 | NEUROBIOLOGY OF EYE MOVEMENTS: FROM MOLECULES TO BEHAVIOR
Copyright © 2002 by the New York Academy of Sciences
description
Annals of the New York Academy of Sciences 956:55-63 (2002)
© 2002 New York Academy of Sciences
Applications of Molecular Genetics to the Understanding of Congenital Ocular Motility Disorders
ELIZABETH C. ENGLE
Neurology and Pediatrics (Genetics) Children's Hospital, Boston, Massachusetts, USA and Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA
Address for correspondence: Elizabeth C. Engle, M.D., Enders 551, The Children's Hospital, 300 Longwood Avenue, Boston, MA 02115. Voice: 617-355-8371; fax: 617-277-0496.
engle{at}enders.tch.harvard.edu
The congenital fibrosis syndromes (CFS), including congenital fibrosis of the extraocular muscles (CFEOM) and Duane syndrome (DS), are rare congenital strabismus syndromes that present with nonprogressive restrictive ophthalmoplegia with or without ptosis. Although historically believed to result from primary extraocular muscle (EOM) fibrosis, our laboratory's work is based on the hypothesis that these disorders result from distinct, but analogous, developmental defects of the oculomotor (nIII), trochlear (nIV), and abducens (nVI) nuclei. We have defined three inherited CFEOM phenotypes (CFEOM1-3) and have mapped each phenotype to a distinct genetic locus ( FEOM1-3). Individuals with CFEOM1 are born with bilateral ptosis and both eyes fixed in a downward position with absent upgaze and aberrant horizontal gaze. This disorder maps to the FEOM1 locus on chromosome 12cen. 1,2 Neuropathology studies of CFEOM1 reveal the absence of the superior division of oculomotor nerve and its corresponding alpha motor neurons in the midbrain, with abnormalities of target EOMs. 3 These neuropathology findings parallel those previously identified in Duane syndrome, in which there is an absence of nVI and the abducens nerve. 4,5 Individuals with CFEOM2 are born with bilateral ptosis and exotropia. This atypical form of CFEOM maps to the FEOM2 locus on chromosome 11q13 and results from mutations in ARIX (PHOX2A). 6,7 ARIX encodes a homeodomain transcription factor protein previously shown to be required for nIII/nIV development in mouse and zebrafish. 8,9 Together, these findings support the hypothesis that the congenital fibrosis syndromes result from parallel defects in nIII, nIV, and nVI nuclear development. Functional studies of the CFEOM genes should provide additional insight into the unique features of the extraocular lower motor neuron axis in health and disease. (For full refs. 1-9, see reference list of the main paper.)
Key Words: strabismus • ophthalmoplegia • genetics • congenital fibrosis • extraocular muscle • oculomotor nuclei
This article has been cited by other articles:
|
|
|
|
 
G. von Scheven, L. E. Alvares, R. C. Mootoosamy, and S. Dietrich
Neural tube derived signals and Fgf8 act antagonistically to specify eye versus mandibular arch muscles
Development,
July 15, 2006;
133(14):
2731 - 2745.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G. Diehl, S. Zareparsi, M. Qian, R. Khanna, R. Angeles, and P. J. Gage
Extraocular Muscle Morphogenesis and Gene Expression Are Regulated by Pitx2 Gene Dose
Invest. Ophthalmol. Vis. Sci.,
May 1, 2006;
47(5):
1785 - 1793.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Yamada, D. G. Hunter, C. Andrews, and E. C. Engle
A Novel KIF21A Mutation in a Patient With Congenital Fibrosis of the Extraocular Muscles and Marcus Gunn Jaw-Winking Phenomenon
Arch Ophthalmol,
September 1, 2005;
123(9):
1254 - 1259.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Fischer, M. T. Budak, M. Bakay, J. R. Gorospe, D. Kjellgren, F. Pedrosa-Domellof, E. P. Hoffman, and T. S. Khurana
Definition of the unique human extraocular muscle allotype by expression profiling
Physiol Genomics,
August 11, 2005;
22(3):
283 - 291.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T Tukel, A Uzumcu, A Gezer, H Kayserili, M Yuksel-Apak, O Uyguner, S H Gultekin, H-C Hennies, P Nurnberg, R J Desnick, et al.
A new syndrome, congenital extraocular muscle fibrosis with ulnar hand anomalies, maps to chromosome 21qter
J. Med. Genet.,
May 1, 2005;
42(5):
408 - 415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P Aubourg, M Krahn, R Bernard, K Nguyen, O Forzano, I Boccaccio, V Delague, A De Sandre-Giovannoli, J Pouget, D Depetris, et al.
Assignment of a new congenital fibrosis of extraocular muscles type 3 (CFEOM3) locus, FEOM4, based on a balanced translocation t(2;13) (q37.3;q12.11) and identification of candidate genes
J. Med. Genet.,
March 1, 2005;
42(3):
253 - 259.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y Jiang, T Matsuo, H Fujiwara, S Hasebe, H Ohtsuki, and T Yasuda
ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy
Br. J. Ophthalmol.,
February 1, 2004;
88(2):
263 - 267.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Parikh, Y. Y. Shugart, K. F. Doheny, J. Zhang, L. Li, J. Williams, D. Hayden, B. Craig, H. Capo, D. Chamblee, et al.
A strabismus susceptibility locus on chromosome 7p
PNAS,
October 14, 2003;
100(21):
12283 - 12288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. T.F.M. Verzijl, B. van der Zwaag, J. R.M. Cruysberg, and G. W. Padberg
Mobius syndrome redefined: A syndrome of rhombencephalic maldevelopment
Neurology,
August 12, 2003;
61(3):
327 - 333.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Spitsbergen and M. L. Kent
The State of the Art of the Zebrafish Model for Toxicology and Toxicologic Pathology Research--Advantages and Current Limitations
Toxicol Pathol,
January 1, 2003;
31(1_suppl):
62 - 87.
[Abstract]
[PDF]
|
|
|
|
