Alpha thalassemia X-linked intellectual disability syndrome

This is the rare association of HbH disease and X linked intellectual disability. Pathogenic variants in the ATRX gene cause alpha thalassemia X-linked intellectual disability syndrome. (1)

‘Chromatin-remodeling' disorders, are unique in medicine because they arise from a general deregulation of DNA transcription. Without proper regulation of transcription, cells produce proteins in a thoroughly disordered way, resulting in dysfunctional macromolecular processes. (2)

There is a remarkably uniform phenotype, comprising:

• severe mental retardation
• characteristic facial dysmorphism
• genital abnormalities
• mild form of HbH disease

There is no treatment for this syndrome.

Note - other names for this condition include:

• Alpha thalassemia/intellectual disability syndrome X-linked

• Alpha-thalassemia/impaired intellectual development syndrome

• ATR-X syndrome

• ATRX syndrome

• XLMR-hypotonic face syndrome

Reference:

1. Leon NY, Harley VR. ATR-X syndrome: genetics, clinical spectrum, and management. Hum Genet. 2021 Dec;140(12):1625-1634
2. Noordhuis-Zijderveld A et al. tel M, Hartman M, Bruggenwirth HT, Zeidler S, Valstar MJ. Clinical variability in individuals withATR-X syndrome in the Netherlands. Eur J Med Genet. 2025 Aug;76:105026.