Emergence of Developmental Delay in Infants and Toddlers With an <i>FMR1</i> Mutation.

Abstract

Children with <i>FMR1</i> gene expansions are known to experience a range of developmental challenges, including fragile X syndrome. However, little is known about early development and symptom onset, information that is critical to guide earlier identification, more accurate prognoses, and improved treatment options. Data from 8 unique studies that used the <i>Mullen Scales of Early Learning</i> to assess children with an <i>FMR1</i> gene expansion were combined to create a data set of 1178 observations of >500 young children. Linear mixed modeling was used to explore developmental trajectories, symptom onset, and unique developmental profiles of children <5 years of age. Boys with an <i>FMR1</i> gene full mutation showed delays in early learning, motor skills, and language development as young as 6 months of age, and both sexes with a full mutation were delayed on all developmental domains by their second birthday. Boys with a full mutation continued to gain skills over early childhood at around half the rate of their typically developing peers; girls with a full mutation 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 delays in fine motor skills by 18 months were detected. Children with the <i>FMR1</i> gene full mutation demonstrate significant developmental challenges within the first 2 years of life, suggesting that earlier identification is needed to facilitate earlier implementation of interventions and therapeutics to maximize effectiveness.