Skeletal health in syndrome.

syndrome results from a reduction in copy number of the gene, which resides on human chromosome 21 (Hsa21). has been implicated in the development of cognitive phenotypes associated with many genetic disorders, including Down syndrome (DS) and Alzheimer's disease (AD). Additionally, overexpression of in DS has been implicated in the development of abnormal skeletal phenotypes in these individuals. Analyses of mouse models with dosage imbalance (overexpression and underexpression) show skeletal deficits and abnormalities. Normalization of copy number in an otherwise trisomic animal rescues some skeletal health parameters, and reduction of copy number in an otherwise euploid (control) animal results in altered skeletal health measurements, including reduced bone mineral density (BMD) in the femur, mandible, and skull. However, little research has been conducted thus far on the implications of reduction on human skeletal health, specifically in individuals with syndrome. This review highlights the skeletal phenotypes of individuals with syndrome, as well as in murine models with reduced copy number, and provides potential pathways altered by a reduction of copy number, which may impact skeletal health and phenotypes in these individuals. Understanding how decreased expression of in individuals with syndrome impacts bone health may increase awareness of skeletal traits and assist in the development of therapies to improve quality of life for these individuals.