Format

Send to

Choose Destination

Congenital Fibrosis of the Extraocular Muscles.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2004 Apr 27 [updated 2016 Jan 14].

Author information

1
Department of Ophthalmology, Boston Children's Hospital, Instructor in Ophthalmology, Harvard Medical School, Boston, Massachusetts
2
Ophthalmologist-in-Chief, Boston Children's Hospital, Professor of Ophthalmology, Harvard Medical School, Boston, Massachusetts
3
Department of Neurology, Children's Hospital Boston, Professor of Neurology and Ophthalmology, Harvard Medical School, Boston, Massachusetts
4
Howard Hughes Medical Institute, Chevy Chase, Maryland

Excerpt

CLINICAL CHARACTERISTICS:

Congenital fibrosis of the extraocular muscles (CFEOM) refers to at least eight genetically defined strabismus syndromes (CFEOM1A, CFEOM1B, CFEOM2, CFEOM3A, CFEOM3B, CFEOM3C, Tukel syndrome, and CFEOM3 with polymicrogyria) characterized by congenital non-progressive ophthalmoplegia (inability to move the eyes) with or without ptosis (droopy eyelids) affecting part or all of the oculomotor nucleus and nerve (cranial nerve III) and its innervated muscles (superior, medial, and inferior recti, inferior oblique, and levator palpabrae superioris) and/or the trochlear nucleus and nerve (cranial nerve IV) and its innervated muscle (the superior oblique). In general, affected individuals have severe limitation of vertical gaze (usually upgaze) and variable limitation of horizontal gaze. Individuals with CFEOM frequently compensate for the ophthalmoplegia by maintaining abnormal head positions at rest and by moving their heads rather than their eyes to track objects. Individuals with CFEOM3A may also have intellectual disability, social disability, Kallmann syndrome, facial weakness, and vocal cord paralysis; and/or may develop a progressive sensorimotor axonal polyneuropathy. Individuals with Tukel syndrome also have postaxial oligodactyly or oligosyndactyly of the hands. Those with CFEOM3 with polymicrogyria also have microcephaly and intellectual disability.

DIAGNOSIS/TESTING:

The diagnosis of CFEOM is based on ophthalmologic findings, and the subtypes depend on the identification of specific eye findings and associated findings. KIF21A pathogenic variants are associated with CFEOM1A and CFEOM3B. PHOX2A pathogenic variants are associated with CFEOM2. TUBB3 pathogenic variants are associated with CFEOM3A and CFEOM1B. TUBB2B pathogenic variants are associated with CFEOM3A and CFEOM3 with polymicrogyria.

MANAGEMENT:

Treatment of manifestations: Refractive errors may be managed with glasses or contact lenses. Amblyopia can be treated effectively with occlusion or penalization of the better-seeing eye. Corneal lubrication may be helpful. Corrective eye muscle and/or ptosis surgery may be required. Prevention of secondary complications: Amblyopia therapy to prevent vision loss in the less-preferred eye. Surveillance: To prevent and treat amblyopia and to address complications of corneal exposure: routine ophthalmologic care with visits every three to four months during the first years of life, and annual or biannual examinations in older affected individuals not at risk for amblyopia. In individuals with specific TUBB3 variants, surveillance for endocrine abnormalities, facial or vocal cord weakness, and interventions for developmental delays are indicated. Evaluation of relatives at risk: Early clinical diagnosis can lead to early treatment and prevention of secondary complications.

GENETIC COUNSELING:

CFEOM is inherited in either an autosomal dominant (CFEOM1, CFEOM3, and CFEOM3 with polymicrogyria) or autosomal recessive (CFEOM2 and Tukel syndrome) manner. CFEOM1, CFEOM3, and CFEOM3 with polymicrogyria. An affected individual may have inherited a pathogenic variant from an affected parent or have the disorder as the result of a de novo pathogenic variant. Each child of an individual with autosomal dominant CFEOM has a 50% chance of inheriting the pathogenic variant. CFEOM2 and Tukel syndrome. The parents of a child with autosomal recessive CFEOM are obligate heterozygotes (i.e., carriers of one pathogenic variant). At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant(s) have been identified in an affected family member.

Copyright © 1993-2019, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

Supplemental Content

Support Center