MTS
MCID: MHR001
MIFTS: 45

Mohr-Tranebjaerg Syndrome (MTS)

Categories: Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Mohr-Tranebjaerg Syndrome

MalaCards integrated aliases for Mohr-Tranebjaerg Syndrome:

Name: Mohr-Tranebjaerg Syndrome 57 12 24 53 75 37 29 13 55 6 44 40 73 25
Jensen Syndrome 57 12 53 25 75 37 13 73
Deafness-Dystonia-Optic Neuronopathy Syndrome 12 24 53 25 15
Deafness Syndrome, Progressive, with Blindness, Dystonia, Fractures, and Mental Deficiency 57 53 25
Opticoacoustic Nerve Atrophy with Dementia 57 25 75
Deafness-Dystonia-Optic Atrophy Syndrome 57 53 25
Dds 57 53 75
Mts 57 53 75
Dystonia-Deafness Syndrome 57 75
Deafness Dystonia Syndrome 12 53
Dfn-1 24 75
Ddp 57 53
Syndrome of Opticoacoustic Nerve Atrophy with Dementia 53
Deafness - Dystonia - Optic Neuronopathy Syndrome 53
Nerve Deafness Optic Nerve Atrophy, and Dementia 53
Deafness-Dystonia-Optic Neuronopathy Syndrome 53
Deafness-Dystonia-Optic Atrophy Syndrome; Ddp 57
Deafness Dystonia Optic Neuronopathy Syndrome 12
Atrophy, Nerve, Opticoacoustic, with Dementia 40
Opticoacustic Nerve Atrophy with Dementia 53
Deafness Dystonia Optic Atrophy Syndrome 12
Opticoacoustic Nerve Atrophy Dementia 53
X-Linked Progressive Deafness Type 1 75
Dystonia-Deafness Syndrome; Dds 57
Dystonia Deafness Syndrome 12
Deafness-Dystonia Syndrome 24
Mohrtranebj�rg Syndrome 76
Ddon Syndrome 53

Characteristics:

OMIM:

57
Miscellaneous:
onset in childhood
deafness is presenting symptom

Inheritance:
x-linked recessive


HPO:

32
mohr-tranebjaerg syndrome:
Onset and clinical course childhood onset
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Mohr-Tranebjaerg Syndrome

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 52368Disease definitionMohr-Tranebjaerg syndrome (MTS) is an X-linked recessive neurodegenerative syndrome characterized by clinical manifestations commencing with early childhood onset hearing loss, followed by adolescent onset progressive dystonia or ataxia, visual impairment from early adulthood onwards and dementia from the 4th decade onwards.EpidemiologyPrevalence is unknown. More than 90 cases (37 families) are known, but not all cases have been reported in the literature.Clinical descriptionThe onset of rapidly progressive prelingual or postlingual sensorineural hearing loss, the only typical symptom, occurs in early childhood (18 months). Neuropsychologic manifestations, such as personality changes, paranoia, and mild intellectual deficit may emerge at the same time. A slowly progressive movement disorder, appearing as gegenhalten (diffuse resistance to limb movement), dystonia (mostly generalized or focal) or ataxia develops from early adolescence and is associated with brisk tendon reflexes, ankle clonus and extensor plantar responses. Patients experience reduced visual acuity, photophobia, acquired color vision defect and central scotomas starting from about 20 years of age and leading to legal blindness at around age 30 to 40. Slowly progressive dementia develops from the 4th decade onwards. In those with a contiguous genedeletion syndrome (CGS), recurrent infections may be present. Carrier females may be mildly affected with mild hearing impairment and focal dystonia.EtiologyMTS is caused by either a mutation in the TIMM8A gene (located to Xq22) or by a CGS at Xq22, resulting in a deafness-dystonia peptide 1 (DDP1) deficiency. If the CGS includes the Bruton agammaglobulinemia tyrosine kinase (BTK) gene, recurrent infections secondary to this X-linked agammaglobulinemia (XLA; see this term) are present.Diagnostic methodsA combination of hearing impairment and recurrent infections due to XLA in a male patient should elicit sequencing of the TIMM8A gene. Neuroimaging is employed to verify the presence of cerebral atrophy. In cases of suspected CGS; testing for XLA is possible.Differential diagnosisDifferential diagnosis includes MELAS syndrome; mitochondrial DNA depletion syndrome (encephalomyopathic form with methylmalonic aciduria); Arts syndrome; X-linked spinocerebellar ataxia type 3 and 4; McLeod neuroacanthocytosis syndrome; Usher syndrome type 1 and 2; Wolfram syndrome; autosomal recessive nonsyndromic sensorineural deafness type DFNB; Pendred syndrome; and other forms of dystonia or rarely Friedreich ataxia (see these terms).Antenatal diagnosisPrenatal diagnosis may be proposed to affected couples or parents for further pregnancies.Genetic counselingMTS is transmitted in an X-linked recessive manner. Genetic counseling should be provided to affected families.Management and treatmentTreatment of MTS is symptomatic and evolves over time. Hearing aids are used with variable success. For mild hearing loss, a hearing device and cochlear implants are an option whereas hearing aids with visual clues are used in cases with more severe hearing loss. Management of dystonia and ataxia includes treatment with GABA β-agonists together with psycho-motor re-education and physical therapy. Other supportive measures include therapies for the deaf-blind, addressing progressive sensory deficits, such as tactile sign language. In those with secondary complications, intravenous immunoglobulin may prevent infections in XLA. Furthermore, live viral vaccines should be avoided in cases of XLA. In adulthood, regular neurological evaluation (assessment for dementia and/or psychiatric manifestations) should be maintained.PrognosisPrognosis is poor. The combination of deafness and blindness severely affects communication, while the ongoing movement disorder results in an increasingly unstable gait. Life expectancy is highly variable and can range from death in the teenage years (after a rapidly progressive dystonia) to those that live into their 60's.Visit the Orphanet disease page for more resources.

