Mohr-Tranebjaerg syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: DDS
MTS
DDP
Dystonia-deafness syndrome
Deafness-dystonia-optic atrophy syndrome
Deafness syndrome, progressive, with blindness, dystonia, fractures, and mental defiency
Deafness - dystonia - optic neuronopathy syndrome
DDON syndrome
Number of Symptoms 50
OrphanetNr: 52368
OMIM Id: 304700
ICD-10: G31.8
UMLs: C0796074
MeSH: C535808
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: > 91 cases [Orphanet]
Inheritance: X-linked recessive
X-linked
22736418 [IBIS]
Age of onset: All ages
22736418 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic neurodegenerative disease
 -Rare genetic disease
Mitochondrial disease with eye involvement
 -Rare eye disease
 -Rare genetic disease
Mitochondrial protein import disorder
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease
Rare neurodegenerative disease
 -Rare neurologic disease
Syndromic genetic deafness
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare otorhinolaryngologic disease
X-linked recessive optic atrophy
 -Rare eye disease
 -Rare genetic disease
X-linked syndromic intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Mohr–Tranebjaerg syndrome (MTS), or deafness–dystonia–optic neuronopathy (DDON) syndrome, is an X-linked recessive disorder resulting from loss-of-function mutations in the nuclear-encoded deafness dystonia peptide 1 (DDP1) / translocase of mitochondrial inner membrane 8A (TIMM8A) gene, located at Xq22.1 (PMID:22736418). The unique association of deafness, spasticity, dystonia, ataxia, mental retardation, neuropathy, hip fractures, and progressive visual disability leading to blindness is strikingly similar in all affected, but with considerable variations in severity (PMID:7643352).

Symptom Information: Sort by abundance 

1
(HPO:0000648) Optic atrophy 22736418 IBIS 238 / 7739
2
(HPO:0000512) Abnormal electroretinogram 9017058 IBIS 61 / 7739
3
(HPO:0000488) Retinopathy 7643352 IBIS 75 / 7739
4
(HPO:0000649) Abnormality of visual evoked potentials 22736418 IBIS 34 / 7739
5
(HPO:0000613) Photophobia 7643352 IBIS 158 / 7739
6
(HPO:0001133) Constriction of peripheral visual field 7643352 IBIS 33 / 7739
7
(HPO:0000603) Central scotoma 7643352 IBIS 18 / 7739
8
(HPO:0000505) Visual impairment Very frequent [IBIS] 100% (n=10) 7643352 IBIS 297 / 7739
9
(HPO:0100704) Cortical visual impairment 22736418 IBIS 28 / 7739
10
(HPO:0007663) Reduced visual acuity 7643352 IBIS 100 / 7739
11
(HPO:0000529) Progressive visual loss 7643352 IBIS 54 / 7739
12
(HPO:0002448) Progressive encephalopathy 7643352 IBIS 6 / 7739
13
(HPO:0001347) Hyperreflexia 7643352 IBIS 363 / 7739
14
(HPO:0001257) Spasticity Very frequent [IBIS] 100% (n=10) 7643352 IBIS 251 / 7739
15
(HPO:0002179) Opisthotonus 7643352 IBIS 35 / 7739
16
(HPO:0000473) Torticollis 22736418 IBIS 42 / 7739
17
(HPO:0000643) Blepharospasm 22736418 IBIS 20 / 7739
18
(HPO:0001332) Dystonia Frequent [IBIS] 60% (n=10) 7643352 IBIS 197 / 7739
19
(HPO:0004373) Focal dystonia 22736418 IBIS 9 / 7739
20
(HPO:0012179) Craniofacial dystonia 22736418 IBIS 4 / 7739
21
(HPO:0007325) Generalized dystonia 22736418 IBIS 7 / 7739
22
(HPO:0002451) Limb dystonia 22736418 IBIS 16 / 7739
23
(HPO:0000708) Behavioral abnormality 7643352 IBIS 212 / 7739
24
(HPO:0000711) Restlessness 7643352 IBIS 18 / 7739
25
(HPO:0000718) Aggressive behavior 7643352 IBIS 109 / 7739
26
(HPO:0000739) Anxiety 7643352 IBIS 67 / 7739
27
(HPO:0001260) Dysarthria 7643352 IBIS 329 / 7739
28
(HPO:0001268) Mental deterioration 7643352 IBIS 88 / 7739
29
(HPO:0001249) Intellectual disability 9017058 IBIS 1089 / 7739
30
(HPO:0000737) Irritability 7643352 IBIS 93 / 7739
31
(HPO:0000709) Psychosis 7643352 IBIS 61 / 7739
32
(HPO:0002533) Abnormal posturing 22736418 IBIS 6 / 7739
33
(HPO:0001337) Tremor 22736418 IBIS 200 / 7739
34
(HPO:0002015) Dysphagia 7643352 IBIS 301 / 7739
35
(HPO:0007377) Abnormality of somatosensory evoked potentials 22736418 IBIS 2 / 7739
36
(HPO:0002650) Scoliosis 7643352 IBIS 705 / 7739
37
(HPO:0002659) Increased susceptibility to fractures 7643352 IBIS 110 / 7739
38
(HPO:0002757) Recurrent fractures Frequent [IBIS] 60% (n=10) 7643352 IBIS 47 / 7739
39
(HPO:0008596) Postlingual sensorineural hearing impairment 7643352 IBIS 2 / 7739
40
(HPO:0000408) Progressive sensorineural hearing impairment 7643352 IBIS 28 / 7739
41
(HPO:0000365) Hearing impairment Very frequent [IBIS] 100% (n=10) 7643352 IBIS 539 / 7739
42
(HPO:0001730) Progressive hearing impairment 7643352 IBIS 29 / 7739
43
(HPO:0012105) Occipital cortical atrophy 22736418 IBIS 1 / 7739
44
(HPO:0003676) Progressive disorder 7643352 IBIS 148 / 7739
45
(MedDRA:10017076) Fracture 7643352 IBIS 18 / 7739
46
(MedDRA:10017322) Fractures 7643352 IBIS 18 / 7739
47
(MedDRA:10070920) Visual cortex atrophy 22736418 IBIS 1 / 7739
48
(MedDRA:10061411) Visual pathway disorder 22736418 IBIS 2 / 7739
49
(OMIM) Retinal dysfunction 7643352 IBIS 2 / 7739
50
(OMIM) Sensorineural deafness, postlingual, progressive 7643352 IBIS 1 / 7739

