1、, ,heridatery myopathy,Approach to myopathy,Hereditary acquired,history,Onset age distribution Course Myalgia Cramp Contracture Dark urine Myotonia ,Stiffness /warming up phenomena Aggravating: exercise /diet/temperature/drug,exam,Limb girdle Scapuloperoneal Distal Ocular or pharyngeal Neck extensor
2、 Atrophy or hypertrophy Myotonia or paramyotonia,Ptosis usually without opthalmoplegia Myotonic dystrophy Congenital myopathyPtosis with opthalmoplegia Oculopharyngeal muscular dystrophy Mitochondrial myopathy,Weakness,Constant fluctuationLonglife acquired MGperiodic Pmetabolic Progressive static Dy
3、strophy congenital,Age Distribution Inheritance,Work up,Muscles enzyme R/o metabolic screen EMG&NCS (myotonia ,fibrillation, R/o neuropathy) Muscle biopsy (dystrophy/ congenital myopathy, stain for enzyme level) Genetic study Other : Forearm exercise testspecific Enzymes level,When do you suspect?,H
4、ereditary myopathy,Structural functional,classification,Dystrophy Congenital myopathy Channelopathies & myotonia Metabolic (fatty acid/ glycogensis/mitochondrial),muscular dystrophy,are inherited myopathy characterized by progressive muscles weakness °eneration &subsequent replacement by fibrous
5、& fatty connective tissue Historically were categorized by their: Age onset /distribution of weakness& pattern of inheritance The genetic mutation &abnormal gene product were defined for many of them,MD,Duchenne MD,Incidence: 1/3500 male birth 1/3 new mutation c/p:as early as 2-3y with delay milesto
6、nes Progressive limb girdle pattern Fall 5-6y/difficult climb stair 8y, confined to wheelchair 12y,Joint constructers 6-10y Calf hypertrophy is early Muscles atrophy late Progressive kyphscliosis due to Paraspinal muscles weakness Reflex: biceps/knee/lost by age 10yankle preserved late in disease Re
7、spiratory s/s after age 10,Cardiac: generally asymptomatic CHF, arrhythmia late 90% abnormal ECG :tall rt R wave,deep left Q wave Echo: hypokinesia ,dilatation of ventricular wall GI: intestinal pseudo obstruction IQ: one SD below N,lab,A dystrophin gene deletion can be detected by: DNA analyses fro
8、m leukocytes by PCR in 2/3 patient or DNA muscles The other 1/3 DX by muscles biopsy( dystrophin def by stain &WB ,typical features of MD) CK:20-100 XN ,decline later EMG:myopathic &fibrillation Note :if DNA study +ve no need for EMG &muscles biopsy,Beckers MD,Is milder form 5/100,000 Age :5-15y Whe
9、elchair at 30y Cardiac similar to duchenne Death by age 40 Dx: DNA, muscle biopsy decrease in dystrophin CK:moderatly elevated,treatment,No treatment prevent the progression corticosteroid :controlled trial with predinsone 0,75mg/kg demonstrate moderate improvement in strength &delay progression to
10、wheel chair& respiratory compromise,Emery-dreifuss,X linkedonset :childhood Triad of: 1-early contracture elbow, ankle &posterior cervical2-progressive scapulohumroperoneal3-cardiomyopathy with atrial conduction defect,CK :normal to or only moderate elevated The muscle biopsy :myopathic &fewer dystr
11、ophic DNA:mutation gene in Xq28 code for protien emerin,Limb girdle dystrophy,AR majority Onset: adolescence or latechildhood: sever child recessive muscular dystrophy,AR: defect in sacroglycan component of the DGC( sacroglycanopathy( Alpha sacrglycan adhelin is account for 20% Onset:childhood& vari
12、able No intellectual impairment or cardiac Muscle biopsy :immune stain absent or diminished for sacroglycan,AD: onset: second and third decades Protein defect:caveolin-3There are multiple subtypes AD type 1:1A,1B AR type 2:,Congenital muscular dystrophy,AR Perinatal onset c/p:hypotonia &proximal wea
13、kness,arthrogryposis Two types CNS involvement: sever mental retardation ,visual, seizure cerebrocular dysplasia, progressive death by age 10-12 No CNS :classic type MRI (hypomyelination), benign outcome, non progressive Muscle biopsy :dystrophy,FSH,Inheritance: AD Variable expression within the fam
