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Deafness dystonia syndrome(MTS)

MedGen UID:
162903
Concept ID:
C0796074
Disease or Syndrome
Synonyms: DDON syndrome; Deafness syndrome, progressive, with blindness, dystonia, fractures, and mental deficiency; Deafness-dystonia-optic atrophy syndrome; Deafness-dystonia-optic neuronopathy (DDON) syndrome; Deafness-Dystonia-Optic Neuronopathy Syndrome; DYSTONIA-DEAFNESS SYNDROME, X-LINKED; Jensen syndrome; Mohr-Tranebjaerg syndrome; MTS; Nerve deafness optic nerve atrophy, and dementia; OPTICOACOUSTIC NERVE ATROPHY WITH DEMENTIA; Opticoacustic nerve atrophy with dementia; Syndrome of opticoacoustic nerve atrophy with dementia
SNOMED CT: Deafness-dystonia syndrome (702423009); Mohr-Tranebjaerg syndrome (702423009); Deafness-dystonia-optic neuronopathy syndrome (702423009)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): TIMM8A (Xq22.1)
 
Monarch Initiative: MONDO:0010578
OMIM®: 304700
Orphanet: ORPHA52368

Disease characteristics

Excerpted from the GeneReview: Deafness-Dystonia-Optic Neuronopathy Syndrome
Males with deafness-dystonia-optic neuronopathy (DDON) syndrome have prelingual or postlingual sensorineural hearing impairment in early childhood, slowly progressive dystonia or ataxia in the teens, slowly progressive decreased visual acuity from optic atrophy beginning at approximately age 20 years, and dementia beginning at approximately age 40 years. Psychiatric symptoms such as personality change and paranoia may appear in childhood and progress. The hearing impairment appears to be consistent in age of onset and progression, whereas the neurologic, visual, and neuropsychiatric signs vary in degree of severity and rate of progression. Females may have mild hearing impairment and focal dystonia. [from GeneReviews]
Authors:
Lisbeth Tranebjærg   view full author information

Additional descriptions

From OMIM
Mohr-Tranebjaerg syndrome (MTS) is characterized by early childhood onset of postlingual progressive sensorineural deafness followed by progressive dystonia, mental deterioration, cortical blindness, spasticity, and psychiatric manifestations (summary by Ujike et al., 2001).  http://www.omim.org/entry/304700
From MedlinePlus Genetics
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.

The first symptom of DDON syndrome is hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), which begins in early childhood. The hearing impairment worsens over time, and most affected individuals have profound hearing loss by age 10.

People with DDON syndrome typically begin to develop problems with movement during their teens, although the onset of these symptoms varies among affected individuals. Some people experience involuntary tensing of the muscles (dystonia), while others have difficulty coordinating movements (ataxia). The problems with movement usually worsen over time.

Individuals with DDON syndrome have normal vision during childhood, but they may develop vision problems due to breakdown of the nerves that carry information from the eyes to the brain (optic atrophy). Affected individuals can develop an increased sensitivity to light (photophobia) or other vision problems beginning in adolescence. Their sharpness of vision (visual acuity) slowly worsens, often leading to legal blindness in mid-adulthood.

People with this condition may also have behavior problems, including changes in personality and aggressive or paranoid behaviors. They also usually develop a gradual decline in thinking and reasoning abilities (dementia) in their forties. The lifespan of individuals with DDON syndrome depends on the severity of the disorder. People with severe cases have survived into their teenage years, while those with milder cases have lived into their sixties.  https://medlineplus.gov/genetics/condition/deafness-dystonia-optic-neuronopathy-syndrome

