Silver-russell Syndrome
Disease Details
Family Health Simplified
- Description
- Silver-Russell syndrome is a rare genetic disorder characterized by growth retardation, distinctive facial features, and asymmetry of the body.
- Type
- Silver-Russell syndrome (SRS) is a congenital disorder characterized by growth retardation. The type of genetic transmission for Silver-Russell syndrome can be complex. It is most commonly associated with genetic or epigenetic changes involving chromosome 11p15 or maternal uniparental disomy of chromosome 7 (mUPD7). These alterations often occur sporadically, but in rare cases, familial transmission has been observed, suggesting a potential autosomal dominant pattern with incomplete penetrance.
- Signs And Symptoms
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Although confirmation of a specific genetic marker is in a significant number of individuals, there are no tests to clearly determine if this is what a person has. As a syndrome, a diagnosis is typically given for children upon confirmation of the presence of several symptoms listed below.Symptoms are intrauterine growth restriction (IUGR) combined with some of the following:
Often small for gestational age (SGA) at birth (birth weight less than 2.8 kg)
Feeding problems: the baby is uninterested in feeding and takes only small amounts with difficulty
Hypoglycemia
Excessive sweating as a baby, especially at night, and a greyness or pallor of the skin. This may be a symptom of hypoglycemia
Triangular face with a small jaw and a pointed chin that tends to lessen slightly with age. The mouth tends to curve down
A blue tinge to the whites of the eyes in younger children
Head circumference may be of normal size and disproportionate to a small body size
Wide and late-closing fontanelle
Clinodactyly
Body asymmetry: one side of the body grows more slowly than the other
Continued poor growth with no "catch up" into the normal centile lines on growth chart
Precocious puberty (occasionally)
Low muscle tone
Gastroesophageal reflux disease
A striking lack of subcutaneous fat
Constipation (sometimes severe)The average adult height for patients without growth hormone treatment is 4'11" (149.9 cm) for males and 4'7" (139.7 cm) for females. - Prognosis
- Silver-Russell syndrome (SRS) is a congenital condition characterized by growth retardation, asymmetry, and various other clinical features. The prognosis for individuals with SRS can vary widely. Generally, those with SRS may experience continued growth challenges and may be shorter than average in adulthood. However, with appropriate medical interventions, including growth hormone therapy, and supportive care, many individuals can lead relatively normal lives. Regular monitoring and management of associated complications, such as hypoglycemia, feeding difficulties, and motor skill development, are crucial for improving outcomes.
- Onset
- Silver-Russell syndrome (SRS) typically has its onset in the prenatal period, with growth restriction often being noticeable by ultrasound. After birth, affected infants may present with features such as low birth weight, poor postnatal growth, and distinctive facial characteristics.
- Prevalence
- Silver-Russell syndrome, also known as Russell-Silver syndrome, is a rare genetic disorder. The estimated prevalence ranges from 1 in 30,000 to 1 in 100,000 live births.
- Epidemiology
- Silver-Russell syndrome (SRS) is a rare genetic disorder characterized by growth retardation that begins in utero. Epidemiologically, its estimated prevalence ranges from 1 in 30,000 to 1 in 100,000 live births. It affects both males and females equally. The disorder can result from various genetic and epigenetic abnormalities, with about 40-60% of cases involving abnormalities on chromosome 11p15 and 7-10% of cases associated with maternal uniparental disomy of chromosome 7 (mUPD7).
- Intractability
- Silver-Russell syndrome (SRS) is not considered intractable. While it is a complex and rare genetic disorder characterized by growth retardation and other physical abnormalities, many of its symptoms can be managed with appropriate medical care and interventions. This may include growth hormone therapy, nutritional support, and treatment of associated conditions. The management and prognosis can vary based on the severity of the individual case.
- Disease Severity
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Silver-Russell syndrome (SRS) is a congenital condition characterized by growth retardation. The severity of symptoms can vary significantly. Common features include:
- Intrauterine growth restriction (IUGR) leading to low birth weight
- Poor postnatal growth
- Asymmetry of the limbs or body
- Characteristic facial features such as a triangular face, prominent forehead, and a small chin
- Feeding difficulties in infancy
Some individuals may have milder forms of the condition, while others may experience more pronounced growth and developmental challenges. Regular monitoring and medical management can help address specific symptoms and improve the quality of life. - Healthcare Professionals
- Disease Ontology ID - DOID:14681
- Pathophysiology
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Silver-Russell syndrome (SRS), also known as Russell-Silver syndrome, is a congenital condition characterized by intrauterine growth restriction and postnatal growth deficiency. The pathophysiology of SRS is complex and not entirely understood, but it primarily involves genetic and epigenetic changes leading to growth abnormalities.
