“Objectives: to describe the rare case of an adult woman presenting with progressive dysphagia, dysphonia, associated with weight loss and diffuse muscle weakness.
Materials: a 67-year-old woman was admitted to our hospital because of worsening bilateral ptosis, dysphagia, dysphonia and weakness of the arm abductor muscles, with onset since her sixties. Of note, our patient exhibited progressive neck weakness, and gait disturbance. The patient was normally delivered at full term and her past medical history was unrelevant. Her brother manifested with an unknown form of spastic paraparesis. She did not benefit from piridostigmin administered.
Methods: diagnostic assessment encompassed blood testing, including creatine kinase, anti-acetylcholine receptor and anti-MuSK antibodies, anti-striated muscle antibody and anti-muscle specific tyrosine kinase antibody, spirometry, echocardiogram, neurophysiological studies, muscle biopsy and genetic testing.
Results: neurophysiological studies showed repetitive cMAP to single stimulus and chronic myopathic changes; antibodies resulted negative; echocardiogram and spirometry were normal; mild myopathic findings were seen by muscle biopsy; surprisingly whole-exome sequencing revealed co-occurence of variants in two genes causative of congenital myasthenic syndromes: the heterozigotic variant c.1367A>G (p.Asn456Ser) in CHRND, and the compound heterozigotic variants c.2992C>T (p.Arg998Cys) and c.1787A>G (p.His596Arg) in LRP4.
Discussion: we suggest that also the occurrence of a late-onset bilateral ptosis, dysphagia, dysphonia, neck and limb weakness require an in-depth genetic counseling.
Conclusion: the early and broader application of (NGS) next generation sequencing could allows even to diagnose and to manage a late-onset congenital myasthenic syndrome.”