A Novel Mutation in PDGFRB in a Patient with Primary Familial Brain Calcification: Case Report (P2-12.005)

Objective:

To describe a case of primary familial brain calcification with a novel variant in the PDGFRB gene.

Background:

Fahr's disease, or primary familial brain calcification (PFBC), is a rare genetic neurologic disease characterized by abnormal calcification in the basal ganglia, subcortical white matter and cerebellum. Common clinical features include parkinsonism, neuropsychiatric symptoms, and cognitive decline. Genes implicated in Fahr's disease include PDGFB, PDGFRB, SLC20A2, XPR1, MYORG and JAM2.

Design/Methods:

Case Report.

Results:

We present the case of a 51-year-old woman with systemic lupus erythematosus who developed subacute cognitive and behavioral changes, parkinsonism and extensive bilateral calcifications in the basal ganglia, subcortical white matter, and cerebellum on neuroimaging. Family history was significant for a paternal aunt with parkinsonism at age of 50, for whom an autopsy was not done. Neuropsychological testing demonstrated a frontal-subcortical pattern of impairment including abnormal processing speed, executive dysfunction, and apathy. Normal parathyroid hormone and calcium levels in the patient's serum ruled out hypoparathyroidism or pseudohypoparathyroidism as causes for the intracranial calcifications. Whole exome sequencing detected a missense mutation in the PDGFRB gene resulting in a p.Arg919Gln substitution in the tyrosine kinase domain of PDGFRB protein, confirming the diagnosis of PFBC.

Conclusions:

This case demonstrates the importance of genetic screening in patients with clinical and neuroimaging features of Fahr's disease. Uncovering the genetic basis of disease in patients with PFBC is key to understand its pathogenesis and potentially developing targeted therapies. Disclosure: Dr. Al Ali has nothing to disclose. Miss Yang has nothing to disclose. Mr. Phillips has nothing to disclose. Joseph Fink has nothing to disclose. Dr. Mastrianni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CVS Caremark. Dr. Mastrianni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. The institution of Dr. Mastrianni has received research support from Brain Research Foundation. The institution of Dr. Seibert has received research support from Retirement Research Foundation. The institution of Dr. Seibert has received research support from Center for Healthcare Delivery Science and Innovation.