Pathophysiology
IBZM single-photon emission computed tomography (SPECT) revealed distinct reduced post-synaptic tracer uptake in the caudate nucleus and putamen, with longer disease duration associated with lower binding ratios [PMID:28236370].
An intronic A-to-C substitution (IVS1-23A>C) in the DDP1 gene was identified in affected individuals, suggesting that such mutations may lead to disease through potential splicing alterations [PMID:15710860].
Unlike previous cases where microdeletions were identified, this study identifies a novel DDP gene mutation (arg80ter) as the genetic cause in a non-white population, reinforcing the DDP gene's role in DDS [PMID:11405816].
Neuropathological examination revealed a mosaic pattern of neuronal loss and gliosis specifically in the caudate and putamen, indicating involvement of basal ganglia [PMID:9539345].
Epidemiology
This study reports the first non-white family with X-linked DDS, involving 5 affected males across 4 generations, expanding the known demographic range of the syndrome [PMID:11405816].
Pedigree analysis suggests an X-linked inheritance pattern, affecting males across two generations [PMID:9539345].
Clinical Presentation
All patients were men suffering from severe, disabling segmental or generalized dystonia and had varying degrees of parkinsonism [PMID:28236370].
Affected family members presented with early-onset deafness followed by progressive dystonia in adulthood, differing from previous reports by the absence of visual disturbances [PMID:11405816].
The syndrome manifests with early-onset deafness and progressive dystonia affecting males exclusively over successive generations, alongside cognitive impairment and corticospinal tract involvement [PMID:9539345].
Diagnosis
All subjects showed slightly reduced FP-CIT uptake values compared to controls, ranging from -37% to -41%, potentially indicating basal ganglia volume loss [PMID:28236370].
Genetic screening beyond the coding regions revealed an intronic mutation present in affected males but not in unaffected family members or controls, highlighting the importance of comprehensive genetic testing [PMID:15710860].
Differential Diagnosis
The identification of an intronic mutation in DDP1 in a family with X-linked inheritance pattern underscores the need to consider this syndrome in differential diagnoses for similar clinical presentations [PMID:15710860].
References
1 Brüggemann N, Rosales RL, Waugh JL, Blood AJ, Domingo A, Heldmann M et al.. Striatal dysfunction in X-linked dystonia-parkinsonism is associated with disease progression. European journal of neurology 2017. link 2 Ezquerra M, Campdelacreu J, Muñoz E, Tolosa E, Martí MJ. A novel intronic mutation in the DDP1 gene in a family with X-linked dystonia-deafness syndrome. Archives of neurology 2005. link 3 Ujike H, Tanabe Y, Takehisa Y, Hayabara T, Kuroda S. A family with X-linked dystonia-deafness syndrome with a novel mutation of the DDP gene. Archives of neurology 2001. link 4 Hayes MW, Ouvrier RA, Evans W, Somerville E, Morris JG. X-linked Dystonia-Deafness syndrome. Movement disorders : official journal of the Movement Disorder Society 1998. link