MalaCards based summary : Mohr-Tranebjaerg Syndrome, also known as jensen syndrome, is related to 3-methylglutaconic aciduria, type iii and gorlin bushkell jensen syndrome, and has symptoms including tremor, photophobia and dystonia. An important gene associated with Mohr-Tranebjaerg Syndrome is TIMM8A (Translocase Of Inner Mitochondrial Membrane 8A), and among its related pathways/superpathways is Mitochondrial protein import. Affiliated tissues include testes, brain and lung, and related phenotypes are spasticity and dysarthria

Disease Ontology : 12 A mitochondrial metabolism disease that is characterized by hearing loss that begins early in life, problems with movement, impaired vision, and behavior problems, and has material basis in mutations in the TIMM8A gene resulting in abnormal protein transport within the mitochondria.

Genetics Home Reference : 25 Deafness-dystonia-optic neuronopathy (DDON) syndrome, also known as Mohr-Tranebjærg syndrome, is characterized by hearing loss that begins early in life, problems with movement, impaired vision, and behavior problems. This condition occurs almost exclusively in males.

UniProtKB/Swiss-Prot : 75 Mohr-Tranebjaerg syndrome: An X-linked recessive disorder characterized by postlingual sensorineural deafness with onset in early childhood, dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness.

Wikipedia : 76 Mohr�??Tranebjærg syndrome (MTS) is a rare X-liked recessive syndrome also known as deafness�??dystonia... more...

Description from OMIM: 304700
GeneReviews: NBK1216

Related Diseases for Mohr-Tranebjaerg Syndrome

Diseases related to Mohr-Tranebjaerg Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 201)
# Related Disease Score Top Affiliating Genes
1 3-methylglutaconic aciduria, type iii 29.9 SERAC1 TIMM8A
2 gorlin bushkell jensen syndrome 12.1
3 dentin dysplasia, type i 12.0
4 denys-drash syndrome 12.0
5 dentin dysplasia, type ii 11.9
6 muir-torre syndrome 11.9
7 dentin dysplasia 11.7
8 diabetes and deafness, maternally inherited 11.5
9 darier-white disease 11.3
10 diastrophic dysplasia 11.3
11 deafness, dystonia, and cerebral hypomyelination 11.1
12 dystonia, juvenile-onset 11.1
13 chondrodysplasia punctata, tibia-metacarpal type 11.0
14 alzheimer disease mitochondrial 11.0
15 myoglobinuria, recurrent 11.0
16 dissociative disorder 11.0
17 acrocallosal syndrome 11.0
18 cardiomyopathy, infantile histiocytoid 11.0
19 myoclonic epilepsy associated with ragged-red fibers 11.0
20 joubert syndrome 2 11.0
21 joubert syndrome 6 11.0
22 joubert syndrome 14 11.0
23 joubert syndrome 32 11.0
24 dystonia 10.9
25 focal dystonia 10.4
26 blepharospasm 10.4
27 lepromatous leprosy 10.4
28 lung cancer 10.4
29 small cell cancer of the lung 10.2
30 arteries, anomalies of 10.2
31 coronary artery anomaly 10.2
32 adenocarcinoma 10.2
33 acute mountain sickness 10.1
34 microvascular complications of diabetes 3 10.1
35 microvascular complications of diabetes 4 10.1
36 microvascular complications of diabetes 6 10.1
37 microvascular complications of diabetes 7 10.1
38 myocardial infarction 10.1
39 global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies 10.1
40 lung cancer susceptibility 3 10.1
41 myopathy 10.1
42 multiple sclerosis 10.0
43 thrombosis 10.0
44 alzheimer disease 10.0
45 epilepsy 10.0
46 multifocal lymphangioendotheliomatosis with thrombocytopenia 10.0
47 ovarian cancer 10.0
48 mitochondrial myopathy 10.0
49 blood group--swann system 10.0
50 agammaglobulinemia 9.9 BTK TIMM8A

