Evaluation of Autism Spectrum Disorders in Females with Fragile X Syndrome

Background: Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and is associated with a behavioral phenotype which may meet the criteria for autism spectrum disorders including autism and pervasive developmental disorder not otherwise specified (PDD NOS).  Previously reported rates for autism in males with FXS range from 15-33% depending on what evaluation method is used.  The prevalence of autism spectrum disorders (ASD) in females with FXS is thought to be lower, although predisposing molecular, medical, and cognitive factors for ASD have not been recently investigated.
Objectives: To estimate the prevalence of autism spectrum disorders in females with fragile X syndrome and to assess the relationship of molecular measures, medical problems, and cognitive factors to autism spectrum disorders in this population.
Methods: We utilized autism assessments including the ADOS, ADI-R, SCQ, as well as the DSM-IV-TR to estimate the prevalence of ASD in a population of females with the full mutation or mosaicism of the FMR1 gene who were evaluated from 2000-2009.  We also assessed the relationship of molecular measures, including FMR1 CGG repeats, FMR1- mRNA level, activation ratio, and FMRP level in addition to IQ and selected medical co-morbidities, to the diagnosis of ASD in females with fragile X syndrome.
Results: One hundred and ten females with the full mutation or mosaicism of the FMR1 gene were evaluated, with an age range of 2-53 years of age and mean age of 11.7 years.  The assessment for ASD demonstrated autism in 10% and PDD NOS in 21%, leading to an overall percentage of ASD in this population of 31%.  Molecular measures were also assessed.  Our preliminary molecular data in 4 females with autism and FXS demonstrate mean FMR1- mRNA levels of 2.55 ±2.3 compared to mean FMR1- mRNA levels of 1.14 ± 0.5 in 27 females with FXS without ASD (NS).
Conclusions: There is a significant portion of females with FXS who meet criteria for autism (10%) or PDD NOS (21%), and this is important to document for treatment planning.  Further details will be presented on FMR1- mRNA, activation ratio, and FMRP levels to assess whether deviations in the FMR1 molecular variables are associated with autism in females with FXS.  Additional risk factors for autism may include a lower IQ, medical problems that affect the CNS, or additional allelic variations, and all of these potential factors will be studied and presented.