Objective: Describe a family with brain calcifications related to new pathogenic variant of SLC20A2 gene.

Background: Three genes are associated with the rare occurrence of autosomal dominant primary familial basal ganglia calcification (PFBC): SLC20A2, PDGFRB, and PDGFB.  Nearly half of families with PFBC have been identified to have a mutation in the SLC20A2 gene, and it is unclear how many families might have mutations in the other two genes.  For families who clearly do have PFBC, there is a 95% penetrance for presence of calcifications on brain imaging and a 70% penetrance for clinical symptoms by the age of 50.

Methods: Case report and literature review

Results: A 59 year old woman presented with abnormal scalp and limb sensations, headaches, fatigue, anxiety, cognitive complaints, and clumsiness of 9 month duration.  Exam showed slight weakness on the right, mild rigidity and bradykinesia, more on the left, subtle chorea of the hand and foot intermittently when trying to perform other motor tasks, mild action/postural tremor, mild gait ataxia, decreased sensation on the left.   Workup for secondary causes was negative.  MRI and CT scans confirmed symmetric calcifications in the globus pallidus, putamen, caudate nucleus, and thalami bilaterally.  Subsequently obtained brain CT scan of mother (asymptomatic) showed a similar pattern of calcifications, prompting genetic workup. A variant was found in the SLC20A2 gene, c.935-2 A>G that has not been seen at the testing lab nor documented previously; it occurs in a splice site preceding an exon, and is therefore highly suspicious to be pathogenic.  Further testing of other family members revealed similar calcifications in brain, carotid vessels, and testicles (first son, asymptomatic); calcifications in carotids, heart, femoral arteries (second son, history of MI age 35), workup pending in other sibling.

Further testing on the patient revealed diffuse atheroclerotic calcifications of the vasculature.  Further testing of other family members revealed calcifications in brain, carotid vessels, and testicles (first son, asymptomatic); calcifications in carotids, heart, femoral arteries (second son, history of MI age 35), with workup pending in other siblings. 

Conclusions: PFBC is likely under-reported; only through follow-through investigation of other family members can the genetic diagnosis be suspected and discovered. 

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MDS Abstracts - https://www.mdsabstracts.org/abstract/familial-idiopathic-basal-ganglia-calcification-with-novel-slc20a2-gene-variant/