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- A neuromuscular (NM) disease presenting with varying weakness that worsens with exercise and improves with rest
- Three types of myasthenia gravis seen in childhood:
- Neonatal transient
- 10–20% of infants born to mothers with autoimmune myasthenia
- Congenital myasthenia
- Rare; represents <10% of all childhood myasthenia
- Weakness usually starts within first 2 years of life.
- Caused by inherited disorder in NM transmission
- Classified by mutation site (presynaptic, postsynaptic) or by molecular genetics
- Juvenile myasthenia
- Relatively rare: one new diagnosis per million per year
- Average age of onset 10 to 13 years, with a female predominance of 2:1 or 4:1
- Autoimmune disorder similar to adult-onset, autoimmune myasthenia gravis; mostly due to production of antibodies against the acetylcholine receptor (AChR)
- Neonatal transient
- Rare: incidence 4 to 6 per million per year
- Prevalence: 40 to 80 per million
- Children account for 10–15% of cases of myasthenia gravis annually in North America.
- Congenital type: generally autosomal recessive (check for consanguinity)
- Occasional family history
- Caused by a disruption in signal transmission from the motor neuron to the muscle. Sensory or cognitive symptoms are absent.
- The motor nerve terminal lies in close proximity to the end plate, a region of the muscle cell membrane with a high concentration of AChR.
- Normally, when stimulated, the motor nerve terminal releases acetylcholine that binds receptors, causing muscle contraction. The cleft contains acetylcholinesterase (AChE), an enzyme that breaks down acetylcholine and helps terminate muscle contractions.
- Autoimmune form (juvenile myasthenia or juvenile myasthenia gravis [JMG])
- Autoantibody blocks AChR activity → increased rate of receptor breakdown → fewer receptors are present → leads to decreased muscle contraction
- AChR antibody accounts for ~85% of JMG.
- Thymic pathology is believed to be central to pathogenesis of autoimmune myasthenia; however, thymic pathology (e.g., hyperplasia) is present in <1/3 of children who undergo thymectomy.
- Of JMG patients without elevated AChR antibody, some are positive for antibodies to muscle-specific kinase (MuSK).
- A small percentage of autoimmune JMG patients do not have an identified antibody.
- Neonatal (transient) myasthenia: Infants are born with weakness and hypotonia.
- Due to maternal–fetal transmission of antibodies against AChR
- Severity of maternal symptoms does NOT predict likelihood that infant will be affected. Occasional arthrogryposis (joint contractures) reflects decreased fetal movement in utero.
- High levels of maternal antibodies against fetal form of AChR pose an increased risk of disease.
- Previous pregnancy with affected infant places future child at much higher risk.
- In rare cases, mother is asymptomatic despite placentally transmitted antibody.
- Congenital myasthenic syndromes: group of genetic disorders of NM junction; classified by site of NM transmission defect and more recently by molecular genetics
- Includes presynaptic defects, synaptic defect (due to end plate AChE deficiency), postsynaptic defects (primary AChR deficiency, primary AChR kinetic abnormality, or perijunctional skeletal muscle sodium channel mutation)
Commonly Associated Conditions
- In juvenile myasthenia, other autoimmune disorders may occur:
- Hyperthyroidism in 3–9% of patients
- Small increase in incidence of type 1 diabetes
- Screening for thymoma at initial diagnosis by chest CT or MRI scan is appropriate:
- Children appear to have lower incidence of thymic tumor or pathology than adults with autoimmune myasthenia.