To describe a family with a genetically confirmed duplication of the Xq28 region, including the genes SLC6A8, L1CAM, MECP2, TKTL1, FLNA, and GDI1, characterized by marked intrafamilial phenotypic variability.
Key Findings:
Three affected individuals from a single family with Xq28 duplication involving multiple genes: SLC6A8, L1CAM, MECP2, TKTL1, FLNA, and GDI1.
Two male siblings exhibited severe phenotypes including profound intellectual disability and other neurological impairments.
The mother displayed mild intellectual disability and skin manifestations.
Family history indicated additional affected male relatives with similar or more severe clinical presentations.
Interpretation:
The duplication of multiple dosage-sensitive genes within the Xq28 region likely accounts for the observed multisystem involvement and phenotypic variability among family members, particularly influenced by the roles of specific genes.
Limitations:
The study only included three family members, limiting the generalizability of findings.
Additional affected relatives were not included in the analysis, and their genetic status remains unexamined.
Conclusion:
Xq28 duplication should be considered in the differential diagnosis of families with X-linked intellectual disability, especially with additional neurological impairments, and genetic counseling is recommended for affected families.
Over two days, specialists across neurology, neurosurgery and related subspecialties came together to discuss advances in stroke care, epilepsy, movement disorders, neurodegenerative disease, neuro-oncology, brain and spine surgery, interventional pain management and emerging technologies.
