Russell-Silver syndrome

The end of the study of the serious disease - Russell-Silver syndrome - has not yet been reached. But the fact is undeniable that the disease begins with intrauterine growth retardation of the fetus, disruption of the skeletal formation process, and the closure of the large fontanelle occurs only at a late stage.

Russell-Silver syndrome combines the names of two pediatricians who successfully practiced in the middle of the last century. The Englishman Russell and the American Silver encountered hundreds of cases of congenital anomalies in their practice. This was a distortion of body symmetry with a characteristic growth hypotrophy. And it was accompanied by premature, accelerated sexual maturity. In 1953, Silver described these anomalies. A year later, Russell supplemented this with information from his practice. He drew a parallel between short stature and increased gonadotropin in the urine. It turns out that the hormone of the anterior pituitary gland or gonadotropin acts as a stimulator of the development of the sex glands in both women and men.

Russell-Silver syndrome is characterized by intrauterine retardation of the child in physical development, abnormal formation of the skeletal system in infancy, and delayed closure of the fontanelle. Fortunately, the disease is not common, but it is precisely because of this that relatively little is known about this pathology, although specialized studies have been and are currently being conducted in many countries around the world.

Lack of information about Russell-Silver syndrome often leads to incorrect diagnosis and, as a result, incorrect treatment of children. Thus, instead of Russell-Silver syndrome, hydrocephalus, pituitary insufficiency, etc. are often treated.

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Epidemiology

To date, more than 400 cases of this disease have been registered. The prevalence of this disease is 1:30,000. The type of inheritance has not been established, although isolated pedigrees with Russell-Silver syndrome are known. Both girls and boys can equally fall ill with Russell-Silver syndrome.

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Causes Russell-Silver syndrome

According to the information obtained as a result of examination of patients with Russell-Silver syndrome, this disease has genetic heterogeneity. This means that the symptoms of gene pathology can be caused by mutations in different loci, or by different mutations in one locus (multiple alleles). In practice, these are nosological forms that differ from each other, etiologically united by clinical coincidence of the phenotype.

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Risk factors

The direct impact of any risk factors on the development of Russell-Silver syndrome has not been proven. However, in addition to genetic causes that cause disturbances in the formation of the fetus (approximately at 6-7 weeks of gestation), several other possible provoking factors are identified:

• birth trauma;
• mechanical compression or prolonged fetal hypoxia;
• infections (especially viral) in the first half of pregnancy.

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Pathogenesis

The pathogenesis of Russell-Silver syndrome is simple: in 10% of patients, the cause of the disease development was uniparental chromosomal disomy (RDD 7) of the maternal type. In this chromosome, groups of imprinted genes GRB 10 (protein that binds HGH 10 - human growth hormone), IGFBP 1 (protein that binds IGF 1), IGFR (IGF receptor) are localized in the region 7 q 31. The listed clusters are defined as genes that can become a possible cause of the development of Russell-Silver syndrome.

In recent years, research has identified another gene localization site, 11 p 15, where disruptions can lead to the development of Russell-Silver syndrome. However, in practice, damage to this site more often provokes the development of another syndrome, Beckwith-Wiedemann.

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Symptoms Russell-Silver syndrome

The most vivid and obvious manifestation or first signs of the disease are noticeable in the youngest children. Symptoms of Russell-Silver syndrome can be seen in a newborn child. This means that intrauterine development was delayed. Hence, the size and weight of the child does not correspond to the gestational age. And the pregnancy itself was often risky, with the threat of its termination at an early stage. The newborn has a small, triangular face, noticeably narrowing downwards. The frontal tubercles are emphasized. An enlarged skull is also noticeable. And the external genitalia are underdeveloped.

Infants often have difficulty breastfeeding. Retrospective studies by Marsaud et al found frequent digestive problems and malnutrition in children with Russell-Silver syndrome. Children have severe gastroesophageal reflux disease (55%), forceful vomiting before age 1 year (50%), persistent vomiting at age 1 year (29%), and constipation (20%).

The first signs of Russell-Silver syndrome are usually noticeable immediately after the baby is born: its weight and height at birth are noticeably lower than those of other children, despite the fact that the pregnancy is full-term. The baby's height at birth is usually less than 45 cm, and its weight is from one and a half to 2.5 kg. The body may be disproportionately built.

