congenital fibrosis of the extraocular muscles

Includes several inherited STRABISMUS syndromes characterized by congenital restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. Classic CFEOM is characterized by bilateral BLEPHAROPTOSIS and ophthalmoplegia with the eyes fixed about 20 to 30 degrees below the horizontal midline. Horizontal extraocular muscles may also be involved. If all affected members of a family have the classic phenotype with bilateral involvement, the disorder is referred to as CFEOM1, which is caused by mutations in the KIF21A (a KINESIN) gene. OMIM: 135700

Also Known As:

Networked: 38 relevant articles (0 outcomes, 4 trials/studies)

Disease Context: Research Results

Related Diseases

1.	3B Congenital Fibrosis of Extraocular Muscles
2.	Oculopharyngeal Muscular Dystrophy
3.	Ophthalmoplegia (External Ophthalmoplegia)
4.	Myositis (Idiopathic Inflammatory Myopathies)
5.	Myasthenia Gravis

Experts

1.	Engle, Elizabeth C: 18 articles (12/2021 - 04/2002)
2.	Chan, Wai-Man: 9 articles (12/2021 - 12/2003)
3.	Andrews, Caroline: 7 articles (02/2016 - 12/2003)
4.	Hunter, David G: 6 articles (12/2021 - 09/2005)
5.	Whitman, Mary C: 4 articles (12/2021 - 02/2016)
6.	Robson, Caroline D: 3 articles (12/2021 - 12/2019)
7.	MacKinnon, Sarah E: 3 articles (02/2016 - 02/2013)
8.	Tischfield, Max A: 3 articles (02/2016 - 09/2010)
9.	Oystreck, Darren T: 3 articles (01/2016 - 09/2006)
10.	Chew, Sheena: 3 articles (03/2015 - 12/2012)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to congenital fibrosis of the extraocular muscles:

