Silver-Russell Syndrome ( RSR ) is a very rare syndrome that is already characterized by prenatal growth disorders with the development of short stature. So far, only about 400 cases of the disease have been documented. The appearance is highly variable and suggests that it is not a uniform disease.
What is Silver Russell Syndrome?
Silver -Russell syndrome is characterized by intrauterine short stature. Intrauterine means that the short stature develops in the womb. The growth of the child is inhibited for reasons that are not yet exactly known. The disease was studied in more detail in 1953 and 1954 by the Englishman Henry Russel and the American Alexander Silver. For hsv definitions, please visit definitionexplorer.com.
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 when investigating. They were able to determine that this is not a uniform disease, but a complex of symptoms that is genetically determined, but which is based on different genetic defects.
The main feature of this condition is intrauterine short stature with malnutrition. Based on the documented cases, the two physicians were able to identify sporadic and familial forms of the disease. From this they concluded that it was a genetic disease.
Causes
According to recent studies, different causes can be assumed for the development of the Silver-Russell syndrome. What all forms have in common, however, is the genetic basis of the disease. So-called maternal uniparental disomy 7 (UPD(7)mat) was discovered in 15 percent of all those affected. Here, the patients each inherited two copies of the maternal chromosome no. 7.
The corresponding paternal chromosome is missing or damaged. This situation speaks for a so-called imprinting. Only one maternal chromosome 7 is active. However, the mechanisms that lead to the short stature are not yet known. In addition to this double maternal chromosome 7, another form of Silver-Russell syndrome is attributed to 40 percent to insufficient methylation of chromosome 11.
The paternal allele H19-DMR in 11p15 is affected. The undermethylated allele encodes a dysfunctional RNA. Normally the paternal H19 gene is well methylated and the corresponding maternal allele is not. If the DMR1 region of the paternal allele is methylated, the growth factor IGF2 is produced. If the paternal allele is only slightly methylated, however, this factor is no longer produced sufficiently.
In addition to the two main causes of Silver-Russell syndrome presented, other structural chromosomal changes have also been found. Extensions in the short arm of chromosome 7 or shortenings in the long arm of chromosome 17 have been found.
Symptoms, Ailments & Signs
Silver-Russell syndrome is characterized by a variety of symptoms. The main 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 set far back.
In addition, a pointed chin, eyelid folds on the eyes and a flat mouth with drooping corners of the mouth characterize those suffering from Silver-Russel Syndrome. The misaligned teeth are striking. The skin is thin and contains white to tan spots. There are deformities of fingers and toes. Bone maturation is significantly delayed, which explains the reduced growth in length. The growth is uneven.
Adult height is below average in two-thirds of those affected. However, one third is of normal size. The 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 everyone affected develops all symptoms. Mental performance is not restricted.
Diagnosis & course of disease
The diagnosis is complicated by the development of the various symptoms. If certain leading symptoms are present, it can be assumed that it is Silver-Russell syndrome. However, it is not yet known which form of the disease is present.
For this purpose, the degree of methylation 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 those affected with this defect. If it is not confirmed, a thorough examination of the genetic material must be carried out.
Complications
Silver-Russell Syndrome can lead to many different symptoms and complications, all of which significantly reduce and limit the quality of life of the affected person. As a rule, this leads to short stature and various malformations. The head of those affected is excessively large.
This complaint can lead to bullying or teasing, especially in children or young people, and thus to depression and other psychological problems. The face is also affected by the malformations, resulting in significantly reduced aesthetics. Furthermore, the Silver-Russell syndrome leads to misalignment of the teeth and problems with the bones.
These can break more easily, so patients are more likely to suffer injuries or fractures. As the disease progresses, hearing and vision problems usually develop. Mental retardation can also occur and make everyday life difficult for those affected. 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 go to the doctor?
Silver-Russell syndrome usually always requires medical treatment. This disease cannot heal itself, so the patient is dependent on treatment by a doctor in any case. Since Silver-Russell syndrome is a hereditary disease, genetic counseling should also be carried out if you wish to have children in order to prevent further complications and the inheritance of the syndrome.
A doctor should be consulted if the person concerned suffers from various malformations on the body. This leads to an oversized head and usually also to a significant underweight directly after birth. Silver-Russell syndrome can also be recognized by severe misalignment of the teeth, with most of those affected also suffering from hearing loss or a cleft palate.
In some cases, short stature also indicates Silver-Russell syndrome and must be examined by a doctor. The first diagnosis of the syndrome is most often made in the hospital right after birth. Those affected with Silver-Russell syndrome are dependent on lifelong therapy in order not to reduce their life expectancy. Since the syndrome can also lead to psychological problems, psychological treatment should also be carried out.
Treatment & Therapy
A causal treatment of the disease is not possible due to the genetic basis of Silver-Russell syndrome. The main aim is to stimulate growth by administering growth hormones. In some cases this works very well. In this way, the growth in length could be significantly increased in some cases. In other affected people, this therapy sometimes shows little or no success.
Since many sufferers also often suffer from hypoglycemia, everything should be done to avoid hypoglycaemia. Otherwise, people with SRS are usually not restricted in their quality of life. With the large number of possible symptoms, however, it can happen that there are certain limitations. In addition to hypoglycemia, possible keratoconus could lead to visual impairment.
This is where the cornea curves into a cone shape, sometimes requiring constant adjustment of glasses or contact lenses. If a cleft palate develops, corrective surgery must be performed.
Prevention
Prophylaxis for Silver-Russell syndrome is very difficult because the disease often occurs sporadically. In familial cases, a human genetic test should be carried out to determine the gene status. The risk for the offspring should then be discussed as part of a genetic consultation.
Aftercare
In most cases, those affected with Silver-Russell syndrome have no special options for aftercare. For this reason, the person affected should ideally contact a doctor at an early stage and thus initiate treatment so that complications or other symptoms do not arise in the further course.
Since Silver-Russell syndrome is a hereditary disease, it cannot usually be completely cured. Therefore, if you wish to have children, genetic counseling and testing should be carried out in any case, so that this disease cannot occur again. Most of those affected depend on the help and support of their own families in their everyday lives.
This can make everyday life much easier for those affected, which can also prevent depression and other mental disorders. In many cases, surgical interventions are necessary to alleviate the symptoms. After such a procedure, the person concerned should rest and take care of his body. You 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.
You can do that yourself
A pregnant woman is well advised to take part in all preventive and check-up examinations that are offered during pregnancy. The state of health of the offspring is checked and documented in various tests and imaging procedures. In the event of irregularities, it can already be found out at this stage which faults 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 precautions.
Stable self-confidence is necessary in everyday dealings with the disease. 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 training and exercises are also carried out independently outside of the therapies to improve the situation. Although this does not result in a cure, a reduction in the symptoms of those affected can be noticed. Coping with everyday life is made easier and well-being is increased.
Since the sick person has an increased risk of injuries or broken bones, this must be taken into account when moving around and performing sports exercises. Leisure activities must also be coordinated with the requirements of the organism.
