Highlighting Gaps in Testing and Diagnosis for Fragile X Syndrome: Craig A. Erickson, MD

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"There are still a lot of folks that are carriers, there are a lot of youth with the full mutation that are not getting tested early and quick enough, and that can make a meaningful difference in their care over time."

Fragile X syndrome is an X-linked triplet repeat expansion disorder caused by CGG repeat expansion in the FMR1 gene and remains the most common inherited cause of developmental delay and autism spectrum disorder.¹ Diagnosis relies on Southern blot and Polymerase Chain Reaction (PCR) testing, generally recommended for children presenting with developmental delay or autism. Men are typically more significantly affected, whereas women show a wide range of presentation, from severe impairment to none at all, a variability that continues to complicate diagnosis in this population.

National and World Fragile X Awareness Day, observed annually on July 22 as part of Fragile X Awareness Month, is intended to raise clinician and public awareness of the rare genetic condition and the testing gaps that persist despite broader insurance coverage over the past couple of decades. Advocates may use this observance day to emphasize that many carriers and affected individuals, particularly women and older adults, are still not identified through routine care, underscoring the need for expanded and earlier testing across multiple clinical settings.^2,3

In recognition of the day, NeurologyLive^® spoke with Craig A. Erickson, MD, professor of psychiatry at Cincinnati Children's Hospital, about where testing access remains inconsistent and who should be considered for it. Erickson discussed the importance of cascade testing across families once an index case is confirmed, and the risks carriers face including fragile X-associated tremor/ataxia syndrome and early ovarian insufficiency. He also talked about the need for testing beyond pediatric developmental clinics, including in women with infertility and older adults presenting with tremor, gait changes, or dementia.

Editor’s Note: Erickson has disclosed that he is currently consultant to a number of treatment developers in the Fragile X and neurodevelopmental disorder space, including Spinogenix and STALICLA.

REFERENCES
1. Salcedo-Arellano MJ, Dufour B, McLennan Y, Martinez-Cerdeno V, Hagerman R. Fragile X syndrome and associated disorders: Clinical aspects and pathology. Neurobiol Dis. 2020;136:104740. doi:10.1016/j.nbd.2020.104740
2. Tassone F, Protic D, Allen EG, et al. Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation. Cells. 2023;12(18):2330. Published 2023 Sep 21. doi:10.3390/cells12182330
3. Ain Q, Hwang YH, Yeung D, et al. Population-based FMR1 carrier screening among reproductive women. J Assist Reprod Genet. 2024;41(11):3237-3243. doi:10.1007/s10815-024-03242-2