Expanding the phenotypic and imaging spectrum of

Introduction: GFPT1-related congenital myasthenic syndrome (CMS) is a rare, autosomal recessive disorder that impairs neuromuscular transmission due to defective glycosylation of the neuromuscular junction. While typically presenting with limb-girdle weakness, tubular aggregates on biopsy, and a favorable response to acetylcholinesterase inhibitors, the full phenotypic and imaging spectrum remains incompletely defined. Methods: We evaluated five Brazilian patients from two unrelated families, all with pathogenic variants in homozygosity in Results: All patients showed early-onset proximal weakness, distal lower limb weakness, and frequent falls. One patient exhibited atypical features, including neonatal onset epilepsy, and cognitive impairment. RNS revealedmarked decrements in proximal upper-limb muscles (deltoid 43.6%, trapezius 37.3%) and in the distal lower-limb tibialis anterior (36.5%), consistent with foot dorsiflexion weakness. Muscle ultrasound revealed varying degrees of myopathic echogenicity. A strong positive correlation was found between MGFA severity and mean Heckmatt score ( Discussion: Our findings expand the clinical spectrum of GFPT1-CMS to include possible central nervous system involvement and demonstrate the value of integrating electrophysiology and muscle ultrasound into diagnostic evaluation. Muscle ultrasound may serve as a structural biomarker for phenotypic stratification in CMS, and distal involvement-particularly foot dorsiflexion weakness-represents an additional diagnostic clue for GFPT1-CMS.