Later, other pathological signs of the syndrome become noticeable:

• boys are found to have cryptorchidism (abnormal positioning of the testicles);
• hypospadias (abnormal opening of the urethra);
• underdevelopment of penile tissue;
• underdevelopment of the scrotum;
• incorrect proportions of the body and limbs;
• enlargement of the cranium (pseudohydrocephalus);
• triangular face shape;
• "carp mouth" feature - a reduced mouth with drooping corners;
• early sexual development;
• high palate (sometimes with a cleft).

Auxiliary diagnostic signs of Russell-Silver syndrome may include:

• incorrect placement of subcutaneous fat;
• narrowed chest shape;
• lumbar lordosis;
• curvature of the little finger.

There are also internal developmental anomalies. Thus, problems with kidney function are often observed: during diagnostics, abnormal organ shape, curvature of the renal pelvis, and acidification of the tubules are detected.

The intellectual abilities of children with Russell-Silver syndrome are not affected.

Stages

Russell-Silver syndrome does not have any stages of development as such. However, some medical reference books sometimes mention the features of the course of the "mild" and "severe" forms of the pathology. It is noted that the term "mild" course is used in the absence of severe anomalies in the development of internal organs, in the absence of a deficiency of somatotropic hormone against the background of a pronounced low bone age.

Complications and consequences

Russell-Silver syndrome may lead to complications if there are serious disorders of the internal organs or endocrine system. Therefore, it is very important to diagnose and treat diseases associated with the syndrome at an early age. Otherwise, a number of complications of the syndrome may arise, which manifest themselves individually:

• kidney dysfunction, chronic pyelonephritis, glomerulonephritis;
• liver dysfunction;
• abnormal thyroid function;
• heart failure.

If rehabilitation measures are successful, doctors indicate a quite optimistic prognosis.

If the diagnosis of Russell-Silver syndrome is considered confirmed, and there are no signs of damage to internal organs, regular medical monitoring is still necessary, since even a minor cold can cause a sick child to develop a serious chronic disease.

Diagnostics Russell-Silver syndrome

The diagnostic method may include the following types of examination:

• collection of information on the anamnesis, including family history, with an assessment of the intensity of growth, starting from the neonatal period until the moment of diagnosis;
• control of growth and proportionality of body development;
• assessment of the biological maturity of the organism – the so-called bone age;
• baseline insulin-like growth factor 1 testing;
• standard tests to determine the presence of pituitary reserves in the production of somatotropic hormone;
• tests to determine the most common somatic pathologies;
• urine analysis for glucocorticosteroid levels;
• blood test for thyroid hormone levels;
• genetic tests (standard cytogenetic testing).

Instrumental diagnostics of the syndrome consists of the following types of research:

• X-ray diagnostics;
• Ultrasound of internal organs and thyroid gland;
• electrocardiography;
• CT and MRI;
• encephalography.

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Differential diagnosis

Russell-Silver syndrome must be differentiated from the following diseases:

1. Fanconi syndrome;
2. Nijmegen syndrome (a genetic disorder that results in a child being born with a small head, short stature, etc.);
3. Bloom syndrome (a genetic disorder characterized by short stature and an increased risk of developing cancer);
4. hydrocephalus;
5. Shereshevsky-Turner syndrome;
6. primary hypothyroidism;
7. emotional deprivation;
8. hypopituitarism.

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Treatment Russell-Silver syndrome

As with most genetic diseases, there is no specific therapy for Russell-Silver syndrome. The measures and medications used for Russell-Silver syndrome are aimed at normalizing the child's appearance and improving his or her quality of life.

In case of significant growth retardation, the patient is prescribed recombinant human growth hormone - a peptide hormonal substance that is completely identical to the human hormone of the anterior pituitary gland. Such treatment begins in childhood, no later than 13-14 years. Recombinant growth hormone consists of 191 amino acids and is produced in the form of a light freeze-dried powder for injections. The duration of treatment with RGHR can be from 3-4 months or more. The dose of the hormone can be 10-20 IU per day (for women, the dosage can be reduced to 4-8 IU). Among the side effects of treatment with RGHR are such symptoms as headache, visual impairment, swelling of the optic disc, hearing impairment, pancreatitis, edema, allergic reactions.

Treatment of the syndrome with growth hormone should be started, the earlier the better. The recommended amount of the drug for use in childhood is 0.1-0.2 U per kilogram of weight three times a week (intramuscularly or subcutaneously).