Associated genes:

TIMM8A;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Mohr and Mageroy (1960) described a family in which males in 4 generations were affected with a progressive form of deafness. Sufficient hearing was present at first such that speech developed normally, then deteriorated. Impaired hearing first became ...
Molecular genetics OMIM Using positional information from a patient with sensorineural deafness and dystonia and a 21-kb deletion in Xq22, Jin et al. (1996) characterized a novel transcript lying within the deletion as a candidate for the complex syndrome of Mohr ...
Diagnosis GeneReviews The deafness-dystonia-optic neuronopathy (DDON) syndrome occurs as either a single-gene disorder resulting from mutation in TIMM8A or a contiguous gene deletion syndrome at Xq22....
Clinical Description GeneReviews Deafness-dystonia-optic neuronopathy (DDON) syndrome is a progressive disorder with prelingual or postlingual sensorineural hearing impairment in early childhood. The hearing impairment is always the presenting symptom. Typically, the disease is associated with slowly progressive dystonia or ataxia in the teens, slowly progressive decreased visual acuity from approximately age 20 years, and dementia from approximately age 40 years. Psychiatric symptoms such as personality change and paranoia may appear in childhood and progress. The deafness and blindness severely compromise communication in late adulthood....
Genotype-Phenotype Correlations GeneReviews The limited number of affected individuals, the extremely variable clinical course, and the family-specific nature of each mutation identified limits detection of genotype-phenotype correlations. It is noteworthy that the clinical features in individuals with a contiguous gene deletion and in individuals with smaller mutations are indistinguishable, apart from presence or absence of agammaglobulinemia [Tranebjaerg 2012]. Female probands have been reported [Swerdlow & Wooten 2001, Klempir et al 2010, Ha et al 2012]....
Differential Diagnosis GeneReviews Specific disorders that share features with deafness-dystonia-optic neuronopathy (DDON) syndrome ...
Management GeneReviews To establish the extent of disease and needs in an individual diagnosed with deafness-dystonia-optic neuronopathy (DDON) syndrome, the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....