Fragile X syndrome in children with learning difficulties and the diagnostic dilemma

Introduction: Fragile X syndrome (FXS) is the commonest inherited cause of intellectual disability. Children with FXS usually present clinically with developmental, learning and behavioural disorders. Physical characteristics of FXS are well documented and are considered a primary guide to recognition. Genetic screening for FXS targets the detection of cytosine-guanine-guanine (CGG) triplet repeats in the FMR1 gene on the X chromosome.  

Objective: Aim was to estimate the frequency, clinically and genetically, in children referred to a specialist child mental health clinic for preschool and school based learning difficulties. 

Design and method: A total population of children referred to a specialist mental health service for learning difficulties during a specified period was screened clinically and genetically for FXS. Clinical diagnosis was based on known physical characteristics. They were further assessed on cognitive functions, learning and behaviour. Optimised and validated conventional polymerase chain reaction (PCR) amplification was used for genetic screening where deoxyribonucleic acid (DNA) for the assay was obtained from buccal cells.

Results: The total sample studied was 286 children, 4-12 years of age. Based on morphological features, 5.9% received the diagnosis of FXS and one child was genetically positive. Of the rest, 2 more children were genetically positive but clinically negative. 

Overall frequency of FXS in the study sample was 1.05%.  Similar proportions of children earned additional diagnoses of autism and attention deficit and hyperactivity disorder (ADHD) in the two groups but differed in their cognitive functions.

Conclusions: The overall frequency of FXS in the study sample was 1.05%.