Familial Brain Calcifications With Leukoencephalopathy: A Novel PDGFB Variant

Abstract

Objective: To describe a family with primary familial brain calcifications (PFBCs) and leukoencephalopathy associated with a novel variant in PDGFB.

Methods: We present 3 generations of a family with PFBC associated with a previously unreported variant in PDGFB.

Results: A 24-year-old woman with migraine, bipolar disorder, and functional neurologic disorder was found to have bilateral calcifications of the basal ganglia and frontally predominant periventricular white matter disease. Her father had mild cognitive impairment and action tremor of the hands with basal ganglia and cerebellar calcifications found incidentally on head CT. Her paternal grandmother had severe parkinsonism and dementia with calcifications of the basal ganglia and cerebellum and diffuse, confluent periventricular white matter disease. Genetic testing in both the proband and her father revealed a PDGFB variant (NM_002608.3:c.298C>T:p.Arg100Cys) not reported in publicly available databases. Multiple in silico analysis tools support pathogenicity.

Discussion: Our report identifies a novel PDGFB variant associated with PFBC and highlights the rare association of leukoencephalopathy with PDGFB-associated PFBC.

Figure. Pedigree and Patient Images

(A) Family tree with symptomatology and genetic testing were available. Neurologic symptoms were present in the proband's father, paternal grandmother, paternal great-uncle, and paternal great-grandmother. (B) Proband MRI and CT with bilenticular calcification, TCS = 5. (C) CT scan of the proband's father, TCS = 45. (D) MRI and CT scan of the proband's paternal grandmother, TCS = 53. TCS = total calcification score (range 0–80).