Silver-Russell syndrome

Silver-Russell syndrome (SRS), also known as Russell-Silver syndrome (RSS), is a rare congenital growth disorder characterized by intrauterine growth restriction (IUGR), postnatal growth failure, and a distinctive set of physical features. It is a clinically heterogeneous condition caused primarily by epigenetic or genetic alterations affecting imprinted gene regions, most commonly loss of methylation at the 11p15.5 region (ICR1 hypomethylation, accounting for approximately 30-60% of cases) or maternal uniparental disomy of chromosome 7 (matUPD7, accounting for approximately 5-10% of cases). Key clinical features include severe prenatal and postnatal growth restriction with relative macrocephaly (a head that appears disproportionately large compared to the small body), a characteristic triangular face with a prominent forehead and small pointed chin, body asymmetry (limb length discrepancy), feeding difficulties and low body mass index in early childhood, and fifth finger clinodactyly (inward curving). Many affected children experience significant feeding problems, including poor appetite and gastrointestinal issues, which can contribute to failure to thrive. Hypoglycemia may occur, particularly in early childhood, due to reduced fat stores and feeding difficulties. Cognitive development is generally normal, though some children may experience learning difficulties or speech delay, particularly those with matUPD7. There is no cure for Silver-Russell syndrome, but management focuses on optimizing growth and development through a multidisciplinary approach. Growth hormone therapy is a cornerstone of treatment and has been shown to improve final adult height, body composition, and muscle strength. Nutritional support is critical in early life to prevent hypoglycemia and promote adequate caloric intake, though excessive early weight gain should be avoided due to the risk of later metabolic complications. Monitoring for precocious puberty is important, as early puberty can further compromise adult height, and gonadotropin-releasing hormone analogs may be considered. Orthopedic evaluation is recommended for significant limb length discrepancy. Long-term follow-up should address potential metabolic risks, including insulin resistance, particularly in individuals who experience rapid postnatal catch-up weight gain.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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