Russell-Silver syndrome

Definition

Russell-Silver syndrome (RSS) is one of the recognized forms of intrauterine growth retardation (IUGR) diseases. It was first independently described by H. K. Silver in 1953 and by A. Russell in 1954.

Description

Russell-Silver syndrome is one of more than 300 recognized forms of genetic disorders that lead to short stature. It is characterized by:

• the presence of a triangular shaped face
• an incurving fifth finger (clinodactyly)
• low birth weight and length (intrauterine growth retardation, or IUGR)
• a poor appetite in the first few years of life

This disorder is alternately known as Russell syndrome, Silver syndrome, or Silver-Russell syndrome. Some clinicians use the term Russell syndrome to indicate this disorder when the size of the sides of the body and the limbs are equal, and the term Silver syndrome to indicate this disorder when the size of the sides of the body or the length of the limbs is different (body asymmetry).

Genetic profile

The exact genetic cause, or causes, of RSS have not been fully identified. It is currently believed that almost all cases of RSS are the result of mutations on a gene , or possibly more than one gene, on chromosome 7.

Demographics

RSS occurs in approximately one in every 200,000 live births. Almost all cases of RSS are sporadic, that is, they appear for the first time in individuals with no family history of RSS. However, case studies indicating all three modes of inheritance—autosomal recessive, autosomal dominant, and X-linked—have been reported.

RSS does not appear to affect any particular race or ethnic group in a greater frequency than others. It is also observed equally in males and females.

Signs and symptoms

There are six characteristics that define Russell-Silver syndrome: a triangular shaped face; down turned corners of the mouth; inwardly curved little fingers (clinodactyly); a combination of low birth weight (intrauterine growth retardation) and short birth length after a full term gestation; a long, narrow head (scaphocephaly); and a poor appetite that causes slow growth after birth. These characteristics are commonly observed in people affected with RSS.

Several other characteristics are found in most, but not all, RSS affected individuals. These include:

• low blood sugar (hypoglycemia) in infancy and early childhood
• unequal body and limb size from one side of the body to the other (body asymmetry)
• late closure of the soft spot in the front of the skull
• a broad forehead
• a small chin and jaw
• crowding of the teeth or abnormally small teeth caused by a smaller than normal jaw
• an abnormally thin upper lip
• low-set, small, and prominent ears
• fusion or webbing of the toes (syndactyly)
• poor muscle tone (hypotonia)
• a condition in which the bones are not as mature as the bones of a typical person of the same age (delayed bone age)
• developmental delays

In males affected with RSS, undescended testicles and a misplacement of the urethral opening (hypospadias ) on the bottom of the penis rather than on the tip of the glans is often seen.

People affected with RSS may show other symptoms on a less uniform basis. These include:

• water on the brain
• a bluish coloration of the whites of the eyes
• a highly-arched palate
• an absence of certain teeth
• frequent ear infections caused by fluid in the ear, which can lead to temporary hearing loss
• migraine headaches
• a curvature of the spine (scoliosis ) or other problems with the spine, often caused by body asymmetry
• abnormalities of the kidneys
• an abnormally early onset of puberty (precocious puberty)
• irregularly colored spots on the skin (café-au-lait spots)
• high energy levels
• attention deficit disorder (ADD)
• fainting spells

Diagnosis

Diagnosis of RSS is generally accomplished by performing a genetic test on cells grown from a skin sample. This test must be performed prior to the fifth year of life and it is not always accurate.

A diagnosis of RSS is supported by examination of the affected individual's growth curve and daily food intakes. In a child affected with RSS, these will fall well short of the mean for children of the same age.

Body measurements for asymmetry and x rays to determine the bone age versus the actual age of the patient are also useful. Additionally, a blood test indicating hypoglycemia may indicate RSS. When RSS is suspected in males, an examination of the genitals may reveal undescended testicles or a misplacement of the urethral opening.

