Silver-Russell syndrome (RSR) represents a very rare syndrome that is characterized by prenatal growth disturbances with the development of short stature. So far, only about 400 cases of the disease have been documented. The presentation is highly variable, suggesting that it is not a uniform disorder.
What is Silver-Russell syndrome?
Silver-Russell syndrome is characterized by intrauterine short stature. Intrauterine means that the short stature is already formed in the womb. For reasons not yet precisely known, the growth of the child is inhibited. The disease was studied in detail in 1953 and 1954 by the Englishman Henry Russel and the American Alexander Silver. In English-speaking countries, the syndrome is also known as Russel-Silver syndrome (RSS). Henry Russel and Alexander Silver were mainly interested in the causes of this disease. In doing so, they were able to determine that it is not a uniform disease, but rather a symptom complex that is genetically determined, but which is based on different genetic defects. The main feature of this disease is intrauterine short stature with malnutrition. Based on the documented cases, the two physicians were able to demonstrate sporadically occurring and familially clustered forms of the disease. From this, they concluded even then that the disease was genetic.
Causes
According to more recent studies, different causes can be assumed for the development of Silver-Russell syndrome. However, common to all forms is the genetic basis of the disease. For example, a so-called maternal uniparental disomy 7 (UPD(7)mat) was discovered in 15 percent of all affected individuals. In this case, the patients each inherited two copies of maternal chromosome number 7. The corresponding paternal chromosome is missing or damaged. This situation is indicative of so-called imprinting. In this case, only one maternal chromosome 7 is active. However, it is not yet known which mechanisms lead to the short stature. In addition to this double maternal chromosome 7, 40 percent of another form of Silver-Russell syndrome is attributed to insufficient methylation of chromosome 11. In this case, the paternal allele H19-DMR in 11p15 is affected. The under-methylated allele encodes a non-functional RNA. Normally, the paternal H19 gene is well methylated and the corresponding maternal allele is not. When the DMR1 region of the paternal allele is methylated, the growth factor IGF2 is produced. However, when the paternal allele is poorly methylated, this factor is not adequately produced. In addition to the two main causes of Silver-Russell syndrome shown, other structural chromosomal alterations have been found. Thus, elongation in the short arm of chromosome 7 or shortening in the long arm of chromosome 17 have been found.
Symptoms, complaints, and signs
Silver-Russell syndrome is characterized by a variety of symptoms. The leading symptom is intrauterine short stature with malnutrition. The child usually weighs less than two kilograms at birth. The head is relatively large in relation to the body. The forehead is often high and bulging. The face is triangular and has low-set ears that are set far back. In addition, a pointed chin, eyelid wrinkles at the eyes and a no mouth with drooping corners of the mouth characterize those suffering from Silver-Russel syndrome. The malocclusions of the teeth are conspicuous. The skin is thin and contains white to brownish spots. There are malpositions of fingers and toes. Bone maturation is significantly delayed, which explains the reduced length growth. Growth is uneven. Adult height is below average in two-thirds of those with the disease. However, one-third exhibit normal height. Weight remains below average. Other symptoms such as cleft palate, very high-pitched voice, hearing loss, hypoglycemia, or keratoconus may occur. Overall, it should be noted that not all affected individuals develop all symptoms. Mental capacity is not impaired.
Diagnosis and course of the disease
Diagnosis is complicated by the development of the various symptoms. If certain leading symptoms are present, it can be assumed that Silver-Russell syndrome is present. However, it is not yet known which form of the disease is present.For this purpose, the methylation level of allele H19-DMR of the 11th chromosome is first determined. If this is too low, the patient is one of the 40 percent of people affected with this defect. If it is not confirmed, a basic examination of the genetic material must be performed.
Complications
Silver-Russell syndrome can lead to many different symptoms and complications, all of which significantly reduce and limit the affected person’s quality of life. It usually results in short stature and various deformities. The head of the affected person is excessively large. This complaint can lead to bullying or teasing, especially in children or adolescents, and thus to depression and other psychological complaints. The face is also affected by the deformities, resulting in significantly reduced aesthetics. Furthermore, Silver-Russell syndrome leads to malocclusions of the teeth and to complaints of the bones. These can break more easily, so that patients suffer more frequently from injuries or bone fractures. As the disease progresses, hearing and vision problems usually develop. Mental retardation can also occur and make the daily life of the affected person more difficult. They are often dependent on the help of other people. A direct and causal treatment of Silver-Russell syndrome is not possible. However, the individual malformations can be treated. In most cases, the life expectancy of those affected is not limited or reduced by the syndrome.
