Novel truncating RAPSN mutations causing congenital myasthenic syndrome responsive to 3,4-diaminopyridine

Brenda L. Banwell, Kinji Ohno, Joern P. Sieb, Andrew G. Engel

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Rapsyn is essential for clustering the acetylcholine receptor at the postsynaptic membrane of the neuromuscular junction. Direct sequencing of RAPSN in two children with congenital myasthenic syndromes with no mutation in any of the AChR subunits identified two heterozygous recessive mutations in each: a previously characterized N88K mutation in both, and a second frameshifting mutation in Patient (Pt) 1 and a nonsense mutation in Pt 2. An intercostal muscle biopsy in Pt 1 revealed decreased AChRs per endplate and decreased amplitude of the miniature endplate potential, predicted consequences of rapsyn deficiency. Clinically, both children manifested with hypomotility in utero, fatigable ocular and limb weakness since birth, decreased strength during viral illness, decremental response on electromyography, and absence of AChR antibodies. Pt 1, however, had a more severe clinical course with recurrent episodes of respiratory failure, contractures, and craniofacial malformations. In both patients, treatment with pyridostigmine was of some benefit, but the addition of 3,4-diaminopyridine led to significant clinical improvement. Thus, rapsyn deficiency predicting similar consequences at the cellular level can result in phenotypes with marked differences in severity of symptoms, risk of respiratory failure, and presence of contractures and craniofacial malformations.

Original languageEnglish (US)
Pages (from-to)202-207
Number of pages6
JournalNeuromuscular Disorders
Issue number3
StatePublished - Mar 2004


  • 3,4-Diaminopyridine
  • Congenital myasthenic syndrome
  • Human rapsyn deficiency
  • Therapy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)


Dive into the research topics of 'Novel truncating RAPSN mutations causing congenital myasthenic syndrome responsive to 3,4-diaminopyridine'. Together they form a unique fingerprint.

Cite this