Russell-Silver Syndrome (RSS) is a rare and genetically heterogeneous disorder characterised by intrauterine and postnatal growth retardation, distinctive facial features, and various other physical and developmental abnormalities. Named after the physicians Alexander Russell and Henry Silver, who independently described the syndrome in the 1950s, RSS typically manifests early in life and presents a unique set of challenges for affected individuals.

The primary hallmark of Russell-Silver Syndrome is growth retardation, often noticeable during pregnancy as intrauterine growth restriction (IUGR). Newborns with RSS tend to be small for gestational age, with low birth weight and short stature persisting throughout childhood and adulthood. The distinctive facial features associated with RSS include a prominent forehead, a triangular-shaped face, a small chin, and a thin upper lip. These facial characteristics contribute to the clinical diagnosis of the syndrome.

Genetic factors play an important role in the aetiology of Russell-Silver Syndrome (RSS). While various genetic abnormalities have been associated with the condition, many cases involve aberrations in the region 7p11.2-p13, specifically the imprinted genes on chromosome 11. Imprinting is the process by which certain genes are expressed in a parent-of-origin-specific manner. In the case of RSS, disruptions in the normal imprinting of genes on chromosome 11 contribute to the characteristic features of the syndrome.

Diagnosing Russell-Silver Syndrome involves a comprehensive assessment of clinical features, growth patterns, and genetic testing. Physical examination, including an evaluation of facial dysmorphism and body proportions, is crucial for diagnosis—additionally, specialised growth charts and measurements aid in assessing growth retardation. Molecular genetic testing, such as DNA methylation analysis and chromosomal microarray analysis, can confirm the presence of genetic abnormalities associated with RSS.

Management of Russell-Silver Syndrome is multidisciplinary, involving coordinated efforts from various healthcare professionals, including paediatricians, geneticists, endocrinologists, and nutritionists. Growth hormone therapy has been explored as a potential treatment to improve height in individuals with RSS. Other interventions may include nutritional support, speech therapy, and physical therapy to address developmental delays and associated challenges.

In conclusion, Russell-Silver Syndrome poses unique clinical and genetic complexities that require a thorough understanding for accurate diagnosis and effective management. Ongoing research continues to solve the intricacies of this rare disorder, contributing to advancements in medical knowledge and potential therapeutic interventions.

What Causes Russell Silver Syndrome?

Silver Russell Syndrome

The exact cause of Russell-Silver Syndrome is not fully understood, but it is believed to be associated with various genetic and epigenetic factors.

1. Genetic Factors: Most cases of Russell-Silver Syndrome are sporadic, which means they occur by chance & are not inherited from parents. However, in some cases, there may be a genetic component. Chromosomal abnormalities, such as maternal uniparental disomy of chromosome 7 (both copies of chromosome 7 inherited from the mother), have been identified in a small percentage of individuals with RSS. Additionally, mutations or alterations in certain genes that affect growth regulation may contribute to the syndrome.

2. Epigenetic Factors: Epigenetics is about changes in how genes work that don’t involve changing the actual DNA code. In the case of Russell-Silver Syndrome, evidence suggests that abnormal epigenetic regulation, particularly DNA methylation, may play a role. Methylation is a chemical transformation of DNA that can affect gene activity. Abnormal methylation patterns in certain genes involved in growth regulation may contribute to the characteristic features of RSS.

3. Imprinting Disorders: Russell-Silver Syndrome is considered an imprinting disorder. Imprinting involves the selective inactivation or activation of certain genes based on their parental origin. In the context of RSS, disruptions in the normal imprinting patterns of genes on chromosome 7, where the critical region for RSS is located, may be implicated in the syndrome.

It’s important to note that Russell-Silver Syndrome is a complex and heterogeneous condition, and not all cases may have a clear genetic or epigenetic basis. Understanding the syndrome continues to evolve as research progresses, and genetic testing may be used to identify specific genetic or epigenetic abnormalities in some individuals with RSS. However, in many medical cases, the exact cause remains unknown. Genetic counselling and thorough medical evaluation are typically recommended for individuals with Russell-Silver Syndrome and their families.

What Is Russell Silver Syndrome?

RSS is also known as Silver-Russell syndrome or Silver-Russell dwarfism. It is one of 200 types of dwarfism & one of five types of primordial dwarfism.Russell-Silver syndrome (RSS) is a rare genetic congenital growth disorder characterised by intrauterine growth restriction, poor growth after birth, a moderately large head size, a triangular facial look, a prominent forehead, body asymmetry, & significant feeding difficulty. 

