DNA photo
Children's Hospital Research Children's Hospital Labs
Engle Laboratory Children's logo Harvard logo
Engle Lab Home Page
Eye disorders studied
Eye muscle anatomy
Common Strabismus
CFEOM overview
CFEOM1/KIF21A
CFEOM2/PHOX2A
CFEOM3
Congenital ptosis
Duane syndrome
Duane syndrome with radial ray anomalies
HOXA1-related syndromes
Horizontal gaze palsy with progressive scoliosis
Marcus Gunn syndrome
Research Participation
Diagnostic testing
Techniques
Engle Lab Publications
Lab Members
Collaborators
Directions
Links
Discussion Forum
Contact Us
Internal Lab Page
X X
CFEOM overview
Congenital fibrosis of the extraocular muscles (CFEOM) describes a group of rare congenital (present at birth) eye movement disorders that result from the dysfunction of all or part of the oculomotor nerve (cranial nerve III) and/or the muscles this cranial nerve innervates. (For a review of extraocular muscles and the nerves that innervate them see Eye Muscle Anatomy). Individuals affected with CFEOM are typically born with ophthalmoplegia (an inability to move the eyes in certain directions) and ptosis (droopy eyelids). In addition, the eyes are usually fixed in an abnormal position. These features can be seen in the mother and daughter in the photo, who both have CFEOM1.
CFEOM is a form of 'strabismus' (misalignment of the eyes), and falls into the subgroup 'incomitant strabismus' (misalignment of the eyes which varies with gaze directions) and the subheading 'extraocular muscle fibrosis syndromes' (conditions associated with restriction of both active and passive movement of the eyeball). Although the term 'muscle fibrosis' suggests that these syndromes result from a primary abnormality of muscle, evidence suggests that CFEOM may actually result from a primary abnormality of the cranial nerve's innervation of these muscles. A review of Congenital Cranial Dysinnervation syndrome can be found below in reference 5.
Top

Clinical classification and description
The earliest description of CFEOM was given by Baumgarten in 18401. Heuck is credited with the first report of a familial occurrence of CFEOM in 18792, and the term "generalized fibrosis syndrome" was first coined by Brown in 19503. Laughlin formally characterized the condition in 19564.

CFEOM is present at birth (congenital), is nonprogressive, and is frequently associated with ptosis (droopy eyelids). Depending on the subtype, it may affect one (unilateral) or both (bilateral) eyes. Affected individuals are born with their eyes fixed in an abnormal position and are unable to move their eyes normally. The specific position of the eyes and pattern of movement defines each clinical subtype of CFEOM. In addition, CFEOM is a form of 'restrictive ophthalmoplegia' and forced duction testing is positive for restriction.

Prior to genetic studies of CFEOM, this group of conditions was defined clinically, and each clinical variation was thought to be a distinct disorder. As the molecular basis of these conditions becomes known, subclassification of CFEOM based on clinical criteria is being replaced by classification based on a combination of genetic and clinical information.

To date, we have identified three genetic CFEOM loci (specific locations on a chromosome which contain a gene for CFEOM), which we refer to as: FEOM1, FEOM2 and FEOM3. We anticipate that additional CFEOM loci will be identified in the future.

We have identified the FEOM1 and FEOM2 disease genes, KIF21A and PHOX2A. We are now working to identify the FEOM3 disease gene.

Top
Clinical Evaluation
When evaluating an individual with CFEOM, a thorough family history is obtained and an ocular (eye) examination performed. In addition, attention is given to the presence of other ocular or systemic malformations. Measurements of ocular misalignment, ocular range of motion, head turn, globe (eyeball) retraction, palpebral fissure (eye opening) size, and up- and down-shoots are indicated. Forced duction and vision tests are also recommended.
Top
Causes
Genetics, and possibly environmental factors, play a role in the cause of CFEOM, and both autosomal dominant and autosomal recessive families with CFEOM have been identified. Our research suggests that mutations in the FEOM1-3 genes cause abnormal development of the oculomotor and trochlear nuclei and nerves and/or the extraocular muscles these nerves normally innervate. Our anatomic studies of CFEOM15 found absence of the superior division of the oculomotor nerve (cranial nerve III) and its corresponding alpha motor neurons in the midbrain. These findings are parallel to those found in Duane syndrome, which is the most common of the CCDD's. For more details and a diagram of these findings, refer to CFEOM1.

To learn more about each of the CFEOM variants, click on CFEOM1, CFEOM2, CFEOM3.

Top
Please contact Caroline Andrews to obtain further information or if you are interested in participating in our research or enrolling a patient.
References
Online Mendelian Inheritance in Man (OMIM). Victor A. McKusick, Editor, Johns Hopkins University, last edit date 12/4/2003 (entry number 135700); 6/13/2002(entry number 602078) and 3/18/2004 (entry number 607034) Home page: http://www3.ncbi.nlm.nih.gov/Omim/.

Andrews CV, Yamada K, Engle EC . Congenital Fibrosis of the Extraocular Muscles. In: GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2004. Available at http://www.genetests.org.

1. Baumgarten, M. Erfahrungen uber den strabismus und die Muskeldurchschneidung am Auge in physiologischpathologischer und therapeutischer Beziehung. Monatsschr Med Augenheilkd Chir 3, 474-499 (1840).

2. Heuck, G. Ueber angeborenen vererbten Beweglichkeits - Defect der Augen. Klin Monatsbl Augenheilkd 17, 253-278 (1879).

3. Brown, H.W. Congenital structural muscle anomalies. in Strabismus Ophthalmic Symposium (ed. Allen, J.H.) 205-236 (C. V. Mosby Co., St. Louis, 1950).

4. Laughlin, R.C. Congenital fibrosis of the extraocular muscles; a report of six cases. Amer J Ophthalmol 41, 432-438 (1956).

5. Engle, E. The genetics of strabismus: Duane, Moebius, and fibrosis syndromes. In Genetic diseases of the eye: a textbook and atlas. (ed. Traboulsi, E.) 477-512 (Oxford University Press, New York, 1998).

Top
X X
Copyright 2004-2007 Children's Hospital Boston