Investigators at Newcastle University, UK, and Hopitaux de Paris, France, report 5 patients from 3 unrelated families with a strikingly homogeneous clinical entity combining congenital myasthenia with distal muscle weakness and atrophy resembling a distal myopathy. MRI and neurophysiological studies were indicative of a mild distal myopathy, but decrement in response to 3 Hz repetitive nerve stimulation suggested a neuromuscular transmission defect. Post-exercise increment up to 285% in distal limb muscles was compatible with presynaptic congenital myasthenic syndrome. Immunofluorescence and ultrastructural analyses of muscle end-plate regions showed synaptic remodelling with denervation-reinnervation. Whole-exome sequencing identified five new recessive mutations in the gene encoding agrin. These findings expand the spectrum of congenital myasthenic syndromes due to agrin mutations. [1]

COMMENTARY. The authors recommend examination of patients with apparent distal myopathy for a neuromuscular transmission disorder and for agrin mutations.

Prevalence of congenital myasthenia. The UK prevalence of genetically confirmed congenital myasthenic syndrome (CMS) is 9.2 per million children under 18 years of age. CMS is equally prevalent in girls and boys. CHRNE, RAPSN and DOK7 are the most commonly identified mutations. Prevalence varies across geographical regions in England (2.8 to 14.8 per million). The mean incidence of antibody-positive autoimmune myasthenia was 1.5 per million children per year. Girls were affected more frequently than boys [2].

Investigators at the John Radcliffe Hospital, University of Oxford, UK, provide a review with updates of new mutations of known CMS causative genes and treatment strategies. The use of salbutamol and ephedrine alone or combined with physostigmine or 3,4-DAP is reported to benefit various CMS subtypes [3].

Of 51 patients attending the myasthenia clinic at the Massachusetts General Hospital, Boston, in 1958–1960, 35 were the juvenile type, 10 the transient neonatal type, and 6 a congenital myasthenia syndrome, under-recognized as a separate phenotype at that time [4].