Syndrome de Silver-Russell

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

Définition

Syndrome de Silver-Russell (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 fingers¹.

It was first described by Silver and co-workers in 1953, then independently by Russell in 1954²³.

Incidence

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 7¹. In addition, there is a further class of mutations which are copy number variations affecting different chromosomes, mainly 11p15 and 7⁵.

Caractéristiques de présentation⁶

SRS is primarily a clinical diagnosis but molecular testing enables confirmation of the clinical diagnosis and defines the subtype⁷. As many of the features of this condition are nonspecific, clinical diagnosis of SRS remains difficult⁸.

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.

Growth

• 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.

Facies

• Normal head circumference but characteristic small, triangular face.

• Sclérotique bleue.

• 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.

Anomalies squelettiques

• 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.

• Causes de un retard de croissance intra-utérin et faltering growth.

• Syndrome d'alcoolisation fœtale et Fanconi's syndrome also present similarly.

• 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-up⁹.

• 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.