Vertical supranuclear gaze palsy in Primary Familial Brain Calcification associated with a novel SLC20A2 mutation (P14-11.003)

Abstract

<h3>Objective:</h3> We herein describe a patient with Primary Familial Brain Calcification secondary to a novel solute carrier family 20 member 2 (<i>SLC20A2</i>) gene mutation presenting with vertical supranuclear gaze palsy (VSGP). <h3>Background:</h3> The spectrum of clinical features associated with PFBC remains broad. Despite considerable clinical heterogeneity, motor abnormalities including parkinsonism, tremor, and speech disturbances have been frequently described in these cases. VSGP has been rarely documented and is posited to arise from calcification-related disruptions of the basal ganglia pathways, specifically those linking the caudate and midbrain. <h3>Design/Methods:</h3> Not applicable. <h3>Results:</h3> This 74-year-old Chinese woman with a negative relevant family history presented with a six-year history of parkinsonism, frequent falls, speech disturbances and VSGP on examination that failed to respond to levodopa/carbidopa. Non-contrast computed tomography revealed abnormal calcium deposition in the bilateral lentiform nuclei, dentate nuclei, occipital subcortical white matter, and right caudate head. Blood investigations including calcium, magnesium, phosphate, alkaline phosphatase, and thyroid and parathyroid hormone levels were normal. A Parkinson’s disease gene panel revealed a heterozygous missense likely pathogenic <i>SLC20A2</i> variant ((c.625del) p. (Val209Phefs*7)) that creates a shift in the reading frame. <h3>Conclusions:</h3> VSGP has been reported in only eight patients with diffuse brain calcification, four diagnosed with PFBC. The increasing number of reported individuals with PSP-like features raises the possibility of this syndrome being a PFBC-associated phenotype, which may arise from inherent PFBC pathophysiological mechanisms irrespective of the causative gene. Given the recent evidence, it is possible that the downstream effects of PFBC pathology including neurovascular unit compromise and neurotoxic astrocytic responses contribute to disruptions in pathways in or projecting to the midbrain, resulting in this patient’s clinical expression. Further work is needed to fully characterize the gaze abnormalities and clinical spectrum of PFBC. Our work also highlights the importance of having oculomotor assessments well documented in future reports of patients with PFBC. <b>Disclosure:</b> Dr. Reyes has nothing to disclose. Dr. Lang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie, Acorda, AFFiRis, Biogen, Denali, Janssen, Intracellular, Kallyope, Lundbeck, Paladin, Retrophin, Roche, Sun Pharma, Theravance, and Corticobasal Degeneration Solutions, Sun Pharma, Medichem, Medtronic, AbbVie and Sunovion. The institution of Dr. Lang has received research support from AbbVie. Dr. Lang has received publishing royalties from a publication relating to health care.