Key features of the pathophysiology of SRS include:
1. **Genetic Imprinting Errors:**
- **Chromosome 11p15.5:** Abnormalities in the imprinted genes on chromosome 11p15.5, such as hypomethylation of the H19/IGF2:IG-DMR (differentially methylated region), are present in about 50% of cases. This region regulates growth by controlling the expression of the insulin-like growth factor 2 (IGF2) gene, which is crucial for fetal development.
- **Chromosome 7:** Maternal uniparental disomy of chromosome 7 (UPD(7)mat) accounts for about 10% of SRS cases. This means that both copies of chromosome 7 are inherited from the mother, disrupting the normal balance of gene expression necessary for growth regulation.
2. **Growth Regulation:**
- **IGF2:** Reduced levels of IGF2, a crucial growth factor, due to the aforementioned genetic and epigenetic anomalies, result in impaired growth both before and after birth.
3. **Epigenetic Modifications:**
- Abnormalities in DNA methylation patterns are a hallmark of SRS, affecting the normal regulation of growth-promoting and growth-inhibiting genes.
These genetic and epigenetic changes disrupt the normal growth regulatory pathways, leading to the clinical manifestations seen in Silver-Russell syndrome, such as growth retardation, asymmetry, and various other physical abnormalities. - Carrier Status
- Carrier status for Silver-Russell syndrome is not typically applicable because it is generally not an inherited condition in the traditional sense. Silver-Russell syndrome usually occurs sporadically due to genetic or epigenetic changes, including abnormalities on chromosome 7 or 11.
- Mechanism
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Silver-Russell syndrome (SRS) is a genetic disorder characterized by intrauterine growth restriction and continued poor growth after birth, along with characteristic facial features and body asymmetry. The molecular mechanisms underlying SRS primarily involve genetic and epigenetic changes.
1. **Genomic Imprinting**: SRS is mainly associated with disruptions in the imprinting of genes on chromosomes 7 and 11. Imprinting refers to parent-of-origin-specific expression of certain genes.
2. **Chromosome 11p15 Abnormalities**: About 40-60% of SRS cases are linked to abnormalities on chromosome 11p15. This region contains genes regulated by imprinting, including IGF2 (Insulin-like Growth Factor 2) and H19. In SRS, there is typically a loss of methylation on the maternal allele at the IGF2/H19 imprinted control region, leading to reduced IGF2 expression, which is crucial for fetal growth.
3. **Maternal Uniparental Disomy for Chromosome 7 (mUPD7)**: Around 10% of SRS cases involve maternal uniparental disomy of chromosome 7, where both copies of chromosome 7 are inherited from the mother. This can disrupt the normal expression of imprinted genes on this chromosome.
4. **Other Genetic/ Epigenetic Causes**: Some SRS cases might involve mutations or epigenetic alterations in other genes and regions, although these are less common compared to the disruption of chromosome 11p15 and mUPD7.
Overall, the primary molecular mechanisms in SRS involve impaired regulation of imprinted genes crucial for normal fetal and postnatal growth, particularly involving alterations in methylation and gene expression patterns on chromosomes 7 and 11. - Treatment
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The caloric intake of children with SRS must be carefully controlled in order to provide the best opportunity for growth. If the child is unable to tolerate oral feeding, then enteral feeding may be used, such as the percutaneous endoscopic gastrostomy.
In children with limb-length differences or scoliosis, physiotherapy can alleviate the problems caused by these symptoms. In more severe cases, surgery to lengthen limbs may be required. To prevent aggravating posture difficulties children with leg length differences may require a raise in their shoe.Growth hormone therapy is often prescribed as part of the treatment of SRS.
The hormones are given by injection typically daily from the age of 2 years old through teenage years.
It may be effective even when the patient does not have a growth hormone deficiency.
Growth hormone therapy has been shown to increase the rate of growth in patients and consequently prompts 'catch up' growth.
This may enable the child to begin their education at a normal height, improving their self-esteem and interaction with other children.
Several studies have shown that growth hormone therapy significantly improves childhood growth and final adult height.
