Silver-Russell dwarfism

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Silver-Russell dwarfism
ICD-10 Q87.1
ICD-9 759.89
OMIM 180860
DiseasesDB 11748
MedlinePlus 001209
eMedicine ped/2099 

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Overview

Silver-Russell dwarfism, also called Silver-Russell syndrome (SRS) or Russell-Silver syndrome (RSS) is a growth disorder characterized by slow growth before and after birth. Babies with this condition have a low birth weight and often fail to grow and gain weight at the expected rate (failure to thrive). Head growth is normal, however, so the head may appear unusually large compared to the rest of the body. Affected children are thin and have poor appetites, and some develop low blood sugar (hypoglycemia) as a result of feeding difficulties. Adults with Russell-Silver syndrome are short; the average height for affected males is about 151 centimeters (4 feet, 11 inches) and the average height for affected females is about 140 centimeters (4 feet, 7 inches).

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.

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 females.

Incidence

The estimated incidence of Russell-Silver syndrome varies widely, from 1 in 3,000 to 1 in 100,000 people. More than 400 cases have been reported worldwide.

Pathophysiology

The genetic causes of Russell-Silver syndrome are complex. The disorder often results from the abnormal regulation of certain genes that control growth. Research has focused on genes located in particular regions of chromosome 7 and chromosome 11.

People normally inherit one copy of each chromosome from their mother and one copy from their father. For most genes, both copies are active, or "turned on," in cells. For some genes, however, only the copy inherited from a person's father (the paternal copy) is active. For other genes, only the copy inherited from a person's mother (the maternal copy) is active. These parent-specific differences in gene activation are caused by a phenomenon called genomic imprinting. Both chromosome 7 and chromosome 11 contain groups of genes that normally undergo genomic imprinting. Abnormalities involving these genes appear to be responsible for many cases of Russell-Silver syndrome.

Researchers suspect that at least one third of all cases of Russell-Silver syndrome result from changes in a process called methylation. Methylation is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. In genes that undergo genomic imprinting, methylation is one way that a gene's parent of origin is marked during the formation of egg and sperm cells. Russell-Silver syndrome has been associated with changes in methylation involving the H19 and IGF2 genes, which are located near one another on chromosome 11. These genes are thought to be involved in directing normal growth. A loss of methylation disrupts the regulation of these genes, which leads to slow growth and the other characteristic features of this disorder.

Abnormalities involving genes on chromosome 7 also cause Russell-Silver syndrome. In 7 percent to 10 percent of cases, people inherit both copies of chromosome 7 from their mother instead of one copy from each parent. This phenomenon is called maternal uniparental disomy (UPD). Maternal UPD causes people to have extra copies of genes that are active only on the maternal copy of the chromosome. These individuals do not have a paternal copy of chromosome 7 and therefore do not have any copies of genes that are active only on the paternal copy. In cases of Russell-Silver syndrome caused by maternal UPD, an imbalance in active paternal and maternal genes on chromosome 7 underlies the signs and symptoms of the disorder.

In at least 40 percent of people with Russell-Silver syndrome, the cause of the condition is unknown. It is possible that changes in chromosomes other than 7 and 11 may play a role. Researchers are working to identify additional genetic changes that underlie this disorder.

Inheritance

Most cases of Russell-Silver syndrome are sporadic, which means they occur in people with no history of the disorder in their family.

Less commonly, Russell-Silver syndrome can run in families. In some affected families, the condition appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of a genetic change in each cell is sufficient to cause the disorder. In other families, the condition has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of a gene are altered in each cell. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

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. The Syndrome is usually caused by an mUPD on chromosome 7, in 7% of the cases, which is an imprinting error where the person receives two copies of chromosome 7 from the mother (maternally inherited).

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 a diagnosis of Small for Gestational Age (SGA) at birth (Birth Weight Less than 2.8kg).
  • Feeding problems: the baby is uninterested in feeding and takes only small amounts with difficulty.
  • Excessive sweating as a baby, especially at night, and a greyness or pallor of the skin. This may be a symptom of low blood sugar (hypoglycemia).
  • Triangular shaped face with a small jaw and a pointed chin. The mouth tends to curve down.
  • A blue tinge to the whites of the eyes in younger children.
  • Head appears large: the head circumference may be of normal size, which means it can appear large in comparison to a small body size.
  • Wide and late-closing fontanelle.
  • Clinodactyly: the little finger on each hand may be small and curve inwards.
  • 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 tone.
  • Gastroesophogeal Reflux.
  • Usually Sporadic
  • A striking lack of subcutaneos fat

Treatment

Growth hormone therapy is often prescribed as part of the treatment of SRS. The hormones are given by injection typically daily from the age of 2 years old through teenage years. It may aid growth even in cases where the patient does not have a growth hormone deficiency, and medical practitioners currently believe it can also help with other related issues such as blood sugar levels. Treatment results vary depending on dosage and the beginning age of treatment. Typically growth hormone therapy will not guarantee the child reaches their "full" height potential, but significantly more than without it. Side effects include an increase in muscle tone and irregular bone growth. It is unknown if SRS and growth hormone deficiency are linked.

Eponym

It is named for Henry Silver and Alexander Russell.[1][2][3]

References

  1. synd/2892 at Who Named It
  2. A. Russell. A syndrome of "intra-uterine" dwarfism recognizable at birth with cranio-facial dysostosis, disproportionately short arms and other anomalies. Proceedings of the Royal Society of Medicine, London, 1954, 47: 1040-1044.
  3. Silver HK, Kiyasu W, George J: Syndrome of congenital hemihypertrophy, shortness of stature and elevated urinary gonadotropins. Pediatrics 1953; 12: 368-75.

External links

de:Silver-Russell-Syndrom fi:Russell-Silverin oireyhtymä



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