Cognitive development in Silver-Russell syndrome: a sibling-controlled study

This study examined cognitive development in Silver-Russell syndrome (SRS), a condition with intrauterine growth retardation, persisting short stature, and specific stigmata. Neuropsychological function and cognitive abilities were assessed in a sample of 36 children with SRS (21 males, 15 females; mean age 7 years 6 months, SD 2 years 8 months; age range 3 to 12 years) and 25 normally developing siblings (mean age 8 years 6 months, SD 2 years 7 months; age range 3 to 12 years) using the Kaufman Assessment Battery for Children. Special measures were taken to control for confounding factors and sample bias. Mean overall IQ score in the total SRS sample (95.7, SD 10.63), as measured by the Mental Processing Composite Scale, was significantly reduced (p=0.021) compared with test norms (IQ 100, SD 15), indicating a moderate cognitive impairment. Subscale analysis revealed some specific deficiencies. However, these cannot be attributed to an established category of specific learning disorder. The mean score in the Achievement Scale (91.25, SD 14.92), which is more sensitive to educational influences, showed stronger deficits (p=0.001). The sibling control group achieved a slightly better mean IQ score (104.20, SD 12.32) than test norms (p=0.10). Direct analysis of paired differences between the subsample of children with SRS and a sibling among the control group (n=25) revealed a significant mean difference of 8.08 IQ points (p=0.011). Risk factor analysis revealed that cognitive development is not associated with birth length (p=0.404), birthweight (p=0.820), growth hormone therapy (p=0.810), phenotypic severity (p=0.828), or sex (p=0.880). Two children with maternal uniparental disomy for the entire chromosome 7 had markedly lower IQ scores (81 and 84 respectively). In contrast to the few previous findings, children with SRS show only moderate, but significant, impairments in cognitive outcome, which are more striking in our sample when compared with siblings than with test norms.