For expectant parents, one of the greatest joys is watching their baby grow and develop, both in the womb and after birth. When a child is born significantly smaller than expected and struggles to gain weight and grow, it can be a source of immense worry and a sign that prompts a search for answers. For some families, this journey leads to a diagnosis of Russell-Silver syndrome (RSS), a rare and complex genetic disorder that affects growth. Living with a rare condition presents a unique set of challenges, particularly with feeding in infancy and managing short stature. However, it is vital for parents to know that RSS is a growth disorder, not a cognitive one. With the support of a dedicated multidisciplinary medical team, children with RSS can overcome their challenges and lead full, productive, and happy lives.

Russell-Silver Dwarfism, also called Russell-Silver Syndrome (RSS), is a rare genetic disorder that affects a child’s growth and development. Children with this condition are born small for their gestational age and remain shorter than average throughout life, often with a slender body, triangular face, and limb asymmetry.

Despite the term “dwarfism” sometimes being used, it’s more accurate to describe Russell-Silver Syndrome as a growth restriction syndrome, not true skeletal dysplasia. The condition may also be associated with feeding difficulties, low blood sugar, and delayed motor skills.

Analogy: Think of a child’s growth like a plant nurtured by sunlight and water. In Russell-Silver Syndrome, the plant is healthy but starts smaller and grows more slowly, not because it lacks care, but because its internal instructions for growth are uniquely calibrated.

The cause of Russell-Silver syndrome is not a “classic” genetic mutation in the way many people think of genetic disorders. Instead, it is primarily caused by a problem with epigenetics, specifically a process called genomic imprinting.

To understand this, it helps to use an analogy. Think of your DNA as a vast library of cookbooks, these are your genes. For most genes, you receive two working copies of each cookbook, one from your mother and one from your father. However, for a small number of crucial genes, especially those that regulate growth, the body follows a special rule called imprinting. Epigenetics acts like placing “sticky notes” on certain recipes. A sticky note might say, “For this recipe, only use the copy from Dad,” while placing another note that says, “For this other recipe, only use the copy from Mom.” This process selectively silences one parent’s copy of a gene, ensuring that only the other parent’s copy is active. This delicate balance is essential for normal growth.

In Russell-Silver syndrome, there is a problem with these “sticky notes” on specific chromosomes that are critical for growth. This leads to an imbalance in the growth signals. The two main known epigenetic causes are:

1. Hypomethylation of Chromosome 11p15.5 (Paternal Copy): This is the most common cause, found in about 50-60% of individuals with RSS. In this case, the “sticky notes” on the father’s copy of chromosome 11 are incorrect. This error effectively silences the father’s copy of a key growth-promoting gene (IGF2). Since the mother’s copy is naturally silenced by imprinting, the child is left with no active copy of this crucial gene, leading to restricted growth (NIH Genetic and Rare Diseases Information Center [GARD], 2021).
2. Maternal Uniparental Disomy for Chromosome 7 (mUPD7): This is the second most common cause, found in about 10% of cases. In this scenario, the child inherits both copies of chromosome 7 from their mother and none from their father. This creates a problem because several growth-regulating genes on chromosome 7 are only supposed to be active from the paternal copy. Since the child has no paternal chromosome 7, these genes are silenced, leading to poor growth.

In approximately 30-40% of people who are clinically diagnosed with RSS, the underlying genetic or epigenetic cause cannot yet be identified with current testing, suggesting there are other mechanisms that are still being discovered.

You get Russell-Silver Syndrome due to genetic or epigenetic changes that affect how growth genes function, especially during fetal development. These changes occur before birth, and the condition is typically evident from infancy.

• It is not an inherited condition in the vast majority of cases. Parents of a child with RSS are typically genetically normal and do not “carry” the condition.
• It is not caused by anything a parent did or did not do before or during pregnancy.

The risk of parents who have one child with RSS having another affected child is extremely low, generally no higher than for the general population. In very rare instances involving mutations in specific genes (not the more common imprinting errors), RSS can be inherited, but this is the exception, not the rule. Genetic counseling can help families understand their specific situation.

Russell-Silver Syndrome can vary in severity and presentation. Some children have only mild growth delays, while others show more distinct features and health issues.

The most common signs and symptoms can be grouped by category.

Growth-Related Features:

• Intrauterine Growth Restriction (IUGR): The baby is born unusually small and light for their gestational age.
• Poor Postnatal Growth: The child grows very slowly after birth, often labeled as “failure to thrive.” They typically remain far below the standard growth curves for height and weight.
• Significant Short Stature: Without treatment, adults with RSS are significantly shorter than average.

