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Abstract Details

C9orf72 Mutation Mimicking Early Onset Alzheimer’s Disease with Prodromal Photosensitive Seizures and Low TDP-43 Pathology: Two Case Reports
Aging, Dementia, and Behavioral Neurology
P5 - Poster Session 5 (11:45 AM-12:45 PM)
13-011

To report two cases of c9orf72-frontotemporal lobar degeneration (FLTD) with atypical clinicopathologic presentation.

Hexanucleotide repeat expansion in the c9orf72 gene commonly presents as frontotemporal dementia and/or amyotrophic lateral sclerosis and is characterized by TDP-43 and p62 pathologic inclusions.

N/A

We present two cases (daughter and father) who developed early-onset (age 48 and 52, respectively) cognitive deterioration with early executive dysfunction, resulting in termination from work due to poor work performance; visuospatial deficits, leading to getting lost in familiar/unfamiliar places and driving cessation; and episodic memory impairment, causing financial issues and impaired household management. They later presented with prominent behavioral symptoms, including emotional lability, anxiety, depression, aggression, apathy, wandering behavior, insomnia, paranoid delusions and repetitive motor movements, along with dynamic aphasia, ataxia and parkinsonism. Clinically, they were suspected to have early-onset AD. Neuroimaging (MRI/CT) showed generalized brain atrophy. Electroencephalogram revealed exaggerated photoparoxysmal response. The daughter did develop focal to bilateral tonic-clonic seizures triggered by sunlight at age 45 (prior to cognitive decline). Both died after a long disease duration (15 and 23 years respectively from onset of cognitive symptoms). Postmortem neuropathological evaluation showing neuronal loss and gliosis in superficial cortical layers of the neocortex with hippocampal sclerosis. AD neuropathologic changes were low. Immunohistochemistry performed on the daughter’s brain showed scarce TDP-43 pathology, mostly limited in the amygdala and hippocampus, rare in the neocortex and none in the brainstem or cerebellum; and abundant and widespread p62-positive inclusions in the neocortex, amygdala, hippocampus, basal ganglia and cerebellum. Genetic testing confirmed a pathogenic c9orf72 gene variant, confirming the diagnosis of c9orf72-FTLD.

C9orf72-FLTD can clinically mimic early-onset AD dementia and present with prodromal adult-onset seizures with exaggerated photoparoxysmal response and pathologically show more widespread and abundant p62 pathology than TDP-43 pathology. Genetic testing for c9orf72 mutation should be considered in patients with similar clinicopathologic features.

Authors/Disclosures
Arenn Faye Carlos, MD (Nebraska Medical Center (UNMC))
PRESENTER
The institution of Dr. Carlos has received research support from 好色先生.
Jie Chen, MD, PhD Dr. Chen has nothing to disclose.
Daniel L. Murman, MD, FAAN (University of Nebraska Medical Center) The institution of Dr. Murman has received research support from Biogen. The institution of Dr. Murman has received research support from EIP Pharma. The institution of Dr. Murman has received research support from Eli Lilly & Co.. The institution of Dr. Murman has received research support from Functional Neuromodulation. The institution of Dr. Murman has received research support from Roche Pharmaceuticals.