Treatment and management

Treatment of RSS varies on a case-by-case basis depending on the symptoms of the affected individual.

Dietary changes to increase food intake are required by all people with RSS. Many patients with RSS also require a diet high in sugars to treat hypoglycemia. When the necessary food intake can not be accomplished by dietary changes, it may be necessary to treat patients with the antihistamine periactin, which also serves as an appetite stimulant. Some patients may also benefit from a feeding pump or gastrostomy. Gastrostomy is a surgical procedure in which a permanent opening is made directly in the stomach for the introduction of food.

In cases of severe growth retardation, certain people will require the administration of an artificial form of growth hormone (recombinant growth hormone) to stimulate growth, increase the rate of growth, and to increase their final adult height.

Ear tubes may be required to improve fluid drainage from the ears of some patients affected with RSS.

In cases of body asymmetry, limb lengthening surgeries may be recommended. Alternatively, shoe lifts may be all that is necessary for the attainment of a normal gait.

Depending on the severity of physical, emotional, and psychological symptoms, some affected individuals may benefit from physical and/or occupational therapy. If ADD or other developmental problems exist, individuals with RSS may require educational assistance, such as remedial reading. In cases where the jaw is extremely small, talking may be difficult. These patients may require speech therapy.

Precocious puberty is the entrance of a child into puberty prior to the age of eight or nine. This early onset of puberty is generally accompanied by a growth spurt prior to puberty. While entering puberty before one is emotionally ready is certainly a serious problem, it is the growth spurt prior to puberty that is of major medical significance and concern.

If this growth spurt occurs prior to puberty, it is generally not as robust as if it had occurred during puberty, which causes the individual undergoing this growth spurt to grow less than a person who undergoes this process during puberty. The result is that a person who undergoes precocious puberty will generally end up much shorter in adulthood than his or her peers.

There are three hormonal therapies available in the United States to treat precocious puberty. Histrelin (trade name: Supprelin) is administered by daily injection. Leuprolide acetate (trade name: Lupron) is available as a depot formulation every four weeks. A depot formulation places medication in a tiny pump that is attached to the patient's body and releases the medication over time. Nafarelin acetate (trade name: Synarel) is administered as a nasal spray three times daily. Because of the age of people being treated, Lupron is most often the medication of choice because it is only administered once a month.

Some doctors have noticed that persons affected with RSS may have a slightly elevated chance of developing Wilm's tumor, the most common form of kidney cancer . Most cases of this type of cancer occur before the age of eight, and this condition is extremely rare in adults. It is important that children with RSS be screened with ultrasound every three months until the age of eight to make sure they have not developed Wilm's tumor. Wilm's tumor is quite treatable via surgery, chemotherapy, and/or radiation.

Prognosis

With proper medical treatment to address their individual symptoms, people affected with RSS do not, in general, have a reduced quality of life relative to the remainder of the population. As these people age, the symptoms of RSS tend to become less noticeable: the triangular shape of the face tends to lessen, muscle tone and coordination improve, appetite improves, speech improves, and learning occurs. An affected adult is generally not less happy and/or healthy than any other person.

Resources

ORGANIZATIONS

MAGIC Foundation for Children's Growth. 1327 N. Harlem Ave., Oak Park, IL 60302. (708) 383-0808 or (800) 362-4423. Fax: (708) 383-0899. mary@magicfoundation.org. <http://www.magicfoundation.org/ghd.html>.

Yahoo Groups: Russell-Silver syndrome Support Group. <http://groups.yahoo.com/group/RSS-Support>.

WEBSITES

Parker, Brandon. "Russell-Silver Syndrome." <http://www.people.unt.edu/~bsp0002/rss.htm>. (February 28, 2001).

"Russell-Silver Syndrome." Online Mendelian Inheritance in Man. <http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=180860>.

"Russell-Silver Syndrome." WebMD. <http://my.webmd.com/content/asset/adam_disease_silver_syndrome>.

Paul A. Johnson