General description

Fragile X syndrome (FXS) represents the most common inherited cause of intellectual disability and autism spectrum disorder, affecting approximately 1 in 4,000 to 7,000 males and 1 in 4,000 to 6,000 females worldwide. This X-linked neurodevelopmental disorder results from expansion of CGG trinucleotide repeats in the FMR1 gene, leading to transcriptional silencing and subsequent loss of the fragile X mental retardation protein (FMRP).

Clinical manifestations

Fragile X syndrome (FXS) presents with a wide range of cognitive, behavioral, and physical features, varying by sex due to X-inactivation. Males with the full FMR1 mutation typically have more severe symptoms, with IQ scores often below 55, while females tend to have milder cognitive impairments, usually in the 70–85 range.

Common physical traits include an elongated face, large or protruding ears, high-arched palate, and macroorchidism in boys. Other features include hyperextensible joints, flat feet, soft skin, and hypotonia.

Seizures affect approximately 10–18% of individuals, with a higher prevalence in males (14%) than females (6%). Medical issues linked to connective tissue abnormalities include recurrent otitis media, sinusitis, GERD, hernias, joint dislocations, and mitral valve prolapse. Vision problems such as strabismus and refractive errors are also common and require early intervention.

References

1. Hagerman, Randi J., et al. "Fragile X syndrome." Nature reviews Disease primers 3.1 (2017): 1-19.
2. Sandoval, Gisela M., et al. "Neuroanatomical abnormalities in fragile X syndrome during the adolescent and young adult years." Journal of psychiatric research 107 (2018): 138-144.