Distinctive Craniofacial Features:

• Relative Macrocephaly: The head appears large in comparison to the small body, though the head circumference itself is usually normal.
• Small, Triangular Face: The face is often small and triangular in shape, tapering to a pointed chin.
• Prominent Forehead: The forehead may appear broad and bossed.
• Downturned Mouth: The corners of the mouth may be turned downward.
• Bluish Sclera: The whites of the eyes may have a bluish tinge in infancy.

Body Asymmetry:

• Hemihypertrophy or Hemihypotrophy: This is a key feature where one side of the body, or one specific limb (like an arm or leg), grows at a different rate than the other side, making it appear larger or smaller.

Feeding and Metabolic Issues:

• Severe Feeding Difficulties: Infants and young children with RSS often have very little appetite, get full quickly, and show little interest in food. This can be extremely challenging for parents and can lead to failure to thrive.
• Risk of Hypoglycemia: Due to their low body weight and lack of muscle and fat stores, children with RSS are at risk for developing dangerously low blood sugar (hypoglycemia), especially when fasting (e.g., overnight or during illness).

Other Physical Features:

• Fifth-finger Clinodactyly: An inward curving of the little finger.
• Café-au-lait spots: The presence of light brown, flat patches on the skin.
• Delayed motor development due to low muscle tone (hypotonia).

While RSS presents many physical challenges, it is important to note that intelligence is typically normal. However, there can be a higher incidence of speech delays or learning disabilities that may require educational support.

Diagnosis

Diagnosis is clinical, based on physical features, growth patterns, and genetic testing.

Doctors often use a formal clinical scoring system to help make the diagnosis, looking for the presence of key features like IUGR, poor postnatal growth, body asymmetry, and the classic facial gestalt.

Once RSS is suspected clinically, specialized laboratory testing is performed to try to confirm the underlying epigenetic cause.

• Molecular Genetic Testing: A blood test is sent to a specialized lab to perform methylation analysis. This test looks for the two most common causes: the imprinting defect on chromosome 11 and maternal UPD7.
• A positive genetic test can confirm a clinical diagnosis. However, a negative test does not rule out RSS. In the 30-40% of cases where the genetic cause is still unknown, the diagnosis remains a clinical one based on the child’s features.

Treatment

There is no cure for Russell-Silver Syndrome, but multidisciplinary care can greatly improve growth, nutrition, and development.

Key management strategies include:

1. Nutritional Support: This is the most critical intervention in infancy and early childhood.

• High-Calorie Diet: A dietitian will work with the family to develop a plan to maximize calorie intake. This may involve high-calorie formulas or food fortifiers.
• Feeding Tube: For infants with severe feeding difficulties and failure to thrive, a feeding tube (either a temporary nasogastric tube or a more permanent gastrostomy tube, or G-tube) is often necessary. This is a crucial intervention to provide the calories needed for growth and, most importantly, to prevent dangerous hypoglycemia.

2. Growth Hormone (GH) Therapy: This is the mainstay of treatment for improving height in children with RSS.

• Daily injections of recombinant human growth hormone can significantly increase a child’s growth velocity and help them achieve a final adult height that is closer to the normal range.
• GH therapy is usually started in early childhood and continues until the child reaches their final adult height (The MAGIC Foundation, n.d.).

3. Managing Asymmetry and Skeletal Issues:

• Regular monitoring by an orthopedist is needed to check for scoliosis or significant leg length discrepancy. A simple shoe lift can often manage leg length differences.
• Physical and occupational therapy can help with low muscle tone and any motor delays.

4. Managing Hypoglycemia:

• Families must be educated on the signs of low blood sugar and the importance of regular meals and snacks. Avoiding prolonged periods of fasting is essential. Cornstarch before bedtime is sometimes used to maintain blood sugar levels overnight.

5. Developmental and Educational Support:

• Early intervention with speech therapy is often needed to address language delays.
• Educational support plans may be necessary to help with any learning challenges.

Russell-Silver syndrome is a rare and complex journey for both the children who have it and the families who love them. It is characterized by significant growth challenges that begin before birth and continue throughout childhood. The diagnosis can be difficult, and the management requires a dedicated team of specialists and a deep commitment from caregivers, especially in overcoming the severe feeding difficulties of infancy. It is vital for parents to know that the condition is the result of a random genetic error and is not their fault. While the challenges are real, the outlook is positive.

• American Academy of Dermatology Association (AADA). (n.d.). Blisters: How to care for them. The MAGIC Foundation. (n.d.). Russell-Silver Syndrome. Retrieved from https://www.magicfoundation.org/growth-disorders/russell-silver-syndrome/
• National Institutes of Health, Genetic and Rare Diseases Information Center (GARD). (2021). Russell-Silver syndrome. Retrieved from https://rarediseases.info.nih.gov/diseases/7592/russell-silver-syndrome
• National Organization for Rare Disorders (NORD). (2022). Russell-Silver Syndrome. Retrieved from https://rarediseases.org/rare-diseases/russell-silver-syndrome/