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Congenital fibrosis of extraocular muscles

MedGen UID:
724506
Concept ID:
C1302995
Disease or Syndrome
Synonyms: Cfeom; congenital fibrosis of the extraocular muscles; General Fibrosis Syndrome
SNOMED CT: Congenital fibrosis syndrome (400946004); Congenital fibrosis of extraocular muscles (400946004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Related genes: KIF21A, TUBB3, PHOX2A
 
HPO: HP:0001491
Monarch Initiative: MONDO:0007614
OMIM® Phenotypic series: PS135700
Orphanet: ORPHA45358

Definition

Congenital fibrosis of the extraocular muscles (CFEOM) is a disorder of the nervous system that affects use of the muscles that surround the eyes (extraocular muscles). These muscles control eye movement and the direction of the eyes (for example, looking straight ahead). CFEOM impairs control of these muscles. As a result, affected individuals are unable to move their eyes normally. Most people with this condition have difficulty looking upward, and their side-to-side eye movement may also be limited. The eyes may look in different directions (strabismus). Instead of moving their eyes, affected individuals may need to turn their head to track moving objects. Additionally, most people with CFEOM have droopy eyelids (ptosis), which further limits their vision.

Researchers have identified several forms of CFEOM, designated CFEOM1, CFEOM2, CFEOM3, and Tukel syndrome (sometimes called CFEOM4). The specific problems with eye movement vary among the types, and some types are associated with additional signs and symptoms. People with CFEOM1 and CFEOM2 have only the eye problems described above. In CFEOM1, the eyes typically point downward, whereas in CFEOM2, the eyes usually turn outward.

CFEOM3 can include additional neurological problems, such as intellectual disability; difficulty with social skills; a smaller-than-normal head size (microcephaly); muscle weakness in the face; nonfunctioning vocal cords; and a set of symptoms called Kallmann syndrome, which features delayed or absent puberty and an impaired sense of smell. Some affected individuals develop pain, weakness, or a decreased ability to feel sensations in the limbs (peripheral neuropathy), which can begin in childhood or adulthood.

Brain abnormalities can also occur in people with CFEOM3. Some have abnormal development of the white matter, which is brain tissue containing nerve cell fibers (axons) that transmit nerve impulses. A particular form of CFEOM3, known as CFEOM3 with polymicrogyria, is characterized by abnormal development of the brain, in which the folds and ridges on the surface of the brain are smaller and more numerous than usual.

Tukel syndrome is characterized by missing fingers (oligodactyly) and other hand abnormalities in addition to problems with eye movement. [from MedlinePlus Genetics]

