White matter involvement in a family with a novel PDGFB mutation

Abstract

Primary familial brain calcification (PFBC) (formerly idiopathic basal ganglia calcification; Fahr disease) is an autosomal dominant cerebral microvascular calcifying disorder with variable clinical and imaging features.(1) Four causative genes have been identified: SLC20A2,(2) PDGFRB,(3) PDGFB,(4) and XPR1.(5).

Figure 1. Overview of the genetic and MRI data of the family and skin biopsy findings of individual III-5

(A) Pedigree and segregation analysis of PDGFB mutation. Individuals who underwent exome sequencing are indicated by arrows. PDGFB genotypes are reported under the symbols (wt, normal allele; mut, c.3G>C). (B) Case IV-2 (age 5 years): axial FLAIR brain MRI images demonstrate focal confluent areas of white matter hyperintensity in the frontal and parietal lobes associated with small cystic lesions (arrowheads). (C) Case IV-1 (age 22 years): coronal FLAIR images reveal similar focal confluent areas of white matter hyperintensity associated with small cystic lesions in the frontoparietal regions (arrowheads). (D) Case III-2 (age 44 years): axial T2-weighted images show confluent calcifications of lenticular, caudate, and pulvinar nuclei associated with multiple patchy hyperintensities of the periventricular and subcortical supratentorial white matter. (E) Case II-2 (age 73 years): coronal FLAIR images reveal scattered foci of white matter hyperintensity in the frontal and insular regions. (F) Case III-5 (age 42 years): axial FLAIR images reveal diffuse and patchy hyperintensities of the periventricular white matter with prevalent involvement of the frontal regions. (G) Electron microscopy of skin biopsy of individual III-5 showing an endothelial cell with areas of membrane fragmentation (arrowhead) and focal interruption (arrow) (magnification ×3,000). (H) High-resolution electron microscopy image of skin biopsy of individual III-5 showing basement membrane with thickened and fragmented areas (asterisks) (magnification ×7,000); EC = endothelial cell; FLAIR = fluid-attenuated inversion recovery; L = lumen.