Fragile X syndrome -- from genes to cognition

Dev Disabil Res Rev. 2009;15(4):333-42. doi: 10.1002/ddrr.80.

Abstract

Fragile X syndrome (FXS), a single gene disorder with an expanded CGG allele on the X chromosome, is the most common form of inherited cognitive impairment. The cognitive deficit ranges from mild learning disabilities to severe intellectual disability. The phenotype includes hyperactivity, short attention span, emotional problems including anxiety, social avoidance, poor eye contact, and hyperarousal to sensory stimuli. Imaging studies in FXS have clarified the impact of the FMR1 mutation on brain development and function by documenting structural abnormalities, predominantly in the caudate nucleus and cerebellum, and functional deficits in the caudate, frontal-striatal circuits, and the limbic system. On the basis of current research results, a targeted treatment for FXS will be available in the near future. Currently, a number of psychopharmacological agents are helpful in treating many of the problems in FXS including hyperactivity, attention deficits, anxiety, episodic aggression, and hyperarousal. Although the targeted treatments aim at strengthening synaptic connections, it is essential that these treatments are combined with learning programs that address the cognitive deficits in FXS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aggression / psychology
  • Alleles
  • Anxiety Disorders / epidemiology
  • Anxiety Disorders / psychology
  • Brain / anatomy & histology
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Syndrome / epidemiology*
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / therapy
  • Humans
  • Intellectual Disability / epidemiology*
  • Intellectual Disability / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Mental Disorders / epidemiology
  • Phenotype
  • Pilot Projects
  • Point Mutation / genetics
  • Pyridines / therapeutic use
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Social Behavior
  • Telomere

Substances

  • Excitatory Amino Acid Antagonists
  • FMR1 protein, human
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Fragile X Mental Retardation Protein
  • 6-methyl-2-(phenylethynyl)pyridine