Long-term follow-up in patients with congenital myasthenic syndrome due to RAPSN mutations

Neuromuscul Disord. 2016 Feb;26(2):153-9. doi: 10.1016/j.nmd.2015.10.013. Epub 2015 Nov 23.


Rapsyn (RAPSN) mutations are a common cause of postsynaptic congenital myasthenic syndromes. We present a comprehensive description of the clinical and molecular findings of ten patients with CMS due to mutations in RAPSN, mostly with a long-term follow-up. Two patients were homozygous and eight were heterozygous for the common p.Asn88Lys mutation. In three of the heterozygous patients we have identified three novel mutations (c.869T > C; p.Leu290Pro, c.1185delG; p.Thr396Profs*12, and c.358delC; p.Gln120Serfs*8). In our cohort, the RAPSN mutations lead to a relatively homogeneous phenotype, characterized by fluctuating ptosis, occasional bulbar symptoms, neck muscle weakness, and mild proximal muscle weakness with exacerbations precipitated by minor infections. Interestingly, episodic exacerbations continue to occur during adulthood. These were characterized by proximal limb girdle weakness and ptosis, and not so much by respiratory insufficiency after age 6. All patients presented during neonatal period and responded to cholinergic agonists. In most of the affected patients, additional use of 3,4-diaminopyridine resulted in significant clinical benefit. The disease course is stable except for intermittent worsening.

Keywords: 3,4-diaminopyridine; Congenital myasthenia; Congenital myasthenic syndrome; Neuromuscular junction; Pyridostigmine; Rapsyn.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / administration & dosage
  • 4-Aminopyridine / analogs & derivatives
  • 4-Aminopyridine / pharmacology
  • Adolescent
  • Adult
  • Amifampridine
  • Child
  • Child, Preschool
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / pharmacology*
  • Disease Progression*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Muscle Proteins / genetics*
  • Mutation
  • Myasthenic Syndromes, Congenital / drug therapy
  • Myasthenic Syndromes, Congenital / genetics*
  • Myasthenic Syndromes, Congenital / physiopathology*
  • Phenotype
  • Potassium Channel Blockers / administration & dosage
  • Potassium Channel Blockers / pharmacology*
  • Pyridostigmine Bromide / administration & dosage
  • Pyridostigmine Bromide / pharmacology
  • Young Adult


  • Cholinesterase Inhibitors
  • Muscle Proteins
  • Potassium Channel Blockers
  • peripheral membrane protein 43K
  • 4-Aminopyridine
  • Pyridostigmine Bromide
  • Amifampridine