Conditions with this feature

Oromandibular-limb hypogenesis spectrum
MedGen UID:
66357
Concept ID:
C0221060
Disease or Syndrome
The most basic description of Moebius syndrome is a congenital facial palsy with impairment of ocular abduction. The facial nerve (cranial nerve VII) and abducens nerve (CN VI) are most frequently involved, but other cranial nerves may be involved as well. Other variable features include orofacial dysmorphism and limb malformations. Mental retardation has been reported in a subset of patients. Most cases of Moebius syndrome are sporadic, but familial occurrence has been reported (Verzijl et al., 2003). The definition of and diagnostic criteria for Moebius syndrome have been controversial and problematic. The syndrome has most frequently been confused with hereditary congenital facial paresis (HCFP; see 601471), which is restricted to involvement of the facial nerve and no other abnormalities. Verzijl et al. (2003) and Verzijl et al. (2005) concluded that HCFP and Moebius syndrome are distinct disorders, and that Moebius syndrome is a complex developmental disorder of the brainstem. Moebius syndrome was defined at the Moebius Syndrome Foundation Research Conference in 2007 as congenital, nonprogressive facial weakness with limited abduction of one or both eyes. Additional features can include hearing loss and other cranial nerve dysfunction, as well as motor, orofacial, musculoskeletal, neurodevelopmental, and social problems (summary by Webb et al., 2012). Kumar (1990) provided a review of Moebius syndrome, which was critiqued by Lipson et al. (1990). Briegel (2006) provided a review of Moebius sequence with special emphasis on neuropsychiatric findings.
Tukel syndrome
MedGen UID:
332153
Concept ID:
C1836217
Disease or Syndrome
Congenital fibrosis of extraocular muscles type 1
MedGen UID:
376943
Concept ID:
C1851102
Disease or Syndrome
Congenital fibrosis of the extraocular muscles (CFEOM) encompasses several different 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 in an infraducted position about 20 to 30 degrees below the horizontal midline. Involvement of the horizontal extraocular muscles is variable. If all affected members of a family have the classic phenotype with bilateral involvement, the disorder is referred to as 'CFEOM1' (Engle et al., 1997; Heidary et al., 2008). CFEOM2 (602078), an autosomal recessive disorder caused by mutation in the ARIX gene (PHOX2A; 602753) on chromosome 11q13, is characterized by bilateral ptosis with eyes fixed in an exotropic position. The CFEOM3 phenotype shows more variable clinical features: affected individuals may have unilateral eye involvement, may be able raise their eyes above midline, or may not have blepharoptosis. CFEOM3 is diagnosed in a family if even 1 member does not have classic findings of the disorder. CFEOM3 is a genetically heterogeneous disorder; CFEOM3A with or without extraocular involvement (600638) is caused by mutation in the TUBB3 gene (602661) on chromosome 16q24; CFEOM3B is caused by mutation in the KIF21A gene (608283) on chromosome 12q12; and CFEOM3C (609384) maps to chromosome 13q. CFEOM4 (609428), also known as Tukel syndrome, maps to chromosome 21q. CFEOM5 (616219) is caused by mutation in the COL25A1 gene (610004) on chromosome 4q25. See also NOMENCLATURE.
Fibrosis of extraocular muscles, congenital, 2
MedGen UID:
356119
Concept ID:
C1865915
Disease or Syndrome
Congenital fibrosis of extraocular muscles-2 (CFEOM2) is an autosomal recessive disorder in which affected individuals are born with bilateral ptosis and restrictive ophthalmoplegia with the globes fixed in extreme abduction (exotropia) (Wang et al., 1998, Nakano et al., 2001). For a general phenotypic description and a discussion of genetic heterogeneity of various forms of CFEOM, see CFEOM1 (135700).
Fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement
MedGen UID:
412638
Concept ID:
C2748801
Disease or Syndrome
Congenital fibrosis of the extraocular muscles (CFEOM) encompasses several different inherited strabismus syndromes characterized by congenital restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. If all affected members of a family have classic CFEOM with bilateral involvement and inability to raise the eyes above midline, the phenotype is classified as CFEOM1 (135700). CFEOM2 (602078) shows autosomal recessive inheritance. CFEOM3 is characterized by autosomal dominant inheritance of a more variable phenotype than classic CFEOM1. Individuals with CFEOM3 may not have bilateral involvement, may be able to raise the eyes above midline, or may not have blepharoptosis (reviews by Yamada et al., 2004 and Heidary et al., 2008). Yamada et al. (2003) concluded that CFEOM3 is a relatively rare form of CFEOM. Genetic Heterogeneity of CFEOM3 The CFEOM3 phenotype is genetically heterogeneous; see also CFEOM3B (135700), caused by mutation in the KIF21A gene on chromosome 12q12, and CFEOM3C (609384), which maps to chromosome 13q.
Fibrosis of extraocular muscles, congenital, 3c
MedGen UID:
412956
Concept ID:
C2750404
Disease or Syndrome
Complex cortical dysplasia with other brain malformations 7
MedGen UID:
765150
Concept ID:
C3552236
Disease or Syndrome
Complex cortical dysplasia with other brain malformations-7 is an autosomal dominant, clinically heterogeneous disorder showing a wide spectrum of abnormalities of cortical brain development. The most severely affected patients are fetuses with microlissencephaly, absence of the cortical plate, agenesis of the corpus callosum, and severely hypoplastic brainstem and cerebellum. Other patients have lissencephaly, polymicrogyria, cortical dysplasia, or neuronal heterotopia. Those with less severe malformations can survive, but usually have some degree of neurologic impairment, such as mental retardation, seizures, and movement abnormalities (summary by Chang et al., 2006; Fallet-Bianco et al., 2014). For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039).

