Successful treatment of congenital myasthenic syndrome caused by a novel compound heterozygous variant in RAPSN.

Abstract

BACKGROUND:

Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous neuromuscular disorder characterized by muscle weakness and caused by mutations in more than 35 different genes. This condition should not be overlooked as a subset of patients with CMS are treatable. However, the diagnosis of CMS is often difficult due to the broad variability in disease severity and course.

CASE REPORT:

A five-year-old boy without remarkable family history was born with marked general muscle hypotonia and weakness, respiratory insufficiency, anomalies, and multiple joint contractures. Congenital myopathy was suspected based upon type 1 fiber predominance on muscle biopsy. However, he was diagnosed with CMS at age 4 years when his ptosis and ophthalmoplegia were found to be improved by edrophonium chloride and repetitive nerve stimulation showed attenuation of compound muscle action potentials. An exome sequencing identified a compound heterozygous missense variant of c.737C > T (p.A246V) and a novel intronic insertion c.1166 + 4_1166 + 5insAAGCCCACCAC in RAPSN. RT-PCR analysis which showed the skipping of exon 7 in a skeletal muscle sample confirmed that the intronic insertion was pathogenic. His myasthenic symptoms were remarkably improved by pyridostigmine.

CONCLUSION:

The patient's diagnosis of CMS was confirmed by exome sequencing, and RT-PCR revealed that the skipping of exon 7 in RAPSN was caused by a novel intronic insertion. The genetic information uncovered in this case should therefore be added to the collection of tools for diagnosing and treating CMS.

• Authors: Maki Saito, Masashi Ogasawara, Yuji Inaba, Yoshihiro Osawa, Makoto Nishioka, Shoko Yamauchi, Kana Atsumi, Shihoko Takeuchi, Ken Imai, Mitsuo Motobayashi, Yuka Misawa, Aritoshi Iida, Ichizo Nishino
• Journal: Brain & development (Brain Dev) Vol. 44 Issue 1 Pg. 50-55 (Jan 2022) ISSN: 1872-7131 [Electronic] Netherlands
• PMID: 34565654 (Publication Type: Case Reports)
• Copyright: Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Muscle Proteins
• peripheral membrane protein 43K

Topics

• Child, Preschool
• Humans
• Male
• Muscle Proteins (genetics)
• Myasthenic Syndromes, Congenital (diagnosis, genetics, physiopathology)