Clinical and genetic basis of congenital myasthenic syndromes

Abstract

Neuromuscular junction disorders represent a wide group of neurological diseases characterized by weakness, fatigability and variable degrees of appendicular, ocular and bulbar musculature involvement. Its main group of disorders includes autoimmune conditions, such as autoimmune acquired myasthenia gravis and Lambert-Eaton syndrome. However, an important group of diseases include congenital myasthenic syndromes with a genetic and sometimes hereditary basis that resemble and mimick many of the classic myasthenia neurological manifestations, but also have different presentations, which makes them a complex clinical, therapeutic and diagnostic challenge for most clinicians. We conducted a wide review of congenital myasthenic syndromes in their clinical, genetic and therapeutic aspects.

Collagen XIII and Other ECM Components in the Assembly and Disease of the Neuromuscular Junction

“…Depending on the molecular complex affected, the pathological processes may be classified as presynaptic, synaptic, or postsynaptic. The two most common NMJ disorders are the autoimmune diseases myasthenia gravis (MG) and Lambert–Eaton myasthenic syndrome (LEMS) (Spillane et al, ; Lorenzoni et al, ; Liang and Han, ; Engel et al, ; Souza et al, ). In the majority of generalized MG cases, the cause is AChR autoantibodies that block ACh binding, thereby inhibiting the opening of the ion channels; decrease AChR levels; and cause complement‐mediated damage to the entire endplate (Ha and Richman, ).…”

“…Typically, decrementing of responses in electromyography studies demonstrates the patient's NMJ dysfunction. To date, mutations in more than 25 separate genes have been linked to CMSs, of various types (Hantai et al, ; Rodriguez Cruz et al, ; Rodriguez Cruz et al, ; Engel et al, ; Souza et al, ; Lee et al, ). Although all CMSs are rare and the diseases' diversity, clinical variability, and diagnostic challenges render prevalence rates difficult to determine with accuracy, the number of confirmed cases among children under 18 years of age in the UK is found approaching 10:1,000,000 (Parr et al, ).…”

Obstructive sleep apnoea and hypoventilation in an adult with congenital myasthenic syndrome

“…Some drugs such as 3,4-diaminopyridine (3,4-DAP), acetylcholinesterase inhibitors, fluoxetine and ephedrine may improve signal transduction and quality of life in patients with CMS 7. For patients with CMS with MuSK mutations, 3,4-DAP can improve muscle weakness8 by increasing acetylcholine release 9. In this case, our patient initially had a favourable response to 3,4-DAP, he but later developed paradoxically worsened weakness leading to discontinuation of the medication.…”

Congenital myasthenic syndromes and myasthenia gravis are challenging diagnoses in neurological practice

“…In this issue of Arquivos de Neuropsiquiatria, Souza et al 9 present a comprehensive review on CMS that will be of great interest to the readers, as they included clinic, genetic and therapeutic particularities according to CMS subtypes. CMS mostly manifest in the first two years of life, leading to difficulties in the differential diagnose with congenital myopathies.…”

“…Considering the importance of genetic testing in the final diagnose of CMS 8,9 and that it is costly and only available in few centers of Brazil, it seems to be of a high demand to reverse this situation. Early and definite diagnoses in CMS lead to a better rational therapeutic choice in benefit to patients.…”