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Genetics Home Reference: your guide to understanding genetic conditions
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Deafness-dystonia-optic neuronopathy syndrome

Reviewed September 2008

What is deafness-dystonia-optic neuronopathy syndrome?

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 begin to develop an increased sensitivity to light (photophobia) or other vision problems during their teens. These people often have a slowly progressive reduction in the sharpness of vision (visual acuity) and become legally blind 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.

How common is deafness-dystonia-optic neuronopathy syndrome?

DDON syndrome is a rare disorder; it has been reported in fewer than 70 people worldwide.

What genes are related to deafness-dystonia-optic neuronopathy syndrome?

Mutations in the TIMM8A gene cause DDON syndrome. The protein produced from this gene is found inside the energy-producing centers of cells (mitochondria). The TIMM8A protein forms a complex (a group of proteins that work together) with a very similar protein called TIMM13. This complex functions by transporting other proteins within the mitochondria.

Most mutations in the TIMM8A gene result in the absence of functional TIMM8A protein inside the mitochondria, which prevents the formation of the TIMM8A/TIMM13 complex. Researchers believe that the lack of this complex leads to abnormal protein transport, although it is unclear how abnormal protein transport affects the function of the mitochondria and causes the signs and symptoms of DDON syndrome.

Related Gene(s)

Changes in this gene are associated with deafness-dystonia-optic neuronopathy syndrome.

  • TIMM8A

How do people inherit deafness-dystonia-optic neuronopathy syndrome?

DDON syndrome is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause DDON syndrome. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females who carry one altered copy of the TIMM8A gene are typically unaffected; however, they may develop mild hearing loss and dystonia. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Where can I find information about diagnosis or management of deafness-dystonia-optic neuronopathy syndrome?

These resources address the diagnosis or management of deafness-dystonia-optic neuronopathy syndrome and may include treatment providers.

  • Gene Review: Deafness-Dystonia-Optic Neuronopathy Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1216/)
  • Genetic Testing Registry: Mohr-Tranebjaerg syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0796074)

You might also find information on the diagnosis or management of deafness-dystonia-optic neuronopathy syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/deafness-dystonia-optic-neuronopathy-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/deafness-dystonia-optic-neuronopathy-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about deafness-dystonia-optic neuronopathy syndrome?

You may find the following resources about deafness-dystonia-optic neuronopathy syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for deafness-dystonia-optic neuronopathy syndrome?

  • Deafness-dystonia syndrome
  • Mohr-Tranebjærg syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about deafness-dystonia-optic neuronopathy syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding deafness-dystonia-optic neuronopathy syndrome?

ataxia ; cell ; chromosome ; dementia ; dystonia ; gene ; inheritance ; involuntary ; mitochondria ; mutation ; photophobia ; protein ; recessive ; sensitivity ; sensorineural ; sensorineural hearing loss ; sex chromosomes ; symptom ; syndrome ; teenage ; visual acuity ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Bahmad F Jr, Merchant SN, Nadol JB Jr, Tranebjaerg L. Otopathology in Mohr-Tranebjaerg syndrome. Laryngoscope. 2007 Jul;117(7):1202-8. (http://www.ncbi.nlm.nih.gov/pubmed/17471106?dopt=Abstract)
  • Binder J, Hofmann S, Kreisel S, Wöhrle JC, Bäzner H, Krauss JK, Hennerici MG, Bauer MF. Clinical and molecular findings in a patient with a novel mutation in the deafness-dystonia peptide (DDP1) gene. Brain. 2003 Aug;126(Pt 8):1814-20. Epub 2003 Jun 4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12805099?dopt=Abstract)
  • Gene Review: Deafness-Dystonia-Optic Neuronopathy Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1216/)
  • OMIM: MOHR-TRANEBJAERG SYNDROME (http://omim.org/entry/304700)
  • Roesch K, Curran SP, Tranebjaerg L, Koehler CM. 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. (http://www.ncbi.nlm.nih.gov/pubmed/11875042?dopt=Abstract)
  • Tranebjaerg L, Schwartz C, Eriksen H, Andreasson S, Ponjavic V, Dahl A, Stevenson RE, May M, Arena F, Barker D, et al. A new X linked recessive deafness syndrome with blindness, dystonia, fractures, and mental deficiency is linked to Xq22. J Med Genet. 1995 Apr;32(4):257-63. (http://www.ncbi.nlm.nih.gov/pubmed/7643352?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2008
Published: April 21, 2014