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Fragile X gene expression evident in white matter during infancy

Study results showed that the effects of fragile X gene expression on the development of connectivity in white matter brain structures are well-established when a child is as young as 6 months old.

“To our knowledge, there are no published data to date on the development of white matter fiber tracts in [fragile X syndrome] during infancy,” Meghan R. Swanson, PhD, Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, and colleagues wrote. “It is during this period that the clinical phenotype of [fragile X syndrome] is typically first observed, when expression of [fragile X retardation protein] is most crucial to the development of neural architecture, and when postnatal alterations in axonal plasticity may affect connectivity and functional specialization.”

Researchers analyzed longitudinal behavioral and brain imaging data from 27 infants with fragile X syndrome and 73 typically developing infants without family history of intellectual or psychiatric disorders to compare the development of white matter across three visits at age 6, 12 and 24 months. Swanson and colleagues assessed 19 major white matter pathways and compared diffusion parameters — such as fractional anisotropy — between the groups. In a subsequent analysis, they examined differences in the fiber pathways associated with verbal and nonverbal development measures.

Analysis revealed significant differences in the development of 12 of 19 white matter fiber pathways between the 27 infants with fragile X syndrome and those in the control group, which were uniformly characterized by lower fractional anisotropy during the 6- to 24-month age period. Specifically, the investigators observed lower fractional anisotropy in bilateral subcortical-frontal, occipital-temporal, temporal-frontal and cerebellar-thalamic tracts, along with four of six subdivisions of the corpus callosum in the infants with fragile X syndrome relative to typically developing infants.

The results also indicated that lower fractional anisotropy was present and stable from age 6 months in children with fragile X syndrome for all 12 white matter pathways, according to the authors. In addition, lower fractional anisotropy measures in the uncinate fasciculi were linked with lower nonverbal developmental quotient in children with fragile X syndrome (left uncinate, P = .03; right uncinate, P = .004).

“The results of this study highlight white matter as a potential target for early intervention,” Swanson and colleagues wrote in JAMA Psychiatry. “Most children with [fragile X syndrome] are not diagnosed in the first year of life. Achieving the goal of infant intervention for [fragile X syndrome], including intervention targeting early developing white matter, would likely require expanded efforts to screen newborns.” – by Savannah Demko

Disclosures: The authors report no relevant financial disclosures.