Case Report: Association of a Variant of Unknown Significance in the FIG4 Gene With Frontotemporal Dementia and Slowly Progressing Motoneuron Disease: A Case Report Depicting Common Challenges in Clinical and Genetic Diagnostics of Rare Neuropsychiatric and Neurologic Disorders

• DOI: 10.3389/fnins.2020.559670
• Publication Date: 2020-12-22T05:14:58Z
• Authors: Caroline Gertrud ...; Christiane Michae...; Claudia Funke; Saskia Biskup; Philipp von Gottberg; Claudia Bartels; Jan Christoph Koch; Katrin Radenbach
• Keywords: Frontotemporal lobar degeneration; Primary progressive aphasia; Cognitive Decline; Semantic dementia

Background Modern genetics have in many ways revolutionized clinical routine and have, for instance, shown that formerly distinct disease entities relate to common pathogenic mutations. One such example is the connection between dementia amyotrophic lateral sclerosis (ALS) a continuous spectrum affirmed by discovery of shared Case Report We describe new variant FIG4 gene patient with slowly progressing frontotemporal (FTD) probable primary (PLS). The initially showed depressive symptoms global cognitive deficits. Severe difficulties language hallucinations became clearer as progressed. Nuclear medicine imaging cerebrospinal fluid (CSF) biomarkers were not specific defined categories dementia, but neuropsychological testing features finally led an allocation syndrome non-fluent progressive aphasia (nfv PPA). Because increasing limb weakness bulbar symptoms, motoneuron form PLS was diagnosed, strongly supported elevated CSF neurofilament electrophysiologic assessments. detected described or likely databases reported once literature. While phenotype our fits description -associated literature, we consider present VUS this case. Conclusion FTD PLS. Mutations been associated ALS PLS; however, exact mutation patients before. case illustrates generic diagnostic challenges presenting genetic variants offer explanation otherwise uncommon symptom combinations yet are unknown significance.