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Journal of Neurodevelopmental Disorders
Published in: Journal of Neurodevelopmental Disorders 1/2019

Open Access 01-12-2019 | Disorders of Intellectual Development | Research

Intellectual functioning and behavioural features associated with mosaicism in fragile X syndrome

Authors: Emma K. Baker, Marta Arpone, Solange Aliaga Vera, Lesley Bretherton, Alexandra Ure, Claudine M. Kraan, Minh Bui, Ling Ling, David Francis, Matthew F. Hunter, Justine Elliott, Carolyn Rogers, Michael J. Field, Jonathan Cohen, Lorena Santa Maria, Victor Faundes, Bianca Curotto, Paulina Morales, Cesar Trigo, Isabel Salas, Angelica M. Alliende, David J. Amor, David E. Godler

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2019

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Abstract

Background

Fragile X syndrome (FXS) is a common cause of intellectual disability and autism spectrum disorder (ASD) usually associated with a CGG expansion, termed full mutation (FM: CGG ≥ 200), increased DNA methylation of the FMR1 promoter and silencing of the gene. Mosaicism for presence of cells with either methylated FM or smaller unmethylated pre-mutation (PM: CGG 55–199) alleles in the same individual have been associated with better cognitive functioning. This study compares age- and sex-matched FM-only and PM/FM mosaic individuals on intellectual functioning, ASD features and maladaptive behaviours.

Methods

This study comprised a large international cohort of 126 male and female participants with FXS (aged 1.15 to 43.17 years) separated into FM-only and PM/FM mosaic groups (90 males, 77.8% FM-only; 36 females, 77.8% FM-only). Intellectual functioning was assessed with age appropriate developmental or intelligence tests. The Autism Diagnostic Observation Schedule-2nd Edition was used to examine ASD features while the Aberrant Behavior Checklist-Community assessed maladaptive behaviours.

Results

Comparing males and females (FM-only + PM/FM mosaic), males had poorer intellectual functioning on all domains (p < 0.0001). Although females had less ASD features and less parent-reported maladaptive behaviours, these differences were no longer significant after controlling for intellectual functioning. Participants with PM/FM mosaicism, regardless of sex, presented with better intellectual functioning and less maladaptive behaviours compared with their age- and sex-matched FM-only counterparts (p < 0.05). ASD features were similar between FM-only and PM/FM mosaics within each sex, after controlling for overall intellectual functioning.

Conclusions

Males with FXS had significantly lower intellectual functioning than females with FXS. However, there were no significant differences in ASD features and maladaptive behaviours, after controlling for intellectual functioning, independent of the presence or absence of mosaicism. This suggests that interventions that primarily target cognitive abilities may in turn reduce the severity of maladaptive behaviours including ASD features in FXS.
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Metadata
Title
Intellectual functioning and behavioural features associated with mosaicism in fragile X syndrome
Authors
Emma K. Baker
Marta Arpone
Solange Aliaga Vera
Lesley Bretherton
Alexandra Ure
Claudine M. Kraan
Minh Bui
Ling Ling
David Francis
Matthew F. Hunter
Justine Elliott
Carolyn Rogers
Michael J. Field
Jonathan Cohen
Lorena Santa Maria
Victor Faundes
Bianca Curotto
Paulina Morales
Cesar Trigo
Isabel Salas
Angelica M. Alliende
David J. Amor
David E. Godler
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Neurodevelopmental Disorders / Issue 1/2019
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI
https://doi.org/10.1186/s11689-019-9288-7

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