Case Report: A Novel AChR Epsilon Variant Causing a Clinically Discordant Salbutamol Responsive Congenital Myasthenic Syndrome in Two Egyptian Siblings

Abstract

Congenital myasthenic syndromes (CMS) are inherited disorders that lead to abnormal neuromuscular transmission. Post-synaptic mutations are the main cause of CMS, particularly mutations in CHRNE. We report a novel homozygous CHRNE pathogenic variant in two Egyptian siblings showing a CMS. Interestingly, they showed different degrees of extraocular and skeletal muscle involvement; both presented only a partial response to cholinesterase inhibitors, and rapidly and substantially ameliorated after the addition of oral β2 adrenergic agonists. Here, we enlarge the genetic spectrum of CHRNE-related congenital myasthenic syndromes and highlight the importance of a β2 adrenergic agonists treatment.

Keywords: CHRNE; congenital myasthenic syndrome; neuromuscular junction; salbutamol; β2 adrenergic agonists.

Figure 1

Clinical features, P1. P1, an 11-year-old boy with before treatment with salbutamol, showing severe bilateral ptosis and facial weakness (A); note the improvement after salbutamol treatment; he showed only mild ptosis (B) and less fatigability, being able to walk without aid (C).

Figure 2

Clinical features, P2. P2, an 8-year-old girl presenting with sever bilateral ptosis before treatment with salbutamol (A); amelioration of the eyelid ptosis (B); amelioration of strength in neck extensor muscles (C).

Figure 3

Genetics. A 2-bp shift of a reading frame from Codon 212 and premature stop codon at codon 214 of CHRNE gene (an image of this part of mRNA was taken from Alamut Visual software, Interactive Biosoftware Sophia Genetics).