MCID: MHR001
MIFTS: 39

Mohr-Tranebjaerg Syndrome

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Mohr-Tranebjaerg Syndrome

MalaCards integrated aliases for Mohr-Tranebjaerg Syndrome:

Name: Mohr-Tranebjaerg Syndrome 53 12 23 49 71 36 28 13 51 69
Jensen Syndrome 53 12 49 71 36 28 13 14 69
Deafness-Dystonia-Optic Neuronopathy Syndrome 23 49 24
Opticoacoustic Nerve Atrophy with Dementia 53 12 71
Deafness Dystonia Syndrome 12 49 14
Dds 53 49 71
Mts 53 49 71
Deafness Syndrome, Progressive, with Blindness, Dystonia, Fractures, and Mental Deficiency 53 49
Deafness-Dystonia-Optic Atrophy Syndrome 53 49
Dystonia-Deafness Syndrome 53 71
Deafness-Dystonia Syndrome 23 24
Dfn-1 23 71
Ddp 53 49
Syndrome of Opticoacoustic Nerve Atrophy with Dementia 49
Deafness - Dystonia - Optic Neuronopathy Syndrome 49
Nerve Deafness Optic Nerve Atrophy, and Dementia 49
Deafness-Dystonia-Optic Neuronopathy Syndrome 49
Deafness-Dystonia-Optic Atrophy Syndrome; Ddp 53
Deafness Dystonia Optic Neuronopathy Syndrome 12
Opticoacustic Nerve Atrophy with Dementia 49
Deafness Dystonia Optic Atrophy Syndrome 12
Opticoacoustic Nerve Atrophy Dementia 49
X-Linked Progressive Deafness Type 1 71
Dystonia-Deafness Syndrome; Dds 53
Dystonia Deafness Syndrome 12
Mohr-Tranebjærg Syndrome 24
Ddon Syndrome 49

Characteristics:

OMIM:

53
Miscellaneous:
onset in childhood
deafness is presenting symptom

Inheritance:
x-linked recessive


HPO:

31
mohr-tranebjaerg syndrome:
Onset and clinical course childhood onset
Inheritance x-linked inheritance x-linked recessive inheritance


Classifications:



Summaries for Mohr-Tranebjaerg Syndrome

NIH Rare Diseases : 49 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. Last updated: 4/20/2013

MalaCards based summary : Mohr-Tranebjaerg Syndrome, also known as jensen syndrome, is related to gorlin bushkell jensen syndrome and dentin dysplasia, type i, and has symptoms including tremor, photophobia and dystonia. An important gene associated with Mohr-Tranebjaerg Syndrome is TIMM8A (Translocase Of Inner Mitochondrial Membrane 8A). Affiliated tissues include testes, brain and bone.

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.

Genetics Home Reference : 24 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 : 71 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.

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 85)
# Related Disease Score Top Affiliating Genes
1 gorlin bushkell jensen syndrome 12.0
2 dentin dysplasia, type i 11.8
3 dentin dysplasia, type ii 11.8
4 muir-torre syndrome 11.8
5 dentin dysplasia 11.6
6 denys-drash syndrome 11.4
7 diabetes and deafness, maternally inherited 11.3
8 may-thurner syndrome 11.2
9 darier-white disease 11.1
10 diastrophic dysplasia 11.1
11 deafness, dystonia, and cerebral hypomyelination 10.9
12 dystonia, juvenile-onset 10.9
13 chondrodysplasia punctata, tibia-metacarpal type 10.9
14 alzheimer disease mitochondrial 10.9
15 myoglobinuria, recurrent 10.9
16 acrocallosal syndrome 10.8
17 cardiomyopathy, infantile histiocytoid 10.8
18 myoclonic epilepsy associated with ragged-red fibers 10.8
19 joubert syndrome 2 10.8
20 joubert syndrome 6 10.8
21 joubert syndrome 14 10.8
22 joubert syndrome 32 10.8
23 dystonia 10.7
24 branchiootic syndrome 1 10.5
25 lung cancer 10.2
26 focal dystonia 10.2
27 blepharospasm 10.2
28 arteries, anomalies of 10.0
29 coronary artery anomaly 10.0
30 acute mountain sickness 10.0
31 endotheliitis 10.0
32 microvascular complications of diabetes 3 10.0
33 microvascular complications of diabetes 4 10.0
34 microvascular complications of diabetes 6 10.0
35 microvascular complications of diabetes 7 10.0
36 ovarian cancer 9.9
37 myocardial infarction 9.9
38 blood group, i system 9.9
39 mycobacterium tuberculosis 1 9.9
40 myopathy 9.9
41 pancreatitis 9.9
42 spasticity 9.9
43 leprosy 3 9.8
44 mental retardation, x-linked, syndromic 13 9.8 DLG3 GDI1
45 alzheimer disease 9.8
46 breast cancer 9.8
47 coloboma, ocular, autosomal dominant 9.8
48 mitochondrial myopathy 9.8
49 leigh syndrome 9.8
50 temporal lobe epilepsy 9.8

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:

53
Neurologic Central Nervous System:
tremor
dystonia
spasticity
dysarthria
hyperreflexia
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:

