MCID: FBR046
MIFTS: 34

Fibrosis of Extraocular Muscles, Congenital, 1

Categories: Genetic diseases

Aliases & Classifications for Fibrosis of Extraocular Muscles, Congenital, 1

MalaCards integrated aliases for Fibrosis of Extraocular Muscles, Congenital, 1:

Name: Fibrosis of Extraocular Muscles, Congenital, 1 57 75 29 13 6 73
Fibrosis of Extraocular Muscles, Congenital, 3b 57 75 29 6 73
Blepharoptosis with Absent Eye Movements 57 75
Fibrosis 44 73
Cfeom1 57 75
Fibrosis, Extraocular Muscles, Congenital, Type 1 40
Congenital Fibrosis of the Extraocular Muscles 73
Ophthalmoplegia, Congenital 57
Congenital Ophthalmoplegia 75
Feom1 Locus 57
Cfeom3b 75
Feom1 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
some patients may have unilateral involvement, may be able to raise the eye above midline, or may not have ptosis--these patients are classified as having cfeom3 (cfeom3b)


HPO:

32
fibrosis of extraocular muscles, congenital, 1:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Fibrosis of Extraocular Muscles, Congenital, 1

OMIM : 57 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 (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 below. (135700)

MalaCards based summary : Fibrosis of Extraocular Muscles, Congenital, 1, also known as fibrosis of extraocular muscles, congenital, 3b, is related to cystic fibrosis and pulmonary fibrosis, idiopathic, and has symptoms including cachexia, cyanosis and dyspnea. An important gene associated with Fibrosis of Extraocular Muscles, Congenital, 1 is KIF21A (Kinesin Family Member 21A). Affiliated tissues include eye and brain, and related phenotypes are esotropia and exotropia

UniProtKB/Swiss-Prot : 75 Fibrosis of extraocular muscles, congenital, 1: A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Patients affected by congenital fibrosis of extraocular muscles type 1 show an absence of the superior division of the oculomotor nerve (cranial nerve III) and corresponding oculomotor subnuclei. Fibrosis of extraocular muscles, congenital, 3B: A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Congenital fibrosis of extraocular muscles type 3 presents as a non-progressive, autosomal dominant disorder with variable expression. Patients may be bilaterally or unilaterally affected, and their oculo-motility defects range from complete ophthalmoplegia (with the eyes fixed in a hypo- and exotropic position), to mild asymptomatic restrictions of ocular movement. Ptosis, refractive error, amblyopia, and compensatory head positions are associated with the more severe forms of the disorder. In some cases, the ocular phenotype is accompanied by additional features including developmental delay, corpus callosum agenesis, basal ganglia dysmorphism, facial weakness, polyneuropathy.

Related Diseases for Fibrosis of Extraocular Muscles, Congenital, 1

Graphical network of the top 20 diseases related to Fibrosis of Extraocular Muscles, Congenital, 1:



Diseases related to Fibrosis of Extraocular Muscles, Congenital, 1

Symptoms & Phenotypes for Fibrosis of Extraocular Muscles, Congenital, 1

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
compensatory chin elevation

Muscle Soft Tissue:
levator palpebrae superioris atrophy
rectus superior atrophy

Head And Neck Eyes:
ptosis, bilateral
congenital fibrosis of extraocular muscles
restrictive external ophthalmoplegia, bilateral
bilateral infraducted eye position (downward gaze)
inability to raise eyes above midline
more
Neurologic Central Nervous System:
absent superior division of oculomotor nerve and corresponding alpha motor neurons


Clinical features from OMIM:

135700

Human phenotypes related to Fibrosis of Extraocular Muscles, Congenital, 1:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 esotropia 32 HP:0000565
2 exotropia 32 HP:0000577
3 compensatory chin elevation 32 HP:0001477
4 bilateral ptosis 32 HP:0001488
5 congenital fibrosis of extraocular muscles 32 HP:0001491
6 restrictive external ophthalmoplegia 32 HP:0007936
7 levator palpebrae superioris atrophy 32 HP:0012241
8 superior rectus atrophy 32 HP:0012242

