What are the other Names for this Condition? (Also known as/Synonyms)

• Russell-Silver Dwarfism
• Silver-Russell Dwarfism
• Silver-Russell Syndrome (SRS)

What is Russell-Silver Syndrome? (Definition/Background Information)

• Russell-Silver Syndrome (RSS) is a prenatal and post-birth growth disorder characterized by stunted appearance, a disproportionately large head, triangular face and abnormalities involving various organ systems in the body
• RSS is one of the 200 types of dwarfism and one of the five types of primordial dwarfism that is recorded in the medical literature. It is an extremely rare disorder
• Russell-Silver Syndrome is known as an “imprinting disorder”. Imprinting is a chemical process of silencing gene expression. The genetic causes for RSS are complex, predominantly involving chromosomes 7 and 11. The risk factors for the disorder are also not clear, since most of the cases occur spontaneously
• Aside from routine tests, growth hormone measurements and chromosome testing may be used to establish a diagnosis of Russell-Silver Syndrome
• Specialists from various medical fields, such as pediatricians, endocrinologists, dentists, and physiotherapists, are often needed for the treatment of RSS. Even though incurable, individuals with Russell-Silver Syndrome are reported to have a normal life expectancy

Who gets Russell-Silver Syndrome? (Age and Sex Distribution)

• Russell-Silver Syndrome is a rare inherited disorder reported worldwide that is typically present at birth
• The condition affects both males and females
• The estimated prevalence of the disorder is between 1:30,000 and 1:100,000. So far, only about 400 cases have been reported in the medical literature

What are the Risk Factors for Russell-Silver Syndrome? (Predisposing Factors)

• The risk factors for Russell-Silver Syndrome are not clearly defined, since the majority of cases arise sporadically with no family history of the disorder
• In rare cases, the disorder may run in families. In such instances, a family history of RSS is a risk factor

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider

What are the Causes of Russell-Silver Syndrome? (Etiology)

The causes of Russell-Silver Syndrome are complex, and thus far, chromosomes 7, 11, and 14 have been identified as contributing to its development. RSS is known as an “imprinting disorder”. 

• An individual inherits one chromosome from each parent. This would mean that the individual has two copies of each gene. However, only one copy is active. The other is “silenced” by the process of methylation of DNA. This silencing of a gene is known as genomic imprinting. Disorders arising from such aberrant imprinting are known as imprinting disorders
• While some genes from the mother may be silenced, others inherited from the father are imprinted

The following are some known reasons for the development of Russell-Silver Syndrome:

Involvement of chromosome 7: Maternal disomy of chromosome 7 (maternal uniparental disomy or matUPD7) is observed in 10-15% of affected children.

• Under normal circumstances, a child inherits one copy of a chromosome from each parent
• In matUPD7, both copies of chromosome 7 are inherited from the mother. This leads to two copies of some silenced genes on chromosome 7, causing a genetic imbalance, leading to the disorder

Involvement of chromosome 11: Abnormalities in methylation of genes in the short arm of chromosome 11 are reported in 30-50% of children with RSS.

• In RSS, a loss of methylation of genes H19 and IGF2 is reported. These genes are known to regulate normal growth of cells
• The reduced or abnormal methylation leads to increased expression of H19 gene and reduced expression of the IGF2 gene, resulting in growth retardation

The known genetic causes account for about 60% of Russell-Silver Syndrome cases.

• In the other 40%, the cause is yet to be determined, although changes in chromosomes 1, 14, 15, 17, and 18 are reported to be involved
• Although most cases of RSS are sporadic, rarely, the disorder can run in families. The inheritance pattern is variable, and both autosomal dominant and autosomal recessive inheritance patterns have been reported

Autosomal dominant: In this type of inheritance, a single copy of a defective gene in each cell of an individual is sufficient for the condition to manifest itself. The affected individual inherits the disorder from an affected parent.

Autosomal recessive: In this type of inheritance, an individual must possess both copies of the causative gene in the defective form in every cell of his/her body for the condition to manifest itself. The affected individual inherits one defective copy from each parent. The parents are carriers of the condition and are generally not affected.

What are the Signs and Symptoms of Russell-Silver Syndrome?

