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

Lookup NU author(s): Dr Teresinha Evangelista, Dr Ana TopfORCiD, Professor Hanns Lochmuller


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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.G1n120Serfs*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. (C) 2015 Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Natera-de Benito D, Bestue M, Vilchez JJ, Evangelista T, Topf A, Garcia-Ribes A, Trujillo-Tiebas MJ, Garcia-Hoyos M, Ortez C, Camacho A, Jimenez E, Dusl M, Abicht A, Lochmuller H, Colomer J, Nascimento A

Publication type: Article

Publication status: Published

Journal: Neuromuscular Disorders

Year: 2016

Volume: 26

Issue: 2

Pages: 153-159

Print publication date: 01/02/2016

Online publication date: 23/11/2015

Acceptance date: 29/10/2015

ISSN (print): 0960-8966

ISSN (electronic): 1873-2364

Publisher: Elsevier


DOI: 10.1016/j.nmd.2015.10.013


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Funder referenceFunder name
SENEP (Spanish Pediatric Neurology Society) fellowship
98482Medical Research Council UK
305121European Union Seventh Framework Programme (FP7)
305444European Union Seventh Framework Programme (FP7)
G1002274Medical Research Council UK