Workshop report110th ENMC International Workshop: The congenital cranial dysinnervation disorders (CCDDs): Naarden, The Netherlands, 25–27 October, 2002
Introduction
A multi-disciplinary group of 13 clinicians and researchers from six countries convened for the first time to study a group of congenital neuromuscular diseases characterized by abnormal eye, eyelid, and/or facial movement. This group of diseases includes Duane syndrome, congenital fibrosis of the extraocular muscles (CFEOM), Möbius syndrome, horizontal gaze palsy, congenital ptosis and congenital facial palsy. Although these disorders were previously referred to in the literature under various terms, including ‘congenital fibrosis syndromes’, we have now chosen to refer to them as the ‘congenital cranial dysinnervation disorders’ or CCDDs. This name reflects our belief that these disorders result from developmental errors in innervation of the ocular and facial muscles. Thus far, members of the consortium have identified ten CCDD genetic loci and two CCDD disease genes (PHOX2A mutated in CFEOM2 and SALL4 mutated in Duane syndrome with radial ray anomalies). A CCDD classification scheme and an International CCDD Consortium have been established. The goals of the Consortium are to foster continuing research into the genetic basis of these disorders by identifying new families and affected individuals and by the sharing of genetic resources. Future studies of the CCDD genes should enhance our understanding of the pathophysiology and treatment of these disorders.
Section snippets
History
Isolated strabismus affects 1–5% of the general population [1]. A subset of isolated strabismus syndromes is characterized by congenital, non-progressive ophthalmoplegia with restriction of globe movement in one or more fields of gaze. This group of sporadic and familial strabismus syndromes was initially referred to as the ‘congenital fibrosis syndromes’ [2], [3] because the primary pathologic process was assumed to reside in the muscles of eye motility. Defined broadly, the concept of the
Summary
- 1.
The CCDDs encompass congenital, non-progressive, sporadic or familial abnormalities of cranial musculature that result from developmental abnormalities of, or the complete absence of, one or more cranial nerves with primary or secondary muscle dysinnervation.
- 2.
Primary dysinnervation in the CCDDs may result from absence of normal muscle innervation because alpha motor neurons of the appropriate cranial nerves either do not develop or are misguided during development. Secondary dysinnervation may
Known CCDD genetic loci and phenotypes
A practical approach to CCDD classification is provided below. This schema will evolve as new phenotype and genotype correlations are made and the genes are identified.
Participants
Dr. Thomas Bosley, Riyadh, Saudi Arabia Dr. Hans Cruysberg, Nijmegen, The Netherlands Dr. Sian Ellard, Exeter, UK Dr. Elizabeth C. Engle, Boston, USA (Chairperson) Dr. Nick Gutowski, Exeter, UK (Chairperson) Dr. Joanna Jen, Los Angeles, USA Dr. Stephen Kraft, Toronto, Canada Dr. Nicolas Levy, Marseilles, France Dr. George Padberg, Nijmegen, The Netherlands Dr. Anthony Quinn, Exeter, UK Dr. Timothy Stout, Portland, USA Dr. David Taylor, London, UK Dr. Martha Tjon Fo Sang, Rotterdam, The Netherlands
Acknowledgements
This workshop was made possible by the financial support of the European Neuromuscular Centre (ENMC) and its main sponsors and associated members: Association Française contre les Myopathies (France); Deutsche Gesellschaft für Muskelkranke (Germany); Telethon Foundation (Italy); Muscular Dystrophy Campaign (UK); Muskelsvindfonden (Denmark); Prinses Beatrix Fonds (Netherlands); Schweizerische Stiftung für die Erforschung der Muskelkrankheiten (Switzerland); Österreichische Muskelforschung
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