Molecular diagnosis of fragile X syndrome among Rwandan children with neurodevelopmental disorders

Abstract

Background: Fragile X syndrome is among the commonest causes of neurodevelopmental disorders, including autism spectrum disorder, intellectual disability and global developmental delay. However, there is no information on the prevalence of Fragile X Syndrome among children with Neurodevelopmental Disorders in Rwanda. This research aimed to determine the prevalence rate of Fragile X Syndrome and the carrier status of mothers among Rwandan children with Neurodevelopmental Disorders, the methylation status of the FMR1 gene and the clinical characteristics of the Fragile X Syndrome children in Rwanda. Methods: This quantitative cross-sectional study used a purposive sampling method to analyze the presence of Fragile X Syndrome among thirty children (aged 2 – 17years) who visited Kigali University Teaching Hospital and Ndera Neuropsychiatric Teaching Hospital, Rwanda for diagnosis of Neurodevelopmental Disorders between November 2023 and May 2025. Results: Among the 30 children with Neurodevelopmental disorder, males predominated (70%), with most children (46.7%) aged between 2 and 5 years. Most of the children had autism spectrum disorder (70%), followed by Global Development Delay (16.7%), Intellectual Disability (10%), and a combination of both autism spectrum disorder and Intellectual Disability (3.3%). Only 3 (10%) males were identified as positive with Full Mutation (>200CGG repeat), Out of which two had autism spectrum disorder, while the third child had Intellectual Disability. They presented with macroorchidism (33%), speech delay (33%), prominent ear (67%), and long face (100%). Furthermore, mental retardation was moderate in two of them (67%) but severe in the third patient (33%). All the Fragile X Syndrome children had complete methylation, with levels above 80%. Lastly, two mothers of the children tested positive for Fragile X Syndrome with premutation status, confirming maternal transmission. Conclusion: About 10% of Rwandan children with Neurodevelopment Disorders have Fragile X Syndrome with full mutation, which is transmitted from their mothers. Screening for Fragile X Syndrome in patients with Neurodevelopmental Disorders is highly recommended to enhance clinical understanding of the genetic etiology of Neurodevelopmental Disorders in Rwanda.