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
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
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
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; Spinal cord
Wasting > Weakness
Pathology: Type II atrophy
Cachexia: Wt loss > 15%
Disuse; Steroid myopathy;
Paraneoplastic; Aging
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
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
Bethlem Myopathy
Congenital MD
Dermatomyositis
Dystrophinopathies
Emery-Dreifuss
IM drug injections
Rigid spine syndrome
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)
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
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 7/12/2017: More information at Neuromuscular Website: http://neuromuscular.wustl.edu