OVERVIEW

What is Russell-Silver Syndrome?

Russell-Silver syndrome (SRS) is a congenital genetic disorder characterized primarily by intrauterine growth restriction (IUGR), postnatal growth failure, distinctive facial features (such as prominent forehead and micrognathia), skeletal asymmetry, congenital clinodactyly of the fifth finger, and other specific manifestations. Laboratory tests often reveal elevated urinary gonadotropins, hence the syndrome is also referred to as congenital hemihypertrophy, short stature, and elevated urinary gonadotropins syndrome. Currently, there is no specific treatment for this condition, requiring multidisciplinary management involving pediatrics, nutrition, endocrinology, and orthopedics.

Is Russell-Silver Syndrome Common?

Russell-Silver syndrome is uncommon and classified as a rare disease. In Western countries, its incidence is approximately 1 in 3,000 to 100,000 individuals. There is currently no epidemiological data on its prevalence in China, with only a few dozen reported cases.

SYMPTOMS

What are the common manifestations of Russell-Silver syndrome?

• Growth retardation: Includes intrauterine growth restriction before birth and postnatal growth delay, resulting in short stature. Affected children are often premature and have low birth weight. Growth retardation is the most characteristic feature of this condition.

• Developmental abnormalities: Characteristic facial features include a triangular face, square skull, prominent forehead, micrognathia (small jaw), low-set ears, downturned corners of the mouth (shark mouth), and dental crowding. Limb asymmetry and clinodactyly (curved fifth finger) may also occur.

• Other manifestations: Feeding difficulties, neonatal hypoglycemia, genitourinary anomalies (hypospadias, cryptorchidism, horseshoe kidney), café-au-lait spots, and gastrointestinal issues like reflux esophagitis. Some patients may experience cognitive, motor, or speech delays, as well as learning disabilities.

What are the complications of Russell-Silver syndrome?

Most affected children struggle with feeding difficulties, leading to malnutrition, hypoglycemia, and potential neurodevelopmental impairments. Significant physical deformities during childhood may contribute to psychological issues, including emotional disorders in adulthood. Therefore, mental health support for these children is crucial.

CAUSES

What is the cause of Russell-Silver syndrome?

The exact cause and pathogenesis of Silver-Russell syndrome remain unclear, but the occurrence of this condition is significantly associated with chromosomal abnormalities.

Who is more likely to develop Russell-Silver syndrome?

The cause of Silver-Russell syndrome is still unknown, and multiple factors contribute to its development. The number of cases is relatively low, making it difficult to identify high-risk populations. However, if there is a positive family history and a female carries abnormal chromosomal genes, prenatal diagnosis before pregnancy is essential. If prenatal ultrasound indicates severe early asymmetric fetal growth restriction with relative macrocephaly, the possibility of this condition should be considered. Prenatal genetic testing may be necessary to determine whether to continue the pregnancy.

Is Russell-Silver syndrome contagious?

Silver-Russell syndrome is not contagious, as it is a congenital genetic disorder.

Is Russell-Silver syndrome hereditary?

Silver-Russell syndrome has a certain degree of heritability. Currently, three inheritance patterns have been identified, including maternal uniparental disomy of chromosome 7, autosomal dominant inheritance, and autosomal recessive inheritance.

DIAGNOSIS

How is Russell-Silver syndrome diagnosed?

When diagnosing Silver-Russell syndrome, doctors primarily rely on genetic testing and the child's distinctive clinical features. The classic SRS diagnostic criteria (Price criteria) are as follows: meeting 3 or more of the following 5 criteria.

• Birth weight more than two standard deviations below the mean;

• Height below the 3rd percentile for age and sex on standard growth charts;

• Characteristic craniofacial abnormalities;

• Body asymmetry;

• Congenital clinodactyly (incurved fifth finger).

What tests are needed for suspected Russell-Silver syndrome?

Generally, physical measurements, blood tests, bone age assessment, and genetic testing are required.

• Physical measurements: Mainly used to assist diagnosis, including body appearance, height, weight, head circumference, and limb measurements.

