Congenital myasthenic syndromes – diagnostics and treatment

Congenital myasthenic syndromes (CMS) are genetically determined disorders affecting safety margins of neural transmission at presynaptic, postsynaptic and synaptic level. Diagnosis of CMS is made based on clinical symptoms including fatigable muscle weakness since infancy or childhood, decremental EMG response and negative antibodies to acetylcholine receptors (AChR) and muscle specific tyrosine kinase (MuSK). In some CMS the onset is delayed, weakness and EMG abnormalities appear intermittently in restricted distribution. Molecular genetic analysis has an important role in diagnosis of CMS. Presynaptic CMS are associated with recessive CHAT (choline acetyltransferase) gene mutations. The synaptic disorder is caused by mutation of the collagenic tail subunit of the COLQ gene. However most CMS are postsynaptic, mostly caused by CHRNE gene mutations of AchR _-subunit. In general, nonsense or frame shifting mutations cause CMS by decreased or absent protein expression and are inherited in autosomal recessive traits. Rapsyn gene (RAPSN) mutations cause primary endplate AchR deficiency. AchE inhibitors are the drugs of first choice in the treatment of CMS. We present children with presynaptic and with postsynaptic defects manifesting remarkable clinical heterogeneity.
Category: Original scientific paper
Volume: Vol. 51, No 4, october - december 2007
Authors: N. Barišić, J. Müller, I. Lehman, A. Šribar, A. Abicht, H. Lochmüller
Reference work: