Update on juvenile myasthenia gravis.

PURPOSE OF REVIEW: Juvenile myasthenia gravis is a relatively rare autoimmune neuromuscular disorder. The pathophysiology of juvenile myasthenia gravis is similar to that of adult myasthenia gravis, though there remain important differences regarding presentation and therapeutic options. We review the pathophysiology, clinical presentation, and treatment options for juvenile myasthenia gravis. RECENT FINDINGS: Randomized clinical studies of myasthenia gravis have been carried out primarily in adult populations. As juvenile myasthenia gravis is rare, it has been difficult to collect prospective randomized controlled data to evaluate treatment outcomes and efficacy. A recent retrospective series suggests that, as in adult myasthenia gravis, thymectomy is a viable therapeutic option for selected cases of generalized juvenile myasthenia gravis. This is corroborated by the clinical experience of the authors in a referral center with a cohort of patients affected by juvenile myasthenia gravis over a number of years. SUMMARY: Recent studies illustrate that some, but not all, adult research on myasthenia gravis is applicable to children and adolescents with juvenile myasthenia gravis. Adult research can inform pediatric studies, but should not be regarded as a substitute for dedicated research in those populations.

Paediatric electromyography in the modern world: a personal view.

Paediatric electromyography (EMG) is an invaluable diagnostic test for the investigation of neuromuscular disease, but its use is inconsistent between and within different countries. One perception is that the procedure is painful; however, in comparison with common investigations performed routinely in children, EMG is better tolerated. While some developments, such as those within clinical genetics, would appear to mark its demise, paradoxically the more genetic abnormalities that are discovered in conditions such as hereditary neuropathy, the more precise a delineation of the phenotype is required. EMG has particular strengths in the diagnosis of neuropathies, motor neuronopathy and neuromuscular transmission disorders such as myasthenia. Also, it can supplement the investigation of myopathies. Areas of development include the diagnosis of myasthenia, delineation of bulbar palsy as a cause of dysphagia, more accurate and earlier prediction of prognosis in neonatal brachial palsy and investigation of channelopathies. It is a valuable diagnostic tool in developed countries and those with limited resources.

Acquired myasthenia gravis in childhood.

PURPOSE OF REVIEW: This review discusses recent studies on myasthenia gravis with onset in childhood (juvenile myasthenia gravis) and neonatal myasthenia gravis. RECENT FINDINGS: The occurrence of myasthenia gravis in childhood is strongly influenced by genetic and environmental factors. Juvenile myasthenia gravis is associated with antibodies to the acetylcholine receptor (AChR) in most patients. Thymoma is rare, but often malignant in children. The frequency of juvenile myasthenia gravis with antibodies to the muscle-specific kinase (MuSK) varies markedly in different countries; some distinct features have been described. Management of juvenile myasthenia gravis does not differ, on the whole, from that of adult myasthenia gravis. Timing of thymectomy in young children is still controversial. Maternal antifetal type AChR antibodies can cause persistent focal weakness in the offspring, while neonatal myasthenia gravis associated with MuSK antibodies is often a severe and protracted albeit transient disease. SUMMARY: Juvenile myasthenia gravis, like its adult-onset counterpart, is a heterogeneous disease. Clinical presentation is influenced by antibody status, ethnicity and age of onset. Treatment is very effective, but guidelines and controlled trials are needed.The risk for neonatal myasthenia gravis appears to be markedly influenced by maternal antibody subclass and antigen specificity. Adequate treatment in mothers can reduce both frequency and severity of neonatal disease.

Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly.

We describe a severe postsynaptic congenital myasthenic syndrome with marked endplate acetylcholine receptor (AChR) deficiency caused by 2 heteroallelic mutations in the beta subunit gene. One mutation causes skipping of exon 8, truncating the beta subunit before its M1 transmembrane domain, and abolishing surface expression of pentameric AChR. The other mutation, a 3-codon deletion (beta426delEQE) in the long cytoplasmic loop between the M3 and M4 domains, curtails but does not abolish expression. By coexpressing beta426delEQE with combinations of wild-type subunits in 293 HEK cells, we demonstrate that beta426delEQE impairs AChR assembly by disrupting a specific interaction between beta and delta subunits. Studies with related deletion and missense mutants indicate that secondary structure in this region of the beta subunit is crucial for interaction with the delta subunit. The findings imply that the mutated residues are positioned at the interface between beta and delta subunits and demonstrate contribution of this local region of the long cytoplasmic loop to AChR assembly.

[Neonatal myasthenic syndromes]. / Síndromes miasténicos del neonato.

INTRODUCTION: In the newborn, myasthenia can present either as transient neonatal myasthenia or as a congenital syndrome. At present at least 8 syndromes involving neonatal neuromuscular junction (NMJ) malfunction have been described; one caused by the passage of transplacental antibodies from mother to child, while all but one of the rest are inherited. Inheritance in all but two syndromes is autosomal recessive. One is an autosomal dominantly inherited illness; in another the mode of inheritance is not clear. The deficit in function of the NMJ is presynaptic in 3 instances, at the junctional gap in 1, and postsynaptic in at least 3 other syndromes. DEVELOPMENT: We will review the clinical symptoms, as well as neurophysiologic and genetic testing available for diagnosis. We explain how, at least, in some of the syndromes, one can begin appropriate therapy based on clinical, neurophysiological and simple pharmacological testing. CONCLUSION: However, in many cases, it becomes necessary to refer the patient or a tissue sample, usually an intercostal nerve muscle preparation, to one of the very few centers in the world where in vitro neurophysiologic, microstructural and genetic procedures leading to a more precise diagnosis can be performed.