P.12.3 Do congenital myasthenic syndromes in childhood have a common face? Clinical profile of slow channel, CHRNE and RAPSYN mutations

Abstract

Congenital myasthenic syndromes (CMSs) form a group of hereditary disorders, which are clinically and genetically heterogeneous. The neuromuscular transmission cascade is disrupted at presynaptic, synaptic or postsynaptic level, the latter is the most common. As a large part of CMSs have their onset in childhood, performing diagnostic studies leading to diagnosis can be very challenging. CMSs are highly treatable but treatment depends on the mutation type, so clinicians are urged to perform tailored genetic testing guided by clinical features. This systematic review of the literature shows the clinical neurological features of published cases with CMS due to a slow channel syndrome, RAPSYN deficiency or acetylcholine receptor (AChR) deficiency. English and Dutch case reports and series describing patients with a genetically proven CHRNE, RAPSYN or slow channel CMS from 1980 to 2012 were collected. Clinical features were evaluated. Findings were mostly in line with clinical features mentioned in previous literature. Minor differences were encountered. Very common were ocular, bulbar and limb weakness for AChR deficiency (N = 100). Cervical and distal weakness was often seen in slow channel syndromes (N = 51). Bulbar symptoms, arthrogryposis multiplex congenita, respiratory difficulties and the N88K founder mutation occurred frequently in the RAPSYN deficient patients (N = 98). Opposed to earlier reports no early- and late-onset phenotype was identified in the latter group and ophthalmoparesis was rare. In slow channel syndromes bulbar (25%) and ocular weakness (50%) was more common than previously reported. Ethnicity was not always in line with previous literature but could still be helpful in more targeted genetic testing. Overall we think that detailed descriptions of clinical features could guide the clinician in the diagnostic process.