14、ilies Age: childhood or adult life C/P: weakness early facial then descending to scapula stabilizer muscles &muscles of the upper limb& distal weakness peroneal ,the rate of progression to forearm &pelvic girdle Asymmetrical/ deltoid preserved / joint contracture are uncommon Popeye hand/ winging sc
15、apula/ no muscle hypertrophy Early onset worse prognosis 20% require wheelchair,Work up,CK:N or mild elevation Muscles biopsy: myopathic dystrophic& occasionally prominent mononuclear infiltrate Gene: ch 4q35 gene deletion,Myotonic dystrophy,AD, CTG repeat Affect : skeletal,cardiac, smooth muscles,
16、eye,endocrine &brainOnset :at any age ,usually at late 2nd decade Some individual can be symptoms free their entire life Sever form :congenital myotonic dystrophy,C/P:weakness: (facial,temporalis wasting,ptosis,neck flexor,distal weakness progress to involve limb girdle) Weakness myotonia May be are
17、flexic,systemic,Posterior sub scapular cataract Testicular atrophy& impotence Intellectual impairment Hypersomnia (central & obstructive) Respiratory failure Elevation of serum glu, rarely frank DM GI: dysphagea, pseudo obstruction Cardiac conduction defect sudden death Fetal loss in female,PROMM,AD
18、 Proximal weakness, no distal weakness Myotonia &myalgia Less cardiac &other organ involvement except cataract,Work up,CK:N or mild elevation EMG: myopathic & myotonia Muscle biopsy: atrophic, non specific Gene :CTG repeat 50 in ch19q13.2,ttt,Myotonia rarely sever to require tt: phenytoin is the onl
19、y safe drug Annual ECG pacemaker may required Positive pressure ventilation support High risk in surgery (cardiac &respiratory) Sedation & opiod use with caution,Distal dystrophy,Types AD:4th &6th decade AR:in early adult onset/late second or early 3rd CK :elevated 200xN AR,oculopharengeal,AD Onset:
20、5th &6th decade Ptosis &dysphagea later all extra ocular muscles &extremities affected (limb girdle) but distal can be significant in some variant Slow progressive ,death from aspiration pneumonia or starvation Ck:n or mild elevated Muscle biopsy :rim vacuoles Genetic GCG repeat in ch14,congenital m
21、yopathy,Congenital myopathy,Are distinguished from dystrophy in three respect: Characteristic morphologic alteration At birth Non progressive However there are exception to all these generalization Inheritance: are variable,c/p: hypotonia with subsequent developmental delay Reduce muscles bulk, slen
22、der body build &long narrow face Skeletal abnormalities: high arched palate ,pectus exacavitum, kyphscliosis, dislocated hip, pes cavus)Absent or reduced muscle stretch reflexWeakness: limb girdle mostly, but distal weakness exist CK &EMG may be normal Muscle biopsy: the diagnostic method,Central co
23、re myopathy,Characterized by discrete zones of myofibrillar disruption in the center of muscles fiber AD but can be sporadic Mutation ch 19,similar to malignant hyperthermia patient So anesthesia precaution are necessary,Nemaline myopathy,Pathology: the presence of rods or melamine bodies within mus
24、cles fiber AD or AR c/p: Sever neonatal form which is fatal in the first year of life Mild static Slowly progressive from birth or early childhood Note :rods can present in HIV related myopathy ,some inflammatory,Centro nuclear (myotubular),Pathology: large central nuclei in the muscle fiber X linke
25、d/AD/ARsever neonatal/static or slowly progressive c/p: ptosis & opthalmoparesis Genetic defect: mutation in myotubularin gene Xp28,Metabolic myopathy,Metabolic myopathy,Glucose/glycogen metabolism Fattay acid metabolism Purine nucleotide mitochondrial,Metabolic myopathy,Clues to hereditary metaboli
26、c myopathy Excersize induce weakness &myoglobinuriaglycogen &lipid Part of diffuse neurological syndromemitochondrial,Glucose/glycogen,Glucose &its storage is essential for the short term anaerobic energy (glycogensis) Two clinical presentation: 1-dynamic:type V/V11/V111/1X/XX1 2-static:fix weakness
27、 1/111/1V Inheritance:AR except for phosphoglycerate kinase,Glycogensis with exercise intolerance,C/P: exercise intolerance in the childhood followed by excertional induced muscle pain &myoglobinurea in sec or 3rd decade (Second wind phenomena)work up: CK/EMG normal between the attack in early stage
