Presentation (CTI)

OBJECTIVES: Fragile X syndrome (FXS) is caused by a mutation in the FMR1 gene, located on the X chromosome. This mutation leads to the absence or deficiency of a protein called FMRP (Fragile X Mental Retardation Protein), which is essential for normal brain development. There may be a delay between first indicative symptoms and diagnosis of FXS. The aim of this study was to investigate the diagnostic pathway for patients with FXS.
METHODS: A retrospective, cohort study was conducted in the Clinical Practice Research Datalink (CPRD). Patients of acceptable research quality, born between 2004-2020, with ≥1 medical code indicative of FXS and registered continuously around their date of birth were selected. FXS cases were matched 1:1 to non-FXS controls on gender, age, and general practice (GP).
RESULTS: 179 patients with FXS were matched to 179 controls. Patients with FXS had significantly greater number of prior co-occurring conditions including learning disability, autism and otitis media. Autism was the prior co-occurring condition with the shortest interval to FXS diagnosis (median 245 days). Patients had a mean 44.5 (SD: 30.4) and median 40.0 (IQR: 22.0-56.0) visits to healthcare providers between registration and diagnosis of FXS; and 34.1% of patients had over 50 contacts before diagnosis. Paediatrics was the healthcare specialty with the highest number of visits in both inpatient and outpatient prior to FXS diagnosis.
CONCLUSIONS: Patients with FXS commonly have multiple healthcare contacts in both primary and secondary care prior to diagnosis of the condition. Diagnosis of a learning disability or autism is associated with the shortest interval to subsequent FXS diagnosis. The presence of otitis media in the context of developmental delay may raise the index of suspicion of fragile X syndrome, although further research is required to clarify this relationship.