Hereditary and acquired disorders of neuromuscular junction in children – novel approach in diagnosis and therapy

Abstract

Neuromuscular junction is the site of communication between motor nerve axons and skeletal muscle fi bers. Hereditary and acquired disorders aff ect presynaptic, intrasynaptic or postsynaptic part of neuromuscular junction causing muscle fatigue and weakness. Genetic defects cause abnormal neuromuscular transmission. Autosomal dominant disorders present as slow channel disease; autosomal recessive are more common and characterized by severe clinical course, as in presynaptic defect, fast channel disorders and rapsyn defi ciency. Acquired neuromuscular diseases are myasthenia gravis, Lambert-Eaton syndrome, botulism, transient neonatal myasthenia gravis and fetal acetylcholine receptor inactivation syndrome. Juvenile myasthenia gravis is usually associated with anti-acetylcholine receptor antibodies, while thymoma in children associated with juvenile myasthenia gravis is extremely rare. The aim is to present the variability of clinical presentation in neuromuscular junction disorders, the complexity of diagnostic approach, especially molecular-genetic diagnosis, and novel therapeutic options. Improvement in the understanding of the molecular- genetic etiology and pathogenesis of congenital myasthenic syndrome is signifi cant not only for diagnosis, but also for selection of the most appropriate therapeutic approach. Clinical presentation of myasthenia gravis in children is very variable, therapy is eff ective, but additional controlled clinical trials and clinical and diagnostic guidelines are still required.