The syndrome was initially described in a group of children with low birth weight, atypical facies, postnatal short stature and body asymmetry independently by Silver et al. (1953) and Russel (1954). The medical condition is thought to be caused by modifications in certain genes that control growth, such as the 11p15 region and the maternally imprinted gene H19.

How Common Is Russell-Silver Syndrome In India?

RSS is a rare condition that affects about one in every 15,000 to 100,000 births worldwide. The exact frequency of RSS in India is not known, but some studies have reported cases of RSS confirmed by genetic analysis and their response to growth hormone therapy. For example, Lohiya et al. (2018) reported two cases of RSS with hypomethylation of the 11p15 region who showed significant improvement in height after receiving growth hormone treatment for five years. However, some studies suggest that RSS may be more common in Asian populations than in other regions.

Russell-Silver Syndrome Life Expectancy

The outlook for RSS depends on the severity of the condition and the associated health complications. Most people with RSS can live normal and healthy lives, but they may need medical and therapeutic support throughout their lives. Russell-Silver syndrome does not affect life expectancy but may affect quality of life. People with RSS may face challenges such as low self-esteem, bullying, or discrimination due to their short stature or facial features. However, with proper care and support, people with RSS can overcome these challenges and achieve their goals in life.

Russell Silver Syndrome Diagnosis

Russell-Silver syndrome (RSS) is associated with several physical and developmental features. Diagnosing Russell-Silver syndrome typically involves a combination of clinical evaluation, growth assessments, and genetic testing. Here are some aspects of the diagnostic process:

1. Clinical Evaluation:

   – Physical Features: Doctors will assess physical characteristics associated with RSS, including small stature, a prominent forehead, a triangular-shaped face, and body asymmetry.

   – Developmental Milestones: Evaluating developmental milestones can help identify any delays or abnormalities in motor skills, speech, and cognitive development.

2. Growth Assessments:

   – Height and Weight Measurements: Children with RSS often exhibit growth failure, leading to short stature and low weight. Growth charts may be used to track height and weight over time.

   – Body Asymmetry: RSS may cause asymmetry in the length of the arms or legs. This can be measured and assessed during the clinical examination.

3. Genetic Testing:

   – Molecular Genetic Testing: Russell-Silver syndrome has been associated with various genetic abnormalities, including imprinting disorders involving genes on chromosome 11 (such as hypomethylation of the H19/IGF2 region). Therefore, genetic testing, such as DNA methylation analysis, may be performed to identify these genetic alterations.

   – Chromosomal Analysis: Chromosomal studies can be conducted to rule out other chromosomal abnormalities that might be causing the growth delays.

4. Additional Evaluations:

   – Endocrine Evaluation: Since growth hormone deficiency can contribute to short stature, an evaluation of the endocrine system may be conducted.

   – Radiological Imaging: X-rays may be used to assess bone age and skeletal abnormalities.

A multidisciplinary approach involving geneticists, endocrinologists, and other specialists may be necessary for a comprehensive diagnosis and management plan. Early intervention and support are often recommended to address growth and developmental challenges associated with RSS. If you suspect that someone may have Russell-Silver syndrome, it is better to consult a medical professional for a thorough evaluation & diagnosis.

Russell Silver Syndrome Treatment

Russell Silver Syndrome Treatment are not meant to cure RSS but to improve the quality of life & health outcomes of people with RSS.

Growth Hormone Therapy

One of the main treatments for RSS is growth hormone therapy (GHT), which involves infusing synthetic growth hormone into the human body to stimulate growth. GHT can help people with RSS grow faster, reach a higher adult height, and improve their body composition, bone density, and metabolism. It can also have a positive influence on cognitive & psychosocial development.

GHT usually starts at an early age (before 4 years) and continues until the end of puberty or until the growth potential is exhausted. The dose and duration of GHT depend on a variety of factors, such as the patient’s age, weight, height, growth velocity, response, and side effects. GHT is generally safe and well-tolerated, but it may have some risks and complications, such as increased intracranial pressure, scoliosis, diabetes, leukaemia, and tumour recurrence.

