Objective: To describe clinical and radiological features of a Spanish family with Primary Familial Brain Calcification (PFBC) and genetic results of the index case.

Background: PFBC is a rare neurological disorder due to bilateral calcifications in the brain with genetic confirmation and autosomal dominant pattern of inheritance. Calcifications are frequently located in the basal ganglia followed by subcortical white matter, cerebellum and thalamus. Clinical presentation is heterogeneous with a variety of neuropsychiatric symptoms such as parkinsonism, dystonia, cerebellar symptoms, cognitive impairment, migraine, seizures, mood disorders or psychosis. Mutations in the Solute Carrier Family 20 Phosphate Transporter (SLC20A2) are the most frequently described. SLC20A2 encodes the inorganic phosphate transporter PiT-2 which is implicated in phosphate homeostasis in different tissues including the brain. Platelet Derived Growth Factor Receptor Beta (PDGFRB), Platelet  Derived Growth Factor Subunit Beta (PDGFB) and Xenotropic and Polytropic Retrovirus Receptor 1 (XPR1) have also been linked to PFBC.

Methods: Case reports. Genetic analysis of SLC20A2, PDGFRB and PDGFB genes by next generation-sequencing (NGS) in the index case. CT scan of some unaffected family members.

Results: The index case is a 35-year-old man with early-onset parkinsonism who began with an akinetic-rigid syndrome in the right limbs three years ago. The CT scan showed extensive brain calcification in basal ganglia, thalamus, cerebellum and subcortical white matter (figure 1). Secondary causes of basal ganglia calcification were ruled out and genetic analysis of SLC20A2, PDGFRB and PDGFB genes were done by NGS. We found a heterozygous mutation c.370G>A (p.Gly124Arg) in the SLC20A2 gene. Two asymptomatic family members of the maternal way had brain calcification in CT scan. Mother’s index case had bilateral brain calcification in basal ganglia, cerebellum and subcortical white matter while in another case CT scan showed minimal brain calcium deposition in basal ganglia (figure 2). Genetic analysis of asymptomatic family members is still underway.

Conclusions: We have identified a Spanish PFBC family. Our results show heterogeneous clinical phenotype with more severe disease in the index case with SLC20A2 variant and clinically unaffected family members albeit having calcifications in the CT scan.

References: Tadic V, Westenberger A, Domingo A, et al. Primary Familial Brain Calcification with known gene mutations. A systematic review and challenges of phenotypic characterization. JAMA Neurol 2105;72(4):460-467.

Lemos R, Ramos E, Legati A, et al. Update and Mutational Analysis of SLC20A2: a major cause of Primary Familial Brain Calcification. Hum Mutat 2015;36(5):489-495.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/spanish-primary-familial-brain-calcification-caused-by-slc20a2-mutation/