P364 Female fragile X premutation carriers do exhibit subclinical neurological signs

Abstract

Objective Premutation of fragile X mental retardation 1 gene is known to cause fragile X associated tremor ataxia syndrome in males at 50–60 years of age, and fragile X associated primary ovarian insufficiency (FXPOI) in females at around 40. Females rarely exhibit tremor/ataxia. The exact molecular pathomechanism of FXPOI is unknown. Our aim was to perform a systematic study on tremor, eye movements and neuropsychological performance in female Fragile X (FraX) premutation carriers. Methods We have examined 13 young female premutation carriers (mean age 38 years) with/without FXPOI. Tremor (resting, postural, intentional, kinetic) was recorded with an accelerometry-based test system. Electrooculography (EOG) system was used for qualitative and quantitative analysis of eye movements. Neuropsychological assessment was performed with a complex battery including Montreal Cognitive Assessment, Rey auditory verbal learning test, Rey Complex Figure Test, and Wisconsin Card Sorting Test. Results We could detect cerebellar tremor in only 1/13 case. Saccadic smooth pursuit eye movements and decreased velocity of the horizontal reflexive saccades were recorded in 6/11 females with valid EOG. Neuropsychology tests showed impaired verbal memory and visuo-spatial memory with preserved visuo-spatial perception. Tests showed neither impairments in the executive functions, nor decrease of general intelligence. Discussion Objective neurophysiological methods are needed to reveal neurological signs of female premutation carriers. Conclusions Female FraX premutation carriers might exhibit subclinical neurological signs at young age. Significance To best of our knowledge, this is the first quantitative study on eye movements of female FraX premutation carriers. Our study provides new insight into movement disorders of female premutation carriers.