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Dystrophies, Inflammatory myopathies & endocrine myopathies

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Presentation on theme: "Dystrophies, Inflammatory myopathies & endocrine myopathies"— Presentation transcript:

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

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