intellectual disability, X-linked syndromic, Turner type

Intellectual disability, X-linked syndromic, Turner type is a condition that primarily affects neurodevelopment, leading to moderate to severe intellectual deficits in boys and moderate impairment in girls. The disorder is caused by changes in the HUWE1 gene, a key gene expressed in brain tissues. It has been described in a multi‐generation family, highlighting its X-linked mode of transmission. Precise prevalence estimates are not well established for this condition.

Affected individuals typically present with cognitive challenges including intellectual disability, and many also experience motor delays, delayed speech and language development, and delayed ability to walk. Additional features observed in some individuals include macrocephaly, long face, high forehead, hypertelorism, and other facial dysmorphisms such as a short philtrum and low-set or posteriorly rotated ears. Variability in expression is common, and not all individuals experience every feature, with severity varying considerably between affected members.

The underlying cause of the condition is linked to pathogenic variants in the HUWE1 gene. This gene plays a crucial role in neuronal development and function, and alterations in its activity contribute to the cognitive impairment and other clinical features observed. The condition follows an X-linked inheritance pattern, meaning that males typically exhibit more severe intellectual deficits while females, due to variable X-inactivation, may experience milder symptoms. Families are encouraged to seek genetic counseling to better understand the implications for family planning.

Currently, management focuses on supportive care and symptom management since there are no treatments specifically approved for this condition. Treatment is tailored to each individual and typically involves a multidisciplinary team that may include neurologists, developmental specialists, and therapists. Regular surveillance is an essential part of long-term care, helping to identify and address potential complications early. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended for families.

The condition is lifelong with a highly variable course, and outcomes can differ significantly from one individual to another. With current standards of care, many individuals benefit from supportive therapies and regular monitoring, which helps stabilize their condition. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists experienced in managing neurodevelopmental disorders and with genetic counselors to navigate ongoing care and future planning.