MYOPATHY, NEUROMUSCULAR JUNCTION & NERVE DISORDERS: Points in differential diagnosis
1. Distinctive Features: Most myopathies have weakness that is maximal proximally.
Extraocular muscles weak Myasthenia Gravis (MG) Thyroid; Botulism Mitochondrial: KS; PEO; MNGIE Centronuclear; Multicore Oculopharyngeal MD; IBM + Contracture Oculopharyngodistal myopathy Congenital ophthalmoplegias	Periocular without   EOM Weakness Dystrophies: Myotonic;   FSH; Oculopharyngeal Myasthenia Gravis (MG) Congenital Myopathies Polymyositis Rule out: VII nerve lesion	Bulbar dysfunction MG; Thyroid; Cranial nerve Δ Oculopharyngeal MD Distal myopathy (MPD2) Polymyositis: IBM; Scleroderma Motor neuron Δ: ALS; BSMA   Pseudobulbar; Fazio-Londe   Brown-Vialetto-van Laere	Posterior neck weak Common: MG; PM; ALS Focal myopathy: Neck; Paraspinous Rare: FSH dyst; LMN synd; IBM;   Rod; PROMM; Acid maltase; ê K+   Carnitine; Endocrine; Desmin
Distal & Proximal weakness Dystrophy: Myotonic; FSH   Scapuloperoneal Myopathy: Congenital; Distal Glygogenoses: Debrancher   Phosphorylase b kinase Neuropathy + Myopathy: Paraneoplastic;   Sarcoid; Mitochondria; HIV;   Drugs (Amiodarone; Doxorubicin     Colchicine; Chloroquine)	Acute weakness Myasthenia gravis; Myoglobinuria Myosin loss myopathy; Carnitine ê Periodic paralysis: X-Episodic Xp22   Hypo K+: CACNA1S; SCN4A; KCNE3   Hyper K+: SCN4A; KCNE3   Andersen: KCNJ2 Electrolyte disorders: K+ é or ê;   Mg é; PO4 ê; Barium Rule out: Neuropathy; Spinal cord	Wasting > Weakness Pathology: Type II atrophy Cachexia: Wt loss > 15% Disuse; Steroid myopathy; Paraneoplastic; Aging	Proximal arms weak Dystrophy: Scapuloperoneal; FSH Absent muscles; Shoulder joint Δ MG; Neuropathic: ALS; P-LMN;   Brachial plexopathy
		Weakness > Wasting Polymyositis; Myoglobinuria; Periodic Paralysis; Myasthenia gravis; Neuropathy + conduction block	Quadriceps weak Myopathy: Becker; Ring fiber Myositis: IBM; Mitochon; Focal Nerve: Femoral; LS plexopathy;   Diabetic amyotrophy; L3-L4 root
Myoglobinuria Hereditary: Glycogenolysis; CPT II; LPIN1   Malignant Hyperthermia; Central core   King-Denborough; DMD (Some) ê K+: Licorice; Li; Thiazide;   Amphotericin; Laxative Infections; Mitochondrial; Trauma Muscle: Ischemia; Overactivity; PM Neuroleptic malignant syndrome Drugs: Heroin; Phencylidine; e-ACA   Clofibrate + Renal failure;   Cyclosporine A + Lovastatin Toxins: Venoms; IV drugs   Oral: Haff; Mushrooms; EtOH	Muscle activity Brody's syndrome: ATP2A1 Cramps: Benign Myoedema Myotonia Congenita   Dominant (Thomsen): CLCN1 (Cl-)   Recessive (Becker): CLCN1   Acetazolamide responsive: SCNA4 Myotonic Dystrophy 1: DMPK, CTG rep Myotonic Dystrophy 2: ZNF9, CCTG rep Paramyotonia: Na+ channel (SCNA4)   Periodic paralysis, Hyperkalemic Schwartz-Jampel: Perlecan Neural & Spinal activity	Cardiac disorders Dystrophy: DMD/Becker;   