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

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

Author information

1
Department of Pediatrics, Hospital Universitario de Fuenlabrada, Madrid, Spain. Electronic address: daninatera@hotmail.com.
2
Department of Neurology, Hospital General San Jorge, Huesca, Spain.
3
Department of Neurology, Hospital Universitari La Fe, Valencia, Spain.
4
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
5
Department of Pediatrics, Hospital Universitario Cruces, Bilbao, Spain.
6
Department of Genetics, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
7
Department of Genetics, Instituto de Medicina Genómica, Valencia, Spain.
8
Department of Neuromuscular Diseases, Hospital Sant Joan de Déu, Barcelona, Spain.
9
Department of Pediatric Neurology, Hospital Universitario 12 de Octubre, Madrid, Spain.
10
Department of Pediatrics, Hospital Universitario Rey Juan Carlos, Madrid, Spain.
11
Friedrich-Baur-Institute, Ludwig-Maximilians-University Munich, Munich 80336,Germany.
12
Friedrich-Baur-Institute, Ludwig-Maximilians-University Munich, Munich 80336,Germany; Medical Genetics Center, Munich, Germany.

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.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

PMID:
26782015
DOI:
10.1016/j.nmd.2015.10.013
[Indexed for MEDLINE]

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