• Blood tests: Include biochemistry, electrolytes, blood gas analysis, and endocrine hormone levels (such as thyroid hormones, glucocorticoids, and growth hormone).

• Bone age assessment: Bone age is an important imaging test for short stature, aiding in diagnosis and assessing growth potential.

• Genetic testing: Primarily used to assist diagnosis, as multiple chromosomal abnormalities are associated with the condition, with abnormalities in chromosomes 11 and 7 being the most common.

What diseases should Russell-Silver syndrome be differentiated from?

The condition should be distinguished from other diseases that cause short stature:

• 3M syndrome: Patients with 3M syndrome also exhibit intrauterine growth retardation, postnatal growth failure, and distinctive facial features, which can be confused with SRS. However, 3M syndrome patients have normal intellectual development, and imaging shows skeletal abnormalities such as slender long bones, lordosis, and tall vertebral bodies. It is an autosomal recessive disorder, commonly caused by mutations in CUL7, OBSL1, or CCDC8.

• SHORT syndrome: Patients have intrauterine growth retardation and normal cognitive development but share similar features with SRS, such as a triangular face, micrognathia, broad forehead, deep-set eyes, prominent nose, low-set and posteriorly rotated ears, facial fat atrophy, fine hair, clinodactyly, joint hyperextensibility, high-pitched voice, and susceptibility to type 2 diabetes and nephrocalcinosis. It is an autosomal dominant disorder, primarily caused by PIK3R1 mutations.

TREATMENT

Which department should I visit for Russell-Silver syndrome?

Depending on the child's specific condition and the main issues to be addressed, multiple departments may be involved, including pediatrics, nutrition, endocrinology, and orthopedics.

Can Russell-Silver syndrome resolve on its own?

No, Silver-Russell syndrome cannot resolve on its own and is a lifelong condition.

How is Russell-Silver syndrome treated?

There is currently no specific cure for Silver-Russell syndrome. Personalized management and treatment are provided by multiple departments, such as pediatrics, nutrition, endocrinology, and orthopedics, based on the child's specific condition and needs to improve quality of life.

• For feeding difficulties: Most children experience feeding difficulties, so early nutritional support is essential to reduce hypoglycemia and poor neurological development.

• For short stature: Early assessment is needed to determine whether growth hormone replacement therapy should be initiated. The U.S. FDA has approved recombinant human growth hormone for long-term use in children under 2 years old who show no catch-up growth. Recombinant human growth hormone can promote height growth, but some children may be insensitive to it, leading to suboptimal results. Therefore, growth hormone levels should be tested before treatment.

• For limb asymmetry: Asymmetry in newborns often becomes less noticeable in adulthood and usually requires no special intervention. For adults with significant limb deformities, corrective surgery may be performed.

• Neurocognitive function: Children with SRS should undergo regular follow-up assessments by pediatricians to detect and treat any language, motor, or learning-related abnormalities early.

• Long-term metabolic complication monitoring: Overfeeding and excessive weight gain in SRS patients can lead to metabolic complications such as insulin resistance and early puberty. Monitoring insulin and blood glucose levels is recommended.

Can Russell-Silver syndrome be completely cured?

There is currently no effective treatment for Silver-Russell syndrome, and it cannot be completely cured.

DIET & LIFESTYLE

Does Russell-Silver Syndrome require follow-up examinations? How to conduct them?

Silver-Russell syndrome requires regular follow-up examinations, especially for children undergoing growth hormone therapy, to monitor changes in height.

PREVENTION

Can Russell-Silver Syndrome Be Prevented?

Silver-Russell syndrome is caused by genetic abnormalities resulting from multiple factors, and there are currently no effective methods to prevent it. Prenatal diagnosis is usually not feasible for this condition.
If a patient has a positive family history or carries maternal uniparental disomy of chromosome 7, prenatal diagnosis is essential before the mother attempts another pregnancy.
If prenatal ultrasound indicates severe early asymmetric fetal growth restriction with relative macrocephaly, the possibility of this syndrome should be considered. Prenatal genetic testing may be necessary to evaluate whether to continue the pregnancy.