Silver-Russell dwarfism

Overview

Silver-Russell dwarfism, also called Silver-Russell syndrome (SRS) or Russell-Silver syndrome (RSS) is a growth disorder occurring in approximately 1/75000 births. In the United States it is usually referred to as Russel-Silver Syndrome, and Silver-Russell Syndrome elsewhere. It is one of 200 types of dwarfism and one of five types of primordial dwarfism and is one of the few forms that is considered treatable. Its exact cause is unknown, but present research points toward a genetic component, possibly following maternal genes. There is no statistical significance of the syndrome occurring in males or

Symptoms

Many children with Russell-Silver syndrome have a small, triangular face with distinctive facial features including a prominent forehead, a narrow chin, a small jaw, and down-turned corners of the mouth. Other features of this disorder can include an unusual curving of the fifth finger (clinodactyly), asymmetric or uneven growth of some parts of the body, and digestive system abnormalities. Russell-Silver syndrome is also associated with an increased risk of delayed development and learning disabilities.

Causes

Its exact cause is unknown, but present research points toward a genetic component, possibly following maternal genes.

It involves hypomethylation of H19 and IGF2.In 10% of the cases the syndrome is associated with maternal uniparental disomy (UPD) on chromosome 7. This is an imprinting error where the person receives two copies of chromosome 7 from the mother (maternally inherited) rather than one from each parent.

Like other imprinting disorders (e.g. Prader–Willi syndrome, Angelman syndrome, and Beckwith–Wiedemann syndrome), Silver–Russell syndrome may be associated with the use of assisted reproductive technologies such as in vitro fertilization.

Diagnosis

Although confirmation of a specific genetic marker is in a significant number of individuals, there are no tests to clearly determine if this is what a person has. As a 'syndrome' a diagnosis is typically given for children upon confirmation of the presence of several 'symptoms' listed below. Symptoms are Intrauterine Growth Restriction (IUGR) combined with some of the following:

  • Often small for gestational age (SGA) at birth (birth weight less than 2.8 kg)
  • Feeding problems: the baby is uninterested in feeding and takes only small amounts with difficulty
  • Hypoglycemia
  • Excessive sweating as a baby, especially at night, and a greyness or pallor of the skin. This may be a symptom of hypoglycemia
  • Triangular shaped face with a small jaw and a pointed chin that tends to lessen slightly with age. The mouth tends to curve down
  • A blue tinge to the whites of the eyes in younger children
  • Head circumference may be of normal size and disproportionate to a small body size
  • Wide and late-closing fontanelle
  • Clinodactyly
  • Body asymmetry: one side of the body grows more slowly than the other
  • Continued poor growth with no "catch up" into the normal centile lines on growth chart
  • Precocious puberty (occasionally)
  • Low muscle tone
  • Gastroesophageal reflux disease
  • A striking lack of subcutaneous fat
  • Late closing of the opening between the heart hemispheres
  • Constipation (sometimes severe)

In a very recent research, Dr. Mustafa Ghanim and colleagues suggested that congenital heart defects are part of this syndrome and according to a large cohort of patients (145), these defects were found in about 5.5% of patients (much more than the prevalence of these defects in the general population, which is about 1%). This new research points to the relation between congenital heart defects and epigenetic anomalies.