Russell-Silver syndrome

Title

Other Names:

Silver-Russell syndrome; Silver-Russell dwarfism

Categories:

Congenital and Genetic Diseases

Summary Summary

Russell-Silver syndrome (RSS) is a congenital disorder that causes poor growth; low birth weight; short height; and size differences (asymmetry) of parts of the body.^[1] Other signs and symptoms may include poor appetite; low blood sugar (hypoglycemia) due to feeding difficulties; a small, triangular face with distinctive facial features; clinodactyly (curved finger); digestive system abnormalities; delayed development; and/or learning disabilities. The genetic causes of RSS are complex and relate to certain genes that control growth. Most cases are not inherited from a parent and occur sporadically. In rare cases, it may be inherited in an autosomal dominant or autosomal recessive manner.^[2]

Last updated: 3/3/2016

Symptoms Symptoms

Signs and symptoms of Russell-Silver syndrome (RSS) can vary and may include:

intrauterine growth restriction
low birth weight
poor growth
short stature
curving of the pinky finger (clinodactyly)
characteristic facial features (wide forehead; small, triangular face; and small, narrow chin)
arms and legs of different lengths
cafe-au-lait spots (birth marks)
delayed bone age
gastroesophageal reflux disease
kidney problems
"stubby" fingers and toes
developmental delay
learning disabilities^[1]^[3]

Last updated: 3/3/2016

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Blue sclerae	90%
Clinodactyly of the 5th finger	90%
Decreased body weight	90%
Downturned corners of mouth	90%
Intrauterine growth retardation	90%
Short stature	90%
Triangular face	90%
Asymmetric growth	50%
Delayed skeletal maturation	50%
Hypoglycemia	50%
Thin vermilion border	50%
Abnormality of the cardiovascular system	7.5%
Abnormality of the urinary system	7.5%
Cognitive impairment	7.5%
Precocious puberty	7.5%
Abnormality of the foot	-
Abnormality of the ureter	-
Cafe-au-lait spot	-
Congenital posterior urethral valve	-
Craniofacial disproportion	-
Craniopharyngioma	-
Delayed cranial suture closure	-
Fasting hypoglycemia	-
Frontal bossing	-
Growth hormone deficiency	-
Hepatocellular carcinoma	-
Hypospadias	-
Nephroblastoma	-
Short distal phalanx of the 5th finger	-
Short middle phalanx of the 5th finger	-
Small for gestational age	-
Sporadic	-
Syndactyly	-
Testicular seminoma	-

Last updated: 9/1/2016

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 the majority of cases:^[4]^[3]

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 involving any of several chromosomes have also been described as causing RSS, or RSS-like syndromes.^[4] In some people with RSS, the underlying cause remains unknown.^[2]

Last updated: 3/3/2016

Inheritance Inheritance

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

Less commonly, Russell-Silver syndrome is inherited. In some families, it appears to be inherited in an autosomal dominant manner.^[3] This means that having one "copy" of a genetic change in each cell is enough to cause the disorder. In some cases, an affected person inherits the genetic change from a parent. In other cases, the change occurs for the first time in an affected person. When a person with a genetic change that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit the genetic change.

In other families, the condition is inherited in an autosomal recessive manner.^[3] This means that to be affected, 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 an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

25% (1 in 4) chance to be affected
50% (1 in 2) chance to be an unaffected carrier like each parent
25% chance to be unaffected and not be a carrier

Last updated: 3/3/2016

Diagnosis Diagnosis

Russell-Silver syndrome (RSS) is currently a clinical diagnosis, based on a combination of characteristic features - especially growth retardation both before and after birth in children with normal head circumference.^[5]^[4] Because the condition varies widely in severity and many of its features are nonspecific, making a diagnosis can be difficult.^[4]

While molecular genetic testing can confirm the diagnosis in around 60% of patients, 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.^[5]

Last updated: 9/13/2016

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

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.
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

Life expectancy for someone with Silver-Russell syndrome does not appear to be shortened.^[6] In 2011, the average life expectancy at birth of the global population was 70 years.^[7]

Last updated: 2/14/2014

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 studying or have studied Russell-Silver syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.
Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD. Suggest an organization to add.

Organizations Supporting this Disease

Little People of America, Inc.
250 El Camino Real, Suite 201
Tustin, CA 92780
Toll-free: 888-572-2001
Telephone: 714-368-3689
Fax: 714-368-3367
E-mail: info@lpaonline.org
Website: http://www.lpaonline.org/
Silver-Russell Support Group
c/o Child Growth Foundation
2 Mayfield Avenue
Chiswick London
W4 1PW
United Kingdom
Telephone: 020 8995 0257; 020 8994 7625
Fax: 020 8995 9075
The MAGIC Foundation
6645 West North Avenue
Oak Park, IL 60302
Toll-free: 800-362-4423
Telephone: 708-383-0808
Fax: 708-383-0899
E-mail: mary@magicfoundation.org
Website: http://magicfoundation.org

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/

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.

Genetics 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 GeneTests, 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.

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

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.

News & Events News & Events

News

GARD Information Navigator
May 10, 2016

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 Russell-Silver syndrome (RSS) and my boyfriend has cystic fibrosis. I recently found out that both are caused by mutations of chromosome 7. Does that mean that I could be a carrier of cystic fibrosis (CF)? 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

References References

Russell-Silver syndrome. MedlinePlus. March 2, 2016; http://www.nlm.nih.gov/medlineplus/ency/article/001209.htm.
Russell-Silver syndrome. Genetics Home Reference. 2008; http://ghr.nlm.nih.gov/condition=russellsilversyndrome.
Howard M Saal. Russell-Silver Syndrome. GeneReviews. June 2, 2011; http://www.ncbi.nlm.nih.gov/books/NBK1324/.
Netchine I and Salem J. Russell Silver syndrome. National Organization for Rare Disorders. February 20 2013; http://rarediseases.org/rare-diseases/russell-silver-syndrome/.
Wakeling EL et al. Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol. September 2, 2016; Epub ahead of print:
Stanhope R. Silver-Russell Syndrome. Contact a Family. 2012; http://www.cafamily.org.uk/medical-information/conditions/s/silver-russell-syndrome/?s=silver. Accessed 2/14/2014.
Life Expectancy. World Health Organization. 2014; http://www.who.int/gho/mortality_burden_disease/life_tables/situation_trends/en/index.html. Accessed 2/14/2014.