A late-onset slowly progressive dystrophic-myasthenic phenotype expands the clinical spectrum of TOR1AIP1-related disease.

The TOR1AIP1 gene encodes the nuclear envelope protein LAP1; pathogenic variants cause distinct phenotypes, from muscular dystrophy to multisystem involvement. This recessive disease presents from in utero to late adulthood. Survival depends on phenotype. A 63-year-old woman first presented at 48 years of age with progressive proximal lower limb weakness since age 28, recently involving the upper limbs. There was no consanguinity, but familial gait impairment was reported. She had lumbar hyperlordosis, proximal tetraparesis, and waddling gait. CK was normal and neurophysiological studies revealed myopathic changes and a 12% decremental response on repetitive nerve stimulation. Muscle biopsy showed muscular dystrophy. Weakness progressively worsened over 15 years of follow-up. Exome sequencing revealed a probably homozygous pathogenic TOR1AIP1 variant. This case contributes to characterizing the TOR1AIP1-related disease phenotypic heterogeneity. The association of myopathy with electrophysiological findings of myasthenic syndrome highlights the overlap between muscle and neuromuscular junction dysfunction.