Graphical network of the top 20 diseases related to Mohr-Tranebjaerg Syndrome:



Diseases related to Mohr-Tranebjaerg Syndrome

Symptoms & Phenotypes for Mohr-Tranebjaerg Syndrome

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
spasticity
dysarthria
tremor
hyperreflexia
dysphagia
more
Skeletal:
fractures

Neurologic Behavioral Psychiatric Manifestations:
behavioral/psychiatric abnormalities

Head And Neck Eyes:
photophobia
abnormal electroretinogram
myopia
decreased visual acuity
constricted visual fields
more
Head And Neck Ears:
sensorineural deafness, postlingual, progressive


Clinical features from OMIM:

304700

Human phenotypes related to Mohr-Tranebjaerg Syndrome:

32 (show all 18)
# Description HPO Frequency HPO Source Accession
1 spasticity 32 HP:0001257
2 dysarthria 32 HP:0001260
3 tremor 32 HP:0001337
4 hyperreflexia 32 HP:0001347
5 dysphagia 32 HP:0002015
6 visual impairment 32 HP:0000505
7 photophobia 32 HP:0000613
8 abnormal electroretinogram 32 HP:0000512
9 myopia 32 HP:0000545
10 dystonia 32 HP:0001332
11 reduced visual acuity 32 HP:0007663
12 mental deterioration 32 HP:0001268
13 constriction of peripheral visual field 32 HP:0001133
14 increased susceptibility to fractures 32 HP:0002659
15 progressive sensorineural hearing impairment 32 HP:0000408
16 abnormal posturing 32 HP:0002533
17 cerebral visual impairment 32 HP:0100704
18 postlingual sensorineural hearing impairment 32 HP:0008596

UMLS symptoms related to Mohr-Tranebjaerg Syndrome:


tremor, photophobia, dystonia, muscle spasticity

GenomeRNAi Phenotypes related to Mohr-Tranebjaerg Syndrome according to GeneCards Suite gene sharing:

26 (show all 18)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-102 9.62 BTK
2 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.62 SLC25A12
3 Increased shRNA abundance (Z-score > 2) GR00366-A-124 9.62 BTK
4 Increased shRNA abundance (Z-score > 2) GR00366-A-137 9.62 BTK SLC25A12 TIMM8A
5 Increased shRNA abundance (Z-score > 2) GR00366-A-140 9.62 BTK
6 Increased shRNA abundance (Z-score > 2) GR00366-A-176 9.62 TIMM8A
7 Increased shRNA abundance (Z-score > 2) GR00366-A-183 9.62 SLC25A12
8 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.62 TIMM8A
9 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.62 SLC25A12
10 Increased shRNA abundance (Z-score > 2) GR00366-A-29 9.62 BTK
11 Increased shRNA abundance (Z-score > 2) GR00366-A-3 9.62 SLC25A12
12 Increased shRNA abundance (Z-score > 2) GR00366-A-32 9.62 TIMM8A
13 Increased shRNA abundance (Z-score > 2) GR00366-A-4 9.62 BTK
14 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.62 SLC25A12
15 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.62 BTK
16 Increased shRNA abundance (Z-score > 2) GR00366-A-74 9.62 SLC25A12
17 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.62 BTK
18 Increased shRNA abundance (Z-score > 2) GR00366-A-97 9.62 TIMM8A