1.	KinesinsIBA 10/13/2010 - "The purpose of this study was to determine if previously described Homo sapiens kinesin family member 21A (KIF21A) mutations were responsible for CFEOM in these two Chinese pedigrees. " 01/01/2014 - "Maternal germline mosaicism of kinesin family member 21A (KIF21A) mutation causes complex phenotypes in a Chinese family with congenital fibrosis of the extraocular muscles." 02/01/2013 - "One of the eight TUBB3 mutations reported to cause congenital fibrosis of the extraocular muscles, c.1228G>A results in a TUBB3 E410K amino acid substitution that directly alters a kinesin motor protein binding site. " 09/01/2017 - "The aim of the study is to characterize the clinical ocular phenotype with congenital fibrosis of the extraocular muscles type 1 (CFEOM1) and to confirm whether the kinesin family member 21A (KIF21A) mutation was the pathogenic gene in this Chinese family.Three" 12/15/2012 - "An inherited TUBB2B mutation alters a kinesin-binding site and causes polymicrogyria, CFEOM and axon dysinnervation."
2.	Retinaldehyde (Retinal)IBA 03/04/2021 - "Our study provides evidence of structural optic nerve and retinal changes in CFEOM. " 03/04/2021 - "We show for the first time that there are widespread retinal changes beyond the retinal ganglion cells in patients with CFEOM. " 03/04/2021 - "Optic Nerve Head and Retinal Abnormalities Associated with Congenital Fibrosis of the Extraocular Muscles." 01/01/2016 - "Retinal Dysfunction in Patients with Congenital Fibrosis of the Extraocular Muscles Type 2."
3.	Lactic Acid (Lactate)FDA LinkGeneric 06/01/2006 - "To exclude myasthenia gravis, ocular myositis, thyroid associated orbitopathy, oculopharyngeal muscular dystrophy, and congenital fibrosis of the extraocular muscles in patients with an early onset or long-lasting very slowly progressive ptosis and external ophthalmoplegia, almost without any diplopia, and normal to mildly elevated serum creatine kinase and lactate, electromyography, nerve conduction studies and MRI of the orbits should be performed. "
4.	Creatine Kinase (Creatine Phosphokinase)IBA 06/01/2006 - "To exclude myasthenia gravis, ocular myositis, thyroid associated orbitopathy, oculopharyngeal muscular dystrophy, and congenital fibrosis of the extraocular muscles in patients with an early onset or long-lasting very slowly progressive ptosis and external ophthalmoplegia, almost without any diplopia, and normal to mildly elevated serum creatine kinase and lactate, electromyography, nerve conduction studies and MRI of the orbits should be performed. "
5.	Proteins (Proteins, Gene)FDA Link 01/01/2017 - "CFEOM-causing mutations in these genes alter protein function and result in axon growth and guidance defects. " 04/16/2014 - "We identify Map1b as a Kif21a-interacting protein and report that Map1b⁻/⁻ mice develop CFEOM. " 01/01/2018 - "Genetic defects in these two proteins are associated with various cancers and developmental diseases, such as congenital fibrosis of the extraocular muscles type 1. However, the molecular mechanism governing the KANK1/KIF21A interaction and the role of the conserved ankyrin (ANK) repeats in this interaction are still unclear. " 02/01/2013 - "Missense mutations in TUBB3, the gene that encodes the neuronal-specific protein β-tubulin isotype 3, can cause isolated or syndromic congenital fibrosis of the extraocular muscles, a form of complex congenital strabismus characterized by cranial nerve misguidance. " 04/01/2002 - "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. "
6.	TubulinIBA 01/01/2021 - "Variants in the alpha tubulin-encoding gene TUBA1A have been associated with MCD, but not with CFEOM. " 01/01/2021 - "Distinct missense variants in the beta-tubulin encoding genes TUBB3 and TUBB2B cause MCD, CFEOM, or both, suggesting substitution-specific mechanisms. " 09/01/2010 - "Orbital magnetic resonance imaging (MRI) was used to investigate the structural basis of motility abnormalities in congenital fibrosis of the extraocular muscles type 3 (CFEOM3), a disorder resulting from missense mutations in TUBB3, which encodes neuron-specific beta-tubulin isotype III. Ophthalmic examinations in 13 volunteers from four CFEOM3 pedigrees and normal control subjects, were correlated with TUBB3 mutation and MRI findings that demonstrated extraocular muscle (EOM) size, location, contractility, and innervation. " 12/01/2021 - "Missense mutations in TUBB3, which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype-phenotype correlations. " 01/01/2021 - "Variants in the TUBB3 gene, one of the tubulin-encoding genes, are known to cause congenital fibrosis of the extraocular muscles type 3 and/or malformations of cortical development. "
7.	Transcription Factors (Transcription Factor)IBA 09/01/2006 - "Congenital fibrosis of the extraocular muscles type 2 (CFEOM2) is a complex strabismus syndrome that results from mutations in the homeodomain transcription factor PHOX2A. " 04/01/2002 - "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. "
8.	AnkyrinsIBA 01/01/2018 - "Genetic defects in these two proteins are associated with various cancers and developmental diseases, such as congenital fibrosis of the extraocular muscles type 1. However, the molecular mechanism governing the KANK1/KIF21A interaction and the role of the conserved ankyrin (ANK) repeats in this interaction are still unclear. "
9.	Troleandomycin (TAO)FDA Link 02/01/2010 - "The underlying causes of lower eyelid retraction included congenital retraction (seven eyelids), congenital fibrosis of the extraocular muscles (CFEOM; seven eyelids), TAO (seven eyelids), post-operative cicatricial retraction (five eyelids), and facial nerve palsy (one eyelid). "
10.	SiliconIBA 03/01/2011 - "The purpose of the implantation of the silicon plate in the orbital floor is to improve the hypotropia caused by CFEOM." 03/01/2011 - "We present the first case report of unilateral CFEOM with palpebral adherence and hypotropia, which was managed with our technique of a silicon plate implant on the orbital floor. " 03/01/2011 - "Unilateral congenital fibrosis of the extraocular muscles with lid retraction: surgical treatment with a silicon plate on the orbital floor."

Therapies and Procedures

1.	Slit Lamp 05/01/2004 - "Twenty-eight affected individuals from 20 families with familial or sporadic CFEOM underwent assessment of ocular motility, visual acuity, slit-lamp biomicroscopy, tonometry, and ophthalmoscopy. " 11/01/2003 - "patient population:Six members of an Iranian family with CFEOM underwent complete ocular examinations including assessment of ocular motility, visual acuity, slit-lamp biomicroscopy, tonometry, and ophthalmoscopy. "
2.	Tenotomy 12/01/2019 - "These features may contribute to the severe upgaze limitation in CFEOM and highlight the importance of superior oblique tenotomy in surgical management."
3.	Toothbrushing 09/01/2005 - "In addition, among our previously described patients with CFEOM and KIF21A mutations, 3 individuals had MG and 1 had hypertropia during toothbrushing. "
4.	Therapeutics 09/01/1969 - "[On the therapy of generalized congenital fibrosis of the extraocular muscles]."
5.	Sutures (Suture) 01/01/2019 - "  To release the fibrotically altered inferior rectus muscle in the double elevator palsy, the congenital fibrosis of the extraocular muscles and the thyroid eye disease, the operation of adjustable sutures was necessary in accordance with our experience with the technigue “cul-de-sac“ in its own modification. " 01/01/2019 - "Key words: adjustable sutures, congenital fibrosis of the extraocular muscles, double elevator palsy, thyroid eye disease, transposition procedure sec. Knapp, vertical strabismus."