Russell-Silver Syndrome

Synonyms: Russell-Silver dwarfism, Silver-Russell syndrome, SRS, Silver syndrome

Incidence

This is very rare.

• Reported cases since the discovery of the syndrome number in the hundreds but it may be under-diagnosed.
• Estimates of incidence vary from 1 in 3,000 births to 1 in 100,000.³

Risk factors

Advanced maternal age - >35 years⁴

The condition occurs sporadically and in most cases no genetic cause can be clearly identified.

• There have been families with autosomal dominant transmission including ring 2 chromosome, balanced translocation of 17q2 and duplication of sections of 7p.⁵
• There is research linking chromosome 11 to growth abnormalities.⁶
  • About 10% have uniparental disomy of chromosome 7 (usually maternal).⁷
  • Genomic imprinting (differing expression of a gene depending on the parent from whom it was inherited and degree of DNA methylation) and placental mosaicism play a role in the manifestations of the condition.⁸
• There are x-linked varieties of the condition.⁹

In general the features of the syndrome are most pronounced in young children and become less obvious as the patient ages.
The face is characteristically small and triangular, but the head circumference is usually normal for age. This, combined with short stature, gives the appearance of having a large head.
Some people with the syndrome have normal intelligence, others have a learning disability.

• Growth:
  • Birthweight < -2 SD from mean
  • Poor post natal growth < -2 SD from mean at diagnosis
  • Normal occipitofrontal circumference despite growth retardation
  • Asymmetrical patterns of growth
• Facies:
  • 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:
  • Feeding difficulties during infancy including gastro-oesophageal reflux, oesophagitis, food aversion and failure to thrive¹⁰
  • Tendency to fasting hypoglycaemia during infancy/early childhood¹¹
• Developmental abnormalities:
  • Poor head control in infancy due to relatively large head compared to 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 anterior fontanelle
  • Limb asymmetry and hemihypertrophy
  • Clinodactyly (incurving) of little finger
  • Camptodactyly (fixed flexion) of fingers
  • Syndactyly (fusion) of toes
  • Sprengel neck deformity - unilateral shortening and webbing to trunk
  • X-ray abnormalities include:
    • Delayed bone age
    • 'Ivory' epiphyses of distal phalanges
    • Small middle phalanx of little finger - present in 4 out of 5 cases
    • Pseudoepiphyses at the base of 2nd metacarpal
• Miscellaneous features:
  • Increased sweating affecting head and upper trunk
  • Urogenital anomalies - hyopspadias, posterior urethral valves
  • Cardiac abnormalities
  • Tendency to tumours such as Wilms' tumour, hepatocellular carcinoma, testicular seminoma and craniopharyngioma

• Causes of intrauterine growth retardation and failure to thrive
• Fetal alcohol syndrome, Fanconi syndrome - present similarly

• Karyotyping of 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
  • Growth hormone has been used in patients with a deficiency, although many have normal GH levels
• Early use of physiotherapy
• Educational support

Good on the whole with reasonably full life expectancy.
However, there have been no long-term follow up studies of sufficient numbers of sufferers to definitively define life expectancy, morbidity and mortality.