Professional guidelines

PubMed

Chen M, Huang R, Zhang Y, Zhu DJ, Shu Q, Xun P, Zhang J, Gu P, Li L
Graefes Arch Clin Exp Ophthalmol 2023 Mar;261(3):879-889. Epub 2022 Sep 23 doi: 10.1007/s00417-022-05830-3. PMID: 36138147Free PMC Article

Recent clinical studies

Etiology

Dizdar Yigit D, İnal A, Gürez C, Gokyigit B
Strabismus 2023 Jun;31(2):135-138. Epub 2023 Jul 31 doi: 10.1080/09273972.2023.2231032. PMID: 37519154
Mravicic I, Lukacevic S, Biscevic A, Pjano MA, Ziga N, Tusek M
Med Arch 2023 Apr;77(2):137-141. doi: 10.5455/medarh.2023.77.137-141. PMID: 37260807Free PMC Article
Jia H, Ma Q, Liang Y, Wang D, Chang Q, Zhao B, Zhang Z, Liang J, Song J, Wang Y, Zhang R, Tu Z, Jiao Y
Orphanet J Rare Dis 2022 Dec 9;17(1):431. doi: 10.1186/s13023-022-02582-5. PMID: 36494820Free PMC Article
Sener EC, Taylan Sekeroglu H, Ural O, Oztürk BT, Sanaç AS
Ophthalmic Genet 2014 Dec;35(4):208-25. Epub 2014 Oct 27 doi: 10.3109/13816810.2014.973044. PMID: 25347047
Lin LK, Chien YH, Wu JY, Wang AH, Chiang SC, Hwu WL
Mol Vis 2005 Apr 1;11:245-8. PMID: 15827546

Diagnosis

Chen M, Huang R, Zhang Y, Zhu DJ, Shu Q, Xun P, Zhang J, Gu P, Li L
Graefes Arch Clin Exp Ophthalmol 2023 Mar;261(3):879-889. Epub 2022 Sep 23 doi: 10.1007/s00417-022-05830-3. PMID: 36138147Free PMC Article
Jia H, Ma Q, Liang Y, Wang D, Chang Q, Zhao B, Zhang Z, Liang J, Song J, Wang Y, Zhang R, Tu Z, Jiao Y
Orphanet J Rare Dis 2022 Dec 9;17(1):431. doi: 10.1186/s13023-022-02582-5. PMID: 36494820Free PMC Article
Jang Y, Kwak E, An JY, Jung JH
Ophthalmic Genet 2022 Oct;43(5):716-719. Epub 2022 Jun 29 doi: 10.1080/13816810.2022.2092753. PMID: 35765833
Miao W, Man F, Wu S, Lv B, Wang Z, Xian J, Sabel BA, He H, Jiao Y
PLoS One 2015;10(7):e0133473. Epub 2015 Jul 17 doi: 10.1371/journal.pone.0133473. PMID: 26186732Free PMC Article
Boricean ID, Bărar A
Oftalmologia 2011;55(1):10-26. PMID: 21774381

Therapy

Dizdar Yigit D, İnal A, Gürez C, Gokyigit B
Strabismus 2023 Jun;31(2):135-138. Epub 2023 Jul 31 doi: 10.1080/09273972.2023.2231032. PMID: 37519154
Pujari A, Sharma P, Basheer S, Obedulla H, Bhaskaran K, Phuljhele S
Indian J Ophthalmol 2019 Jul;67(7):1229-1230. doi: 10.4103/ijo.IJO_1542_18. PMID: 31238477Free PMC Article
Rajamani M, Nagasubramanian V, Ayyavoo A, Raghupathy P, Dandapani R
Strabismus 2017 Mar;25(1):39-42. Epub 2017 Jan 31 doi: 10.1080/09273972.2016.1277768. PMID: 28140732

Prognosis

Matalia JH, Panmand P, Ghalla P
Indian J Ophthalmol 2017 Oct;65(10):1061-1063. doi: 10.4103/ijo.IJO_377_17. PMID: 29044091Free PMC Article
Boricean ID, Bărar A
Oftalmologia 2011;55(1):10-26. PMID: 21774381

Clinical prediction guides

Pujari A, Sharma P, Basheer S, Obedulla H, Bhaskaran K, Phuljhele S
Indian J Ophthalmol 2019 Jul;67(7):1229-1230. doi: 10.4103/ijo.IJO_1542_18. PMID: 31238477Free PMC Article
Yazdani A, Traboulsi EI
Ophthalmology 2004 May;111(5):1035-42. doi: 10.1016/j.ophtha.2003.08.030. PMID: 15121385

Recent systematic reviews

Van Swol JM, Myers WK, Nguyen SA, Wilson ME
J Binocul Vis Ocul Motil 2023 Apr-Jun;73(2):43-52. Epub 2023 Feb 13 PMID: 36780505

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