Recently I have come across a post by a Facebook page named “Fatema, s Congenital heart desk” about a very rare disease Silver Russell syndrome. It is associated with poor growth both before and after birth. This disease is also known as Russell Silver syndrome (RSS). The newborn baby usually has IUGR but sparing head growth. Dr. Silver and Dr. Russell independently described this disease back in 1953 and 1954. The most common findings are short stature without catch-up growth, normal head size for age, a distinctive triangular face, low-set ears, and incurving fifth fingers. Silver-Russell syndrome (SRS) is a genetically heterogeneous disorder.
Russell-Silver syndrome (RSS) is a genetic disorder that usually results from the abnormal regulation of certain genes that control growth. Two genetic causes have been found to result in about 60% of the cases. Most cases of Russell-Silver syndrome (RSS) are sporadic (not inherited), occurring in people with no family history of RSS. Maternal uniparental disomy of chromosome 7 is observed in 10% of patients. Approximately 30% of the cases show hypomethylation of the H19 gene, located in the 11p15 imprinted region. Approximately 50% of Silver–Russell patients have hypomethylation of H19 and IGF2. This is thought to lead to low expression of IGF2 and over-expression of the H19 gene.
Silver Russell syndrome Symptoms
Features of Silver Russell syndrome can vary.
- Poor growth before birth with Low birth weight.
- Macrocephaly or large head compared to body proportion.
- Feeding difficulties.
- Broad protruding forehead
- Low-set, posteriorly rotated prominent ears
- Clinodactyly or inward curving of the 5th finger.
- Inadequate catch-up growth in the first 2 years
- Low weight-for-height.
- Underdeveloped chin & midface with Triangular face.
- Thin upper lip
- High-arched palate
- Small, crowded teeth
- Asymmetrical upper limbs.
- Congenital heart defects.
- Delayed closure of the anterior fontanel.
- Delayed development.
- Congenital hemihypertrophy.
- Low muscle mass.
- Scoliosis &/or kyphosis.
Silver Russell syndrome is usually diagnosed clinically. But sometimes difficult due to the wide variety of features. A Flow chart for investigation and diagnosis of SRS has been published by Nature.com. Molecular genetic testing can confirm the diagnosis. But a negative result does not exclude the diseases.
Silver-Russell syndrome (SRS) should be suspected in individuals who meet the NH-CSS clinical criteria [Azzi et al 2015] as follows:
- Small for gestational age (birth weight and/or length ≥2 SD below the mean for gestational age)
- Postnatal growth failure (length/height ≥ SD below the mean at 24 months)
- Relative macrocephaly at birth (head circumference >1.5 SD above birth weight and/or length)
- Frontal bossing or prominent forehead (forehead projecting beyond the facial plane on a side view as a toddler [1–3 years])
- Body asymmetry (limb length discrepancy ≥0.5 cm, or <0.5 cm with ≥2 other asymmetric body parts)
- Feeding difficulties or body mass index ≤2 SD at 24 months or current use of a feeding tube or cyproheptadine for appetite stimulation
If an individual meets four of the six criteria, the clinical diagnosis is suspected and molecular confirmation testing is warranted.
Treatment is supportive. Growth hormone therapy can speed up the growth and increases the final height but does not allow the target height to be reached. Beyond short stature and slender build, the long-term prognosis is good. Hemihypertrophy is not associated with an increased tumoral risk.
Check other Genetic Diseases.
Russell Silver Syndrome Pictures
Sources and Further reading:
- Diagnosis and management of Silver–Russell syndrome: a first international consensus statement.
- Silver-Russell Syndrome in www.ncbi.nlm.nih.gov.