Details of Disease

General Information of Disease (ID: DIS0480U)

• Disease Name: Deafness dystonia syndrome
• Synonyms: MOHR-Tranebjaerg syndrome; DDP; MTS; deafness syndrome, progressive, with blindness, dystonia, fractures, and mental deficiency; deafness - dystonia - optic neuronopathy syndrome; deafness-Dystonia-optic atrophy syndrome; deafness-dystonia-optic neuronopathy (DDON) syndrome; dystonia-deafness syndrome; deafness dystonia optic neuronopathy syndrome; deafness dystonia syndrome; deafness-dystonia-optic neuronopathy syndrome; deafness dystonia optic atrophy syndrome; DDON syndrome; Mohr-Tranebjaerg syndrome, X-linked recessive; dystonia deafness syndrome; Mohr-Tranebjaerg syndrome; deafness dystonia optic neuronopathy syndrome (DDON)
• Definition: 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.
• Disease Hierarchy:
  DISPN7D2: Inherited neurodegenerative disorder
  DIS0480U: Deafness dystonia syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0010578
  MESH ID: C535808
  UMLS CUI: C0796074
  OMIM ID: 304700
  MedGen ID: 162903
  Orphanet ID: 52368
  SNOMED CT ID: 702423009

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
STK38	TT27XFN	Limited	Genetic Variation	[1]
MLH1	TTISG27	Strong	Biomarker	[2]
MRC1	TTKV8W5	Strong	Biomarker	[3]
MSH2	TTCAWRT	Strong	Biomarker	[2]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
KCNK2	DTENHUP	Limited	Altered Expression	[4]

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DCAF17	OTFNVJLN	Limited	Genetic Variation	[5]
DNAJC19	OTLA1V91	Limited	Biomarker	[6]
HEMGN	OTZPYUOY	Limited	Genetic Variation	[1]
MYH1	OT8YBDOT	Limited	Genetic Variation	[7]
PEBP4	OTKDCVC6	Limited	Altered Expression	[8]
TIMM23	OTAAS85T	Limited	Altered Expression	[9]
TIMM8B	OTGZO1MT	Limited	Biomarker	[10]
FITM2	OTED0W1S	Strong	Genetic Variation	[11]
MSH6	OT46FP09	Strong	Biomarker	[2]
POTEF	OTV3WXYE	Strong	Genetic Variation	[12]
TIMM8A	OTDX9687	Definitive	X-linked	[13]

References

• [1] Prognostic factors in patients with mesial temporal lobe epilepsy.Epilepsia. 2009 Jan;50 Suppl 1:41-4. doi: 10.1111/j.1528-1167.2008.01969.x.
• [2] Sebaceous Carcinoma Treated With Mohs Micrographic Surgery.Dermatol Surg. 2017 Feb;43(2):281-286. doi: 10.1097/DSS.0000000000000943.
• [3] Prevalence and molecular characteristics of DNA mismatch repair protein-deficient sebaceous neoplasms and keratoacanthomas in a Japanese hospital-based population.Jpn J Clin Oncol. 2018 Jun 1;48(6):514-521. doi: 10.1093/jjco/hyy055.
• [4] Pharmacologically reversible, loss of function mutations in the TM2 and TM4 inner pore helices of TREK-1 K2P channels.Sci Rep. 2019 Aug 27;9(1):12394. doi: 10.1038/s41598-019-48855-1.
• [5] The syndrome of deafness-dystonia: clinical and genetic heterogeneity.Mov Disord. 2013 Jun;28(6):795-803. doi: 10.1002/mds.25394. Epub 2013 Feb 15.
• [6] Underappreciated Roles of the Translocase of the Outer and Inner Mitochondrial Membrane Protein Complexes in Human Disease.DNA Cell Biol. 2019 Jan;38(1):23-40. doi: 10.1089/dna.2018.4292. Epub 2018 Nov 27.
• [7] An individual with Muir-Torre syndrome found to have a pathogenic MSH6 gene mutation.Fam Cancer. 2007;6(3):317-21. doi: 10.1007/s10689-007-9119-y. Epub 2007 Feb 24.
• [8] Downregulation of PEBP4, a target of miR-34a, sensitizes drug-resistant lung cancer cells.Tumour Biol. 2014 Oct;35(10):10341-9. doi: 10.1007/s13277-014-2284-3. Epub 2014 Jul 21.
• [9] Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex.Hum Mol Genet. 2002 Mar 1;11(5):477-86. doi: 10.1093/hmg/11.5.477.
• [10] Novel mutations in the SDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss.Genes Chromosomes Cancer. 2001 Jul;31(3):255-63. doi: 10.1002/gcc.1142.
• [11] A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy. Dis Model Mech. 2017 Feb 1;10(2):105-118. doi: 10.1242/dmm.026476. Epub 2016 Dec 15.
• [12] Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation.J Neurodev Disord. 2018 May 22;10(1):17. doi: 10.1186/s11689-018-9235-z.
• [13] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.