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A Rare MED13 Variant as the Potential Cause of Early Onset Cognitive Decline and Brain Iron Accumulation: A Case Report (P5-6.002)
Abstract   Peer reviewed

A Rare MED13 Variant as the Potential Cause of Early Onset Cognitive Decline and Brain Iron Accumulation: A Case Report (P5-6.002)

Kaancan Deniz, Tiffany Grider, Chad Grueter and Joel Geerling
Neurology, Vol.98(18_supplement)
05/03/2022
DOI: 10.1212/WNL.98.18_supplement.809

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Abstract

Objective: To identify a rare genetic variant as a potential cause of iron deposition in deep brain nuclei in an adult patient with progressive cognitive and behavioral decline as well as bilateral, early-onset cataracts atop baseline mild intellectual disability. Background: MED13 variants have previously been described in pediatric patients as the cause of a complex of neurodevelopmental symptoms including developmental delay, language deficits, Autism-spectrum disorders, attention-deficit disorders, and congenital cardiac abnormalities. None of the prior studies have shown an index case with adult-onset cognitive decline, bilateral cataracts and MRI susceptibility signal suggesting brain iron accumulation. Design/Methods: NA Results: We report a 45-year-old woman with history of mild intellectual disability, ADHD, early adult-onset cataracts. Her mother requested evaluation in the neurology clinic due to progressive cognitive decline and behavioral symptoms involving forgetfulness, executive dysfunction, apraxia, and neuropsychiatric symptoms. Brain MRI was notable for hypointense (dark) susceptibility signal throughout the globus pallidi, substantia nigra and cerebellar dentate nuclei. There was no cerebral atrophy except for possible, mild bi-parietal cortical volume loss. An initial screening panel for genes previously linked to brain iron accumulation did not reveal any clinically significant mutations, but exome sequencing identified a rare MED13 variant (c.979C>T, p.Pro327Ser). This variant was previously reported as a cause of mild intellectual disability and neurodevelopmental delay in a child. This is the first adult case of a patient with this MED13 variant presenting with early-onset dementia, behavioral changes, bilateral cataracts, and brain iron accumulation. Conclusions: MED13 variant (c.979C>T, p.Pro327Ser) was previously reported in pediatric cases with autism spectrum disorder and mild intellectual disability. None of the prior reports included a case with early adult-onset cataracts, progressive cognitive decline, neuropsychiatric symptoms, and SWI changes on brain MRI suggesting a neurodegenerative process with brain iron accumulation (NBIA). This case could further expand the phenotypic spectrum of this MED13 variant.

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