Background and objectives

Given the nature of FMR1 gene expansions, most biological mothers, and often multiple other family members of children with fragile X syndrome (FXS), will have a premutation, which may increase individual and family vulnerabilities. This article summarizes important gaps in knowledge and notes potential implications for pediatric providers with regard to developmental and medical risks for children and adolescents with an FMR1 premutation, including possible implications into adulthood.

Methods

A structured electronic literature search was conducted on FMR1 pre- and full mutations, yielding a total of 306 articles examined. Of these, 116 focused primarily on the premutation and are included in this review.

Results

Based on the literature review, 5 topic areas are discussed: genetics and epidemiology; phenotypic characteristics of individuals with the premutation; implications for carrier parents of children with FXS; implications for the extended family; and implications for pediatricians.

Conclusions

Although the premutation phenotype is typically less severe in clinical presentation than in FXS, premutation carriers are much more common and are therefore more likely to be seen in a typical pediatric practice. In addition, there is a wide range of medical, cognitive/developmental, and psychiatric associated features that individuals with a premutation are at increased risk for having, which underscores the importance of awareness on the part of pediatricians in identifying and monitoring premutation carriers and recognizing the impact this identification may have on family members.