Russell-Silver syndrome

Información en español Title

Other Names:

Silver-Russell syndrome; Silver-Russell dwarfism; Russell Silver syndrome; Silver-Russell syndrome; Silver-Russell dwarfism; Russell Silver syndrome; Silver Russell syndrome See More

Categories:

Congenital and Genetic Diseases

Summary 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]

Last updated: 6/29/2017

Symptoms 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

Last updated: 6/29/2017

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.

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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	Underdeveloped muscles	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	Shoulder dimples	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	Abnormal curving of the spine	0002650
Percent of people who have these symptoms is not available through HPO
Abnormality of the foot	Abnormal feet morphology Abnormality of the feet Foot deformities Foot deformity [ more ]	0001760
Abnormality of the ureter		0000069
Autosomal dominant inheritance		0000006
Congenital posterior urethral valve		0010957
Craniofacial disproportion		0005461
Craniopharyngioma		0030062
Fasting hypoglycemia	Low blood sugar when fasting	0003162
Frontal bossing		0002007
Global developmental delay		0001263
Growth hormone deficiency		0000824
Hepatocellular carcinoma		0001402
Nephroblastoma		0002667
Short distal phalanx of the 5th finger	Short outermost little finger bone Short outermost pinkie finger bone Short outermost pinky finger bone [ more ]	0004227
Short middle phalanx of the 5th finger	Short middle bone of the little finger Short middle bone of the pinkie finger Short middle bone of the pinky finger [ more ]	0004220
Small for gestational age	Birth weight less than 10th percentile Low birth weight [ more ]	0001518
Sporadic	No previous family history	0003745
Syndactyly	Webbed fingers or toes	0001159
Testicular seminoma		0100617
Urethral valve		0010481

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2020

Do you have updated information on this disease? We want to hear from you.

Cause 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]

Last updated: 6/29/2017

Inheritance Inheritance

Most cases of Russell-Silver syndrome (RSS) are sporadic (not inherited), occurring in people with no family history of RSS.^[2]

Rarely, RSS may be inherited. In some families, it appears to be inherited in an autosomal dominant manner.^[4] This means that having a genetic change in only one copy of the responsible gene in each cell is enough to cause the disorder. In other families, RSS is inherited in an autosomal recessive manner.^[4] This means that to have RSS, a person must have a change in both copies of the responsible gene in each cell. Affected people inherit one copy from each parent, who is referred to as a carrier. Carriers of autosomal recessive conditions typically do not have any signs or symptoms (they are unaffected).

Last updated: 6/29/2017

Diagnosis 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]

Last updated: 6/29/2017

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 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.

Prognosis Prognosis

The long-term outlook associated with Russell-Silver syndrome is generally good,^[6] but may depend on how severely affected a person is and whether complications arise. People with RSS may face challenges from birth to adulthood. While some people with RSS believe that they are not at risk for associated health issues once they reach their adult height, recent research has shown there may be increased risks for certain health issues in adulthood. These possible risks include:^[3]

Metabolic syndrome
Uterine and vaginal dysgenesis (in females with 11p15-related RSS)
Gonadal hypofunction or testicular cancer in males
Low muscle mass or low bone mineral density
Myoclonus dystonia (in people with chromosome 7-related RSS)

Last updated: 6/29/2017

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes intrauterine growth retardation due to impaired placental function, structural or mosaic chromosomal abnormalities, neonatal progeria (Wiedemann-Rautenstrauch syndrome), 3M syndrome and Mulibrey dwarfism (see these terms). Genetic counselling depends on the molecular mechanism involved. Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Russell-Silver syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Organizations 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

Child Growth Foundation
United Kingdom
Telephone: 020 8995 0257
E-mail: info@childgrowthfoundation.org
Website: http://www.childgrowthfoundation.org
Little People of America, Inc.
617 Broadway #518
Sonoma, CA 95476
Toll-free: 1-888-572-2001
Telephone: +1-714-368-3689
Fax: +1-707-721-1896
E-mail: info@lpaonline.org
Website: https://www.lpaonline.org/
Russell Silver Syndrome Patient Support Division of the MAGIC Foundation
E-mail: rss@magicfoundation.org
Website: https://www.magicfoundation.org/
Silver Russell Syndrome Global Alliance
E-mail: http://silverrussellsyndrome.org/contact-us/
Website: http://silverrussellsyndrome.org/
The MAGIC Foundation
4200 Cantera Dr. #106
Warrenville, IL 60555
Toll-free: 800-362-4423
Telephone: 630-836-8200
Fax: 630-836-8181
E-mail: contactus@magicfoundation.org
Website: https://www.magicfoundation.org/

Social Networking Websites

Visit the following Facebook groups related to Russell-Silver syndrome:
A Day in the Life - Russell Silver Syndrome & SGA Families - MAGIC Foundation
Russell-Silver Syndrome Support
Russell Silver Syndrome RSS/SGA-Information & Support
SGA/Small for Gestational Age Parent Support-The MAGIC Foundation

Organizations Providing General Support

Human Growth Foundation
997 Glen Cove Avenue, Suite 5
Glen Head, NY 11545
Toll-free: 1-800-451-6434
Fax: 516-671-4055
E-mail: hgf1@hgfound.org
Website: http://www.hgfound.org/

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Education Resources

The Genetics Education Materials for School Success aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

Learn More 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

Genetics Home Reference (GHR) contains information on Russell-Silver syndrome. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
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

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.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

Could you advise whether there are other rare syndromes that have similar symptoms to Russell-Silver syndrome? I am asking on behalf of a mother whose child has had various tests and extensive genetic screening and is as yet undiagnosed. She has been tube fed since birth and is now nearly three years old. RSS has been suggested as a possible diagnosis. See answer
I have a niece diagnosed at approximately age 3 with RSS. She is 8 weeks pregnant. We're wondering what are the chances her baby will also have it? Possible? Probable? Not likely? Would appreciate your thoughts. See answer
I am a speech-language pathologist who has a student that was recently diagnosed with RSS. I have attempted to research the impacts of RSS on speech and language development, but have only found very generic information such as these children have small jaws and mouth and often have speech and learning delays. Do you have any specific information regarding the types of speech disorders that these children experience? Any information would be helpful since I am unfamiliar with this syndrome. See answer
What is the average lifespan for a male with Russell-Silver syndrome? See answer
Are there any other diseases with the same symptoms as Duchenne muscular dystrophy? Can Silver-Russell syndrome mimic muscular dystrophy? See answer
How can I meet other families with children with Russell-Silver syndrome? My granddaughter was recently diagnosed with this condition. I want to know how I can best support and help her as she grows. See answer