Congenital Myasthenic Syndromes – Case Reports
Authors:
M. Adamovičova 1,2; D. Šišková 2
Authors‘ workplace:
Klinika dětského a dorostového lékařství 1. LF UK a VFN v Praze
1; Oddělení dětské neurologie, pracoviště IPVZ, Fakultní Thomayerova nemocnice s poliklinikou, Praha
2
Published in:
Cesk Slov Neurol N 2010; 73/106(1): 62-67
Category:
Case Report
Overview
Congenital myasthenic syndromes started to be recognised and categorised in the 1970s, when they were first distinguished from myasthenia gravis. They are based on a genetic disorders affecting any of the proteins taking part in neuromuscular transmission. They comprise a clinically and genetically heterogeneous group of disorders, largely of autosomal recessive mode of inheritance. Fatigable weakness of skeletal muscles, also involving ocular and bulbar muscles, often manifests as early as in neonates and infants in the form of feeding difficulties with poor suck and swallowing, weak cry, ptosis, ophthalmoplegia, hypotonia, weakness and delayed motor development. The symptoms may fluctuate: crises with life-threatening acute respiratory failure are typical of some forms. Other forms may manifest as arthrogryposis or myopathy. Rarer are mild cases with onset later in childhood or in adolescence. Patients are often misdiagnosed with congenital or metabolic myopathy, muscle dystrophy or classical myasthenia. What is usually a good response to symptomatic therapy significantly changes the prognosis of the disease. In many instances, molecular genetic diagnosis is possible and prenatal testing is available. Most common in the Czech Republic is a mutation of the epsilon subunit of the acetylcholine receptor in patients of Roma ethnic origin. However, the range of congenital myasthenic syndromes is much wider. We present an overview, illustrated by case reports of the most frequent types.
Key words:
congenital myasthenic syndromes – respiratory failure – neuromuscular transmission disorders – muscle hypotonia – muscle weakness – fatigue – ptosis – ophthalmoplegia
Sources
1. Engel AG, Ohno K, Sine SM. Congenital myasthenic syndromes: a diverse array of molecular targets. J Neurocytol 2003; 32(5–8): 1017–1037.
2. Harper CM. Congenital myasthenic syndromes. Semin Neurol 2004; 24(1): 111–123.
3. Engel AG, Sine SM. Current understanding of congenital myasthenic syndromes. Curr Opin Pharmacol 2005; 5(3): 308–321.
4. Abicht A, Stucka R, Karcagi V, Herczegfalvi A, Horváth R, Mortier W et al. A common mutation (epsilon1267delG) in congenital myasthenic patients of Gypsy ethnic origin. Neurology 1999; 53(7): 1564–1569.
5. Ohno K, Tsujino A, Brengman JM, Harper CM, Bajzer Z, Udd B et al. Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. Proc Natl Acad Sci U S A 2001; 98(4): 2017–2022.
6. Byring RF, Pihko H, Tsujino A, Shen XM, Gustafsson B,Hackman P et al. Congenital myasthenic syndrome associated with episodic apnea and sudden infant death. Neuromuscul Disord 2002; 12(6): 548–553.
7. Barisic N, Müller JS, Paucic‑Kirincic E, Gazdik M, Lah‑Tomulic K, Pertl A 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(1): 7–12.
8. Kraner S, Laufenberg I, Strassburg HM, Sieb JP, Steinlein OK. Congenital myasthenic syndrome with episodic apnea in patients homozygous for a CHAT missense mutation. Arch Neurol 2003; 60(5): 761–763.
9. Mihaylova V, Müller JS, Vilchez JJ, Salih MA, Kabiraj MM, D’Amico A et al. Clinical and molecular genetic findings in COLQ‑mutant congenital myasthenic syndromes. Brain 2008; 131(3): 747–759.
10. Bestue‑Cardiel M, Sáenz de Cabezón‑Alvarez A, Capablo‑Liesa JL, López‑Pisón J, Peña‑Segura JL, Martin‑Martinez J et al. Congenital endplate acetylcholinesterase deficiency responsive to ephedrin. Neurology 2005; 65(1): 144–146.
