Congenital myasthenic syndrome due to novel GFPT1 variant presenting with head drop and visual impairment: A case report

Background Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) gene variants are a known cause of congenital myasthenic syndrome (CMS), typically presenting with fatigable limb-girdle weakness and characteristic tubular aggregates on muscle biopsy, though recent reports have broadened the clinical spectrum. Methods We describe a 5-year-old boy presenting with hypotonia, progressive muscle weakness with head drop, cognitive delay, and visual impairment, found on neuromuscular genetic panel to have a novel homozygous missense variant in GFPT1 (c.1154G>A, p.Arg385Gln). Results Further workup revealed white matter abnormalities with atrophy of corpus callosum and cerebellum on neuroimaging, myopathic motor unit potentials on electromyography, and non-specific changes on the left biceps muscle biopsy with absence of tubular aggregates. Stimulated jitter analysis of the right orbicularis oculi muscle showed increased jitter and blocking indicative of neuromuscular junction (NMJ) transmission defect. Trio whole-exome and trio whole-genome sequencing confirmed autosomal recessive GFPT1 -related myasthenia. Discussion The muscle-eye-brain (MEB) phenotype of our case was like that of alpha-dystroglycanopathy, a glycosylation-related severe congenital muscular dystrophy. The presence of NMJ abnormalities expands the novel GFPT1 variant genotype-phenotype to include central nervous system features and muscle-eye-brain congenital myasthenic syndrome (MEB-CMS). This case study highlights the role of multiple specialists (neurologist, radiologist, ophthalmologist, pathologist, geneticist) and neurodiagnostic techniques (neuroimaging, electrodiagnostic, muscle pathology) to help deep phenotype symptomatic patients with novel gene variants found on next-generation sequencing.