Kongenitale myasthene Syndrome

Zusammenfassung

Kongenitale myasthene Syndrome (CMS) stellen eine Gruppe seltener, klinisch und genetisch heterogener Erkrankungen der neuromuskulären Übertragung dar. Abhängig von der Lokalisation des genetisch determinierten Defekts unterscheidet man präsynaptische Störungen am Nervenende, Störungen im Bereich des synaptischen Spaltes und Defekte der postsynaptischen Muskelmembran. Derzeit sind 13 verschiedene genetische Defekte bekannt, die ca. 50% der klinisch diagnostizierten CMS verursachen. Die Patienten bleiben häufig lange ohne Diagnose, sodass die Prävalenz höher liegt als bekannt. Der Erfolg einer medikamentösen Therapie mit Esterase-Inhibitoren, 3,4-Diaminopyridin, Ephedrin, Fluoxetin oder Chinidinsulfat ist vom genetischen Defekt abhängig. Grundsätzlich können die Symptome bei den Betroffenen sehr variabel sein, sodass die Diagnosestellung häufig verspätet erfolgt. Viele Patienten werden, trotz vorhandenen therapeutischen Möglichkeiten, verspätet oder inadäquat behandelt, was schwerwiegende Folgen für den einzelnen Patienten haben kann. In dieser Übersicht sind klinische Symptome, diagnostisches Vorgehen und therapeutische Ansätze beim Verdacht auf CMS aufgeführt.

Summary

Congenital myasthenic syndromes (CMS) are rare genetically and clinically heterogeneous disorders characterized by an impaired neuromuscular transmission. Causal defects in presynaptic nerve terminal, synaptic cleft, and postsynaptic apparatus have been identified. To date, genetic defects of 13 different genes are estimated to cause at least 50% of all clinically diagnosed CMS. CMS are often missed and their prevalence may be underestimated. Most patients are eligible for drug therapy with esterase inhibitors, 3,4-Diaminopyridine, ephedrine, fluoxetine or quinidine, but the effect of these drugs differs depending on the underlying genetic defect. Despite potential pharmacotherapeutic treatment options for most CMS forms many patients are treated delayed or inadequately. Delayed or inadequate treatment of CMS can possibly have deleterious consequences for the patient. However, clinical phenotypes in CMS may vary widely and symptoms can be unspecific hindering a timely diagnosis of this rare condition. This article contains an overview of specific clinical symptoms, diagnostic workup and possible pharmacotherapy in case of CMS.

Schlüsselwörter

Kongenitale myasthene Syndrome - Phänotyp - Genotyp - Diagnostik - Therapie

Keywords

Congenital myasthenic syndromes - phenotype - genotype - diagnostic work-up - treatment

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