FEOM
MCID: TKL001
MIFTS: 47

Tukel Syndrome (FEOM)

Categories: Eye diseases, Fetal diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Tukel Syndrome

MalaCards integrated aliases for Tukel Syndrome:

Name: Tukel Syndrome 57 12 53 29 13 72
Congenital Fibrosis of the Extraocular Muscles 12 24 25 37 29 6 15 17 72
Congenital Fibrosis of Extraocular Muscles 53 25 59 29
Cfeom 24 25 55
Cfeom-U 57 53
Feom 53 59
Fibrosis of Extraocular Muscles, Congenital, with Ulnar Hand Anomalies 57
Congenital Extraocular Muscle Fibrosis with Ulnar Hand Anomalies 53
Fibrosis of Extraocular Muscles, Congenital, 4; Cfeom4 57
Congenital Fibrosis of the Extraocular Muscles 4 29
Fibrosis of Extraocular Muscles, Congenital, 4 57
Congenital External Ophthalmoplegia 25
Congenital Fibrosis Syndrome 25
General Fibrosis Syndrome 25
Cfeom4 57

Characteristics:

Orphanet epidemiological data:

59
congenital fibrosis of extraocular muscles
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
tukel syndrome:
Inheritance autosomal recessive inheritance


GeneReviews:

24
Penetrance Penetrance in cfeom1a, cfeom1b, cfeom2, cfeom3b, cfeom3c, and tukel syndrome is complete....

Classifications:



External Ids:

Disease Ontology 12 DOID:0080143
KEGG 37 H00838
ICD10 via Orphanet 34 H49.8
UMLS via Orphanet 73 C1302995
Orphanet 59 ORPHA45358
MedGen 42 C1836217
UMLS 72 C1302995 C1836217

Summaries for Tukel Syndrome

Genetics Home Reference : 25 Congenital fibrosis of the extraocular muscles is a disorder that affects the muscles that surround the eyes. These muscles control eye movement and the position of the eyes (for example, looking straight ahead). Congenital fibrosis of the extraocular muscles prevents the normal development and function 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 be misaligned such that they look in different directions (strabismus). Instead of moving their eyes, affected individuals may need to turn their head to track moving objects. Additionally, many people with congenital fibrosis of the extraocular muscles have droopy eyelids (ptosis), which further limits their vision. Researchers have identified at least four forms of congenital fibrosis of the extraocular muscles, designated CFEOM1, CFEOM2, CFEOM3, and Tukel syndrome. The specific problems with eye movement vary among the types. Tukel syndrome is characterized by missing fingers (oligodactyly) and other hand abnormalities in addition to problems with eye movement.

MalaCards based summary : Tukel Syndrome, also known as congenital fibrosis of the extraocular muscles, is related to fibrosis of extraocular muscles, congenital, 2 and kearns-sayre syndrome, and has symptoms including ophthalmoplegia An important gene associated with Tukel Syndrome is KIF21A (Kinesin Family Member 21A), and among its related pathways/superpathways are Phagosome and Gap junction. The drugs Angiogenesis Inhibitors and Vaccines have been mentioned in the context of this disorder. Affiliated tissues include eye, bone and brain, and related phenotypes are ptosis and syndactyly

NIH Rare Diseases : 53 Congenital fibrosis of extraocular muscles (CFEOM) refers to a group of rare conditions that affect the normal development and function of the muscles that control eye movement and position. In general, people affected by these conditions are unable to move their eyes in certain directions and often have strabismus and/or droopy eyelids (ptosis); however, the severity of the condition and the associated signs and symptoms vary significantly by subtype. CFEOM can be caused by changes (mutations) in several genes, including KIF21A, TUBB3, PHOX2A, and TUBB2B. In some cases, the underlying genetic cause is unknown. CFEOM can be inherited in an autosomal dominant or autosomal recessive manner, depending on the subtype. Treatment is based on the signs and symptoms present in each person.

KEGG : 37
Congenital fibrosis of the extraocular muscles (CFEOM) describes a group of rare congenital eye movement disorders that result from the dysfunction of all or part of the oculomotor (CN 3) and the trochlear (CN 4) nerves, and/or the muscles these nerves innervate. CFEOM is characterized by non-progressive, restrictive ophthalmoplegia of the extraocular muscles and congenital blepharoptosis. Several clinical phenotypes for familial CFEOM have been delineated.

