We present a 71-year-old woman who suffered from dysarthria and a progressive movement disorder with prominent dystonia, on-setting at age 10. CT scans during adulthood demonstrated extensive symmetric calcification of the basal ganglia, thalamus, cerebellum, cerebral white matter and cortex. Biochemical studies, including serum calcium, phosphate and iron levels were normal. Towards the end of her life, she experienced depression, but remained mentally intact. Many other members of her large Canadian family suffered from a similar dystonia-plus syndrome associated with cerebral calcification.
Post mortem examination demonstrated extensive calcification of the brain parenchyma and blood vessels, ranging from small calcospherites to large solid concretions. Recently, whole-genome sequencing identified a ~563 kb genomic deletion on chromosome 8 affecting multiple genes, including SLC20A2 and TAHP1, that segregated with disease in the family. SLC20A2 encodes a type III sodium–dependent phosphate transporter and loss-of-function mutations were recently identified as an important cause of familial and sporadic idiopathic basal ganglia calcification that may be associated with a variety of neuropsychiatric and motor syndromes. In addition, loss-of-function mutations in TAHP1 are known to cause a variety of dystonia syndromes. Therefore, it is believed that brain calcinosis in this family is related to the deletion of SLC20A2, while the TAHP1 deletion likely contributes to the early onset dystonia phenotype.
Conflictsof Interest:
None.