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Progressive sensorineural hearing impairment
MedGen UID:
335894
Concept ID:
C1843156
Disease or Syndrome
A progressive form of sensorineural hearing impairment.
Postlingual sensorineural hearing impairment
MedGen UID:
870217
Concept ID:
C4024654
Pathologic Function
A form of sensorineural hearing impairment with onset after the acquisition of speech.
Atypical behavior
MedGen UID:
14048
Concept ID:
C0004941
Sign or Symptom
Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Photophobia
MedGen UID:
43220
Concept ID:
C0085636
Sign or Symptom
Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Abnormal posturing
MedGen UID:
66660
Concept ID:
C0231471
Finding
Involuntary flexion or extension of the arms and legs.
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
Increased susceptibility to fractures
MedGen UID:
234655
Concept ID:
C1390474
Finding
An abnormally increased tendency to fractures of bones caused by an abnormal reduction in bone strength that is generally associated with an increased risk of fracture.
Intrinsic hand muscle atrophy
MedGen UID:
351202
Concept ID:
C1864716
Finding
Atrophy of the intrinsic muscle groups of the hand, comprising the thenar and hypothenar muscles; the interossei muscles; and the lumbrical muscles.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Constriction of peripheral visual field
MedGen UID:
68613
Concept ID:
C0235095
Finding
An absolute or relative decrease in retinal sensitivity extending from edge (periphery) of the visual field in a concentric pattern. The visual field is the area that is perceived simultaneously by a fixating eye.
Abnormal electroretinogram
MedGen UID:
96908
Concept ID:
C0476397
Finding
Any abnormality of the electrical responses of various cell types in the retina as measured by electroretinography.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Cerebral visual impairment
MedGen UID:
890568
Concept ID:
C4048268
Pathologic Function
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Deafness dystonia syndrome in Orphanet.

Professional guidelines

PubMed

Balint B, Bhatia KP
Curr Opin Neurol 2014 Aug;27(4):468-76. doi: 10.1097/WCO.0000000000000114. PMID: 24978640

Recent clinical studies

Etiology

Maas RR, Iwanicka-Pronicka K, Kalkan Ucar S, Alhaddad B, AlSayed M, Al-Owain MA, Al-Zaidan HI, Balasubramaniam S, Barić I, Bubshait DK, Burlina A, Christodoulou J, Chung WK, Colombo R, Darin N, Freisinger P, Garcia Silva MT, Grunewald S, Haack TB, van Hasselt PM, Hikmat O, Hörster F, Isohanni P, Ramzan K, Kovacs-Nagy R, Krumina Z, Martin-Hernandez E, Mayr JA, McClean P, De Meirleir L, Naess K, Ngu LH, Pajdowska M, Rahman S, Riordan G, Riley L, Roeben B, Rutsch F, Santer R, Schiff M, Seders M, Sequeira S, Sperl W, Staufner C, Synofzik M, Taylor RW, Trubicka J, Tsiakas K, Unal O, Wassmer E, Wedatilake Y, Wolff T, Prokisch H, Morava E, Pronicka E, Wevers RA, de Brouwer AP, Wortmann SB
Ann Neurol 2017 Dec;82(6):1004-1015. doi: 10.1002/ana.25110. PMID: 29205472Free PMC Article
Dulski J, Schinwelski M, Mandat T, Pienczk-Ręcławowicz K, Sławek J
Stereotact Funct Neurosurg 2016;94(2):123-5. Epub 2016 Apr 22 doi: 10.1159/000445078. PMID: 27100856
Balint B, Bhatia KP
Curr Opin Neurol 2014 Aug;27(4):468-76. doi: 10.1097/WCO.0000000000000114. PMID: 24978640
Kojovic M, Pareés I, Lampreia T, Pienczk-Reclawowicz K, Xiromerisiou G, Rubio-Agusti I, Kramberger M, Carecchio M, Alazami AM, Brancati F, Slawek J, Pirtosek Z, Valente EM, Alkuraya FS, Edwards MJ, Bhatia KP
Mov Disord 2013 Jun;28(6):795-803. Epub 2013 Feb 15 doi: 10.1002/mds.25394. PMID: 23418071
Németh AH
Brain 2002 Apr;125(Pt 4):695-721. doi: 10.1093/brain/awf090. PMID: 11912106

