The impact of spermine synthase (SMS) mutations on brain morphology

Snyder–Robinson syndrome (SRS) is a form of X-linked mental retardation resulting from mutations in spermine synthase (SMS), which impact neurodevelopment and cognitive outcome. We obtained cerebral, cerebellum, hippocampus, and red nucleus volumes from two males with SRS and 24 age- and gender-matched typically developing controls using volumetric neuroimaging analyses. Total brain volume was enlarged in males with SRS while cerebellum, hippocampus, and red nucleus volumes tended to be reduced compared to controls. Mutations of the X chromosome may modulate the risk for mental retardation through altered early neurodevelopment, disruption in receptor function, and ongoing neural organization and plasticity. Disruption of SMS function may negatively affect regional brain volumes that subserve cognitive and motor abilities. This research provides valuable insight into the effects of polyamine function on brain development.