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Abstract Details

PSEN1 Mutation Presenting as Isolated Hereditary Spastic Paraplegia
Neuromuscular and Clinical Neurophysiology (EMG)
P5 - Poster Session 5 (11:45 AM-12:45 PM)
9-018
This case describes a patient who presented with myelopathy concerning for hereditary spastic paraplegia (HSP) and was found to have a pathogenic mutation in PSEN1.
HSP is a genetically heterogenous condition presenting typically with slowly progressive gait changes and myelopathic findings.  Mutations in PSEN1 are associated with familial early-onset Alzheimer’s disease (EOAD), although presentations with preceding HSP are described, as well.
NA
A 34-year old male presented to our neuromuscular clinic with 6 months of progressive bilateral lower extremity weakness. The patient had no developmental delay or family history of neurologic disease.  The examination was notable for a spastic gait and hyperreflexia. Structural imaging of the spinal cord was normal, and HSP was suspected.  A next generation sequencing panel for causes of HSP was unrevealing. Subsequently, whole exome sequencing (WES) revealed a pathogenic mutation in the PSEN1 gene (L381V). To date, the patient’s gait abnormality has progressed but his memory and cognition remain intact.

This report presents an illustrative case of a presenilin-1 mutation presenting with isolated spastic paraplegia. Denovo L381V mutations in the PSEN1 gene have been reported in individuals presenting with spastic paraplegia and followed by EOAD as early as the third decade of life. Given the high penetrance of PSEN1-associated EOAD, the patient will likely develop dementia. This case study illustrates both the yield and challenges of using broad genetic testing such as WES in clinical practice. The results of this patient’s WES demonstrated that they were at risk of a more severe neurodegenerative disease, and demanded intensive genetic counseling and support to the patient and family.
Authors/Disclosures
Jessica Joyce
PRESENTER 		Ms. Joyce has nothing to disclose.
Richard Dineen (RUSH University Medical Center) Richard Dineen has nothing to disclose.
Ryan D. Jacobson, MD Dr. Jacobson has nothing to disclose.