More information from OMIM: 609428 PS135700
GeneReviews: NBK1348

Related Diseases for Tukel Syndrome

Diseases related to Tukel Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 87)
# Related Disease Score Top Affiliating Genes
1 fibrosis of extraocular muscles, congenital, 2 31.5 PHOX2A KIF21A
2 kearns-sayre syndrome 31.3 TUBB3 PHOX2A KIF21A
3 ptosis 30.9 TUBB6 TUBB3 PHOX2A KIF21A
4 enophthalmos 30.7 TNNI3K CHN1
5 amblyopia 30.5 TUBB3 PHOX2A CHN1
6 marcus gunn phenomenon 30.4 TUBB3 CHN1
7 strabismus 30.3 TUBB3 PHOX2A KIF21A HOXB1 CHN1
8 hypertropia 30.3 TUBB3 KIF21A CHN1
9 esotropia 30.1 TUBB3 ROBO3 CHN1
10 exotropia 30.1 TUBB3 TNNI3K PHOX2A KIF21A CHN1
11 congenital ptosis 30.1 TUBB3 TNNI3K KIF21A CHN1
12 facial paralysis 30.0 TUBB3 TNNI3K HOXB1
13 tubulin, beta 30.0 TUBB6 TUBB3 TUBB2B
14 hypotropia 29.9 TUBB3 PHOX2A KIF21A CHN1 APPL1
15 duane retraction syndrome 29.8 TUBB3 TNNI3K KIF21A CHN1
16 paralytic squint 29.6 TUBB3 TUBB2B PHOX2A KIF21A CHN1
17 ocular motility disease 29.1 TUBB3 TNNI3K ROBO3 PHOX2A KIF21A CHN1
18 fibrosis of extraocular muscles, congenital, 3a, with or without extraocular involvement 11.7
19 fibrosis of extraocular muscles, congenital, with synergistic divergence 11.5
20 fibrosis of extraocular muscles, congenital, 1 11.3
21 mechanical strabismus 10.7
22 tubulinopathy-associated dysgyria 10.4 TUBB3 TUBB2B
23 alternating exotropia 10.4
24 suppression amblyopia 10.3
25 movement disease 10.3
26 moebius syndrome 10.2 TUBB3 PHOX2A
27 astigmatism 10.2
28 cortical dysplasia, complex, with other brain malformations 7 10.2
29 autosomal recessive disease 10.2
30 lagophthalmos 10.2
31 keratopathy 10.2
32 myopathy 10.2
33 deafness, autosomal dominant 28 10.1 TUBB3 KIF21A CHN1
34 orbital disease 10.1 TNNI3K CHN1
35 neonatal anemia 10.1 TUBB3 TUBB2B
36 cardiac conduction disease with or without dilated cardiomyopathy 10.1
37 tubulinopathies 10.1
38 duane retraction syndrome 1 10.0
39 noonan syndrome 1 10.0
40 optic nerve hypoplasia, bilateral 10.0
41 corpus callosum, agenesis of 10.0
42 3-methylglutaconic aciduria, type iii 10.0
43 ataxia and polyneuropathy, adult-onset 10.0
44 aceruloplasminemia 10.0
45 duane retraction syndrome 2 10.0
46 meningioma, radiation-induced 10.0
47 meningioma, familial 10.0
48 fibrosis of extraocular muscles, congenital, 3c 10.0
49 alacrima, achalasia, and mental retardation syndrome 10.0
50 ophthalmoplegia, external, with rib and vertebral anomalies 10.0

Graphical network of the top 20 diseases related to Tukel Syndrome:



Diseases related to Tukel Syndrome

Symptoms & Phenotypes for Tukel Syndrome

Human phenotypes related to Tukel Syndrome:

32 (show all 9)
# Description HPO Frequency HPO Source Accession
1 ptosis 32 HP:0000508
2 syndactyly 32 HP:0001159
3 carpal synostosis 32 HP:0009702
4 congenital fibrosis of extraocular muscles 32 HP:0001491
5 postaxial oligodactyly 32 HP:0006210
6 compensatory chin elevation 32 HP:0001477
7 restrictive external ophthalmoplegia 32 HP:0007936
8 carpal bone aplasia 32 HP:0004231
9 nonprogressive restrictive external ophthalmoplegia 32 HP:0007831

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
blepharoptosis
congenital fibrosis of extraocular muscles (cfeom)
unilateral (right eye) involvement
nonprogressive restrictive ophthalmoplegia (superior rectus, inferior oblique, levator palpebralis dysfunction)

Head And Neck Head:
compensatory head tilt/chin elevation

Skeletal Hands:
fused carpal bones
bilateral postaxial oligodactyly/oligosyndactyly (right side affected greater than left)
absent carpal bones

Clinical features from OMIM:

609428

UMLS symptoms related to Tukel Syndrome:


ophthalmoplegia

MGI Mouse Phenotypes related to Tukel Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.23 APPL1 CHN1 HOXB1 PHOX2A ROBO3 TNNI3K