The cost of GHT in India varies depending on the type and brand of growth hormone used, the dose required, the frequency of injections, and the availability of insurance or government subsidies. The average cost ranges from Rs. 15,000 to Rs. 40,000 per month, which can go high up to Rs. 18 lakhs to Rs. 48 lakhs for 10 years. However, some patients may be eligible for free or subsidised GHT under certain schemes or programs offered by the government or non-governmental organisations.

Feeding Tube

Another treatment for RSS is feeding tube insertion, which involves placing a flexible tube through the nose or abdomen into the stomach or intestine to deliver liquid nutrition. A feeding tube can help people with RSS with severe feeding difficulties, such as poor appetite, vomiting, reflux, oral aversion, or swallowing problems. It can provide adequate calories and nutrients to support growth and development and prevent dehydration and malnutrition.

Feeding tube insertion is usually done in a hospital setting under general anaesthesia or sedation. The type and size of the feeding tube depend on the patient’s age, weight, and medical condition. The feeding tube may be temporary or permanent, depending on the patient’s need and prognosis. The feeding tube requires regular care and monitoring to prevent infections, blockages, or dislodgement.

The cost of feeding tube insertion in India varies depending on the type and size of feeding tube used, the hospital charges, the duration of stay and the follow-up visits. The average cost of feeding tube insertion in India ranges from Rs. 10,000 to Rs. 30,000 for a one-time procedure, plus Rs. 5,000 to Rs. 10,000 per month for maintenance and supplies. However, some patients may be eligible for free or subsidised feeding tube insertion under certain schemes or programs offered by the government or non-governmental organisations.

Bone Lengthening Surgery

Another treatment for RSS is bone lengthening surgery, which can help correct the body asymmetry and limb length discrepancy that some people with RSS have. Bone lengthening surgery is a complex procedure that involves cutting a bone and gradually stretching it using an external or internal device. This allows new bone tissue to grow & fill the gap, resulting in increased bone length.

The cost of bone lengthening surgery in India depends on the type, size, and location of the bone, the device used, and the hospital and surgeon fees. The average cost ranges from 2,00,000 to 5,00,000 INR per limb. However, this cost may vary depending on the required number and frequency of surgeries. Some insurance companies may cover part or all of the cost of bone-lengthening surgery, but this may require prior authorisation and documentation.

Other Treatments

Besides GHT and feeding tube insertion, other treatments may be beneficial for people with RSS, depending on their symptoms and complications. These include:

– Speech therapy: This can help people with RSS with speech delay or impairment due to oral-motor dysfunction or cognitive impairment. Speech therapy can improve their communication skills, language development, and social interaction.

Physiotherapy: This can help people with RSS who have motor delay or impairment due to muscle weakness or joint contractures. Physiotherapy can improve their mobility, balance, and coordination.

– Psychological counselling: This can help people with RSS who have emotional or behavioural problems due to low self-esteem, bullying or social isolation. Psychological counselling can provide them with coping strategies, emotional support and positive reinforcement.

The cost of these treatments in India varies depending on the type and frequency of therapy or surgery required, the qualification and experience of the therapist or surgeon, and the availability of insurance or government subsidies. The average cost of these treatments in India ranges from Rs. 500 to Rs. 5,000 per session for speech therapy or physiotherapy and Rs. 1,000 to Rs. 3,000 per session for psychological counselling.

Symptoms Of Russell-Silver Syndrome

The symptoms of Russell-Silver Syndrome can vary, but common features include:

1. Intrauterine Growth Restriction (IUGR): Children with RSS often exhibit poor growth while in the womb, resulting in low birth weight and length.

2. Postnatal Growth Retardation: After birth, individuals with RSS continue to experience slow growth, leading to short stature. This growth failure is typically more noticeable during the first few years of life.

3. Proportionate Short Stature: Unlike some other growth disorders, individuals with RSS usually have proportionate short stature, meaning their trunk and limbs are proportionally small for their age.

4. Feeding Difficulties: Infants with Russell-Silver Syndrome may experience feeding difficulties, which can contribute to their slow growth. This may require specialised feeding techniques or nutritional support.

5. Facial Features: Some individuals with RSS may exhibit distinctive facial features, such as a prominent forehead, a triangular-shaped face, a small chin, and a thin upper lip.

6. Body Asymmetry: Asymmetry in the length of arms or legs may be observed in individuals with RSS. One side of the body may be slightly shorter than the other.

7. Delayed Bone Age: X-rays of the hand and wrist may reveal a delay in bone age, which means the bones appear younger than expected for the individual’s chronological age.

