👤 Josef Finsterer

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. Show less

Left ventricular hypertrabeculation (LVHT), also known as noncompaction or spongy myocardium, is a cardiac abnormality of unknown etiology and pathogenesis frequently associated with genetic cardiac and noncardiac disorders, particularly genetic neuromuscular disease. This study aimed to review the current knowledge about the genetic or pathogenetic background of LVHT. A literature review of all human studies dealing with the association of LVHT with genetic cardiac and noncardiac disorders, particularly neuromuscular disorders, was conducted. Most frequently, LVHT is associated with mitochondrial disorders (mtDNA, nDNA mutations), Barth syndrome (G4.5, TAZ mutations), hypertrophic cardiomyopathy (MYH7, ACTC mutations), zaspopathy (ZASP/LDB3 mutations), myotonic dystrophy 1 (DMPK mutations), and dystrobrevinopathy (DTNA mutations). More rarely, LVHT is associated with mutations in the DMD, SCNA5, MYBPC3, FNLA1, PTPN11, LMNA, ZNF9, AMPD1, PMP22, TNNT2, fibrillin2, SHP2, MMACHC, LMX1B, HCCS, or NR0B1 genes. Additionally, LVHT occurs with a number of chromosomal disorders, polymorphisms, and not yet identified genes, as well in a familial context. The broad heterogeneity of LVHT's genetic background suggests that the uniform morphology of LVHT not only is attributable to embryonic noncompaction but also may result from induction of hypertrabeculation as a compensatory reaction of an impaired myocardium. Most frequently, LVHT is associated with mutations in genes causing muscle or cardiac disease, or with chromosomal disorders. These associations require comprehensive cardiac, neurologic, and cytogenetic investigations. Show less