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Disease Profile

Russell-Silver syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Silver-Russell syndrome; Silver-Russell dwarfism; Russell Silver syndrome;

Categories

Congenital and Genetic Diseases

Summary

Russell-Silver syndrome (RSS) is a rare condition associated with poor growth both before and after birth.[1] Signs and symptoms vary and may include low birth weight, short stature, characteristic facial features, large head in relation to body size, body asymmetry, and feeding difficulties. Other features may include poor appetite, clinodactyly (curved finger), digestive system abnormalities, delayed development, and/or learning disabilities.[1][2] The genetic causes of RSS are complex and relate to certain genes that control growth. Sometimes, the genetic cause cannot be identified. Most cases are not inherited from a parent and occur sporadically. In rare cases, RSS may be inherited in an autosomal dominant or autosomal recessive manner.[2] Because RSS can lead to a wide variety of physical abnormalities and health problems, treatment ideally should be managed by a team of specialists with knowledge of RSS. Early intervention is recommended to help children with RSS reach their full potential.[1]

Symptoms

Features of Russell-Silver syndrome (RSS) can vary. Some people with RSS have many features, while others have very few features.[3] Signs and symptoms may include:[1][2][4]

  • Intrauterine growth restriction (poor growth before birth)
  • Low birth weight
  • Head that appears large in relation to body size (relative macrocephaly)
  • Poor appetite and feeding difficulties
  • Hypoglycemia
  • Poor growth after birth, leading to short stature
  • Scoliosis
  • Curving of the pinky finger (clinodactyly)
  • Characteristic facial features (prominent forehead; small, triangular-shaped face; a small jaw; a narrow chin; and down-turned corners of the mouth)
  • Arms and legs of different lengths (body asymmetry)
  • Delayed bone age
  • Gastroesophageal reflux disease or other digestive problems
  • Kidney problems
  • Developmental delay and/or learning disabilities
  • Psychosocial challenges

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Cachexia
Wasting syndrome
0004326
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Postnatal growth retardation
Growth delay as children
0008897
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Relative macrocephaly
Relatively large head
0004482
Short stature
Decreased body height
Small stature

[ more ]

0004322
Triangular face
Face with broad temples and narrow chin
Triangular facial shape

[ more ]

0000325
30%-79% of people have these symptoms
Abnormality of the calcaneus
Abnormal heel bone
0008364
Arthralgia
Joint pain
0002829
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Constipation
0002019
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Decreased muscle mass
0003199
Decreased testicular size
Small testes
Small testis

[ more ]

0008734
Delayed cranial suture closure
0000270
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Dental crowding
Crowded teeth
Dental overcrowding
Overcrowding of teeth

[ more ]

0000678
Downturned corners of mouth
Downturned corners of the mouth
Downturned mouth

[ more ]

0002714
Failure to thrive in infancy
Faltering weight in infancy
Weight faltering in infancy

[ more ]

0001531
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
High pitched voice
0001620
Insulin resistance
Body fails to respond to insulin
0000855
Lower limb asymmetry
Left and right leg differ in length or width
0100559
Low-set, posteriorly rotated ears
0000368
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Motor delay
0001270
Premature adrenarche
0012412
Premature birth
Premature delivery of affected infants
Preterm delivery

[ more ]

0001622
Recurrent hypoglycemia
Recurrent low blood sugar levels
0001988
Shoulder dimple
0010782
Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

0002360
Thin vermilion border
Decreased volume of lip
Thin lips

[ more ]

0000233
Upper limb asymmetry
Unequal size of arms
0100560
5%-29% of people have these symptoms
Abnormal vagina morphology
0000142
Abnormality of the cardiovascular system
Cardiovascular abnormality
0001626
Autistic behavior
0000729
Cafe-au-lait spot
0000957
Generalized neonatal hypotonia
Generalized low muscle tone in neonate
0008935
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Hypospadias
0000047
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Obesity
Having too much body fat
0001513
Postnatal microcephaly
0005484
Precocious puberty
Early onset of puberty
Early puberty

