Silver-Russell Syndrome Clinical Presentation

Updated: May 31, 2017
  • Author: Sunil Kumar Sinha, MD; Chief Editor: Luis O Rohena, MD, FAAP, FACMG  more...
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Presentation

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
  • 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

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  • 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

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  • 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 [6]

Genital anomalies

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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

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  • 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. To date, genetic and epigenetic alteration can be detected in only half of cases with typical features. Various molecular defects have been reported, mostly involving chromosomes 7 and 11. Defects have also been reported in chromosomes 1, 15, 17 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. [7]
  • 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. [8]
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