Intractable Rare Dis Res. 2026;15(3):232-246. (DOI: 10.5582/irdr.2026.01037)

Phenotypic variability of Fragile-X syndrome in Asian population: A systematic review

Napitupulu CLM, Tengkawan J, Utari A, Winarni TI, Sihombing NRB

Fragile X syndrome (FXS) is the most common genetic cause of inherited intellectual disabilities. Individuals with full mutation of FXS exhibit physical and behavioral symptoms in addition to other comorbidities. The clinical features of FXS have been widely studied in Caucasians; however, they remain limited in the Asian population. This study aimed to characterize the spectrum and variability of physical and behavioral phenotypes in Asian populations. A total of 5,830 studies from the PubMed, ScienceDirect, Scopus, and Cochrane/CENTRAL databases were screened using the Covidence software. We identified FXS-specific research studies conducted in Asia that reported the clinical characteristics of individuals with FXS. This review summarizes 51 studies from different Asian regions. The frequently reported physical characteristics were large and prominent ears (72.63%), an elongated face (57.49%), and macroorchidism (45.21%). The three most prevalent behavioral characteristics were intellectual disability (ID), hyperactivity, and social withdrawal, reported in 99%, 77%, and 55% of all cases, respectively. Our findings show that the physical characteristics of FXS are variable in the Asian group but similar to those in other populations and are not recommended for early recognition. Individuals with intellectual disabilities, especially when combined with autism spectrum disorders and large prominent ears, are suggestive of further genetic testing for FXS.

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