Diagnosis

Dulski J, Schinwelski M, Mandat T, Pienczk-Ręcławowicz K, Sławek J
Stereotact Funct Neurosurg 2016;94(2):123-5. Epub 2016 Apr 22 doi: 10.1159/000445078. PMID: 27100856
Balint B, Bhatia KP
Curr Opin Neurol 2014 Aug;27(4):468-76. doi: 10.1097/WCO.0000000000000114. PMID: 24978640
Blesa JR, Solano A, Briones P, Prieto-Ruiz JA, Hernández-Yago J, Coria F
Neuromolecular Med 2007;9(4):285-91. Epub 2007 Aug 3 doi: 10.1007/s12017-007-8000-3. PMID: 17999202
Roesch K, Hynds PJ, Varga R, Tranebjaerg L, Koehler CM
Hum Mol Genet 2004 Sep 15;13(18):2101-11. Epub 2004 Jul 14 doi: 10.1093/hmg/ddh217. PMID: 15254020
Tranebjaerg L, Jensen PK, Van Ghelue M, Vnencak-Jones CL, Sund S, Elgjo K, Jakobsen J, Lindal S, Warburg M, Fuglsang-Frederiksen A, Skullerud K
Ophthalmic Genet 2001 Dec;22(4):207-23. doi: 10.1076/opge.22.4.207.2220. PMID: 11803487

Prognosis

Maas RR, Iwanicka-Pronicka K, Kalkan Ucar S, Alhaddad B, AlSayed M, Al-Owain MA, Al-Zaidan HI, Balasubramaniam S, Barić I, Bubshait DK, Burlina A, Christodoulou J, Chung WK, Colombo R, Darin N, Freisinger P, Garcia Silva MT, Grunewald S, Haack TB, van Hasselt PM, Hikmat O, Hörster F, Isohanni P, Ramzan K, Kovacs-Nagy R, Krumina Z, Martin-Hernandez E, Mayr JA, McClean P, De Meirleir L, Naess K, Ngu LH, Pajdowska M, Rahman S, Riordan G, Riley L, Roeben B, Rutsch F, Santer R, Schiff M, Seders M, Sequeira S, Sperl W, Staufner C, Synofzik M, Taylor RW, Trubicka J, Tsiakas K, Unal O, Wassmer E, Wedatilake Y, Wolff T, Prokisch H, Morava E, Pronicka E, Wevers RA, de Brouwer AP, Wortmann SB
Ann Neurol 2017 Dec;82(6):1004-1015. doi: 10.1002/ana.25110. PMID: 29205472Free PMC Article
Dulski J, Schinwelski M, Mandat T, Pienczk-Ręcławowicz K, Sławek J
Stereotact Funct Neurosurg 2016;94(2):123-5. Epub 2016 Apr 22 doi: 10.1159/000445078. PMID: 27100856

Clinical prediction guides

Zazo Seco C, Castells-Nobau A, Joo SH, Schraders M, Foo JN, van der Voet M, Velan SS, Nijhof B, Oostrik J, de Vrieze E, Katana R, Mansoor A, Huynen M, Szklarczyk R, Oti M, Tranebjærg L, van Wijk E, Scheffer-de Gooyert JM, Siddique S, Baets J, de Jonghe P, Kazmi SA, Sadananthan SA, van de Warrenburg BP, Khor CC, Göpfert MC, Qamar R, Schenck A, Kremer H, Siddiqi S
Dis Model Mech 2017 Feb 1;10(2):105-118. Epub 2016 Dec 15 doi: 10.1242/dmm.026476. PMID: 28067622Free PMC Article
Dulski J, Schinwelski M, Mandat T, Pienczk-Ręcławowicz K, Sławek J
Stereotact Funct Neurosurg 2016;94(2):123-5. Epub 2016 Apr 22 doi: 10.1159/000445078. PMID: 27100856
Kojovic M, Pareés I, Lampreia T, Pienczk-Reclawowicz K, Xiromerisiou G, Rubio-Agusti I, Kramberger M, Carecchio M, Alazami AM, Brancati F, Slawek J, Pirtosek Z, Valente EM, Alkuraya FS, Edwards MJ, Bhatia KP
Mov Disord 2013 Jun;28(6):795-803. Epub 2013 Feb 15 doi: 10.1002/mds.25394. PMID: 23418071

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