Drugs & Therapeutics for Tukel Syndrome

Drugs for Tukel Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Angiogenesis Inhibitors Phase 1
2 Vaccines Phase 1
3 Immunologic Factors Phase 1
4 Angiogenesis Modulating Agents Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase 1 Study of HLA-A*2402 Restricted Antiangiogenic Peptide Vaccine Therapy Using Epitope Peptide Derived Feom VEGFR1 and VEGFR2 in Treating Patients With Unresectable, Recurrent, or Metastatic Hepatocellular Carcinoma Unknown status NCT01266707 Phase 1
2 Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies Recruiting NCT03059420

Search NIH Clinical Center for Tukel Syndrome

Genetic Tests for Tukel Syndrome

Genetic tests related to Tukel Syndrome:

# Genetic test Affiliating Genes
1 Congenital Fibrosis of the Extraocular Muscles 29
2 Congenital Fibrosis of the Extraocular Muscles 4 29
3 Tukel Syndrome 29
4 Congenital Fibrosis of Extraocular Muscles 29

Anatomical Context for Tukel Syndrome

MalaCards organs/tissues related to Tukel Syndrome:

41
Eye, Bone, Brain, Testes, Cortex

Publications for Tukel Syndrome

Articles related to Tukel Syndrome:

(show top 50) (show all 171)
# Title Authors PMID Year
1
A new syndrome, congenital extraocular muscle fibrosis with ulnar hand anomalies, maps to chromosome 21qter. 38 4 8
15863670 2005
2
KIF21A variant R954W in familial or sporadic cases of CFEOM1. 9 38 4
19551685 2009
3
A novel KIF21A mutation in a patient with congenital fibrosis of the extraocular muscles and Marcus Gunn jaw-winking phenomenon. 9 38 4
16157808 2005
4
KIF21A gene c.2860C>T mutation in congenital fibrosis of extraocular muscles type 1 and 3. 9 38 4
15827546 2005
5
Mutation analysis of KIF21A in congenital fibrosis of the extraocular muscles (CFEOM) patients. 9 38 4
15621876 2004
6
A novel PHOX2A/ARIX mutation in an Iranian family with congenital fibrosis of extraocular muscles type 2 (CFEOM2). 9 38 4
14597037 2003
7
Two unique TUBB3 mutations cause both CFEOM3 and malformations of cortical development. 38 4
26639658 2016
8
A rare case of congenital fibrosis of extraocular muscle type 1A due to KIF21A mutation with Marcus Gunn jaw-winking phenomenon. 38 4
26190014 2015
9
Expanding the phenotypic spectrum and variability of endocrine abnormalities associated with TUBB3 E410K syndrome. 38 4
25559402 2015
10
Diagnostic distinctions and genetic analysis of patients diagnosed with moebius syndrome. 38 4
24612975 2014
11
Human CFEOM1 mutations attenuate KIF21A autoinhibition and cause oculomotor axon stalling. 38 4
24656932 2014
12
Maternal germline mosaicism of kinesin family member 21A (KIF21A) mutation causes complex phenotypes in a Chinese family with congenital fibrosis of the extraocular muscles. 38 4
24426772 2014
13
A novel de novo KIF21A mutation in a patient with congenital fibrosis of the extraocular muscles and Möbius syndrome. 38 4
24715754 2014
14
CFEOM1-associated kinesin KIF21A is a cortical microtubule growth inhibitor. 38 4
24120883 2013
15
Inherited KIF21A and PAX6 gene mutations in a boy with congenital fibrosis of extraocular muscles and aniridia. 38 4
23799907 2013
16
A novel syndrome caused by the E410K amino acid substitution in the neuronal β-tubulin isotype 3. 38 4
23378218 2013
17
An inherited TUBB2B mutation alters a kinesin-binding site and causes polymicrogyria, CFEOM and axon dysinnervation. 38 4
23001566 2012
18
Spatiotemporal expression pattern of KIF21A during normal embryonic development and in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). 38 4
22465342 2012
19
KIF21A novel deletion and recurrent mutation in patients with congenital fibrosis of the extraocular muscles-1. 38 4
21805025 2011
20
Lack of KIF21A mutations in congenital fibrosis of the extraocular muscles type I patients from consanguineous Saudi Arabian families. 38 4
21264235 2011
21
KIF21A mutations in two Chinese families with congenital fibrosis of the extraocular muscles (CFEOM). 38 4
21042561 2010
22
Evidence of an asymmetrical endophenotype in congenital fibrosis of extraocular muscles type 3 resulting from TUBB3 mutations. 38 4
20393110 2010
23
Germline Mosaicism for KIF21A Mutation (p.R954L) Mimicking Recessive Inheritance for Congenital Fibrosis of the Extraocular Muscles. 38 4
19896199 2010
24
Unexpected clinical involvement of hereditary total leuconychia with congenital fibrosis of the extraocular muscles in three generations. 38 4
19489868 2009
25
[Magnetic resonance imaging features in two Chinese family with congenital fibrosis of extraocular muscles]. 38 4
20137413 2009
26
Novel and recurrent KIF21A mutations in congenital fibrosis of the extraocular muscles type 1 and 3. 38 4
18332320 2008
27
Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1. 38 4
17511870 2007
28
Abnormalities of the oculomotor nerve in congenital fibrosis of the extraocular muscles and congenital oculomotor palsy. 38 4
17389489 2007
29
Neurological features of congenital fibrosis of the extraocular muscles type 2 with mutations in PHOX2A. 38 4
16815872 2006
30
Recurrent mutation of the KIF21A gene in Japanese patients with congenital fibrosis of the extraocular muscles. 38 4
16365788 2005
31
Anterior uveitis and congenital fibrosis of the extraocular muscles in a patient with Noonan syndrome. 38 4
16388177 2005
32
Hypoplastic oculomotor nerve and absent abducens nerve in congenital fibrosis syndrome and synergistic divergence with magnetic resonance imaging. 38 4
15808269 2005
33
Magnetic resonance imaging evidence for widespread orbital dysinnervation in congenital fibrosis of extraocular muscles due to mutations in KIF21A. 38 4
15671279 2005
34
Congenital fibrosis of the extraocular muscles with brain-stem abnormalities: a novel finding. 38 4
15491041 2004
35
Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3). 38 4
15223798 2004
36
Classification and surgical management of patients with familial and sporadic forms of congenital fibrosis of the extraocular muscles. 38 4
15121385 2004
37
Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). 38 4
14595441 2003
38
Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2. 38 4
11600883 2001
39
Congenital fibrosis of the extraocular muscles associated with cortical dysplasia and maldevelopment of the basal ganglia. 38 4
11425694 2001
40
CFEOM3: a new extraocular congenital fibrosis syndrome that maps to 16q24.2-q24.3. 38 4
10393037 1999
41
Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13. 38 4
9683611 1998
42
Phenotypic heterogeneity may occur in congenital fibrosis of the extraocular muscles. 38 4
9797671 1998
43
Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles. 38 4
9066352 1997
44
Recognizable cerebellar dysplasia associated with mutations in multiple tubulin genes. 4
26130693 2015
45
Prosthetic replacement of the ocular surface ecosystem as treatment for ocular surface disease in patients with a history of Stevens-Johnson syndrome/toxic epidermal necrolysis. 4
25282251 2015
46
Recessive mutations in COL25A1 are a cause of congenital cranial dysinnervation disorder. 4
25500261 2015
47
Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly. 4
25059107 2014
48
The wide spectrum of tubulinopathies: what are the key features for the diagnosis? 4
24860126 2014
49
Congenital fibrosis of extraocular muscle type 1A due to KIF21A mutation: first case report from Hong Kong. 4
23535681 2013
50
Phenotypic spectrum of the tubulin-related disorders and functional implications of disease-causing mutations. 4
21292473 2011

