High-functioning autism spectrum disorder and fragile X syndrome: report of two affected sisters

Pauline Chaste,Catalina Betancur,Marion Gérard-Blanluet,Richard Delorme,Séverine Drunat,Marion Leboyer,Anne Bargiacchi,Thomas Bourgeron,Suzanne Kuzbari

doi:10.1186/2040-2392-3-5

Abstract

BackgroundFragile X syndrome (FXS) is the most common inherited cause of intellectual disability (ID), as well as the most frequent monogenic cause of autism spectrum disorder (ASD). Men with FXS exhibit ID, often associated with autistics features, whereas women heterozygous for the full mutation are typically less severely affected; about half have a normal or borderline intelligence quotient (IQ). Previous findings have shown a strong association between ID and ASD in both men and women with FXS. We describe here the case of two sisters with ASD and FXS but without ID. One of the sisters presented with high-functioning autism, the other one with pervasive developmental disorder not otherwise specified and low normal IQ.MethodsThe methylation status of the mutated FMR1 alleles was examined by Southern blot and methylation-sensitive polymerase chain reaction. The X-chromosome inactivation was determined by analyzing the methylation status of the androgen receptor at Xq12.ResultsBoth sisters carried a full mutation in the FMR1 gene, with complete methylation and random X chromosome inactivation. We present the phenotype of the two sisters and other family members.ConclusionsThese findings suggest that autistic behaviors and cognitive impairment can manifest as independent traits in FXS. Mutations in FMR1, known to cause syndromic autism, may also contribute to the etiology of high-functioning, non-syndromic ASD, particularly in women. Thus, screening for FXS in patients with ASD should not be limited to those with comorbid ID.

Highlights

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability (ID), as well as the most frequent monogenic cause of autism spectrum disorder (ASD)
In contrast with the frequent claim that cognitive impairment accounts for the co-morbidity between FXS and autism [13,20,21], here we describe the case of two sisters, one with high-functioning autism and the other with pervasive developmental disorder not otherwise specified (PDD-NOS), both with low normal intelligence quotient (IQ)
In women as well as in men with FXS, the literature reports a strong association between ID and autistic features, with individuals with a lower IQ being more likely to be diagnosed with autism [8,9,10,12,14,15,20,26]

Summary

Introduction

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability (ID), as well as the most frequent monogenic cause of autism spectrum disorder (ASD). In contrast with the frequent claim that cognitive impairment accounts for the co-morbidity between FXS and autism [13,20,21], here we describe the case of two sisters, one with high-functioning autism and the other with pervasive developmental disorder not otherwise specified (PDD-NOS), both with low normal IQ. Both carried a full mutation in the FMR1 gene with random X inactivation

Methods

Results

Discussion

Conclusion