The phenotypic spectrum of dystonia in Mohr-Tranebjaerg syndrome.
Mohr-Tranebjaerg syndrome (MTS) is an X-linked recessive disorder characterized by deafness and dystonia. However the phenotypic expression of dystonia has not been systematically defined. We report clinical, neurophysiological, and ophthalmological data on 6 subjects from 3 Australian kindreds, including 2 with novel mutations, together with a systematic review of the literature, in order to define the phenotypic expression of dystonia. Profound hearing impairment in affected males develops by infancy and precedes the development of dystonia, which varies in time of onset from the first to the sixth decades, with a peak in the second and third decades. Dystonia in MTS tends to be focal, segmental, or multifocal in distribution at onset, with a predilection for the upper body, variably involving the head, neck, and upper limbs. The majority of patients have progression or generalization of their dystonia regardless of age of onset. Within our 3 kindreds, we observed relative intrafamilial homogeneity but interfamilial variation. The median time to the development of moderate-severely disabling dystonia in these subjects was 11 years. Associated features included progressive cognitive decline, pyramidal signs, and in 1 patient, gait freezing and postural instability. Optic atrophy and cortical visual impairment were both observed. We report for the first time a female patient who developed multiple disabling neurological complications of MTS. Our findings more clearly define and expand the phenotype of both the dystonia and other neurological features of MTS and have implications for the diagnosis and management of this condition.
Movement Disorders Unit, Department of Neurology, Westmead Hospital, Sydney, NSW 2145, Australia.
Ainhi D
AD
Ha
Kaitlyn L
KL
Parratt
Nanna D
ND
Rendtorff
Marianne
M
Lodahl
Karl
K
Ng
Dominic B
DB
Rowe
Carolyn M
CM
Sue
Michael W
MW
Hayes
Lisbeth
L
Tranebjaerg
Victor S C
VS
Fung
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001315:Australia; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology; D054062:Deaf-Blind Disorders / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D018450:Disease Progression; D004421:Dystonia / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D005073:Evoked Potentials, Somatosensory; D005074:Evoked Potentials, Visual; D005091:Exons; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D007438:Introns; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009154:Mutation; D009483:Neuropsychological Tests; D009896:Optic Atrophy / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D010375:Pedigree; D012727:Sex Characteristics; D055815:Young Adult
D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C118122:TIMM8A protein, human