8. Speech and Motor Delays: Some children with RSS may experience delays in speech and motor development.

It’s crucial to note that the severity & combination of symptoms can vary among individuals with Russell-Silver Syndrome. Additionally, not all individuals with RSS will exhibit every characteristic mentioned above. 

Complications Of Russell-Silver Syndrome

While the severity and specific features can vary among individuals, there are some potential complications associated with Russell-Silver Syndrome. It’s important to note that not all individuals with RSS will experience these complications, and the degree of severity can vary. Some potential complications may include:

1. Short Stature: One of the primary characteristics of RSS is short stature, which may persist throughout life. Growth hormone therapy is sometimes considered to help improve height in some cases.

2. Feeding Difficulties: Infants with RSS may experience difficulties with feeding, either due to poor sucking reflex or other oral-motor issues. This may lead to slow weight gain and require specialised feeding interventions.

3. Developmental Delays: Some children with RSS may experience delays in reaching developmental milestones, including motor skills and speech development.

4. Speech and Language Disorders: Speech and language delays are common in individuals with RSS. This may be related to oral-motor difficulties or other factors, and speech therapy may be beneficial.

5. Learning Disabilities: There can be an increased risk of learning disabilities in individuals with RSS, affecting academic performance. Educational support and interventions may be necessary.

6. Body Asymmetry: Asymmetry in limb or body size may occur in some cases. This can lead to functional issues and may require orthopaedic interventions.

7. Genitourinary Abnormalities: Some individuals with RSS may have genitourinary abnormalities, such as undescended testicles in males. Regular monitoring and appropriate medical management may be needed.

8. Puberty Delay: Delayed onset of puberty is observed in some cases. This may require hormonal therapy to induce and maintain puberty.

9. Scoliosis: There is an increased risk of scoliosis (abnormal curvature of the spine) in individuals with RSS. Regular monitoring and, if necessary, orthopaedic intervention may be required.

10. Dental Issues: Dental problems, such as delayed eruption of teeth and malocclusion, may be more common in individuals with RSS. Regular dental check-ups and interventions may be needed.

It’s crucial to note that the severity of these complications can vary widely among individuals with Russell-Silver Syndrome, and many people with RSS lead fulfilling and productive lives with appropriate medical and educational support. 

Difference Between Russell-Silver Syndrome & Silver Syndrome

Russell-Silver syndrome (RSS) and Silver syndrome are both rare genetic conditions that affect growth and development. However, they are not the same disorder. Here are some key differences between them:

– RSS is caused by changes in certain genes that control growth, such as H19 and IGF2 on chromosome 11, or by maternal uniparental disomy (UPD) of chromosome 7, which means inheriting 2 copies of chromosome 7 from the mother instead of 1 from each parent. Silver syndrome is caused by a variation in the BSCL2 gene on chromosome 11, which affects the function of nerve cells.

– RSS is characterised by low birth weight, poor growth, triangular face, small jaw, body asymmetry, feeding problems, hypoglycemia, and other features. Silver syndrome is characterised by spasticity and weakness of the lower limbs, hand deformities, and mild intellectual disability.

– RSS is diagnosed by a clinical exam and genetic testing. Silver syndrome is diagnosed by neurological exam and genetic testing.

– RSS can be treated with growth hormone therapy, nutritional support, and other interventions depending on the symptoms. The silver syndrome can be treated with physical therapy, orthopaedic surgery, and other supportive measures.

Both RSS and Silver syndrome are rare and have no cure, but with proper care and management, people with these conditions can live fulfilling lives.

Conclusion

In conclusion, Russell-Silver Syndrome (RSS) is a rare genetic disorder characterised by growth retardation, distinctive facial features, and various other physical and developmental abnormalities. The underlying causes of RSS are primarily associated with genetic mutations and imprinting disturbances, particularly involving genes on chromosome 11. The intricate interplay of these genetic factors can result in dysregulation of growth-related processes, leading to the characteristic features of the syndrome.

While there is no cure for Russell-Silver Syndrome, advancements in genetic research and medical interventions continue to enhance our understanding of the disorder & improve the management options available. As research progresses, there is hope for the development of more targeted and personalised therapies that could further enhance the outcomes for individuals with RSS. Overall, a comprehensive understanding of the causes, diagnostic methods, and treatment modalities is crucial for healthcare professionals and families navigating the complexities of Russell-Silver Syndrome.

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