The signs and symptoms of Russell-Silver Syndrome may vary in type and severity among the affected individuals. The common signs and symptoms may include:

• Low birth weight
• Inability to gain weight, low growth rate
• Feeding difficulties
• Birthmarks that are brown in color (described as the color of “coffee with milk”)
• Delay in the maturation of bones
• Gastro-esophageal reflux disease (GERD)
• Kidney abnormalities such as:
  • Horseshoe kidney - where the two kidneys fuse to form horseshoe-like shape
  • Hydronephrosis - excess fluid accumulation in the kidneys
  • Posterior urethral valves (PUV): An abnormality in the urethra - the tube that takes urine outside the body. The opening is slit-like in PUV, blocking the flow of urine
  • Renal tubular acidosis - kidney malfunction causing reduced acidity of urine and a consequent increase in acidity of blood
• Circumference of the head is large compared to the body size
• Wide forehead; triangular face and small narrow chin
• Dental abnormalities
• Very short arms; short and stout fingers and toes
• The little finger is bent permanently toward the ring finger
• Short stature in both genders:
  • An adult male’s average height is 4 feet 11 inches
  • An adult female’s average height is 4 feet 7 inches
• Frequent constipation
• Stomach emptying process if often delayed; it does not take place regularly

How is Russell-Silver Syndrome Diagnosed?

The diagnosis of Russell-Silver Syndrome is made often in early childhood, based on clinical observations, and if required, laboratory tests.

• A physical examination may reveal the following:
  • A triangle-shaped face
  • Broad forehead
  • A pointed and underdeveloped chin
  • Wide and thin mouth
• An assessment of symptoms
• An evaluation of the affected individual’s family medical history
• Laboratory tests to check for the following:
  • Sugar levels in blood
  • Bone age testing, to check if they match the child’s age
  • Measuring growth hormone levels in blood
  • Chromosome testing
  • Skeletal survey: It is an imaging test to check for fractures, tumors, and conditions that may lead to wear and tear of bones. It may be also performed to rule out other conditions that can produce symptoms similar to RSS

Prenatal diagnosis of RSS is possible through an ultrasound examination of the developing fetus, which may reveal intra-uterine growth retardation; the fetus growth may indicate that it is ‘small for gestational age (SGA)’.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Russell-Silver Syndrome?

The possible complications in individuals with Russell-Silver Syndrome include:

• Difficulties with chewing, owing to malformed chin
• Speech impediment and learning disabilities

How is Russell-Silver Syndrome Treated?

The treatment for Russell-Silver Syndrome often requires the coordinated effort of specialists from multiple medical disciplines. The treatment measures may include the following:

• Growth hormone replacement therapy, if blood tests reveal a deficiency
• Proper diet with ingestion of sufficient caloric count to ensure good glycemic control
• Reducing the intake of fatty food and eating small meals to aid regular bowel emptying
• Medications for acid-reflux such as proton pump inhibitors and H2 blockers
• Surgery for severe cases of gastroesophageal reflux; to strengthen the sphincter valve muscles
• Braces or surgery for repair of dental issues
• Physiotherapy to improve muscle tone
• Special education to address learning disabilities
• Psychological counseling may help with problems of self-image, which may arise owing to short stature

How can Russell-Silver Syndrome be Prevented?

At the present time, no methods or guidelines exit for the prevention of Russell-Silver Syndrome, since it is a genetic disorder.

• However, Russell-Silver Syndrome may be efficiently managed using:
  • Growth hormone replacement therapy to overcome deficiency
  • Good glycemic control with proper diet
  • Physical therapy
  • Special education
  • Involvement of family and friends for support
• In rare cases, where there is a family history of the condition, genetic counseling may help prospective parents in understanding the risks of having a child with RSS
• Active research is currently being conducted to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as RSS

Regular medical screening at periodic intervals with tests and physical examinations are strongly recommended.

What is the Prognosis of Russell-Silver Syndrome? (Outcomes/Resolutions)

• The prognosis of Russell-Silver Syndrome is generally favorable. Most individuals have normal life expectancy
• The typical features of RSS exhibited in infancy and childhood are not very apparent in adulthood
• Although affected individuals may have learning disabilities, intelligence is normal

Additional and relevant useful information for Russell-Silver Syndrome:

Russel-Silver Syndrome is also known by the following additional synonyms:

• Russel Syndrome
• Silver Syndrome