Congenital Myasthenic Syndromes in childhood: Diagnostic and manag... https://www.jni-journal.

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The congenital myasthenic How myasthenia gravis

syndromes M.C. Pittc , H. Jungbluthd, A.K. Simondse, A. Alo
alters the safety factor for
Palace, Jackie et al. C. Jimenez-Mallebreraa, C. Sewrya,i, F. Muntonneuromuscular transmission
Ruff, Robert L. et al.
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DOI: https://doi.org/10.1016/j.jneuroim.2008.06.026

Article Info

Abstract Full Text Images References

The Congenital Myasthenic Syndromes (CMS), a group of heterogeneous genetic disorders of neuromu
transmission, are often misdiagnosed as congenital muscular dystrophy (CMD) or myopathies and pres
particular management problems. We present our experience of 46 children with CMS, referred to us be
1992–2007 with provisional diagnoses of congenital myopathy (22/46), CMS or limb-girdle myasthenia
central hypotonia or neurometabolic disease (5/46), myasthenia gravis (4/46), limb–girdle or congenital
dystrophy (4/46) and SMA (2/46). Diagnosis was often considerably delayed (up to 18y4 m), despite the
symptoms in most cases. Diagnostic clues in the neonates were feeding difficulties (29/46), hypotonia w
without limb weakness (21/46), ptosis (19/46), respiratory insufficiency (12/46), contractures (4/46) and
(6/46). Twenty–five children had delayed motor milestones. Fatigability developed in 43 and a variable d
ptosis was eventually present in 40.

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Congenital Myasthenic Syndromes in childhood: Diagnostic and manag... https://www.jni-journal.com/article/S0165-5728(08)00197-5/pdf

Over the period of the study, the mainstay of EMG diagnosis evolved from repetitive nerve stimulation to
stimulation single fibre EMG. The patients were studied by several different operators. 66 EMGs were p
in 40 children, 29 showed a neuromuscular junction abnormality, 7 were myopathic, 2 had possible neu
changes and 28 were normal or inconclusive. A repetitive CMAP was detected in only one of seven chil
a COLQ mutation and neither of the two children with Slow Channel Syndrome mutations.

Mutations have been identified so far in 32/46 children: 10 RAPSN, 7 COLQ, 6 CHRNE, 7 DOK7, 1 CH
and 1 CHAT. 24 of 25 muscle biopsies showed myopathic changes with fibre size variation; 14 had type
predominance. Three cases showed small type-1 fibres resembling fibre type disproportion, and four sh
core-like lesions. No specific myopathic features were associated with any of the genes. Twenty childre
responded to Pyridostigmine treatment alone, 11 to Pyridostigmine with either 3, 4 DAP or Ephedrine an
Ephedrine alone. Twenty one children required acute or chronic respiratory support, with tracheostomy
nocturnal or emergency non-invasive ventilation in 9. Eight children had gastrostomy. Another 11 were
underweight for height indicative of failure to thrive and required dietetic input.

A high index of clinical suspicion, repeat EMG by an experienced electromyographer and, if necessary,
therapeutic trial of Pyridostigmine facilitates the diagnosis of CMS with subsequent molecular genetic
confirmation. This guides rational therapy and multidisciplinary management, which may be crucial for s
particularly in pedigrees where previous deaths have occurred in infancy.

The congenital myasthenic How myasthenia gravis

syndromes alters the safety factor for
Palace, Jackie et al. neuromuscular transmission
Congenital Myasthenic Syndrome, Management, Diagnosis Ruff, Robert L. et al.

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Congenital Myasthenic Syndromes in childhood: Diagnostic and manag... https://www.jni-journal.com/article/S0165-5728(08)00197-5/pdf

© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.

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< Previous Article September 15, 2008 Volumes 201-202, Pages 6–12

The congenital myasthenic How myasthenia gravis

syndromes alters the safety factor for
Palace, Jackie et al. neuromuscular transmission
Ruff, Robert L. et al.
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