Silver-Russell Syndrome Workup

Updated: Feb 11, 2019
  • Author: Sunil Kumar Sinha, MD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Approach Considerations

Even with recent advancements in molecular diagnosis, Silver-Russell syndrome remains a clinical diagnosis based on a combination of characteristic features and a scoring system. To date, about 40% of cases of suspected Silver-Russell syndrome remain unexplained by currently offered molecular investigations.

Several scoring systems exist in the literature, but a published international consensus statement on the clinical diagnosis, investigation, and management of Silver-Russell syndrome endorsed the Netchine-Harbison clinical scoring system (NH-CSS), based on favorable sensitivity (98%) and negative predictive (89%) values. [14]  The NH-CSS scoring system is based on six clinical criteria, including the following:

  • Degree of SGA
  • Postnatal growth failure
  • Relative macrocephaly at birth
  • Protruding forehead
  • Body asymmetry
  • Feeding difficulty and/or low body mass index (BMI)

The presence of at least four of these six factors was classified as "likely" Silver-Russell syndrome by Azzi et al, while a determination of "unlikely" Silver-Russell syndrome was reached if three or fewer factors were found during study. [15]


Laboratory Studies

An NH-CSS–based diagnostic flow chart published in a 2017 international consensus statement on the diagnosis and management of Silver-Russell syndrome recommended 11p15 loss of methylation (LOM) and UPD(7)mat as the initial molecular studies in likely Silver-Russell syndrome. If these are negative, additional diagnostic testing may be required, including copy number variant (CNV) and/or chromosome 14q32 analysis, with subsequent UPD(14)mat, UPD(16)mat, UPD(20)mat, and CDKN1C or IGF2 mutation analysis. [14]


Imaging Studies

Obtain a hand radiograph to determine bone age. Plain film hand radiographic findings include the following:

  • Delayed bone age

  • Ivory epiphyses of distal phalanges

  • Small middle phalanx of the fifth finger in 80% of patients with Silver-Russell syndrome

  • Pseudoepiphyses at base of second metacarpal