11. Ohno K, Engel AG, Shen XM, Selcen D, Brengman J, Harper CM et al. Rapsyn mutations in humans cause endplate acetylcholine‑receptor deficiency and myasthenic syndrome. Am J Hum Genet 2002; 70(4): 875–885.
12. Burke G, Cossins J, Maxwell S, Owens G, Vincent A,Robb S et al. Rapsyn mutations in hereditary myasthenia: distinct early‑ and late‑onset phenotypes. Neurology 2003; 61(6): 826–828.
13. Ioos C, Barois A, Richard P, Eymard B, Hantaï D, Estournet‑Mathiaud B. Congenital myasthenic syndrome due to rapsyn deficiency: three cases with arthrogryposis and bulbar symptoms. Neuropediatrics 2004; 35(4): 246–249.
14. Müller JS, Mildner G, Müller‑Felber W, Schara U, Krampfl K, Petersen B et al. Rapsyn N88K is a frequent cause of congenital myasthenic syndromes in European patients. Neurology 2003; 60(11): 1805–1810.
15. Ohno K, Sadeh M, Blatt I, Brengman JM, Engel AG. E‑box mutations in the RAPSN promotor region in eight cases with congenital myasthenic syndrome. Hum Mol Genet 2003; 12(7): 739–748.
16. Tsujino A, Maertens C, Ohno K, Shen XM, Fukuda T,Harper CM et al. Myasthenic syndrome caused by mutation of the SCN4A sodium channel. Proc Natl Acad Sci U S A 2003; 100(12): 7377–7382.
17. Selcen D, Milone M, Shen XM, Harper CM, Stans AA, Wieben ED et al. Dok‑7 Myasthenia: Phenotypic and Molecular Genetic Studies in 16 Patients. Ann Neurol 2008; 64(1): 71–87.
18. Okada K, Inoue A, Okada M, Murata Y, Kakuta S,Jigami T et al. The muscle protein Dok‑7 is essential for neuromuscular synaptogenesis. Science 2006; 312(5781): 1802–1805.
19. Beeson D, Higuchi O, Palace J, Cossins J, Spearman H, Maxwell S et al. Dok‑7 mutations underlie a neuromuscular junction synaptopathy. Science 2006; 313(5795): 1975–1978.
20. Palace J, Lashley D, Newsom‑Davis J, Cossins J, Maxwell S, Kennett R et al. Clinical features of the DOK7 neuromuscular junction synaptopathy. Brain 2007; 130: 1507–1515.
21. Müller JS, Herczegfalvi A, Vilchez JJ, Colomer J,Bachinski LL, Mihaylova V et al. Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes. Brain 2007; 130(6): 1497–1506.
22. Morar B, Gresham D, Angelicheva D, Tournev I, Gooding R, Guergueltcheva V et al. Mutation history of the roma/gypsies. Am J Hum Genet 2004; 75(4): 596–609.
23. Seeman P, Sisková D. Autosomal recessive ethnic diseases of Czech Gypsies. Čas Lék Česk 2006; 145(7): 557–560.
24. Bestue‑Cardiel M, Sáenz de Cabezón‑Alvarez A, Capablo‑Liesa JL, López‑Pisón J, Peña‑Segura JL, Martin‑Martinez J et al. Congenital endplate acetylcholinesterase deficiency responsive to ephedrin. Neurology 2005; 65(1): 144–146.
25. Chevessier F, Faraut B, Ravel‑Chapuis A, Richard P,Gaudon K, Bauché S et al. MUSK, a new target for mutations causing congenital myasthenic syndrome. Human Molecular Genetics 2004 13(24): 3229–3240.
26. Chevessier F, Faraut B, Ravel‑Chapuis A, Richard P,Gaudon K, Bauché S et al. Identification of an Agrin Mutation that Causes Congenital Myasthenia and Affects Synapse Function. Am J Hum Genet 2009; 85(2):155–167.
27. Maselli RA, Ng JJ, Anderson JA, Cagney O, Arredondo J, Williams C et al. Mutations in LAMB2 causing a severe form of synaptic congenital myasthenic syndrome. J Med Genet 2009; 46(3): 203–208.
Labels
Paediatric neurology Neurosurgery NeurologyArticle was published in
Czech and Slovak Neurology and Neurosurgery
2010 Issue 1
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