When should you see a doctor?
Silver-Russell syndrome usually always requires medical treatment. There can be no self-healing in this condition, so the patient will always need treatment from a doctor. Since Silver-Russell syndrome is a hereditary disease, genetic counseling should also be performed if the patient wishes to have children in order to prevent further complications and inheritance of the syndrome. A doctor should be consulted if the affected person suffers from various malformations on the body. This results in an oversized head and usually a significant underweight immediately after birth. Silver-Russell syndrome can also be recognized by severe malocclusions of the teeth, and most affected individuals also suffer from hearing loss or cleft palate. In some cases, short stature also indicates Silver-Russell syndrome and must be evaluated by a physician. The initial diagnosis of the syndrome is usually made in the hospital immediately after birth. Those affected with Silver-Russell syndrome are dependent on lifelong therapy in order not to reduce their life expectancy. Because the syndrome can also lead to psychological symptoms, psychological treatment should also be provided.
Treatment and therapy
Causal treatment of the disease is not possible because of the genetic basis of Silver-Russell syndrome. The main attempt is to stimulate growth by administering growth hormones. This is very successful in some cases. In some cases, the growth in length could be significantly increased. In other patients, this therapy sometimes shows little or no success. Since many sufferers also often suffer from hypoglycemia, everything should be done to avoid hypoglycemia. Otherwise, people with SRS are usually not restricted in their quality of life. However, with the variety of possible symptoms, some limitations may occur. In addition to hypoglycemia, a possible keratoconus could lead to visual impairment. In this case, the cornea of the eye bends in a cone shape, sometimes requiring constant adjustment of glasses or contact lenses. At
Development of a cleft palate, corrective surgery must be performed.
Prevention
Prophylaxis for Silver-Russell syndrome is very difficult because the condition often occurs sporadically. In familial clustered cases, human genetic testing should be performed to determine gene status. Human genetic counseling should then discuss the risk to offspring.
Follow-up
In most cases, no specific options for follow-up care are available to the affected person with Silver-Russell syndrome.For this reason, the affected person should ideally contact a doctor at an early stage and thus also initiate treatment so that complications or other complaints do not arise in the further course. Since Silver-Russell syndrome is a hereditary disease, it cannot usually be completely cured. Therefore, genetic counseling and testing should be performed in any case if the patient wishes to have a child, so that the disease does not recur. Most affected persons are dependent on the help and support of their own family in their daily lives. This can make the daily life of the affected person much easier, which can also prevent depression and other psychological upsets. In many cases, surgical interventions are also necessary to alleviate the symptoms. After such an operation, the affected person should rest and take care of his body. They should refrain from exertion or from stressful and physical activities. In some cases, Silver-Russell syndrome reduces the life expectancy of the affected person, although a general prediction is not possible.
Here’s what you can do yourself
A pregnant woman is well advised to participate in all the screening and checkups offered during pregnancy. In various tests and imaging procedures, the health of the offspring is checked and documented. In the event of irregularities, it is already possible at this stage to find out what disorders may be present. This gives the parents-to-be the opportunity to react to the situation at an early stage and to make appropriate decisions and take precautions. A stable self-confidence is necessary in the everyday handling of the disorder. The social environment should be informed about the disorder and the corresponding complaints. This helps to prevent misunderstandings or conflicts. Since the patient’s mental capacity is limited, support measures should be initiated at an early stage. It is helpful if, in addition, training and exercises are carried out independently outside of the therapies to improve the situation. Although this does not lead to a cure, it does alleviate the symptoms of those affected. Coping with everyday life is made easier and the sense of well-being is increased. Since patients are at increased risk of injuries or bone fractures, this must be taken into account when moving around and performing sporting exercises. Likewise, leisure activities should be adapted to the organism’s specifications.