Myotonic; McLeod;   Emery-Dreifuss; Barth;   Scapuloperoneal; Desmin Polymyositis; Nemaline rod Acid Maltase; Debrancher Carnitine ê; Desmin é Mitochondrial; Amyloid Drugs: Metronidazole;   Emetine; Chloroquine;   Clofibrate; Colchicine Cardiomyopathy + cores Periodic paralyses	Respiratory Failure Myasthenia gravis Myosin-loss myopathy Acid Maltase Amyloid; Desmin Polymyositis (Jo-1) Congenital Myopathy:   Rod; Centronuclear Hydroxychloroquine Neural: Phrenic lesions   Arnold-Chiari; Churg-Strauss   Brachial plexopathy; ALS GI disorders: See Neuropathy
Muscle pain Myositis: + Connective tissue dis Polymyalgia; Rhabdomyolysis Infections: Trichinosis; Brucellosis Myoadenylate deaminase ê (< 2%) Myopathy +: Tubular aggregates;   Focal ê mitochondria Drugs: Azathioprine; Steroid ê... Rule out:   Small fiber neuropathy; Phlebitis   Bone & joint pain; Muscle Ischemia	Large muscles Overusage: Myotonia; Exercise   Neural Overactivity Partial denervation Endocrine: ê Thyroid; Acromegaly Hered: DMD; LGMD; Lipodyst; Myostatin Infection: Cysticercosis;   Trichinosis; Schistosomiasis Drugs: β2 adrenergic; Androgen Storage: Glycogen; Amyloid   Fat; Gangliosides Short stature: Schwartz-Jampel; Myhre	Cramps Normal: Single Muscles   Post-contraction; Sleep Electrolyte: Dehydration   ê Na, Mg, Ca, Glucose Endocrine: Thyroid; ê Adrenal Drugs; Pregnant; Spine stenosis Cramp-fasciculation; Familial Myopathy: Becker Motor neuron: ALS Elecrically silent: phosphorylase   Rippling muscle; Brody's	Contractures Arthrogryposis Bethlem Myopathy Congenital MD Dermatomyositis Dystrophinopathies Emery-Dreifuss IM drug injections Rigid spine syndrome SMA: 5q; X-linked Tel Hashomer Williams-Beuren
CNS + Myopathy Congenital MD: Santavuori POMGnT1 1p32;   Merosin 6q22; Fukuyama Fukutin; 9q31   Integrin-α7 12q13 Dystrophy: DMD; McLeod   DM1; PROMM; HIBM 9p13 Thyroid; Mitochondrial   Acid Maltase: Aneurysms   Phosphoglycerate Kinase Myosin-loss Necrotizing   Encephalopathy; Pipestem capillaries Hearing loss: FSH; Scapuloperoneal	Antibodies + Myopathy MG: Anti-AChR   Binding & Modulating MG + Thymoma: Anti-striational   vs. Titin; Actinin; Ryanodine R LEMS: P-type Ca++ channel Polymyositis:   t-RNA synthetase (Jo-1):     Lung; Raynaud's; Arthritis   Signal recognition Particle: Acute   Mi-2: Dermatomyositis; Nail Δ   PM-Scl: PM + Scleroderma Decorin: M-protein; Myopathy	CK: High > 1,000 Dystrophy   X-linked: DMD/Becker   Recessive: 2A-2I   Dominant: 1C; Ankle contract Distal myopathy: Miyoshi Polymyositis Acid maltase Acute damage: Injection   Rhabdomyolysis; Trauma Thyroid: Hypo-	Inflammatory myopathies Antibodies: Decorin; SRP; Mi-2;   t-RNA synthetase (Jo-1 75%) Dermatomyositis: Child; Mi-2; Adult Microvasculopathies: DM; SRP Brachio-cervical inflammatory (BCIM) Granulomatous ± Sarcoid Idiopathic myositis: Poly-; Focal Inclusion body (IBM); PM-Mitochondrial Systemic disease: Drugs; GVHD   Collagen vascular; Infection;   Malignancy; Toxic Hereditary: FSH

