Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP)
Article first published online: 11 OCT 2007
Copyright © 2007 American Neurological Association
Annals of Neurology
Volume 63, Issue 1, pages 40–51, January 2008
How to Cite
Gothelf, D., Furfaro, J. A., Hoeft, F., Eckert, M. A., Hall, S. S., O'Hara, R., Erba, H. W., Ringel, J., Hayashi, K. M., Patnaik, S., Golianu, B., Kraemer, H. C., Thompson, P. M., Piven, J. and Reiss, A. L. (2008), Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP). Ann Neurol., 63: 40–51. doi: 10.1002/ana.21243
- Issue published online: 29 JAN 2008
- Article first published online: 11 OCT 2007
- Manuscript Accepted: 28 AUG 2007
- Manuscript Revised: 27 AUG 2007
- Manuscript Received: 15 MAR 2007
- NIMH. Grant Numbers: MH50047, MH01142
- NICHD. Grant Number: HD31715
- Lynda and Scott Canel Fund for Fragile X Research
- NIBIB. Grant Number: EB01651
- NCRR. Grant Number: RR019771
- NARSAD Young Investigator Award
To determine how neuroanatomic variation in children and adolescents with fragile X syndrome is linked to reduced levels of the fragile X mental retardation-1 protein and to aberrant cognition and behavior.
This study included 84 children and adolescents with the fragile X full mutation and 72 typically developing control subjects matched for age and sex. Brain morphology was assessed with volumetric, voxel-based, and surface-based modeling approaches. Intelligence quotient was evaluated with standard cognitive testing, whereas abnormal behaviors were measured with the Autism Behavior Checklist and the Aberrant Behavior Checklist.
Significantly increased size of the caudate nucleus and decreased size of the posterior cerebellar vermis, amygdala, and superior temporal gyrus were present in the fragile X group. Subjects with fragile X also demonstrated an abnormal profile of cortical lobe volumes. A receiver operating characteristic analysis identified the combination of a large caudate with small posterior cerebellar vermis, amygdala, and superior temporal gyrus as distinguishing children with fragile X from control subjects with a high level of sensitivity and specificity. Large caudate and small posterior cerebellar vermis were associated with lower fragile X mental retardation protein levels and more pronounced cognitive deficits and aberrant behaviors.
Abnormal development of specific brain regions characterizes a neuroanatomic phenotype associated with fragile X syndrome and may mediate the effects of FMR1 gene mutations on the cognitive and behavioral features of the disorder. Fragile X syndrome provides a model for elucidating critical linkages among gene, brain, and cognition in children with serious neurodevelopmental disorders. Ann Neurol 2007