There are some theories suggesting that the therapy also assists with muscular development and managing hypoglycemia. - Compassionate Use Treatment
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Silver-Russell Syndrome (SRS), also known as Russell-Silver Syndrome, is a rare genetic disorder characterized by growth retardation, facial asymmetry, and other developmental anomalies. For off-label or experimental treatments:
1. **Growth Hormone Therapy:** Although primarily approved for growth hormone deficiency, this treatment is often used off-label to promote growth in children with SRS.
2. **Nutritional Interventions:** High-calorie diets and supplements are sometimes used experimentally to address growth issues and improve overall health.
3. **Orthopedic Interventions:** Experimental treatments for addressing limb length discrepancies, such as limb lengthening procedures, may be considered.
4. **Metformin:** Off-label use of metformin to address insulin resistance and metabolic issues in SRS patients has been explored.
5. **Compassionate Use Programs:** These may be available for experimental drugs or treatments, based on individual patient needs and regulatory approvals.
Always consult healthcare providers for personalized medical advice and information on emerging treatments. - Lifestyle Recommendations
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Lifestyle recommendations for individuals with Silver-Russell Syndrome typically include:
1. **Nutritional Support**: Ensure adequate nutrition to support growth and manage feeding difficulties that are common in infants and young children with the syndrome. This may involve working with a dietitian.
2. **Medical Monitoring**: Regular follow-ups with healthcare providers, including endocrinologists, to monitor growth and development. Growth hormone therapy may be considered.
3. **Physical Activity**: Encourage age-appropriate physical activities to promote physical development and overall health. Adaptations may be necessary to accommodate any physical limitations.
4. **Education and Support**: Provide educational support to address any learning difficulties. An individualized education plan (IEP) might be necessary to meet the child’s unique needs.
5. **Psychological Support**: Psychological counseling or support groups can be beneficial for coping with any social or emotional challenges associated with the syndrome.
6. **Regular Health Check-Ups**: Regular screening and management of possible associated conditions, such as skeletal anomalies, gastrointestinal issues, and dental problems.
Implementing these recommendations can help manage the condition and improve the quality of life for individuals with Silver-Russell Syndrome. - Medication
- Silver-Russell syndrome (SRS) is a congenital condition characterized by growth retardation and various physical abnormalities. There is no specific medication to treat SRS itself. Management typically focuses on addressing the individual symptoms and growth issues. Growth hormone therapy is commonly used to promote growth in children with SRS. Nutritional support, physical therapy, and developmental interventions may also be part of the treatment plan. Regular monitoring and consultations with various specialists such as endocrinologists, nutritionists, and developmental pediatricians are essential for comprehensive care.
- Repurposable Drugs
- Silver-Russell syndrome (SRS) is a rare genetic disorder characterized by growth restriction and other distinctive features. There is no specific cure for SRS, and treatment typically focuses on managing symptoms and improving quality of life. Currently, there are no widely recognized repurposable drugs specifically for the treatment of SRS. Management often includes growth hormone therapy to address growth deficiencies and supportive treatments for related conditions. Always consult a healthcare professional for the most appropriate treatment options.
- Metabolites
- Silver-Russell syndrome (SRS) is a rare congenital condition characterized by growth retardation. There isn't a specific set of metabolites uniquely associated with SRS, primarily because the syndrome results from a variety of genetic and epigenetic alterations, especially affecting chromosomes 7 and 11. The metabolic profile of individuals with SRS can vary widely and isn't typically used for diagnosis. Instead, diagnosis is based on clinical features and genetic testing.
- Nutraceuticals
- There is no established evidence to support the use of nutraceuticals for Silver-Russell syndrome. The management typically focuses on addressing growth and developmental issues through conventional medical treatments such as growth hormone therapy and nutritional support under professional guidance.
- Peptides
- Silver-Russell syndrome (SRS) is a genetic disorder primarily characterized by poor growth before and after birth, leading to short stature. It often involves specific and recognizable facial features, asymmetry of body parts, and feeding difficulties during infancy. SRS is not typically discussed in the context of peptides or nanotechnology directly. However, this syndrome is associated with genetic and epigenetic changes, particularly involving the imprinted genes on chromosomes 7 and 11. If research or therapeutic approaches involving peptides or nanotechnology are applied to genetic disorders like SRS, it would be highly specialized and experimental in nature.