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Synonyms: Russell-Silver syndrome, Russell-Silver dwarfism, Silver's syndrome

Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous condition characterised by severe intrauterine and postnatal growth restriction, craniofacial disproportion and normal intelligence, downward curvature of the corner of the mouth, syndactyly and webbed fingers[1].

It was first described by Silver and co-workers in 1953, then independently by Russell in 1954[2, 3].


This is very rare.

  • Reported cases since the discovery of the syndrome number in the hundreds but it is likely to be underdiagnosed.
  • Estimates of incidence vary from 1 in 75,000 births to 1 in 100,000.

The condition occurs sporadically and, in many cases, no genetic cause can be clearly identified. SRS is genetically heterogeneous.

In recent years, it has been shown that more than 38% of patients have hypomethylation in the imprinting control region 1 of 11p15 and around 10% of patients carry a maternal uniparental disomy of chromosome 7[1]. In addition, there is a further class of mutations which are copy number variations affecting different chromosomes, mainly 11p15 and 7[5].

Presenting features[6]

SRS is primarily a clinical diagnosis but molecular testing enables confirmation of the clinical diagnosis and defines the subtype[7]. As many of the features of this condition are nonspecific, clinical diagnosis of SRS remains difficult[8].

In general the features of the syndrome are most pronounced in young children and become less obvious as the patient becomes older.

The face is characteristically small and triangular; however, the head circumference is usually normal for age. This, combined with short stature, gives the appearance of having a large head.


  • Birth weight less than 2 standard deviation (SD) from mean.
  • Poor postnatal growth - less than 2 SD from mean at diagnosis.
  • Normal occipitofrontal circumference despite growth restriction.
  • Asymmetrical patterns of growth.
  • The average height for affected males is about 151 cm and about 140 cm for affected females.


  • Normal head circumference but characteristic small, triangular face.
  • Blue sclerae.
  • High forehead tapering to micrognathic jaw.
  • Prominent nasal bridge and down-turned corners of mouth.

Gastrointestinal/metabolic difficulties

  • Feeding difficulties during infancy, including gastro-oesophageal reflux, oesophagitis, food aversion, poor appetite and faltering growth.
  • Tendency to fasting hypoglycaemia during infancy, as a result of feeding difficulties.

Developmental abnormalities

  • Poor head control in infancy, due to a relatively large head compared with the neck/trunk. Motor impairment due to poor muscle mass/function.
  • About half have learning difficulties, particularly problems with arithmetic and language.

Skeletal abnormalities

  • Late closure of the anterior fontanelle.
  • Limb asymmetry and hemihypertrophy.
  • Clinodactyly (incurving) of the little finger.
  • Camptodactyly (fixed flexion) of fingers.
  • Syndactyly (fusion) of toes.
  • Sprengel's neck deformity - unilateral shortening and webbing to trunk.
  • X-ray abnormalities include:
    • Delayed bone age.
    • 'Ivory' epiphyses of distal phalanges.
    • Small middle phalanx of the little finger - present in 4 out of 5 cases.
    • Pseudo-epiphyses at the base of second metacarpal.

Miscellaneous features

  • Increased sweating affecting the head and upper trunk.
  • Urogenital anomalies - hypospadias, posterior urethral valves.
  • Cardiac abnormalities.
  • Tendency to tumours such as Wilms' tumour, hepatocellular carcinoma, testicular seminoma and craniopharyngioma.
  • Karyotyping of a child and both parents to look for known underlying genetic abnormalities.
  • Radiographs of the hand may detect typical skeletal abnormalities.
  • Growth can be improved by optimising nutrition:
    • Enteral feeding may be needed.
    • Short stature in SRS can be treated by use of pharmacological doses of recombinant growth hormone, resulting in good short-term catch-up[9].
  • Early use of physiotherapy.
  • Educational support.

The prognosis is generally good but morbidity is very variable and will depend on the severity of associated features.

There have been no long-term follow-up studies of sufficient numbers of those with the condition to define life expectancy, morbidity and mortality definitively.

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Further reading and references

  1. Varma SN, Varma BR; Clinical spectrum of Silver - Russell syndrome. Contemp Clin Dent. 2013 Jul4(3):363-5. doi: 10.4103/0976-237X.118346.

  2. Silver HK, Kiyasu W, George J, et al; Syndrome of congenital hemihypertrophy, shortness of stature, and elevated urinary gonadotropins. Pediatrics. 1953 Oct12(4):368-76.

  3. Russell A; A syndrome of intra-uterine dwarfism recognizable at birth with cranio-facial dysostosis, disproportionately short arms, and other anomalies (5 examples). Proc R Soc Med. 1954 Dec47(12):1040-4.

  4. Ishida M; New developments in Silver-Russell syndrome and implications for clinical practice. Epigenomics. 2016 Apr8(4):563-80. doi: 10.2217/epi-2015-0010. Epub 2016 Apr 12.

  5. Eggermann T, Spengler S, Gogiel M, et al; Epigenetic and genetic diagnosis of Silver-Russell syndrome. Expert Rev Mol Diagn. 2012 Jun12(5):459-71. doi: 10.1586/erm.12.43.

  6. Marczak-Halupka A, Kalina MA, Tanska A, et al; Silver-Russell Syndrome - Part I: Clinical Characteristics and Genetic Background. Pediatr Endocrinol Diabetes Metab. 201520(3):101-6. doi: 10.18544/PEDM-20.03.0009.

  7. Wakeling EL, Brioude F, Lokulo-Sodipe O, et al; Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol. 2017 Feb13(2):105-124. doi: 10.1038/nrendo.2016.138. Epub 2016 Sep 2.

  8. Wakeling EL; Silver-Russell syndrome. Arch Dis Child. 2011 Dec96(12):1156-61. doi: 10.1136/adc.2010.190165. Epub 2011 Feb 24.

  9. Binder G, Begemann M, Eggermann T, et al; Silver-Russell syndrome. Best Pract Res Clin Endocrinol Metab. 2011 Feb25(1):153-60. doi: 10.1016/j.beem.2010.06.005.