Congenital myasthenic syndromes

• Published in: Orphanet journal of rare diseases Vol. 14; no. 1; pp. 57 - 22
• Main Author: Finsterer, Josef
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26-02-2019; BioMed Central; BMC
• Subjects: Acetylcholinesterase; Albuterol; Alkaloids; Antidepressants; Atracurium; Care and treatment; Cholinesterase Inhibitors - therapeutic use; Cognitive ability; Cognitive disorders; Congenital defects; Congenital diseases; Control; Defects; Diagnosis; Disease transmission; Electromyography; Enzymes; Ephedrine; Epilepsy; Esterase; Etiology; Etiology (Medicine); Fatigue; Fluoxetine; Gene mutation; Genes; Genetic disorders; Hereditary; Humans; Literature reviews; Medical research; Muscles; Mutation; Myasthenia; Myasthenic syndrome; Myasthenic Syndromes, Congenital - diagnosis; Myasthenic Syndromes, Congenital - genetics; Myasthenic Syndromes, Congenital - pathology; Myasthenic Syndromes, Congenital - therapy; Neuromuscular Agents - therapeutic use; Neuromuscular blocking agents; Neuromuscular diseases; Neuromuscular junctions; Neuropathy; Proteins; Proteins - genetics; Pyridine; Pyridines; Rare diseases; Repetitive nerve stimulation; Resveratrol; Review; Salbutamol; Sensors; Weakness; Genes; Myasthenic syndrome; Weakness; Fatigue; Myasthenia; Mutation; Hereditary; Repetitive nerve stimulation
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-019-1025-5

Congenital myasthenic syndromes (CMSs) are a genotypically and phenotypically heterogeneous group of neuromuscular disorders, which have in common an impaired neuromuscular transmission. Since the field of CMSs is steadily expanding, the present review aimed at summarizing and discussing current knowledge and recent advances concerning the etiology, clinical presentation, diagnosis, and treatment of CMSs.
Systematic literature review.
Currently, mutations in 32 genes are made responsible for autosomal dominant or autosomal recessive CMSs. These mutations concern 8 presynaptic, 4 synaptic, 15 post-synaptic, and 5 glycosilation proteins. These proteins function as ion-channels, enzymes, or structural, signalling, sensor, or transporter proteins. The most common causative genes are CHAT, COLQ, RAPSN, CHRNE, DOK7, and GFPT1. Phenotypically, these mutations manifest as abnormal fatigability or permanent or fluctuating weakness of extra-ocular, facial, bulbar, axial, respiratory, or limb muscles, hypotonia, or developmental delay. Cognitive disability, dysmorphism, neuropathy, or epilepsy are rare. Low- or high-frequency repetitive nerve stimulation may show an abnormal increment or decrement, and SF-EMG an increased jitter or blockings. Most CMSs respond favourably to acetylcholine-esterase inhibitors, 3,4-diamino-pyridine, salbutamol, albuterol, ephedrine, fluoxetine, or atracurium.
CMSs are an increasingly recognised group of genetically transmitted defects, which usually respond favorably to drugs enhancing the neuromuscular transmission. CMSs need to be differentiated from neuromuscular disorders due to muscle or nerve dysfunction.