Juvenile myasthenia gravis (ORPHA:391497)
Juvenile myasthenia gravis (MG; see this term) is a rare form of MG, an autoimmune disorder of the neuromuscular junction resulting in ocular manifestations or generalized weakness, with onset before 18 years of age.
Epidemiology
The exact prevalence and incidence of juvenile MG are not known. Estimated incidence has been reported at 1/1,000,000 to 1/200,000. The disorder is uncommon in Europe and North America (10% to 15% of cases of myasthenia gravis; see this term). In the Asian population, a much higher proportion of cases (up to 50%) with mainly ocular manifestations occurs in children below 15 years of age.
Clinical description
Onset may be prepubertal (before 12 years of age) or postpubertal (over 12 years). The hallmark of MG is fatigable muscle weakness. Initial presentation may be acute or subacute, and the course is usually chronic with remission and relapses. Prepubertal children more commonly have the ocular presentation (fatigable ptosis, ophthalmoplegia, and diplopia) while postpubertal patients more often develop generalized weakness. The proportion of patients having only ocular symptoms is higher than in adult MG, particularly in the prepubertal group in which half of cases are purely ocular. In generalized cases, manifestations include facial weakness, dysarthria, and dysphagia. In severe cases (myasthenic crisis), respiratory muscle involvement may be life-threatening and require respiratory support. Thymoma (see this term) development is rare in juvenile MG.
Etiology
The exact pathogenesis is not known but MG is related to circulating antibodies to various muscle receptors, including, in most of patients, acetylcholine receptor (AChR) and, rarely, muscle-specific receptor tyrosine kinase (MuSK). The thymus is thought to trigger antibody production in the form with anti-AChR antibodies. In the prepubertal form, there is a high rate of the MG form with no antibodies detectable (30-50%). It is currently unknown whether anti-LRP4 antibodies could be found in these patients. The disorder can also be drug-induced.
Diagnostic methods
The diagnosis is primarily clinical and is suspected on the basis of fatigable muscle weakness. Specific serum antibody tests, including acetylcholine antibody test, are diagnostic. Other tests that support diagnosis include repetitive nerve stimulation and single-fiber electromyography. Edrophonium testing has been used and involves administration of this short-acting cholinesterase inhibitor intravenously. The test is positive if there is a rapid but transient improvement in a monitored clinical sign (usually ptosis). Computed tomography (CT) or magnetic resonance imaging (MRI) should be used to screen for thymoma.
Differential diagnosis
Congenital myasthenic syndrome (CMS; see this term) should be considered in case of seronegativity.
Management and treatment
Acetylcholinesterase inhibitors (pyridostigmine) are recommended as first-line treatment in juvenile MG and may be sufficient in ocular forms. Corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, and cyclophosphamide have been used in children with refractory MG, but adverse effects limit their usefulness. Plasmapheresis and intravenous immunoglobulin (IVIg) can also be used, mainly in severe exacerbation or myasthenic crisis, and pre- or postoperatively in the context of thymectomy. Thymectomy has been recommended for the treatment of generalized juvenile MG in patients not responding to anticholinesterase treatment, nor immunomodulatory or immunosuppressive treatments. Age at thymectomy is debated.
Prognosis
Severe cases may be life-threatening, but the prognosis is generally very good. In the prepuberal form, there is a higher rate of remission in patients with the ocular form.

                            Last update: 
                            October 2014


                            - Expert reviewer(s): 
                            Dr Sonia BERRIH-AKNIN  - Pr Bruno EYMARD