MYOPATHY, NEUROMUSCULAR JUNCTION & NERVE DISORDERS: Points in differential diagnosis
Distinctive Features: Most myopathies have weakness that is maximal proximally.
Extraocular muscles weak Myasthenia Gravis (MG) Thyroid; Botulism; Ocular myositis 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 Rule out: VII nerve lesion	Bulbar dysfunction MG; Thyroid; Cranial nerve Δ Oculopharyngeal MD; MG Distal myopathy (MPD2) IBM (IM-VAMP); 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; ↓ K+   Carnitine; Endocrine; Desmin Camptocormia
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 ↓ Periodic paralysis: X-Episodic Xp22   Hypo K: CACNA1S; SCN4A; KCNE3   Hyper K: SCN4A; KCNE3   Andersen: KCNJ2 Electrolyte disorders: K ↑ or ↓;   Mg ↑; PO4 ↓; Barium Rule out: Neuropathy (GBS);     Spinal cord	Wasting > Weakness (Muscle) Pathology: Type II atrophy Sarcopenia; Disuse; Cachexia: Wt loss > 15%; Age Paraneoplastic	Proximal arms weak Dystrophy: Scapuloperoneal; FSH BCIM; Absent muscles; Shoulder joint Δ MG; Neuropathic: ALS; P-LMN;   Brachial plexopathy
		Weakness > Wasting Immune myopathy; Myoglobinuria; Periodic Paralysis; Myasthenia gravis; Neuropathy + conduction block	Quadriceps weak LGD: Becker; 1B; 2B; 2H; Ring fib 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) ↓ 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 rpt Myotonic Dystrophy 2: ZNF9, CCTG rpt 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 ↓; Desmin ↑ 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: + Conn tissue dis; Aldolase ↑ Polymyalgia; Rhabdomyolysis Infections: Trichinosis; Brucellosis Myoadenylate deaminase ↓ (< 2%) Myopathy +: Tubular aggregates;   Focal ↓ mitochondria Drugs: Azathioprine; Steroid ↓... Rule out:   Small fiber neuropathy; Phlebitis   Bone & joint pain; Muscle Ischemia	Large muscles Overusage: Myotonia; Exercise   Neural Overactivity Partial denervation Endocrine: ↓ 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: Nerve > Muscle Normal: Single Muscles   Post-contraction; Sleep Electrolyte: Dehydration   ↓ Na, Mg, Ca, Glucose Endocrine: Thyroid; ↓ Adrenal Drugs; Pregnant; Spine stenosis Cramp-fasciculation; Familial Myopathy: Becker Motor neuron: ALS Elecrically silent: phosphorylase   Rippling muscle; Brody's	Contractures Arthrogryposis Ullrich/Bethlem: COL6 & 12A1 Congenital MD Dermatomyositis (DM-VP) LGMD: Dystrophin; CAPN3 Emery-Dreifuss IM drug injections Rigid spine SMA: SMN; X-linked Tel Hashomer Williams-Beuren
CNS + Myopathy Congenital MD: Santavuori POMGnT1;   Merosin; Fukuyama Fukutin;   Integrin-α7 Dystrophy: DMD; McLeod   DM1; DM2; HIBM Other hereditary: Mitochondrial   Acid Maltase: Aneurysms   Phosphoglycerate Kinase Acquired: Myosin-loss; Thyroid Necrotizing   Encephalopathy; Pipestem capillaries Hearing loss: FSH; Scapuloperoneal; Mito	Antibodies + Myopathy MG: Anti-AChR Binding  + Thymoma: Striation TTN, ACTN, RYR1 LEMS: P-type Calcium channel Immune myopathies   t-RNA synthetase (Jo-1 + other):     Lung; Raynaud's; Arthritis   Signal recognition Particle: Severe   HMGCR: IMPP + Necrosis   TIF1γ: DM-VP; Neoplasm-associated   DM: Mi-2 Nail Δ; MDA5 Ulcers   NT5C1A: IM-VAMP (sIBM)   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 Immune myopathy   SRP, HMGCoAR & Jo-1 