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

Autores de IIS La Fe

• Juan Jesús Vílchez Padilla

  Autor

• Maria Garcia Hoyos

  Autor

• Arantxa Camacho Camacho

  Autor

• María Estrella Jimenez Trigos

  Autor

Participantes ajenos a IIS La Fe

• Natera-de Benito D
• Bestué M
• Evangelista T
• Töpf A
• García-Ribes A
• Trujillo-Tiebas MJ
• Ortez C
• Dusl M
• Abicht A
• Lochmüller H
• Colomer J
• Nascimento A

Grupos

• Patología Neuromuscular y Ataxias

  

  Investigador Principal

  Teresa Sevilla Mantecón

Abstract

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.

Keywords

• Rapsyn; Congenital myasthenic syndrome; Congenital myasthenia; Neuromuscular junction; Pyridostigmine; 3,4-diaminopyridine