Elsevier

Neuromuscular Disorders

Volume 13, Issues 7–8, September 2003, Pages 573-578
Neuromuscular Disorders

Workshop report
110th ENMC International Workshop: The congenital cranial dysinnervation disorders (CCDDs): Naarden, The Netherlands, 25–27 October, 2002

https://doi.org/10.1016/S0960-8966(03)00043-9Get rights and content

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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References (59)

  • H. Brown

    Congenital structural muscle anomalies

  • E. Engle

    Applications of molecular genetics to the understanding of congenital ocular motility disorders

    Ann N Y Acad Sci

    (2002)
  • R. Harley et al.

    Congenital fibrosis of the extraocular muscles

    Trans Am Ophthalmol Soc

    (1978)
  • G. Hueck

    Über Angeborenenvererbten Beweglichkeitsdefect der Augen

    Klin Monatsbl Augenheilkd

    (1879)
  • J. Stilling
  • S. Turk

    Über retraktionsbewegungen der Augen

    Deutsch Med Wochenschr

    (1896)
  • A. Duane

    Congenital deficiency of abduction, associated with impairment of adduction, retraction movements, contractions of the palpebral fissure and oblique movements of the eye

    Arch Ophthalmol

    (1905)
  • Handbuch der Gesammten Augenheilkunde

    (1880)
  • P. Möbius

    Über Angeborenen Doppelseitige Abducens-Facialis-Lahmung

    München Med Wochenschr

    (1888)
  • J. Towfighi et al.

    Möbius syndrome. Neuropathological observations

    Acta Neuropathol

    (1979)
  • E. Traboulsi et al.

    Extraocular muscle aplasia in Möbius syndrome

    J Pediatr Ophthalmol Strabismus

    (1986)
  • J. Glaser et al.

    Congenital motor and sensory anomalies

  • M. Parks et al.

    Ophthalmoplegic syndromes and trauma

  • W. Philips et al.

    Congenital bilateral palsy of the abducens

    Arch Ophthalmol

    (1932)
  • P. Matteucci

    I difetti congeniti di abduzione con particolare riguardo alla patogenesi

    Rassegna Italiana d'Ottalmologia

    (1946)
  • M. Hotchkiss et al.

    Bilateral Duane's retraction syndrome: a clinical-pathological case report

    Arch Ophthalmol

    (1980)
  • N.R. Miller et al.

    Unilateral Duane's retraction syndrome

    Arch Ophthalmol

    (1982)
  • W. Hickey et al.

    Bilateral congenital absence of the abducens nerve

    Virchows Arch

    (1983)
  • F. Blodi

    Electromyographic evidence for supranuclear gaze palsies

    Trans Ophthalmol Soc UK

    (1970)
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