Silver-Russell Syndrome Clinical Presentation

  • Author: Robert J Ferry Jr, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Jun 14, 2011
 

History

Diagnostic criteria are not strictly established and were only recently proposed by a group whose homogeneous patients with Silver-Russell syndrome (SRS) generally had at least 4 of the following features:

  • Birthweight less than or equal to -2 standard deviations (SD) from the mean
  • Poor postnatal growth, less than or equal to -2 SD from the mean at diagnosis
  • Preservation of occipitofrontal circumference
  • Classic facial phenotype
  • Asymmetry
  • Low birthweight (≤ -2 SD)
  • Feeding difficulties during infancy
  • Tendency for fasting hypoglycemia during infancy and early childhood
  • Tendency for increased sweating during infancy, particularly on the head and upper trunk
  • Developmental delay
  • Poor head control during infancy caused by relatively large size of head compared to a small body
  • Motor impairment caused by lack of muscle bulk and strength
  • Impairment of cognitive abilities (language, arithmetic) during childhood in about 50% of patients
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Physical

Dysmorphic facies

  • Classic features include normal head circumference (head may appear large because of small body size), blue sclerae, small triangular facies, a high forehead that tapers to a small jaw, micrognathia, prominent nasal bridge, and down-turning corners of the mouth.
  • Mild dysmorphic facies include some features of the classic facies.

Growth and skeletal

  • Prenatal onset short stature (final height ≤ -3.6 SD)
  • Late closure of anterior fontanelle
  • Asymmetry, usually of the limbs
  • Hemihypertrophy
  • Clinodactyly of the fifth finger
  • Camptodactyly
  • Syndactyly of second and third toes
  • Sprengel deformity or other hand anomalies[2]

Genital anomalies

Radiographic findings, hand

Delayed bone age, ivory epiphyses of the distal phalanges, small middle phalanx of the fifth finger (80%), pseudoepiphyses at the base of the second metacarpal

Other (occasional)

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Causes

  • Silver-Russell syndrome is both clinically and genetically a heterogeneous disorder, and the basic underlying defect is not known. Silver-Russell syndrome usually occurs sporadically and its etiology is not identified in most cases. Various molecular defects have been reported, mostly involving chromosomes 7 and 17. Defects have also been reported in chromosomes 1 and X. A few cases of autosomal dominant transmission have been described, including ring 2 chromosome, balanced translocation of band 17q25, and duplication of band 7p11.2-p13.
  • Approximately 10% of patients have proven uniparental disomy (UPD) and abnormal methylation. Imprinting may play a role in the clinical phenotype of Silver-Russell syndrome in these patients. UPD results from inheritance of both alleles from one parent and no allele from the other parent (ie, loss of the allele contributed by one of the parents). Multiple reports suggest that approximately 10% of patients may have maternal UPD of chromosome 7 (mUPD7). Heterodisomy (inheritance of both alleles from one parent) and isodisomy (inheritance of 2 copies of a single allele from one parent) are both demonstrated. Partial heterodisomy or isodisomy have also been shown. Findings also suggest that imprinting defects on chromosome 11 within the 11p15 region may also play a role in Silver-Russell syndrome.[3]
  • Imprinting involves the methylation of particular bases within an allele. The methylation pattern differs depending on whether the allele is obtained from the mother or from the father's genome. If the allele is methylated, then that gene selectively is turned off.
  • Assisted reproduction technologies (ART) may increase the risk of imprinting disorders such as Silver-Russell syndrome.[4]
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Contributor Information and Disclosures
Author

Robert J Ferry Jr, MD  Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN; Brigade Surgeon, 36th Sustainment Brigade, US Army; Adjunct Professor, Pediatric Surgery Department, King Saud University, Riyadh, Saudi Arabia

Robert J Ferry Jr, MD, is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Nutropin Speakers Bureau Honoraria Speaking and teaching; Genotropin Speakers Bureau Honoraria Speaking and teaching; Eli Lilly & Co. Grant/research funds Investigator; MacroGenics, Inc. Grant/research funds Investigator; Ipsen, S.A. (formerly Tercica, Inc.) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Investigator

Specialty Editor Board

Elaine H Zackai, MD  Professor of Pediatrics, Professor of Obstetrics and Gynecology, Professor of Pediatrics in Human Genetics, University of Pennsylvania School of Medicine; Director, Clinical Genetics Center, University of Pennsylvania; Senior Physician and Director of Clinical Genetics, The Children's Hospital of Philadelphia

Elaine H Zackai, MD is a member of the following medical societies: American Cleft Palate/Craniofacial Association, American College of Medical Genetics, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Robert Anthony Saul, MD  Clinical Professor, Department of Pediatrics, University of South Carolina; Senior Clinical Geneticist, Greenwood Genetic Center

Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives

Disclosure: Nothing to disclose.

Daniel Rauch, MD, FAAP  Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine

Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine

Disclosure: Baxter Honoraria Consulting

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Ainu Prakash-Cheng, MD, PhD; Lawrence A Wetterau, MD; and Margaret M McGovern, MD, PhD, to the development and writing of this article.

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Failure of growth in weight, length, and head circumference starting at birth, suggesting an organic etiology that occurred in utero.
 
 
 
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