Molecular screening for fragile X syndrome in children with unexplained intellectual disability and/or autistic behaviour

Abstract

Introduction: Fragile X syndrome (FXS, OMIM #300624) is the most common inherited form of intellectual disability and the leading monogenic cause of autism.  Aim: To present our experience with selective screening for FXS among high-risk children with intellectual disability/developmental delay/autistic behaviour and to further prove the importance of performing selective screening in a high-risk population. Materials and methods: Fifty-two children (45 boys and 7 girls) hospitalized in pediatric clinics or referred to genetic counseling services were tested with triplet repeat primed PCR based commercial kit. The mean age of participants was 6 years (the youngest was 2 years old, the oldest - 15 years old). These patients were selected based on the presence of at least one of the following clinical features: developmental delay, intellectual disability, and autistic-like behaviour. Results: All patients presented with developmental delay, including language delay. Intellectual disability and autistic-like behaviour were the most consistent features. Thirty-three children (63.4%) were with intellectual disability. Autism and autistic-like behaviour were observed in 22 patients (42.3%). Only 9 male patients (17.3%) presented with dysmorphic features typical for FXS. Three boys (5.7%) were found to be affected and two of their mothers - premutation carriers.  Conclusions: The present study is the first attempt for molecular genetic selective screening for FXS among high-risk groups in north-eastern Bulgaria. Screening for FXS helps in making a definitive diagnosis along with providing genetic counseling to the family which includes reproductive planning and risk assessment.