Drugs & Therapeutics for Mohr-Tranebjaerg Syndrome

Search Clinical Trials , NIH Clinical Center for Mohr-Tranebjaerg Syndrome

Cochrane evidence based reviews: mohr-tranebjaerg syndrome

Genetic Tests for Mohr-Tranebjaerg Syndrome

Genetic tests related to Mohr-Tranebjaerg Syndrome:

# Genetic test Affiliating Genes
1 Mohr-Tranebjaerg Syndrome 29 TIMM8A

Anatomical Context for Mohr-Tranebjaerg Syndrome

MalaCards organs/tissues related to Mohr-Tranebjaerg Syndrome:

41
Testes, Brain, Lung, Liver, Heart, Ovary, Prostate

Publications for Mohr-Tranebjaerg Syndrome

Articles related to Mohr-Tranebjaerg Syndrome:

(show all 16)
# Title Authors Year
1
Bilateral Globus Pallidus Internus Deep Brain Stimulation in a Case of Progressive Dystonia in Mohr-Tranebjaerg Syndrome with Bilateral Cochlear Implants. ( 30290379 )
2018
2
Peripheral blood epi-signature of Claes-Jensen syndrome enables sensitive and specific identification of patients and healthy carriers with pathogenic mutations in KDM5C. ( 29456765 )
2018
3
First Report of a Filipino with Mohr-Tranebjaerg Syndrome. ( 30363500 )
2015
4
Progressive dystonia in Mohr-Tranebjaerg syndrome with cochlear implant and deep brain stimulation. ( 23801560 )
2013
5
The phenotypic spectrum of dystonia in Mohr-Tranebjaerg syndrome. ( 22736418 )
2012
6
A Spanish sporadic case of deafness-dystonia (Mohr-Tranebjaerg) syndrome with a novel mutation in the gene encoding TIMM8a, a component of the mitochondrial protein translocase complexes. ( 18952432 )
2008
7
Blepharospasm and limb dystonia caused by Mohr-Tranebjaerg syndrome with a novel splice-site mutation in the deafness/dystonia peptide gene. ( 17534980 )
2007
8
Otopathology in Mohr-Tranebjaerg syndrome. ( 17471106 )
2007
9
Molecular genetics of a patient with Mohr-Tranebjaerg Syndrome due to a new mutation in the DDP1 gene. ( 17999202 )
2007
10
A novel mutation in the gene encoding TIMM8a, a component of the mitochondrial protein translocase complexes, in a Spanish familial case of deafness-dystonia (Mohr-Tranebjaerg) syndrome. ( 16411215 )
2006
11
Focal dystonia caused by Mohr-Tranebjaerg syndrome with complete deletion of the DDP1 gene. ( 15037720 )
2004
12
Dystonia in the Mohr-Tranebjaerg syndrome responds to GABAergic substances. ( 15390009 )
2004
13
A novel deafness/dystonia peptide gene mutation that causes dystonia in female carriers of Mohr-Tranebjaerg syndrome. ( 11601506 )
2001
14
Temporal bone histopathologic and genetic studies in Mohr-Tranebjaerg syndrome (DFN-1). ( 11449109 )
2001
15
X-linked recessive deafness-dystonia syndrome (Mohr-Tranebjaerg syndrome). ( 10868232 )
2000
16
Full-field electroretinograms in a family with Mohr-Tranebjaerg syndrome. ( 9017058 )
1996

Variations for Mohr-Tranebjaerg Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Mohr-Tranebjaerg Syndrome:

75
# Symbol AA change Variation ID SNP ID
1 TIMM8A p.Cys66Trp VAR_010237 rs80356560

ClinVar genetic disease variations for Mohr-Tranebjaerg Syndrome:

6 (show all 21)
# Gene Variation Type Significance SNP ID Assembly Location
1 TIMM8A NM_004085.3(TIMM8A): c.116delT (p.Met39Argfs) deletion Pathogenic rs869320664 GRCh37 Chromosome X, 100603537: 100603537
2 TIMM8A NM_004085.3(TIMM8A): c.116delT (p.Met39Argfs) deletion Pathogenic rs869320664 GRCh38 Chromosome X, 101348549: 101348549
3 TIMM8A NM_004085.3(TIMM8A): c.148_157delAAGCCTGGGC (p.Lys50Glnfs) deletion Pathogenic rs869320733 GRCh38 Chromosome X, 101346636: 101346645
4 TIMM8A NM_004085.3(TIMM8A): c.148_157delAAGCCTGGGC (p.Lys50Glnfs) deletion Pathogenic rs869320733 GRCh37 Chromosome X, 100601624: 100601633
5 TIMM8A NM_004085.3(TIMM8A): c.70G> T (p.Glu24Ter) single nucleotide variant Pathogenic rs111033631 GRCh37 Chromosome X, 100603583: 100603583
6 TIMM8A NM_004085.3(TIMM8A): c.70G> T (p.Glu24Ter) single nucleotide variant Pathogenic rs111033631 GRCh38 Chromosome X, 101348595: 101348595
7 TIMM8A NM_004085.3(TIMM8A): c.198C> G (p.Cys66Trp) single nucleotide variant Pathogenic rs80356560 GRCh37 Chromosome X, 100601583: 100601583
8 TIMM8A NM_004085.3(TIMM8A): c.198C> G (p.Cys66Trp) single nucleotide variant Pathogenic rs80356560 GRCh38 Chromosome X, 101346595: 101346595
9 TIMM8A NM_004085.3(TIMM8A): c.73delG (p.Val25Terfs) deletion Pathogenic rs869320665 GRCh37 Chromosome X, 100603580: 100603580
10 TIMM8A NM_004085.3(TIMM8A): c.73delG (p.Val25Terfs) deletion Pathogenic rs869320665 GRCh38 Chromosome X, 101348592: 101348592
11 TIMM8A TIMM8A, DEL deletion Pathogenic
12 TIMM8A NM_004085.3(TIMM8A): c.238C> T (p.Arg80Ter) single nucleotide variant Pathogenic rs1054894 GRCh37 Chromosome X, 100601543: 100601543
13 TIMM8A NM_004085.3(TIMM8A): c.238C> T (p.Arg80Ter) single nucleotide variant Pathogenic rs1054894 GRCh38 Chromosome X, 101346555: 101346555
14 TIMM8A NM_004085.3(TIMM8A): c.133-23A> C single nucleotide variant Pathogenic rs869320666 GRCh37 Chromosome X, 100601671: 100601671
15 TIMM8A NM_004085.3(TIMM8A): c.133-23A> C single nucleotide variant Pathogenic rs869320666 GRCh38 Chromosome X, 101346683: 101346683
16 TIMM8A NM_004085.3(TIMM8A): c.127delT (p.Cys43Valfs) deletion Pathogenic rs869320667 GRCh37 Chromosome X, 100603526: 100603526
17 TIMM8A NM_004085.3(TIMM8A): c.127delT (p.Cys43Valfs) deletion Pathogenic rs869320667 GRCh38 Chromosome X, 101348538: 101348538
18 TIMM8A NM_004085.3(TIMM8A): c.112C> T (p.Gln38Ter) single nucleotide variant Pathogenic rs80356559 GRCh37 Chromosome X, 100603541: 100603541
19 TIMM8A NM_004085.3(TIMM8A): c.112C> T (p.Gln38Ter) single nucleotide variant Pathogenic rs80356559 GRCh38 Chromosome X, 101348553: 101348553
20 TIMM8A NM_004085.3(TIMM8A): c.*502_*504dupTGA duplication Benign rs4024308 GRCh37 Chromosome X, 100600983: 100600985
21 TIMM8A NM_004085.3(TIMM8A): c.*502_*504dupTGA duplication Benign rs4024308 GRCh38 Chromosome X, 101345995: 101345997

Expression for Mohr-Tranebjaerg Syndrome

Search GEO for disease gene expression data for Mohr-Tranebjaerg Syndrome.

Pathways for Mohr-Tranebjaerg Syndrome

Pathways related to Mohr-Tranebjaerg Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.59 SLC25A12 TIMM13 TIMM8A

GO Terms for Mohr-Tranebjaerg Syndrome

Cellular components related to Mohr-Tranebjaerg Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.46 SERAC1 SLC25A12 TIMM13 TIMM8A
2 mitochondrial intermembrane space GO:0005758 8.96 TIMM13 TIMM8A
3 mitochondrial inner membrane GO:0005743 8.8 SLC25A12 TIMM13 TIMM8A

Biological processes related to Mohr-Tranebjaerg Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phospholipid biosynthetic process GO:0008654 8.96 FITM2 SERAC1
2 chaperone-mediated protein transport GO:0072321 8.62 TIMM13 TIMM8A

Molecular functions related to Mohr-Tranebjaerg Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 molecular_function GO:0003674 8.8 FITM2 SERAC1 TAF7L

Sources for Mohr-Tranebjaerg Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....