Download PDF
Neuropediatrics 2018; 49(04): 283-288
DOI: 10.1055/s-0038-1654706
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

Clinical and Genetic Features of Congenital Myasthenic Syndromes due to CHAT Mutations: Case Report and Literature Review

Pinar Arican
1   Department of Pediatric Neurology, Izmir Tepecik Education and Research Hospital, Izmir, Turkey
,
Pinar Gencpinar
2   Department of Pediatric Neurology, Izmir Katip Celebi University, Izmir, Turkey
,
Dilek Cavusoglu
3   Department of Pediatric Neurology, Afyon Kocatepe University, Afyon, Turkey
,
Nihal Olgac Dundar
2   Department of Pediatric Neurology, Izmir Katip Celebi University, Izmir, Turkey
› Author Affiliations Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Further Information

Publication History

06 February 2018

12 April 2018

Publication Date:
21 May 2018 (online)

Also available at
    Permissions and Reprints

Abstract

Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. CMS due to choline acetyltransferase (CHAT) gene is characterized by episodic apnea. We report a case of a 12-month-old female patient presented with recurrent episodic apnea carrying a mutation in CHAT gene, p.I336T. Furthermore, we describe the genetic and clinical findings in 44 CMS patients due to CHAT mutations in the literature up to date. Episodes of apnea and respiratory insufficiency are the hallmarks of CHAT mutations. Clinical manifestations usually provoked by infections and fever. CMS due to CHAT mutations are rare, but it is important to diagnosis. Early diagnosis and appropriate treatment can improve morbidity and mortality.

Keywords

congenital myasthenic syndrome - choline acetyltransferase - episodic apnea

Author Contributions

PA prepared the original manuscript. NOD and PG contributed to the revision of the final manuscript. DC assisted in the preparation of the manuscript.


Declaration of Conflicting Interest

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.


 

  • References

  • 1 Engel AG. Current status of the congenital myasthenic syndromes. Neuromuscul Disord 2012; 22 (02) 99-111
    CrossrefPubMedGoogle Scholar
  • 2 Lorenzoni PJ, Scola RH, Kay CS, Werneck LC. Congenital myasthenic syndrome: a brief review. Pediatr Neurol 2012; 46 (03) 141-148
    CrossrefPubMedGoogle Scholar
  • 3 Natera-de Benito D, Töpf A, Vilchez JJ. , et al. Molecular characterization of congenital myasthenic syndromes in Spain. Neuromuscul Disord 2017; 27 (12) 1087-1098
    CrossrefPubMedGoogle Scholar
  • 4 Yiş U, Becker K, Kurul SH. , et al. Genetic landscape of congenital myasthenic syndromes from Turkey: novel mutations and clinical insights. J Child Neurol 2017; 32 (08) 759-765
    CrossrefPubMedGoogle Scholar
  • 5 Ohno K, Tsujino A, Brengman JM. , et al. Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. Proc Natl Acad Sci U S A 2001; 98 (04) 2017-2022
    CrossrefPubMedGoogle Scholar
  • 6 Maselli RA, Chen D, Mo D, Bowe C, Fenton G, Wollmann RL. Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis. Muscle Nerve 2003; 27 (02) 180-187
    CrossrefPubMedGoogle Scholar
  • 7 Barisic N, Müller JS, Paucic-Kirincic E. , et al. Clinical variability of CMS-EA (congenital myasthenic syndrome with episodic apnea) due to identical CHAT mutations in two infants. Eur J Paediatr Neurol 2005; 9 (01) 7-12
    CrossrefPubMedGoogle Scholar
  • 8 Schara U, Christen HJ, Durmus H. , et al. Long-term follow-up in patients with congenital myasthenic syndrome due to CHAT mutations. Eur J Paediatr Neurol 2010; 14 (04) 326-333
    CrossrefPubMedGoogle Scholar
  • 9 Mallory LA, Shaw JG, Burgess SL. , et al. Congenital myasthenic syndrome with episodic apnea. Pediatr Neurol 2009; 41 (01) 42-45
    CrossrefPubMedGoogle Scholar
  • 10 Shen XM, Crawford TO, Brengman J. , et al. Functional consequences and structural interpretation of mutations of human choline acetyltransferase. Hum Mutat 2011; 32 (11) 1259-1267
    CrossrefPubMedGoogle Scholar
  • 11 Arredondo J, Lara M, Gospe Jr SM. , et al. Choline acetyltransferase mutations causing congenital myasthenic syndrome: molecular findings and genotype-phenotype correlations. Hum Mutat 2015; 36 (09) 881-893
    CrossrefPubMedGoogle Scholar
  • 12 Tan JS, Ambang T, Ahmad-Annuar A, Rajahram GS, Wong KT, Goh KJ. Congenital myasthenic syndrome due to novel CHAT mutations in an ethnic kadazandusun family. Muscle Nerve 2016; 53 (05) 822-826
    CrossrefPubMedGoogle Scholar