31 (show all 24)
# Description HPO Frequency HPO Source Accession
1 tremor 31 HP:0001337
2 photophobia 31 HP:0000613
3 dystonia 31 HP:0001332
4 spasticity 31 HP:0001257
5 dysarthria 31 HP:0001260
6 hyperreflexia 31 HP:0001347
7 dysphagia 31 HP:0002015
8 cerebral calcification 31 HP:0002514
9 visual impairment 31 HP:0000505
10 optic atrophy 31 HP:0000648
11 blindness 31 HP:0000618
12 abnormal electroretinogram 31 HP:0000512
13 myopia 31 HP:0000545
14 reduced visual acuity 31 HP:0007663
15 dementia 31 HP:0000726
16 mental deterioration 31 HP:0001268
17 generalized amyotrophy 31 HP:0003700
18 increased susceptibility to fractures 31 HP:0002659
19 progressive sensorineural hearing impairment 31 HP:0000408
20 cortical visual impairment 31 HP:0100704
21 abnormal posturing 31 HP:0002533
22 constriction of peripheral visual field 31 HP:0001133
23 postlingual sensorineural hearing impairment 31 HP:0008596
24 infantile sensorineural hearing impairment 31 HP:0008610

UMLS symptoms related to Mohr-Tranebjaerg Syndrome:


photophobia, tremor, muscle spasticity, dystonia

Drugs & Therapeutics for Mohr-Tranebjaerg Syndrome

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

Genetic Tests for Mohr-Tranebjaerg Syndrome

Genetic tests related to Mohr-Tranebjaerg Syndrome:

# Genetic test Affiliating Genes
1 Mohr-Tranebjaerg Syndrome 28 TIMM8A
2 Jensen Syndrome 28 TIMM8A

Anatomical Context for Mohr-Tranebjaerg Syndrome

MalaCards organs/tissues related to Mohr-Tranebjaerg Syndrome:

38
Testes, Brain, Bone

Publications for Mohr-Tranebjaerg Syndrome

Articles related to Mohr-Tranebjaerg Syndrome:

(show all 13)
# Title Authors Year
1
Progressive dystonia in Mohr-Tranebjaerg syndrome with cochlear implant and deep brain stimulation. ( 23801560 )
2013
2
The phenotypic spectrum of dystonia in Mohr-Tranebjaerg syndrome. ( 22736418 )
2012
3
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
4
Molecular genetics of a patient with Mohr-Tranebjaerg Syndrome due to a new mutation in the DDP1 gene. ( 17999202 )
2007
5
Blepharospasm and limb dystonia caused by Mohr-Tranebjaerg syndrome with a novel splice-site mutation in the deafness/dystonia peptide gene. ( 17534980 )
2007
6
Otopathology in Mohr-Tranebjaerg syndrome. ( 17471106 )
2007
7
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
8
Dystonia in the Mohr-Tranebjaerg syndrome responds to GABAergic substances. ( 15390009 )
2004
9
Focal dystonia caused by Mohr-Tranebjaerg syndrome with complete deletion of the DDP1 gene. ( 15037720 )
2004
10
Temporal bone histopathologic and genetic studies in Mohr-Tranebjaerg syndrome (DFN-1). ( 11449109 )
2001
11
A novel deafness/dystonia peptide gene mutation that causes dystonia in female carriers of Mohr-Tranebjaerg syndrome. ( 11601506 )
2001
12
X-linked recessive deafness-dystonia syndrome (Mohr-Tranebjaerg syndrome). ( 10868232 )
2000
13
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:

71
# Symbol AA change Variation ID SNP ID
1 TIMM8A p.Cys66Trp VAR_010237 rs80356560

ClinVar genetic disease variations for Mohr-Tranebjaerg Syndrome:

6
# 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.148_157delAAGCCTGGGC (p.Lys50Glnfs) deletion Pathogenic rs869320733 GRCh38 Chromosome X, 101346636: 101346645
3 TIMM8A NM_004085.3(TIMM8A): c.70G> T (p.Glu24Ter) single nucleotide variant Pathogenic rs111033631 GRCh37 Chromosome X, 100603583: 100603583
4 TIMM8A NM_004085.3(TIMM8A): c.198C> G (p.Cys66Trp) single nucleotide variant Pathogenic rs80356560 GRCh37 Chromosome X, 100601583: 100601583
5 TIMM8A NM_004085.3(TIMM8A): c.73delG (p.Val25Terfs) deletion Pathogenic rs869320665 GRCh37 Chromosome X, 100603580: 100603580
6 TIMM8A TIMM8A, DEL deletion Pathogenic
7 TIMM8A NM_004085.3(TIMM8A): c.238C> T (p.Arg80Ter) single nucleotide variant Pathogenic rs1054894 GRCh37 Chromosome X, 100601543: 100601543
8 TIMM8A NM_004085.3(TIMM8A): c.133-23A> C single nucleotide variant Pathogenic rs869320666 GRCh37 Chromosome X, 100601671: 100601671
9 TIMM8A NM_004085.3(TIMM8A): c.127delT (p.Cys43Valfs) deletion Pathogenic rs869320667 GRCh37 Chromosome X, 100603526: 100603526
10 TIMM8A NM_004085.3(TIMM8A): c.112C> T (p.Gln38Ter) single nucleotide variant Pathogenic rs80356559 GRCh37 Chromosome X, 100603541: 100603541

Expression for Mohr-Tranebjaerg Syndrome

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

Pathways for Mohr-Tranebjaerg Syndrome

GO Terms for Mohr-Tranebjaerg Syndrome

Sources for Mohr-Tranebjaerg Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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