Behavior Problems and Social Competence in Fragile X Syndrome: A Systematic Review.

Olga Cregenzán-Royo,Albert Fornieles-Deu,Carme Brun-Gasca

doi:10.3390/genes13020280

Olga Cregenzán-Royo, Albert Fornieles-Deu + Show 1 more

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https://doi.org/10.3390/genes13020280

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Abstract

Fragile X syndrome (FXS) causes intellectual disability and is the known leading cause of autism. Common problems in FXS include behavior and social problems. Along with syndromic characteristics and autism comorbidity, environmental factors might influence these difficulties. This systematic review focuses on the last 20 years of studies concerning behavior and social problems in FXS, considering environmental and personal variables that might influence both problems. Three databases were reviewed, leading to fifty-one studies meeting the inclusion criteria. Attention deficit hyperactivity disorder (ADHD) problems remain the greatest behavior problems, with behavioral problems and social competence being stable during the 20 years. Some developmental trajectories might have changed due to higher methodological control, such as aggressive behavior and attention problems. The socialization trajectory from childhood to adolescence remains unclear. Comorbidity with autism in individuals with FXS increased behavior problems and worsened social competence profiles. At the same time, comparisons between individuals with comorbid FXS and autism and individuals with autism might help define the comorbid phenotype. Environmental factors and parental characteristics influenced behavior problems and social competence. Higher methodological control is needed in studies including autism symptomatology and parental characteristics. More studies comparing autism in FXS with idiopathic autism are needed to discern differences between conditions.

Highlights

As one of the most frequent inherited reasons for intellectual disability (ID) [1,2], fragile X syndrome (FXS) is caused by silencing of the fragile X gene FMR1 due to large expansions of non-coding CGG repeats [3]
This review summarizes results for behavior problems and social competence profiles in individuals with FXS by selecting the studies that best fit behavioral phenotypes and show the best methodology criteria
Most of the studies that controlled for autism spectrum disorder (ASD) symptomatology and achieved a good methodological quality were developed in the social competence area, while less methodological quality was found in studies addressing behavior problems

Summary

Introduction

As one of the most frequent inherited reasons for intellectual disability (ID) [1,2], fragile X syndrome (FXS) is caused by silencing of the fragile X gene FMR1 due to large expansions of non-coding CGG repeats [3]. The trinucleotide expansion inactivates the FMR1 gene, resulting in an absence of the fragile X mental retardation protein (FMRP), which is fundamental for natural neural development [4]. As a result of genetic inheritance, these PM alleles tend to expand to a full mutation in family members [5]. The members with the full mutation (FM) expansions, which implies more than 200 CGG repeats of the gene, have a silenced gene, resulting in the absence of the FMRP protein and the full development of FXS [2]. Via increased FMR1 mRNA production and toxicity, the PM alleles can produce a family of neurodevelopmental phenotypes (ADHD, autism spectrum disorder, seizure disorder) and neurodegenerative phenotypes (fragile X-associated tremor/ataxia syndrome) [3]

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