Silver-Russell syndrome

Silver-Russell Syndrome (SRS), also known as Russell-Silver Syndrome (RSS), is a rare congenital condition characterized by growth restriction before and after birth, distinctive facial features, and asymmetry of body parts. This condition is a form of intrauterine growth restriction (IUGR) and is known for its clinical variability.

Etiology

The exact cause of Silver-Russell Syndrome is complex and involves genetic factors. Two key regions of the genome are often implicated: chromosome 11 (specifically the region 11p15.5, which is involved in genomic imprinting) and chromosome 7. Approximately 40-60% of individuals with SRS have a hypomethylation of the imprinting control region 1 (ICR1) on chromosome 11p15.5. Additionally, maternal uniparental disomy of chromosome 7 (mUPD7) is found in about 10% of cases. However, not all individuals with SRS have identifiable genetic abnormalities, suggesting that other genetic or epigenetic factors may be involved.

Clinical Features

The hallmark features of Silver-Russell Syndrome include:

• Pre- and postnatal growth restriction, leading to short stature.
• Relative macrocephaly at birth.
• Triangular facial appearance with a prominent forehead, a small chin, and down-turned corners of the mouth.
• Body asymmetry, where one side of the body is noticeably larger than the other.
• Feeding difficulties and failure to thrive in infancy.

Other features may include:

• Clinodactyly (curved finger)
• Cryptorchidism (undescended testicles) in males
• Gastroesophageal reflux
• Developmental delays or learning disabilities

Diagnosis

Diagnosis of Silver-Russell Syndrome is based on clinical criteria and genetic testing. The Netchine-Harbison clinical scoring system (NH-CSS) is commonly used to guide diagnosis, which includes specific growth and physical criteria. Genetic testing can confirm a diagnosis by identifying hypomethylation of the 11p15.5 region or maternal uniparental disomy of chromosome 7.

Management

Management of SRS is multidisciplinary and focuses on the specific symptoms present in the individual. Growth hormone therapy may be considered to improve growth in some children. Nutritional support is crucial, especially in early childhood, to address feeding difficulties and failure to thrive. Orthopedic interventions may be necessary for significant limb length discrepancies. Regular monitoring and supportive therapies (e.g., speech therapy, physical therapy) can help address developmental delays and learning disabilities.

Prognosis

The prognosis for individuals with Silver-Russell Syndrome varies. Growth hormone therapy can improve growth in some children, but they often remain shorter than average as adults. Most individuals with SRS have normal intelligence, although learning disabilities and developmental delays are not uncommon. Lifespan is typically normal, but the condition can be associated with various health challenges that require ongoing management.

See Also

• Genomic imprinting
• Intrauterine growth restriction
• Growth hormone therapy

Silver-Russell syndrome Resources
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