Cerebellum neuropathology and motor skill deficits in fragile X syndrome
- 4 August 2022
- journal article
- review article
- Published by Wiley in International Journal of Developmental Neuroscience
- Vol. 82 (7), 557-568
- https://doi.org/10.1002/jdn.10217
Abstract
Fragile X syndrome (FXS) is a leading form of inherited intellectual disability and single-gene cause of autism spectrum disorder (ASD) and is characterized by core deficits in cognitive flexibility, sensory sensitivity, emotion, and social interactions. Motor deficits are a shared feature of FXS and autism. The cerebellum has emerged as one of the target brain areas affected by neurodevelopmental diseases. Alterations in the cerebellar structure, circuits, and function may be the key drivers of impaired fine and gross motor skills in FXS and fragile X-associated tremor/ataxia syndrome (FXTAS). In this review, we briefly examined recent findings in FXS and present a discussion on the literature supporting motor skill deficits in FXS. Subsequently, we focused on neuropathological alterations in the cerebellum in FXS and FXTAS. We highlight studies that have directly examined the function of fragile X mental retardation protein and related epigenetic variations in the cerebellum. Overall, we obtained considerable supporting evidence for the hypothesis that cerebellar dysfunction is evident in FXS and FXTAS; however, compared with studies on other ASD models, studies on motor skills related to fragile X disorders are particularly rare and inconclusive. Hence, future research should address FXS-related motor and behavioral trajectories and examine the underlying mechanisms at both the cell and circuit levels.Keywords
Funding Information
- National Natural Science Foundation of China (81870901, 82071272, 81771488)
This publication has 101 references indexed in Scilit:
- Consensus Paper: Pathological Role of the Cerebellum in AutismThe Cerebellum, 2012
- A voxel-based morphometry comparison of regional gray matter between fragile X syndrome and autismPsychiatry Research: Neuroimaging, 2009
- Incidence of Fragile X Syndrome by Newborn Screening for Methylated FMR1 DNAAmerican Journal of Human Genetics, 2009
- Penetrance of FMR1 premutation associated pathologies in fragile X syndrome familiesEuropean Journal of Human Genetics, 2009
- Morphometric Spatial Patterns Differentiating Boys With Fragile X Syndrome, Typically Developing Boys, and Developmentally Delayed Boys Aged 1 to 3 YearsArchives of General Psychiatry, 2008
- Prevalence and Instability of Fragile X AllelesObstetrics & Gynecology, 2008
- A computational neuroanatomy for motor controlExperimental Brain Research, 2008
- Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP)Annals of Neurology, 2007
- Deletion of FMR1 in Purkinje Cells Enhances Parallel Fiber LTD, Enlarges Spines, and Attenuates Cerebellar Eyelid Conditioning in Fragile X SyndromeNeuron, 2005
- Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndromeCell, 1991