Myasthenia Gravis: Differential Diagnosis

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Differential Diagnosis of Myasthenia Gravis

Fatigue (Ptosis): Familial MG

Prominent ocular signs
- Mitochondrial Myopathy: PEO
- Oculopharyngeal muscular dystrophy
- Intracranial mass lesion
- Senile ptosis
Bulbar dysfunction
Generalized MG
- Lambert-Eaton syndrome (LES)
- Botulism
- Congenital myasthenic syndromes
- Myopathies or muscular dystrophies
Serum creatine kinase (CK)
- Usually normal in MG
- Elevated in ~10% of MG
Inherited MG
- Consider when
  - Persistent weakness begins in infancy or early childhood
  - Muscle biopsy changes do not explain degree of weakness
- Frequency: Uncommon
- Usually an autosomal recessive disorder: Positive family histories in minority
- Muscle biopsy: Type 2 muscle fiber atrophy; Small NMJs
- Treatment
  - Some forms of hereditary MG improve with anti-cholinesterases or quinidine
  - None respond to immunosuppression

	CHILDHOOD MYASTHENIA GRAVIS: TYPES
	Neonatal	Congenital	Familial Infantile	Acquired Juvenile	Recurrent Arthrogryposis
Maternal MG	+	-	-	-	+
Onset	0 to 3 days post natal	Birth	Birth to 1 year	> 1 year More in Orientals	Congenital
Weakness	Generalized	Ocular ± Generalized	Respiratory Generalized	Ocular ± Generalized	Generalized
Time course	Remission 1 to 6 weeks	Fixed weakness	Fatal early, or Improvement > 2 years	Improvement over years	Static
Family history	± Other sibs Mother Untreated	Often	Usual	Rare	Other sibs Mother Untreated
Anti-AChR antibodies	Most	-	-	50% More in Orientals	+ vs Fetal AChR

Neonatal MG: Transient

Epidemiology
- Frequency
  - 10% to 30% of infants born to mothers with autoimmune MG
  - Less common when MG in mother treated with immunosuppression
  - ? more common when infant inherits maternal HLA type (A1, B8, DR3)
- Antibody associations
  - High anti-fetal/anti-adult muscle anti-AChR antibody ratio in mother
  - No correlation with maternal antibody titer or disease severity
Clinical
- Local or generalized weakness
- Respiratory depression
- Symptoms subside over 1 to 4 weeks
Associated disorders: Arthrogryposis
Diagnosis
- Confirm MG in mother
- Anti-AChR antibodies: Usually positive; May occur in children of mothers with Antibody - MG
- Anticholinesterase inhibitors
  - Edrophonium: 0.1 mg/kg; IV over 1 minute
  - Neostigmine: 0.04 mg/kg IM
Treatment
- Pyridostigmine
  - p.o.: 1 mg q3h; 20 min before feeding
  - IM: 0.2 to 0.4 mg / dose
- Neostigmine
  - p.o.: 0.2 mg, 20 min before feeding
  - IM: 0.01 to 0.04 mg/kg/dose
  - iv: 2% to 3% of total daily oral Pyridostigmine dose/24 hours
    as constant infusion

Recurrent Congenital Arthrogryposis¹

Occurs with Maternal MG
- Usually in untreated MG patients
- Some patients with antibodies are asymptomatic
Clinical
- Recurrent congenital arthrogryposis
- Pena-Shokeir phenotype
  - Fetal akinesia
  - Arthrogryposis
  - Facial anomalies
  - Lung hypoplasia: May be fatal
  - Survivor: Dysarthria; Myopathic faces; high arched palate
AChR antibody: Maternal
- Antibodies more common in patients with previous childbirths
- Antigenic target: Fetal AChR
  - Binds to γ subunit of AChR
  - Overlaps ACh binding site
- Antibody effect: Abolishes AChR function
Treat MG in mother: Reduces risk of arthrogryposis in subsequent pregnancies
Analogus hereditary disorder
- Multiple pterygium syndrome: AChR, γ-subunit mutations

Thomas Willis 1621-1675

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References
1. Am J Med Genet 2000; 92:1-6

4/22/2009