2. Myasthenic Syndromes	3. Hereditary Myopathy Syndromes
Acquired MG: Immune ± Thyroid or Thymoma;   Childhood; Drug-induced; Neonatal Transient Lambert-Eaton myasthenic syndrome (LEMS) Congenital & Familial:   Presynaptic: Familial infantile (ChAT; 10q11)     ê Synaptic vesicles & Quantal release     Congenital Lambert-Eaton-like     Episodic ataxia 2: CACNA1A; 19p13   Synaptic: AChE deficiency (ColQ; 3p25)   Postsynaptic: AChR α β δ e; Rapsyn; Plectin     AChRs: Kinetic Δ & ê # @ NMJs       Slow AChR channel; ê Channel open time     AChRs: Kinetic Δ & Normal # @ NMJs       é Conductance & Fast closure of AChRs       ê ACh-affinity & Fast-channel     AChRs: ê #s @ NMJs & Kinetic WNL     Rapsyn (11p11): ê AChRs @ NMJs     Plectin 8q24; MuSK 9q31; Dok-7 4     Apnea & Bulbar: SCN4A 17q35   Other syndromes: Familial limb-girdle;     Benign congenital MG & Facial malform     Congenital LEMS-like; Familial immune	Dystrophies: Limb-Girdle & Other Dominant: 1A Myotilin (TTID), 5q31; 1B LMNA, 1q11;   1C Cav-3, 3p25; 1D 7q; 1E 6q23; 1F 7q32; 1G 4p21;   Cytoplasmic body 2q24 & 2q21; Emery-Dreifuss LMNA;   DM1 DMPK CTG rpt, 19q13; DM2 ZNF9, 3q21   Bethlem COL6A, 21q22 & 2q37; FSH 4q35;   IBM3 Myosin HC2, 17p13; ZASP, 10q22;   Oculopharyngeal PABP2 GCG rpt, 14q11; Spheroid body   Desmin 2q35; αB-crystallin 11q22; Paget VCP, 9p13   Dysplasia Diaphys TGFB1, 19q13; Epiphys COL9A3, 20q13 Recessive: 2A Calpain-3, 15q15; 2B Dysferlin, 2p12; Cav-3;   Sarcoglycan 2C γ, 13q12; 2D α, 17q21; 2E β, 4q12; 2F δ, 5q33   2G Telethonin, 17q11; 2H TRIM32, 9q31; 2I FKRP, 19q13;   2J Titin, 2q31; 2K POMT1, 9q34; 2L, 11p13; 2M Fukutin, 9q31;   CMD: Nl CNS FKRP, 19q13; Rigid spine SEPN1, 1p35     Respiratory failure 1q42; Ullrich COL6A; 21q22 & 2q37 X-linked: Barth Tafazzin, Xp28; Autophagy Xq28;   Emery-Dreifuss Emerin, Xq28; McLeod XK, Xp21   Becker & Duchenne Dystrophin; Xq21;   Danon LAMP-2; Xq24; Scapuloperoneal	Distal Myopathies Dominant:   Welander 2p13: Late; Hands & Ant. Legs   Finnish Titin, 2q31: Late; Ant Tib   Gowers-Laing (MPD1) MYH7, 14q11: Adult; Ant leg   Dystrophy + Rimmed vacuoles 19p13   IBM1: Quad weakness   MPD3: Adult, Asymmetric; LGD 1A & 1C   IBM +: Paget's VCP, 9p13; Resp failure 6q27   Oculopharyngodistal; Scapuloperoneal 12q13   Vocal cord & Pharyngeal (MPD2) 5q31   Myofibrillar: Desmin; αB-crystallin; TTID; ZASP     SEPN1; Filamin C; BAG3 Recessive:   Nonaka & IBM2 GNE, 9p12: Quad sparing   Miyoshi & LGD 2B Dysferlin, 2p12-14     Early adult; Posterior leg   LGD 2G Telethonin, 17q11: Teens; Ant leg & Prox Other myopathies   Barnes; Congenital; Lipid; Glycogen;   Familial MG; Tubular Aggregates

Alan Pestronk 10/1/2008: More information at Neuromuscular Website: http://neuromuscular.wustl.edu