Congenital Myasthenia as a Cause of Respiratory Failure in two Infants and a Toddler – Case Reports

Česká verzia

Authors: M. Adamovičova ¹; K. Fabríciová ²; M. Jakubíková ³; I. Příhodová ³; P. Klement ¹; P. Sýkora ⁴; M. Dusl ⁵; A. Abicht ⁵; J. Zeman ¹; P. Seeman ^6,7; T. Honzík ¹
Authors place of work: Klinika dětského a dorostového lékařství 1. LF UK a VFN v Praze ¹; I. detská klinika LF UK a DFNsP Bratislava ²; Neurologická klinika a Centrum klinických neurověd 1. LF UK a VFN v Praze ³; Klinika detskej neurológie LF UK a DFNsP Bratislava ⁴; Univerzita Ludvika Maximiliana, Laboratoř molekulární myologie Mnichov ⁵; Klinika dětské neurologie 2. LF UK a FN v Motole, Praha ⁶; Centrum lékařské genetiky Gennet, Praha ⁷
Published in the journal: Cesk Slov Neurol N 2012; 75/108(6): 757-762
Category: Case Report

Poděkování Prof. dr. med. Hannsi Lochmullerovi a dr. med. Violetě Mihaylové, Univerzita Ludvika Maximiliana, Laboratoř molekulární myologie a Neurologická klinika, Mnichov za provedená DNA vyšetření COLQ genu, prof. dr. med. Andrew G. Engelovi, Mayo Clinic, USA a dr. med Ulrike Schara z Neuropediatrické kliniky v Essenu za cenné rady při nastavování léčby efedrinem. Práce vznikla s podporou těchto projektů: PRVOUK P24/LF/3, RVOVFN64165, VZ MSM 0021620849, PRVOUK-P26/LF1/4, GA UK v rámci projektu Klinická, laboratorní a socioekonomická analýza u pacientů s myasthenia gravis v ČR, č. 351011/2011.

Summary

Congenital myasthenic syndromes (CMS) are rare autosomal recessive disorders of neuromuscular transmission. They manifest early, but although symptoms can be improved with treatment, they often remain unrecognized. In our region, CMS with mutations of CHNE gene is well known and is particularly common in the gypsy ethnic group. However, there also are other, much more severe types, such as COLQ CMS that may be complicated by respiratory failure. In COLQ CMS, decomposition of acetylcholine at a synapse is disrupted. The synapse is overloaded and, therefore, syntostigmine as well as acetylcholinesterase inhibitors worsen the symptoms. Ephedrine is the treatment of choice. Apnoea monitor and resuscitation training in parents can be life-saving. In cases where both pathogenic mutations are known, prenatal or preimplantation diagnostics are available. We present three CMS patients who suffered from respiratory crises at an early age. The outcome was variable – a boy died at 6 months of age, a 7-year old girl needs nocturnal ventilation support and walks 10 meters, an adult patient has minimal sequelae. In two patients, COLQ mutations have been confirmed as a cause of CMS and COLQ CMS is suspected in the remaining patient (patient P2).

Key words:
congenital myasthenic syndrome – respiratory failure – neuromuscular transmission disorders – muscle hypotonia – muscle weakness

Zdroje

1. Engel AG. Current status of the congenital myasthenic syndromes. Neuromuscul Disord 2012; 22(2): 99–111.

2. Jakubíková M. Kongenitální myastenické syndromy a myasthenie dětského věku. Neurol Prax 2010; 11(2): 100–103.

3. Kolníková M, Sýkora P, Seeman P. Kongenitálny myastenický syndróm. Pediatr Prax 2009; 10(5): 268–269

4. Seeman P, Sisková D. Autosomal recessive ethnic diseases of Czech Gypsies. Čas Lék Česk 2006; 145(7): 557–560.

5. Hálek J, Neklanová M, Seeman P. Kongenitální myastenický syndrom (CMS). Čes-slov Pediat 2007; 62(6): 393–397.

6. Adamovičová M, Šišková D. Kongenitální myastenické syndromy – kazuistiky. Cesk Slov Neurol N 2010; 73/106(1): 62–67.

7. Engel AG, Lambert EH, Gomez MR. A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small nerve terminals, and reduced acetylcholine release. Ann Neurol 1977; 1(4): 315–330.

8. Donger C, Krejci E, Serradell AP, Eymard B, Bon S, Nicole S et al. Mutation in the human acetylcholinesterase-associated collagen gene, COLQ, is responsible for congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency (Type Ic). Am J Hum Genet 1998; 63(4): 967–975.

9. Ohno K, Brengman J, Tsujino A, Engel AG. Human endplate acetylcholinesterase deficiency caused by mutations in the collagenlike tail subunit (ColQ) of the asymmetric enzyme. Proc Natl Acad Sci USA 1998; 95(16): 9654–9659.

10. Hutchinson DO, Walls TJ, Nakano S. Congenital endplate acetylcholinesterase deficienty. Brain 1993; 116(3): 633–653.

11. 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.

12. Wargon I , Richard P, Kuntzer T, Sternberg D, Nafissi S, Gaudon K et al. Long-term follow-up of patients with congenital myasthenic syndrome caused by COLQ mutations. Neuromuscul Disord 2012; 22(4): 318–324.

13. Kinali M, Beeson D, Pitt MC, Jungbluth H, Simonds AK, Aloysius A et al. Congenital myasthenic syndromes in childhood: diagnostic and management challenges. J Neuroimmunol 2008; 15(201–202): 6–12.

14. Lashley D, Palace J, Jayawant S, Robb S, Beeson D. Ephedrine treatment in congenital myasthenic syndrome due to mutations in DOK7. Neurology 2010; 74(19): 1517–1523.

15. HGMD Professional Database. On-line. Available from URL: https://portal.biobase-international.com/hgmd.

16. Yeung WL, Lam CW, Ng PC. Intra-familial variation in clinical manifestations and response to ephedrine in siblings with congenital myasthenic syndrome caused by novel COLQ mutations. Dev Med Child Neurol 2010; 52(10): e243–e244.

17. Jakubíková M, Seeman P. Kongenitální myastenické syndromy. In: Piťha J et al (eds). Myasthenia gravis a ostatní poruchy nervosvalového přenosu. Praha: Maxdorf Jessenius 2010: 319–341.