolism/ steroid myopathy: Women more prone to develop exogenous steroid induced myopathy. Usually when prednisone dosage is > 30mg/ day. Fluorinated steroids like triamcinolone> betamethasone> dexamethasone greater propensity. Proximal muscle weakness. Serum CPK , EMG is normal. Biopsy shows preferential atrophy of Type 2 fibres.
Hypocortisolism: Generalised weakness, fatigue, cramps
Diabetes when uncontrolled can produce diabetic muscle infarction especially in the thighs and can manifest as a painful swelling. CPK is normal.

18. Myotonic dystrophy Laboratory features: CPK mildly elevated
EMG: myotonic discharges “dive bomber”
Genetic screening: CTG repeat on chromosome 19 on leukocyte DNA
Treatment:
Supportive care
Phenytoin, procainamide and mexiletine for myotonia

19. Myotonic dystrophy Systemic features
Ocular : Cataract, ptosis, retinal degeneration
Cardiac:Conduction disease, arryhtmias,cardiomyopathy
Gastrointestinal: Dysphagia, colonic dysmotility, megacolon
Endocrine: Diabetes due to insulin resistance, testicular atrophy, abnormal GH release
Immune: reduced serum immunoglobulins
Miscellaneous: Frontal balding, cranial hyperostosis

20. Myotonic dystrophy
This is the most common inherited muscle disorder affecting adults
Autosomal dominant
15 cases per live births and M:F is 1:1
Varies from a mild late onset form of the disease to a severe congenital disorder. Severity depends on the number of CTG repeats in the DMPK gene on chromosome 19
The classical form usually present in adolescence or early adulthood
The most frequent symptoms are muscle weakness and stiffness affecting the distal limbs and myotonia