Mohr-Tranebjaerg syndrome. Deafness-dystonia-optic atrophy syndrome.
Incidence
The syndrome is familial and is transmitted as an X-linked recessive trait linked to the long arm of chromosome X (Xq22). MTS is a very rare disorder and prevalence figures do not exist.
Clinical Characteristics
It is a syndrome of deafness, visual impairment leading to blindness, dystonia, multiple fractures, and mental retardation without other clinical manifestations. Mohr-Tranebjaerg syndrome (MTS) (formerly DFN-1) is an X-linked neurodegenerative syndrome characterized by prelingual or postlingual sensorineural hearing loss, progressive dystonia and visual impairment. In addition, psychiatric symptoms, cognitive impairment and behavioral problems may appear. Early-onset deafness is the only obligatory symptom; all other clinical signs vary in degree of severity and clinical course. A multifocal and progressive neurodegeneration affecting distinct areas of the CNS is typically found in patients suffering from MTS. MTS is a very rare disorder and prevalence figures do not exist. Underlying genetic defects are found in the TIMM8A/DDP1 gene located on chromosome Xq22. Most of the mutations described so far are inactivating mutations such as stop mutations, insertions and deletions. Only two missense mutations were reported: one affects the ATG start codon (M1I), the other changes a highly conserved cysteine residue (C66W). Both mutations result in complete loss of the TIMM8A/DDP1 gene product. The DDP1/TIMM8A encodes a small polypeptide of 97 amino acid residues, the deafness-dystonia peptide 1 (DDP1). Functional studies revealed that DDP1 locates to mitochondria, the ``power houses'' of the cell, and acts during the import for nuclear-encoded preproteins into the mitochondrial inner membrane. Loss of DDP1 therefore leads to impairment of specific mitochondrial functions and, subsequently, to degeneration of neuronal cells. As with other mitochondrial disorders, a satisfying therapeutic concept is missing for MTS.
Precipitants
None
Provocation Tests
None
Diagnostic Procedures
DNA testing. Caused by mutations in the deafness/dystonia-1 gene (TIMM8A)