Silver-Russell syndrome due to an imprinting defect of 11p15

Silver-Russell syndrome due to an imprinting defect of 11p15 (SRS) is a specific molecular subtype of Silver-Russell syndrome caused by epigenetic alterations at the imprinted region on chromosome 11p15.5. This region contains two imprinting control regions (ICR1 and ICR2) that regulate the expression of growth-related genes, including IGF2 and H19. In this subtype, loss of methylation (hypomethylation) at ICR1 on the paternal allele leads to reduced expression of IGF2, a key growth factor, resulting in significant prenatal and postnatal growth restriction. This molecular mechanism accounts for approximately 30-60% of all Silver-Russell syndrome cases. The condition is characterized by severe intrauterine growth restriction (IUGR), low birth weight and length, postnatal growth failure with relative macrocephaly, a triangular face with a prominent forehead and small pointed chin, body asymmetry (limb length discrepancy), feeding difficulties in early childhood, and fifth finger clinodactyly. Affected children often have poor appetite, low body mass index, and may experience hypoglycemia due to limited fat stores and feeding problems. Cognitive development is generally normal, though some children may experience mild learning difficulties or speech delay. Management of Silver-Russell syndrome due to 11p15 imprinting defects is multidisciplinary. Growth hormone therapy is a well-established treatment that can improve final adult height and body composition, and is typically initiated in early childhood. Nutritional support is critical, particularly in infancy and early childhood, to prevent hypoglycemia and ensure adequate caloric intake. Monitoring for premature adrenarche and early or precocious puberty is recommended, as these may further compromise final height. Orthopedic evaluation may be needed for significant limb length discrepancy. Long-term follow-up includes monitoring for metabolic complications and psychosocial support.

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