Ab;   Paraneoplastic (RIIM); LHIM Acid maltase Acute damage: Injection   Rhabdomyolysis; Trauma Thyroid: Hypo-	Immune & Inflammatory Myopathy Antibodies: Decorin; SRP; Mi-2;   t-RNA synthetase (Jo-1 75%); HMGCR Perimysial pathology (IMPP) Vasculopathy: Dermatomyositis; RIIM Brachio-cervical inflammatory (BCIM) Granulomatous ± Sarcoid Polymyopathy (CK high; No inflammation):   SRP; Paraneoplastic (RIIM); LHIM IM-VAMP: Inclusion body; PM-Mitochondria Systemic disease: Drugs; GVHD   Collagen vascular; Infection;   Malignancy; Toxic Hereditary: FSH

Myasthenic Syndromes	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)     ↓ Synaptic vesicles & Quantal release     Congenital Lambert-Eaton-like; SLC18A3     Episodic ataxia 2: CACNA1A; SLC5A7   Synaptic: AChE deficiency (ColQ)   Postsynaptic: AChR α β δ e; Rapsyn; Plectin     AChRs: Kinetic Δ & ↓ # @ NMJs       Slow AChR channel; ↓ Channel open time     AChRs: Kinetic Δ & Normal # @ NMJs       ↑ Conductance & Fast closure of AChRs       ↓ ACh-affinity & Fast-channel     AChRs: ↓ #s @ NMJs & Kinetic WNL     Rapsyn: ↓ AChRs @ NMJs     Plectin; MuSK; Dok-7; LRP4; SNAP25     SCN4A (Apnea & Bulbar);   Limb-girdle MG: GFPT1; DPAGT1; ALG2; RYR1   Other: Agrin; ALG14; SCN4A; ZC4H2; CNTN1     TPM3; Congenital LEMS-like; COL13A1     Familial immune; PREPL	Dystrophies: Limb-Girdle & Other Dominant: 1A MYOT; 1B LMNA; 1C Cav3 (AD & AR);   1D DNAJB6; 1E DES; 1F TNPO3; 1G 4p21; 1H 3p23   Cytoplasmic body MYH7, Titin; Bethlem COL6A1,2,3   Emery-Dreifuss LMNA, SYNE 1&2; Hyaline body MYH7   Myotonic dyst: 1 DMPK CTG rpt; 2 ZNF9 CCTG rpt   IBM: 1 Desmin; 3 Myosin HC2; Paget VCP   FSH DUX4 del;. Oculopharyngeal PABP2 GCG rpt;   Myofibrillar: Desmin; αB-crystallin; BAG3; ACTA1     ZASP; Myotilin; FLNC; SEPN1; RBCK1; TPM2; TPM3   Dysplasia Diaphys TGFB1; Epiphys COL9A 2& 3, COMP Recessive: 2A Calpain-3; 2B DYSF; 2G TCAP; 2H TRIM32;   Sarcoglycan 2C γ; 2D α; 2E β; 2F δ; 2I FKRP; 2J Titin;   2K POMT1; 2L; 2M FKTN; 2N POMT2; 2O POMGnT1;   2P DAG1; 2Q Plectin; 2R Desmin; 2S TRAPPC11; 2T GMPPB   2U ISPD; 2V GAA; 2W LIM2; 2X POPDC1; 2Y TOR1AIP1   2Z POGLUT1; COL6A2; MYH2   DPM2 (Epilepsy); DPM3 (Cardiomyopathy); PTRF; POMGNT2   CMD: FKRP; SEPN1; POMT1;; POMT2; FKTN; LARGE;   GTDC2; TMEM5; B3GALNT2; SGK196; B3GNT1; GMPPB     ISPD; Resp fail 1q42; Ullrich COL6A; Laminin α-2 X-linked: Barth Tafazzin; Autophagy VMA21; XMEA VMA21   Emery-Dreifuss Emerin; Danon LAMP-2; McLeod XK;   Becker & Duchenne Dystrophin; Scapuloperoneal FHL1	Distal Myopathies Dominant:   Welander TIA1: Late; Hands & Ant. Legs   Finnish Titin: Late; Ant Tib   Gowers-Laing (MPD1) MYH7: Adult; Ant leg   Dystrophy + Rimmed vacuoles   IBM1 (Quad) Desmin; MPD2 (Vocal cord) MATR3   MPD3: Adult, Asymmetric; LGD 1A & 1C   IBM +: Paget VCP; HNRNPA2B1; HNRNPA1   Oculopharyngodistal; Scapuloperoneal   Myofibrillar Recessive:   Nonaka & IBM2 GNE: Quad sparing   Miyoshi & LGD 2B DYSF: Early adult; Post leg   MMD3 ANO5: Post leg   LGD 2G Telethonin: Teens; Ant leg & Prox Congenital myopathy Core RYR1; Rod;   Centronuclear; Spindle excess HRAS Other myopathies   Barnes; Congenital; Lipid; Glycogen;   Familial MG; Tubular Aggregates

Alan Pestronk 7/2/2019: More information at Neuromuscular Website: http://neuromuscular.wustl.edu