Russell-Silver syndrome (RSS) is a rare genetic disorder involving slow growth before and after birth.
RSS results in short stature and various distinctive physical features. It can significantly affect growth and development and requires lifelong management.
Children with RSS often have asymmetrical growth, meaning one side of the body may be smaller. Other key characteristics include feeding difficulties, a triangular-shaped face, a high forehead, and low birth weight. While genetic changes cause some cases, many instances have no identifiable genetic mutation.
Despite its challenges, early diagnosis and appropriate interventions can improve quality of life for individuals with RSS. Treatment focuses on managing growth, ensuring proper nutrition, and addressing developmental delays or complications.
The term RSS came into use from Dr. Henry Silver in 1953 and Dr. Alexander Russell in 1954. Health experts sometimes refer to it as Silver-Russell syndrome (SRS).
RSS is a growth disorder that affects a child’s physical development. Infants with RSS are typically born small for their gestational age and often remain shorter than average throughout life. The syndrome relates to genetic changes that disrupt typical growth regulation, but the exact cause remains unknown in many cases.
RSS is rare — around 1 in 15,000 children have the condition.
Learn more about rare growth disorders.
The symptoms of RSS vary widely, but common features
- low birth weight
- short stature
- body asymmetry, where one side of the body is smaller than the other
- a triangular-shaped face with a prominent forehead
- large head size relative to body size
- feeding difficulties, including appetite issues and difficulty gaining weight
- low muscle tone, or hypotonia
- delayed bone age, meaning skeletal development is atypically slower
- curved pinky fingers, clinodactyly
- low blood sugar or hypoglycemia, especially in infancy
- delayed motor and speech development
- gastrointestinal issues, such as reflux or constipation
- learning difficulties or mild intellectual disabilities in some cases
Parents and caregivers need to consult a doctor if a child shows signs of growth issues, feeding difficulties, or developmental delays. A doctor may refer the child to a pediatric endocrinologist, geneticist, or developmental specialist for further evaluation.
Early medical attention is essential for managing symptoms and improving long-term outcomes.
RSS is primarily a genetic condition, though in many cases, there is no identifiable genetic mutation. The most common known causes
- Loss of methylation at 11p15.5: This affects the regulation of genes responsible for growth, particularly IGF2 (insulin-like growth factor 2). This growth issue is present in about 35% to 67% of RSS cases.
- Unknown genetic causes: In approximately 30% to 40% of cases, clinicians identify no apparent genetic alteration.
- Maternal uniparental disomy of chromosome 7 (UPD7): This occurs in about 7% to 10% of cases and results in two maternal copies of chromosome 7 instead of one from each parent, disrupting typical growth.
Diagnosing RSS is challenging due to its wide range of symptoms and genetic variability. It may require a multidisciplinary approach involving pediatricians, geneticists, endocrinologists, and other specialists. The diagnostic process typically involves:
- Clinical evaluation: A doctor assesses growth patterns, including birth weight, height, and head circumference. They also examine physical characteristics and consider a history of feeding difficulties, delayed motor development, and related symptoms.
- Genetic testing: A molecular analysis can confirm genetic causes. When these abnormalities are absent, whole-genome or exome sequencing can rule out related syndromes or rare genetic variations.
- Hormone testing: Testing may include growth hormone stimulation tests and insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) levels, which provide insight into growth hormone activity.
- Bone age assessment: X-ray imaging of the hand and wrist helps determine bone maturity and delayed skeletal development, which is common in RSS. A discrepancy between bone age and chronological age can help confirm the diagnosis.
- Blood sugar monitoring: Glucose tolerance tests or continuous glucose monitoring can assess blood sugar stability and prevent complications.
There is no cure for RSS, but early intervention can help manage symptoms. Common treatments include:
- Growth hormone therapy: This can improve height and muscle development, even if growth hormones are at typical levels.
- Nutritional support: Infants and young children can benefit from high calorie diets, specialized feeding techniques, or feeding tubes.
- Physical and occupational therapy: These techniques help with muscle tone, motor skills, and coordination.
- Speech therapy: This approach supports language development if delays are present.
- Blood sugar management: Frequent small meals and medical monitoring may help prevent hypoglycemia.
- Orthopedic care: This approach helps correct skeletal asymmetry or other related conditions.
- Educational support: Some children may need individualized education plans for learning difficulties.
With early diagnosis and proper medical management, most individuals with RSS have a typical life expectancy. While growth challenges and other symptoms persist, treatments can significantly improve quality of life.
Some children may experience learning difficulties or mild cognitive (thinking) impairments, but many can achieve typical intellectual development with proper support.
Russell-Silver syndrome (RSS) is a rare genetic growth disorder that affects physical development. It often leads to short stature, feeding difficulties, and body asymmetry.
Though the exact cause is not always identifiable, known genetic changes such as loss of methylation at 11p15.5 and UPD7 contribute to its occurrence.
Diagnosis consists of clinical evaluation and genetic testing, and treatment focuses on growth hormone therapy, nutrition, and developmental support. Early intervention allows individuals with RSS to manage symptoms effectively and lead typical lives.