Variations for Tukel Syndrome

Expression for Tukel Syndrome

Search GEO for disease gene expression data for Tukel Syndrome.

Pathways for Tukel Syndrome

Pathways related to Tukel Syndrome according to KEGG:

37
# Name Kegg Source Accession
1 Phagosome hsa04145
2 Gap junction hsa04540

Pathways related to Tukel Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.04 TUBB6 TUBB3 TUBB2B
2
Show member pathways
12.01 TUBB6 TUBB3 TUBB2B
3
Show member pathways
11.86 TUBB6 TUBB3 TUBB2B ROBO3
4
Show member pathways
11.83 TUBB6 TUBB3 TUBB2B
5 11.76 TUBB6 TUBB3 TUBB2B
6
Show member pathways
11.7 TUBB6 TUBB3 TUBB2B
7
Show member pathways
11.58 TUBB6 TUBB3 TUBB2B
8
Show member pathways
11.47 TUBB6 TUBB3 TUBB2B
9 11.11 TUBB6 TUBB3 TUBB2B
10 10.74 TUBB6 TUBB3 TUBB2B

GO Terms for Tukel Syndrome

Cellular components related to Tukel Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule GO:0005874 9.02 TUBB6 TUBB3 TUBB2B KIF21B KIF21A
2 kinesin complex GO:0005871 8.96 KIF21B KIF21A

Biological processes related to Tukel Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitotic cell cycle GO:0000278 9.33 TUBB6 TUBB3 TUBB2B
2 microtubule-based process GO:0007017 9.13 TUBB6 TUBB3 TUBB2B
3 microtubule cytoskeleton organization GO:0000226 8.92 TUBB6 TUBB3 TUBB2B PHLDB2

Molecular functions related to Tukel Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 structural constituent of cytoskeleton GO:0005200 8.8 TUBB6 TUBB3 TUBB2B

Sources for Tukel Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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