Mohr–Tranebjærg syndrome (MTS) is a rare X-linked recessive syndrome also known as deafness–dystonia syndrome and caused by mutation in the

TIMM8A Mitochondrial import inner membrane translocase subunit Tim8 A, also known as deafness-dystonia peptide or protein is an enzyme that in humans is encoded by the ''TIMM8A'' gene. This translocase has similarity to yeast mitochondrial proteins that ...

gene. It is characterized by clinical manifestations commencing with early childhood onset hearing loss, followed by adolescent onset progressive or , visual impairment from early adulthood onwards and dementia from the 4th decade onwards. The severity of the symptoms may vary, but they progress usually to severe

deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is writte ...

and

dystonia Dystonia is a neurology, neurological Hyperkinesia, hyperkinetic Movement disorders, movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed po ...

and sometimes are accompanied by cortical deterioration of

vision Vision, Visions, or The Vision may refer to: Perception Optical perception * Visual perception, the sense of sight * Visual system, the physical mechanism of eyesight * Computer vision, a field dealing with how computers can be made to gain und ...

and mental deterioration.

Signs and symptoms

Mohr-Tranebjærg is characterized by a variety of symptoms affecting hearing loss. In the span of a subject with Mohr-Tranebjærg, by the age of early childhood, around 18 months, the development of quickly progressive prelingual or postlingual sensorineural hearing loss. The presence of auditory symptoms is characterized by preserved oto-acoustic emissions, abnormal auditory brain stem response, poor speech, and worsening in auditory symptoms even with auditory devices. Also, neuropsychological manifestations, possibly consisting of personality changes, paranoia, and mild intellectual deficit could emerge. During adolescence, there is a possibility that a slowly progressive movement disorder, similar to gegenhalten, dystonia, or ataxia could develop. Patients with Mohr-Tranebjærg experience reduced visual acuity, photophobia, acquired color vision defect and central scotomas developing at around 20 years of age, and leading to more severe blindness by age 30 or 40. 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. Individuals with Mohr Tranebjærg 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.

Genetics

This condition is caused by mutations in the TIMM8A gene. This gene is located on the long arm of

X chromosome The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...

(Xq22). The protein encoded by this gene localizes to the intermembrane space in mitochondria where it functions in the import of nuclear encoded proteins into the mitochondrial inner membrane. How this produces the clinical picture is not yet clear. The pattern of inheritance is X-linked recessive. Where the female is a carrier, male offspring have a 50 percent chance of inheriting the disease and female offspring have a 50 percent chance of being a carrier. Where the male is affected, male offspring do not inherit the pathogenic mutation and females are obligate carriers. TIMM8A is also referred to as DDP. Koehler determined the function of the DDP gene and concluded that the Mohr-Tranebjaerg syndrome is a novel type of mitochondrial disease that is most likely caused by a defective mitochondrial protein-import system.

Diagnosis

A 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 diagnosis

This is long and includes *

Arts syndrome Arts syndrome is a rare metabolic disorder that causes serious neurological problems in males due to a malfunction of the PRPP synthetase 1 enzyme. Arts syndrome is part of a spectrum of PRPS-1 related disorders with reduced activity of the enzym ...

Autosomal recessive nonsyndromic sensorineural deafness An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosomes i ...

type DFNB *

Friedreich ataxia Friedreich's ataxia (FRDA) is a rare, inherited, autosomal recessive neurodegenerative disorder that primarily affects the nervous system, causing progressive damage to the spinal cord, peripheral nerves, and cerebellum, leading to impaired ...

MELAS syndrome MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes) is one of the family of mitochondrial diseases, which also include MIDD (maternally inherited diabetes and deafness), MERRF syndrome, and Leber's hereditary opti ...

Mitochondrial DNA depletion syndrome Mitochondrial DNA depletion syndrome (MDS or MDDS), or Alper's disease, is any of a group of autosomal recessive disorders that cause a significant drop in mitochondrial DNA in affected tissues. Symptoms can be any combination of myopathic, hep ...

(encephalomyopathic form with methylmalonic aciduria) *

McLeod neuroacanthocytosis syndrome McLeod may refer to: * McLeod (surname) * Clan MacLeod, a Highland Scottish clan associated with the Isle of Skye Places Canada * McLeod (Edmonton), a residential neighbourhood in Edmonton, Canada * Rural Municipality of McLeod No. 185, Saskatch ...

Pendred syndrome Pendred syndrome is a genetic disorder leading to congenital bilateral (both sides) sensorineural hearing loss and goitre with euthyroid or mild hypothyroidism (decreased thyroid gland function). There is no specific treatment, other than supporti ...

Usher syndrome Usher syndrome, also known as Hallgren syndrome, Usher–Hallgren syndrome, retinitis pigmentosa–dysacusis syndrome or dystrophia retinae dysacusis syndrome, is a rare genetic disorder caused by a mutation in any one of at least 11 genes result ...

type 1 and 2 *

Wolfram syndrome Wolfram syndrome, also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare autosomal-recessive genetic disorder that causes childhood-onset diabetes mellitus, optic atrophy, and deafness as well as vario ...

X-linked spinocerebellar ataxia Sex linkage describes the sex-specific patterns of inheritance and expression when a gene is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). Genes situated on the X-chromosome are thus termed X-linked, and ar ...

type 3 and 4

Treatment

Symptomatic Treatment

The treatment for Mohr-Tranebjærg vary depending on the symptoms and the evolution of these symptoms over time. Since hearing loss is prevalent in those with Mohr-Tranebjærg, hearing aids, devices, or cochlear implants are considered for increasingly serious cases.

Immunoglobin

In those patients with secondary complications from the syndrome, intravenous immunoglobin may act to prevent infections in X-linked agammaglobulinemia, an inherited immune system disorder that can reduce the ability to fight infections. Similarly, those with XLA should avoid live viral vaccines. Patients that reach adulthood should seek regular evaluations from a neurologist to test the advancement of possible dementia and psychiatric manifestations

Genetic Counseling

Since the pattern of inheritance for Mohr-Tranebjærg is known to be X-linked recessive, genetic counseling is considered beneficial to families with known carriers. In the case that a female is a carrier, the statistical risk of male offspring inheriting the disease is 50%, while the probability that a female offspring will be a carrier is 50%. However, when a male is the carrier, the probability of having a female carrier offspring is 100%, and male offspring will not have any chance of inheriting the syndrome. Because of the statistical probabilities that each sex inherits the syndrome, males are affected by Mohr-Tranebjærg more frequently than females are. Females who carry one copy of the TIMM8A gene (described in Genetics) are usually unaffected, however, may develop mild hearing loss and dystonia.

Prognosis

Prognosis 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.

History

This condition was first described in 1960.

Epidemiology

Mohr-Tranebjærg syndrome (MTS) prevalence is unknown. More than 90 cases (in 37 families) are known, but not all cases have been reported in the literature.

References

External links

GeneReviews/NCBI/NIH/UW entry on Deafness–Dystonia–Optic Neuronopathy Syndrome

MTS
— a page at NIH website {{DEFAULTSORT:Mohr-Tranebjaerg syndrome Extrapyramidal and movement disorders Syndromes affecting hearing