[ more ]

0000826
Sandal gap
Gap between 1st and 2nd toes
Gap between first and second toe
Increased space between first and second toes
Sandal gap between first and second toes
Wide space between 1st, 2nd toes
Wide space between first and second toes
Wide-spaced big toe
Widely spaced 1st-2nd toes
Widely spaced first and second toes
Widened gap 1st-2nd toes
Widened gap first and second toe

[ more ]

0001852
Scoliosis
0002650
Percent of people who have these symptoms is not available through HPO
Abnormal foot morphology
Abnormal feet structure
Abnormality of the feet
Abnormality of the foot
Foot deformities
Foot deformity

[ more ]

0001760
Abnormality of the ureter
0000069
Autosomal dominant inheritance
0000006
Congenital posterior urethral valve
0010957

Cause

Russell-Silver syndrome (RSS) is a genetic disorder that usually results from the abnormal regulation of certain genes that control growth.[2] Two genetic causes have been found to result in about 60% of the cases:[5][4]

  • Abnormalities at an imprinted region on chromosome 11p15 for some genes, only the copy inherited from a person's father (paternal copy) or mother (maternal copy) is "turned on," or expressed. These parent-specific differences in gene expression are caused by a phenomenon called genomic imprinting. Abnormalities involving genes that undergo imprinting are responsible for many cases of RSS.
  • Maternal disomy of chromosome 7 (written as matUPD7) this occurs when a child inherits both copies of chromosome 7 from the mother, instead of one copy from the mother and one copy from the father.
Other chromosome abnormalities have also been described as causing RSS, or RSS-like syndromes.[5]

In many people with RSS, the cause of the condition is unknown. Researchers are working to identify additional genetic changes that cause RSS.[2]

Diagnosis

Russell-Silver syndrome (RSS) is currently a clinical diagnosis, based on a combination of characteristic features.[1] Because the condition varies widely in severity and many of its features are nonspecific, making a diagnosis can be difficult.[1][5] Consensus guidelines including a summary of recommendations for clinical diagnosis have recently been published and can be viewed here.

Molecular genetic testing can confirm the diagnosis in around 60% of patients, and may be useful in guiding management. However, genetic testing results are negative ("normal") in a notable proportion of patients with the characteristic features of RSS. Therefore, a negative genetic test result does not exclude the diagnosis of RSS.[1]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

    Management Guidelines

    • Wakeling EL, Brioude F, Lokulo-Sodipe O, et. al. Diagnosis and management of Silver–Russell syndrome: first international consensus statement. Nat Rev Endocrinol. 2017 Feb;13(2):105-124.
    • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Organizations Providing General Support

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

          • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
          • Genetics Home Reference (GHR) contains information on Russell-Silver syndrome. This website is maintained by the National Library of Medicine.
          • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
          • The MAGIC Foundation has an information page on Russell-Silver syndrome. Please click on the link to access this resource.

            In-Depth Information

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Russell-Silver syndrome. Click on the link to view a sample search on this topic.

              Selected Full-Text Journal Articles

                References

                1. Wakeling EL, Brioude F, Lokulo-Sodipe O, et al. Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol. February, 2017; 13(2):105-124. https://www.nature.com/nrendo/journal/v13/n2/full/nrendo.2016.138.html.
                2. Russell-Silver syndrome. Genetics Home Reference. September 2016; https://ghr.nlm.nih.gov/condition=russellsilversyndrome.
                3. Russell Silver Syndrome. The MAGIC Foundation. 2018; https://www.magicfoundation.org/Growth-Disorders/Russell-Silver-Syndrome/.
                4. Howard M Saal. Russell-Silver Syndrome. GeneReviews. June 2, 2011; https://www.ncbi.nlm.nih.gov/books/NBK1324/.
                5. Netchine I and Salem J. Russell Silver syndrome. National Organization for Rare Disorders. 2017; https://rarediseases.org/rare-diseases/russell-silver-syndrome/.
                6. Toutain A. Orphanet. September, 2007; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=813.

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