Autosomal dominant dystonia-plus with cerebral calcifications.

Area of Science:

• Neurology
• Genetics
• Radiology

Background:

• A Canadian family with dystonia and brain calcinosis was initially described in 1985.
• Further investigation was needed to characterize the phenotype and genetics of this kindred.

Purpose of the Study:

• To comprehensively report updated genealogic, clinical, imaging, neuropathologic, and genetic data.
• To investigate the underlying causes of dystonia and brain calcinosis in this family.

Main Methods:

• Expanded family tree analysis to 166 individuals.
• Clinical examinations, head CT and PET scans, and blood sample analysis.
• Neuropathologic examination via autopsy in one affected individual.

Main Results:

• Dystonia onset averaged 19 years, with varied types and additional neurological signs observed.
• Brain calcinosis was present in all affected and some at-risk individuals.
• PET scans showed reduced dopamine receptor binding and tracer uptake; autopsy revealed extensive calcium deposits without specific immunohistochemistry findings.
• Genome search excluded linkage to known dystonia and brain calcification loci (IBGC1, DYT1, DYT12).

Conclusions:

• The family exhibits a dystonia-plus syndrome with heterogeneous brain calcification.
• Calcification severity and distribution do not fully explain the clinical presentation.
• The etiology of this disorder remains elusive, necessitating further research into this heterogeneous group.