Fragile X in Females- Recognizing the Phenotype of Premutation and Full Mutation

Objective: Carriers of Fragile X premutation may have associated medical comorbidities, such as Fragile X Associated Tremor and Ataxia (FXTAS) and Fragile X Associated Premature Ovarian Insufficiency (FXPOI). Fragile-X premutation effect on cognition is investigated. We assume that there is a continuum of specific learning and attention deficits that correlate with increased number of Cytosine-Guanine-Guanine CGG repeats on FMR1 gene.
Methods: 98 women were referred due to a related Fragile X Syndrome (FXS) patient, 79 women carried a premutation of 56-199 repeats and 19 women carried a full mutation of more than 200 CGG repeats on the FMR1 gene. Genetic results of CGG repeats, demographic information, structured questionnaires for ADHD, learning disabilities of language and mathematics, and independence was analyzed in females carrying FMR1 premutation and compared to the group carrying full mutation. Females with fully symptomatic FXS, were excluded. Results: When analyzed as a continuum, there was a significant increase in the following complaints correlated with higher number of repeats: labor difficulties and C-Section - FXPOI - Not being able to drive a car - ADHD severity - Learning disabilities and specifically - language difficulties, dyscalculia, inattentiveness, spelling difficulties - Executive dysfunction. Conclusions: ADHD and learning difficulties correlate with increased number of CGG repeats and are prevalent features of premutation and of full mutation in females. There is a continuum of learning and attention difficulties in females with Fragile X, extending from premutation to full mutation.