Estimate Fragile X syndrome (FXS) diagnosis rates in a multistate population and assess differences by sex and race.
Approach:
Design and data: Cross-sectional analysis of deidentified electronic health records from Atrium Health, covering 7,381,668 patients in Alabama, Georgia, North Carolina, and South Carolina. Records spanned 1973–2026.
Case definition and analysis: FXS cases required at least two diagnostic-code encounters; manually identified FMR1 premutation carriers were excluded. Diagnosis rates compared recorded cases with expected counts based on published prevalence estimates, overall and by sex and race.
Key Findings:
The cohort included 231 recorded FXS cases, compared with 839 expected cases; the overall diagnosis rate was 27.5%.
Diagnosis rates were lower among Black patients than White patients: 17.9% versus 30.6% (P < .001).
Women had lower diagnosis rates than men overall (18.3% vs 34.1%) and within both racial groups.
Among men, the difference between Black and White patients was not statistically significant (28.5% vs 35.8%; P = .14). Among women, the rate was lower for Black than White patients (3.5% vs 23.1%; P < .001).
Interpretation:
The authors report substantial FXS underdiagnosis, with lower diagnosis rates among women and particularly low rates among Black women. They suggest that milder or more variable presentations in women and inequities in access to developmental, genetic, and specialty care may contribute.
Limitations:
The records span more than five decades, during which clinical knowledge, testing, and documentation practices may have changed.
Case ascertainment relied on diagnostic codes; clinical verification and validation across health systems are needed.
Actual FXS prevalence is unknown, and expected case counts relied on published prevalence estimates.
Conclusion:
The authors call for improved screening and diagnostic approaches, particularly for people without severe or classic phenotypes, and broader access to genetic testing and specialty care for underrepresented populations.