UMLS symptoms related to Fibrosis of Extraocular Muscles, Congenital, 1:


cachexia, cyanosis, dyspnea, edema, fever, headache, icterus, seizures, signs and symptoms, signs and symptoms, digestive, syncope, vertigo, polydipsia, muscle weakness, hot flushes, ophthalmoplegia

Drugs & Therapeutics for Fibrosis of Extraocular Muscles, Congenital, 1

Search Clinical Trials , NIH Clinical Center for Fibrosis of Extraocular Muscles, Congenital, 1

Inferred drug relations via UMLS 73 / NDF-RT 51 :


Cochrane evidence based reviews: fibrosis

Genetic Tests for Fibrosis of Extraocular Muscles, Congenital, 1

Genetic tests related to Fibrosis of Extraocular Muscles, Congenital, 1:

# Genetic test Affiliating Genes
1 Fibrosis of Extraocular Muscles, Congenital, 3b 29
2 Fibrosis of Extraocular Muscles, Congenital, 1 29 KIF21A

Anatomical Context for Fibrosis of Extraocular Muscles, Congenital, 1

MalaCards organs/tissues related to Fibrosis of Extraocular Muscles, Congenital, 1:

41
Eye, Brain

Publications for Fibrosis of Extraocular Muscles, Congenital, 1

Articles related to Fibrosis of Extraocular Muscles, Congenital, 1:

(show all 39)
# Title Authors Year
1
Clinical characteristics of a KIF21A mutation in a Chinese family with congenital fibrosis of the extraocular muscles type 1. ( 28930843 )
2017
2
Clinical heterogeneity associated with TUBB3 gene mutation in a Turkish family with congenital fibrosis of the extraocular muscles. ( 27428177 )
2016
3
KIF21A mutation in two Chinese families with congenital fibrosis of the extraocular muscles type 1 and 3. ( 27513105 )
2016
4
Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study. ( 26186732 )
2015
5
Maternal germline mosaicism of kinesin family member 21A (KIF21A) mutation causes complex phenotypes in a Chinese family with congenital fibrosis of the extraocular muscles. ( 24426772 )
2014
6
Retinal Dysfunction in Patients with Congenital Fibrosis of the Extraocular Muscles Type 2. ( 24940936 )
2014
7
Strabismus surgery in congenital fibrosis of the extraocular muscles: a paradigm. ( 25347047 )
2014
8
A novel de novo KIF21A mutation in a patient with congenital fibrosis of the extraocular muscles and MAPbius syndrome. ( 24715754 )
2014
9
Sclerosing cavernous hemangioma of the cavernous sinus mimicking congenital fibrosis of the extraocular muscles. ( 24751811 )
2014
10
Cerebellar atrophy in congenital fibrosis of the extraocular muscles type 1. ( 22699964 )
2013
11
Congenital fibrosis of the extraocular muscles: magnetic resonance imaging findings and surgical treatment. ( 23978146 )
2013
12
Dissociated vertical deviation in congenital fibrosis of the extraocular muscles. ( 22415008 )
2013
13
Spatiotemporal expression pattern of KIF21A during normal embryonic development and in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). ( 22465342 )
2012
14
Surgically mismanaged ptosis in a patient with congenital fibrosis of the extraocular muscles type I. ( 23248547 )
2012
15
Lack of KIF21A mutations in congenital fibrosis of the extraocular muscles type I patients from consanguineous Saudi Arabian families. ( 21264235 )
2011
16
Unilateral congenital fibrosis of the extraocular muscles with lid retraction: surgical treatment with a silicon plate on the orbital floor. ( 21314337 )
2011
17
The optic nerve head in congenital fibrosis of the extraocular muscles. ( 21449832 )
2011
18
[Mutation analysis of KIF21A gene in a Chinese family with congenital fibrosis of the extraocular muscles type I]. ( 21983718 )
2011
19
Congenital fibrosis of the extraocular muscles. ( 21120060 )
2010
20
KIF21A mutations in two Chinese families with congenital fibrosis of the extraocular muscles (CFEOM). ( 21042561 )
2010
21
Germline Mosaicism for KIF21A Mutation (p.R954L) Mimicking Recessive Inheritance for Congenital Fibrosis of the Extraocular Muscles. ( 19896199 )
2010
22
Congenital fibrosis of the extraocular muscles. ( 21217899 )
2010
23
A major mutation of KIF21A associated with congenital fibrosis of the extraocular muscles type 1 (CFEOM1) enhances translocation of Kank1 to the membrane. ( 19559006 )
2009
24
Congenital fibrosis of the extraocular muscles type 1, distinctive conjunctival changes and intrapapillary disc colobomata. ( 19373680 )
2009
25
Novel and recurrent KIF21A mutations in congenital fibrosis of the extraocular muscles type 1 and 3. ( 18332320 )
2008
26
Congenital fibrosis of the extraocular muscles. ( 18214786 )
2008
27
Congenital fibrosis of the extraocular muscles (CFEOM) syndrome associated with progressive cerebellar ataxia. ( 17551929 )
2007
28
Mutation p.Arg954Trp of KIF21A causes congenital fibrosis of the extraocular muscles in a Chinese family. ( 16939002 )
2006
29
A novel KIF21A mutation in a patient with congenital fibrosis of the extraocular muscles and Marcus Gunn jaw-winking phenomenon. ( 16157808 )
2005
30
Anterior uveitis and congenital fibrosis of the extraocular muscles in a patient with Noonan syndrome. ( 16388177 )
2005
31
Recurrent mutation of the KIF21A gene in Japanese patients with congenital fibrosis of the extraocular muscles. ( 16365788 )
2005
32
Mutation analysis of KIF21A in congenital fibrosis of the extraocular muscles (CFEOM) patients. ( 15621876 )
2004
33
Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3). ( 15223798 )
2004
34
Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). ( 14595441 )
2003
35
CFEOM1, the classic familial form of congenital fibrosis of the extraocular muscles, is genetically heterogeneous but does not result from mutations in ARIX. ( 11882252 )
2002
36
Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2. ( 11600883 )
2001
37
Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13. ( 9683611 )
1998
38
Mapping a gene for congenital fibrosis of the extraocular muscles to the centromeric region of chromosome 12. ( 8075644 )
1994
39
Congenital Fibrosis of the Extraocular Muscles ( 20301522 )
1993

Variations for Fibrosis of Extraocular Muscles, Congenital, 1

UniProtKB/Swiss-Prot genetic disease variations for Fibrosis of Extraocular Muscles, Congenital, 1:

75 (show all 11)
# Symbol AA change Variation ID SNP ID
1 KIF21A p.Met356Thr VAR_019399 rs121912588
2 KIF21A p.Met947Arg VAR_019400 rs121912590
3 KIF21A p.Met947Val VAR_019401 rs121912589
4 KIF21A p.Arg954Gln VAR_019402 rs121912586
5 KIF21A p.Arg954Trp VAR_019403 rs121912585
6 KIF21A p.Ile1010Thr VAR_019404 rs121912587
7 KIF21A p.Met947Thr VAR_027021
8 KIF21A p.Asp352Glu VAR_074031
9 KIF21A p.Glu944Gln VAR_074032
10 KIF21A p.Arg954Leu VAR_074033
11 KIF21A p.Ala1008Pro VAR_074034

ClinVar genetic disease variations for Fibrosis of Extraocular Muscles, Congenital, 1:

6
(show all 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 KIF21A NM_001173464.1(KIF21A): c.2860C> T (p.Arg954Trp) single nucleotide variant Pathogenic rs121912585 GRCh37 Chromosome 12, 39726207: 39726207
2 KIF21A NM_001173464.1(KIF21A): c.2860C> T (p.Arg954Trp) single nucleotide variant Pathogenic rs121912585 GRCh38 Chromosome 12, 39332405: 39332405
3 KIF21A NM_001173464.1(KIF21A): c.2861G> A (p.Arg954Gln) single nucleotide variant Pathogenic rs121912586 GRCh37 Chromosome 12, 39726206: 39726206
4 KIF21A NM_001173464.1(KIF21A): c.2861G> A (p.Arg954Gln) single nucleotide variant Pathogenic rs121912586 GRCh38 Chromosome 12, 39332404: 39332404
5 KIF21A NM_001173464.1(KIF21A): c.3029T> C (p.Ile1010Thr) single nucleotide variant Pathogenic rs121912587 GRCh37 Chromosome 12, 39726038: 39726038
6 KIF21A NM_001173464.1(KIF21A): c.3029T> C (p.Ile1010Thr) single nucleotide variant Pathogenic rs121912587 GRCh38 Chromosome 12, 39332236: 39332236
7 KIF21A NM_001173464.1(KIF21A): c.1067T> C (p.Met356Thr) single nucleotide variant Pathogenic rs121912588 GRCh37 Chromosome 12, 39752128: 39752128
8 KIF21A NM_001173464.1(KIF21A): c.1067T> C (p.Met356Thr) single nucleotide variant Pathogenic rs121912588 GRCh38 Chromosome 12, 39358326: 39358326
9 KIF21A NM_001173464.1(KIF21A): c.2839A> G (p.Met947Val) single nucleotide variant Pathogenic rs121912589 GRCh37 Chromosome 12, 39726410: 39726410
10 KIF21A NM_001173464.1(KIF21A): c.2839A> G (p.Met947Val) single nucleotide variant Pathogenic rs121912589 GRCh38 Chromosome 12, 39332608: 39332608
11 KIF21A NM_001173464.1(KIF21A): c.2840T> G (p.Met947Arg) single nucleotide variant Pathogenic rs121912590 GRCh37 Chromosome 12, 39726409: 39726409
12 KIF21A NM_001173464.1(KIF21A): c.2840T> G (p.Met947Arg) single nucleotide variant Pathogenic rs121912590 GRCh38 Chromosome 12, 39332607: 39332607
13 KIF21A NM_001173464.1(KIF21A): c.2841G> A (p.Met947Ile) single nucleotide variant Pathogenic rs267607200 GRCh37 Chromosome 12, 39726408: 39726408
14 KIF21A NM_001173464.1(KIF21A): c.2841G> A (p.Met947Ile) single nucleotide variant Pathogenic rs267607200 GRCh38 Chromosome 12, 39332606: 39332606
15 KIF21A NM_001173464.1(KIF21A): c.84C> G (p.Cys28Trp) single nucleotide variant Pathogenic rs864321718 GRCh37 Chromosome 12, 39764024: 39764024
16 KIF21A NM_001173464.1(KIF21A): c.84C> G (p.Cys28Trp) single nucleotide variant Pathogenic rs864321718 GRCh38 Chromosome 12, 39370222: 39370222
17 MT-TL1 NC_012920.1: m.3275C> T single nucleotide variant Uncertain significance rs1057516057 GRCh37 Chromosome MT, 3275: 3275
18 MT-TL1 NC_012920.1: m.3275C> T single nucleotide variant Uncertain significance rs1057516057 GRCh38 Chromosome MT, 3275: 3275

Expression for Fibrosis of Extraocular Muscles, Congenital, 1

Search GEO for disease gene expression data for Fibrosis of Extraocular Muscles, Congenital, 1.

Pathways for Fibrosis of Extraocular Muscles, Congenital, 1

GO Terms for Fibrosis of Extraocular Muscles, Congenital, 1

Sources for Fibrosis of Extraocular Muscles, Congenital, 1

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