28、 but after attack( myopathic &fibrillation) Forearm exercise test Enzyme assay Muscle biopsy Genetic for mutation,What is 0ther causes of myoglobinurea?,Glycogensis with fixed weakness,Acid maltase deficiency: Enzyme convert glycogen to glucose Three clinical variant: Infantile: pompes: progressive
29、weakness ,enlargement of heart, tongue &liver death by age 2 Juvenile type: proximal weakness, may calf hypertrophy death by age 20 from respiratory failure Adult type:2&7th progressive limb girdle or scapuloperoneal .no liver ,no heart involvement,Work up,CK :moderately increased EMG: myopathic cha
30、nges &myotonic discharge in paraspinus Enzyme assay: Muscle biopsy: a vacuolar myopathy with high glycogen content Genetic: mutation in ch 17,Fatty acid metabolism,Lipids are essential for aerobic metabolism Dynamic & static CPT:carnitine palmitoyl transeferase deficiency Carnitine deficiency,CPT,Ty
31、pe 1:infancy &child hood with hepatic dysfunction Type 2:exertional myalgia &myoglobinurea, it is the most frequently definable metabolic defect presenting with myoglobinurea AR ,gene 1p32 The attacks occur after prolonged exercise, fasting, febrile illness Unlike mecardle disease the patient can to
32、lerate brief exercise ,no second wind phenomena Muscle strength are normal at rest,lab,CK:n at rest Forearm exercise test :N EMG: n at rest ,&myopathic during the attack Muscle biopsy: usually N ,except of myopathic changes after rhabdomylsis Enzyme assay ttt &meal frequency: increase CHO intake &ed
33、ucation about fasting &exercise,Mitochondrial,Kearns-sayer: opthalmoplegia, retinitis pigmentosa, heart block, hearing loss, short stature, ataxia, delayed 2nd sexual characteristic, PN, respiratory MERF: myoclonic epilepsy, generalized seizure, ataxia, dementia, hearing loss, optic atrophy ,PN, car
34、diomyopathy &cutenous lipomaMNGLE: mitochondrial neurogastrointestinal encephalomyopathy POLIP :polyneuropathy,opthalmoplasia,leukoencephalopathy& intestinal pseudo obstruction,channelopathy,Non dystrophic myotonia Periodic paralysis It due to mutation in different channels gene leading to : Hyper e
35、xcitability :myotonia In excitability: paralysis,Chloride channelopathy,Mutation in CL channelhyperexcitability after depolarization Myotonia congenita: ADthomsen /AR:becker C/P: muscle hypertrophy, myotonia/becker type has fluctuating limb girdle weakness,Sodium channleopathy,AD Onset: first decade
36、 Phenotypic types: Paramyotonia congenitaHyperkalemic periodic paralysismyotonia :Potassium sensitive disorder : myotonia fluctuantmyotonia permanentacetazolamide responsive myotonia,Calcium channelopathy,Hypokalemicmalignant hyperthermia,C/P of channelopathy,Paramytonia congenita,AD Onset :1st deca
37、de Paradoxical myotonia (Aggravated by warm as well cold) Face ,neck,forearm After several attempt of eye closure the patient can not open the eye ttt: Na channels blocker mexiletine,Hyperkalamic periodic paralysis,K sensitive periodic paralysis Onset :1st decade Attack last:1-2 h During attack: are
38、flexic with no ocular or respiratory muscles weakness Strength is n between the attack, but some patient has interictal limb girdle weakness Some families have myotonia ¶myotonia Aggravated: fasting/cold, shortly after exercise, K load, early AM,Episodes are rarely serous enough to require acute
39、 ttt ttt: oral CHO Prevention: thiazide,B agonist, low K,high CHO Avoid fasting, strenuous exercise/,myotonia,No weakness Aggravated by K diet/ excretion Can response to acetazolamide,hypokalemia,AD: It is the most frequent form of periodic paralysis Common in male Age: adolescence The attacks 3-24h
40、/vague prodorme of stiffness &heaviness& rarely ocular, bulbar, respiratory involved Early Myotonia of eyelid & late interictal proximal weakness,Aggravated: CHO meal, cold,hrs post exercise, sleep Work up:K level q 30min /TFT/ R/O 2nd causes of hypokalemia Tttt: Acute: oral K Q30min ,if symptoms sever iv K Prevention: Low CHO, low sodium diet ,spirnolactone, trimetrine,thanks,
