As part of our commitment to keep you informed on research findings, we provide a summary of the latest research results, including why they’re important to the Fragile X community and our analysis of the next steps. You can also subscribe to receive these by email.
Authors: Anne C. Wheeler, Angela Gwaltney, Melissa Raspa, Katherine C. Okoniewski, Elizabeth Berry-Kravis, Kelly N. Botteron, Dejan Budimirovic, Heather Cody Hazlett, David Hessl, Molly Losh, Gary E. Martin, Susan M. Rivera, Jane E. Roberts & Donald B. Bailey
Summary
Background, Methods & Results
FMR1 mutations result when CGG repeats on the FMR1 gene expand to over 54 repeats; those with 55–200 repeats have the premutation and those with >200 have the full mutation or Fragile X syndrome (FXS). Children with FMR1 gene expansions experience a variety of developmental challenges, including FXS. Even though there has been a lot of research on premutation and full mutation Fragile X, there are gaps in the knowledge about when and how symptoms begin and what development looks like in the early years of life. Typically children do not receive a Fragile X diagnosis until 3–5 years old, which contributes to that gap in knowledge. In this summary, FMR1 gene mutation is an umbrella term that includes children with the premutation and full mutation FXS. If a finding is specific to either children with the premutation or full mutation FXS, that will be specified.
This study, led by RTI International, aimed to understand more about the early years of life with an FMR1 gene mutation. The study team encompassed eight different research teams who had completed over 1,000 developmental assessments on 500 children under the age of 5 with FMR1 gene mutations. This developmental assessment, the Mullen Scales of Early Learning, assesses how toddlers and preschoolers are developing in different areas, including language, motor skills, and other thinking abilities. The study team used linear mixed modeling — which helps researchers track how scores change over time, even when not everyone had the same number of assessments conducted — to explore the developmental paths of children with FMR1 gene mutations and how they may differ from children who do not have FMR1 gene mutations.
The research team found that boys with full mutation FXS showed delays in early learning, motor skills, and language development as young as 6 months old. Girls with full mutation FXS showed delays in gross motor skills and expressive language by their first birthday. Both boys and girls with full mutation FXS were delayed on all developmental domains by their second birthday. This is important because those noticeable delays are occurring much earlier than when children typically receive their FXS diagnosis. This study suggested that children with full mutation FXS continued to gain skills over the first five years of their life at around half the rate of their peers without FXS. Girls with full mutation FXS showed growth at around three-quarters of the rate of their typically developing peers. Although children with a premutation were mostly typical in their developmental profiles and trajectories, mild but significant motor delays were found in boys by the age of 3.
Why This Matters
The findings suggest that noticeable developmental delays are occurring much earlier than when children typically receive their FXS diagnosis. Understanding the early presentation of FXS is critical to children receiving access to medical and non-medical interventions early in their life. These findings help clinicians and family members understand what to expect in the early years of life with an FMR1 gene mutation, empowering them to seek interventions that may give their child the best possible quality of life.
This study also contributes to the body of knowledge that suggests there may be a motor phenotype associated with having the premutation. A phenotype is a physical or observable characteristic that is a result of the person’s genes, like your eye color.
Next Steps
This publication speaks to the necessity of early identification of FXS. Early identification of FXS leads to earlier, effective medical and non-medical interventions. Improving quality of life for individuals with FXS and their family is always a good thing!
FOR MORE DETAILS VISIT:
Emergence of Developmental Delay in Infants and Toddlers With an FMR1 Mutation
Acknowledgements/Funding: Data collection for the eight studies that contributed Mullen data was primarily funded by various NIH grants. The preparation of the paper was funded by the John Merck Fund.
more research results
The effect of college degree attainment on neurodegenerative symptoms in genetically at-risk women
Researchers at the University of Wisconsin explored the relationship between obtaining a college degree and the manifestation of the neurodegenerative symptoms of FXTAS among women at elevated genetic risk.
Fragile X-associated tremor/ataxia syndrome rating scale: Revision and content validity using a mixed method approach
Researchers across several institutions set out to develop a revised version of the FXTAS-RS designed to specifically assess FXTAS motor signs.
FMR1 CGG Repeats and Stress Influence Self-Reported Cognitive Functioning in Mothers
Researchers at the University of Wisconsin looked at the relationship and influence of FMR1 CGG repeats and stress on self-reported cognitive functioning in mothers.
The diagnostic experience of women with fragile X–associated primary ovarian insufficiency (FXPOI)
Researchers at Emory University conducted qualitative interviews with 24 women with FXPOI exploring how FMR1 screening, physician education, and supportive care impacted their experience receiving a diagnosis. Their results are in!
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Featured photo by Igordoon Primus on Unsplash