Long term follow-up of three children with COLQ-related congenital Myasthenic syndrome of different mutations responsive to salbutamol

Abstract

Congenital myasthenic syndromes (CMS) are a group of rare inherited disorders characterised by impaired neuromuscular transmission. Mutations in the acetylcholinesterase (AChE) collagenlike tail subunit gene (COLQ) cause recessive forms of CMS causing end-plate AChE deficiency. We present 3 children with different COLQ − mutations treated with salbutamol and followed for 1-9 years. All three children have diagnostic electrophysiological findings with decremental repetitive at low-frequency motor nerve stimulation response and positive repetitive compound muscle action potentials. All showed significant improvement in motor performance and extraocular movements after salbutamol but minimal change in bilateral eyelid ptosis. The most severely affected child with a homozygous exon 14 and partial exon 15 deletion in COLQ gene severely affected child with a homozygous exon 14 and partial exon 15 deletion in COLQ gene with early age of onset required ventilator support and gastrostomy feeding before salbutamol therapy. Exon 14 and part of exon 15 are in translated to the C-terminal domain of the COLQ in a region that interacts with the muscle-specific kinase (MUSK) and helps anchoring the endplate AChE to the basal lamina. A child with two splice site mutations had the mildest presentation with predominant limb girdle weakness and no respiratory involvement.