Excessively early sexual development can be corrected by using hormonal drugs. Boys are prescribed human chorionic gonadotropin for 3 months in combination with methyltestosterone. Girls are treated with estrogens. Sinestrol (in the first half of the monthly cycle) and human chorionic gonadotropin (in the second half of the monthly cycle) are also used.

In case of thyroid stimulating hormone deficiency, replacement therapy with thyroid hormones is used.

In case of corticotropin deficiency, hydrocortisone is taken in a dosage of no more than 10-15 mg per m² per day.

In case of gonadotropic hormone deficiency, steroid hormones are prescribed until the bone age associated with the onset of puberty matches. It is better to start such treatment from the age of 5-7, but not later than 18 years.

Children with genital dwarfism are given several three-month courses of intramuscular injections of testosterone enanthate, in the amount of 25 mg once every 4 weeks. This treatment will allow the size of the genitals to be corrected without side effects on the musculoskeletal system.

In case of insufficient pituitary function and releasing factor deficiency, a good effect is expected from the use of releasing hormone. It is prescribed for six months every 3 hours.

Additionally, for Russell-Silver syndrome, general strengthening treatment is prescribed:

• vitamins A and D;
• complex preparations with calcium, phosphorus and zinc;
• dietary nutrition with an emphasis on protein products and vitamins (vegetables, fruits, greens, berries, nuts, etc.).

Physiotherapy treatment

Physiotherapeutic methods are used to improve the function of the neuromuscular system, to normalize vegetative processes, to eliminate and prevent dystrophic disorders. The following methods can be a good choice for treating Russell-Silver syndrome:

• neuroelectrical stimulation, drug electrophoresis with anticholinesterase drugs;
• electrostatic massage, amplipulsophoresis, diadynamic therapy, myoelectric stimulation;
• darsonvalization, manual therapy;
• therapeutic baths (pearl, pine), contrast shower, aerotherapy;
• non-selective chromotherapy.

Sanatorium and spa treatment in specialized sanatoriums is encouraged, depending on the presence of underlying diseases of internal organs.

Folk remedies

The condition of a patient with Russell-Silver syndrome can be improved with the help of traditional medicine recipes.

1. Take three heads of garlic, separate the cloves and chop. Add four lemons, minced together with the peel, 200 g of flaxseed oil and 1 l of honey. Mix all the ingredients with a wooden spatula. Take 1 teaspoon three times a day half an hour before meals.
2. Take 200 g of chopped onion and the same amount of sugar, pour in 0.5 l of water, mix, put on low heat. Boil for an hour and a half, cool, add 3-4 tbsp. honey. Take 1 tbsp. three times a day.
3. You should eat 100 g of dried fruits such as dried apricots, bananas, and raisins every day.
4. Take 1 glass of whole clean oats, pour 0.5 l of hot water and boil over low heat for about 40 minutes. Then remove from heat and leave under a lid for at least an hour. Filter the broth, add honey to taste. Take 100-150 ml 4 times a day 30 minutes before meals.

The total duration of treatment with folk methods is from 3 months to 1 year, depending on the severity of the symptoms of the disease.

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Herbal treatment

• Pour quality vodka over the bark of the barberry bush in a ratio of 1:10, leave for 7 days in the dark. Drink 30 drops three times a day, having previously diluted it in 100 ml of water.
• Steam 1 teaspoon of dried adonis herb in 250 ml of boiling water, leave for 1 hour under the lid. Drink 1 tablespoon three times a day.
• Steam 1 teaspoon of dried borage in 250 ml of boiling water, leave overnight under a lid. Start taking in the morning: 1 tablespoon up to 6 times a day.

In addition to folk treatment of the syndrome, it is recommended to regularly add cinnamon, pine nuts, cedar oil, and flaxseed oil to food.

Homeopathy

Homeopathic treatment of patients with Russell-Silver syndrome can have a positive impact on overall well-being and quality of life if treatment is started early in the development of the main symptoms.

To improve the condition, the following homeopathic remedies may be recommended:

• Belladona 200, twice a week, for frequent acute respiratory viral infections, teething problems;
• Sulphuris LMI once a week for weak immunity, skin problems;
• Calcium fluoricum 1000 – 1 granule per 100 ml of water, one teaspoon once a week;
• Growth-norm - in case of mineral metabolism disorders, dysfunction of the central and autonomic nervous system, osteoporosis, immunodeficiency - three times a week, 5 granules under the tongue.

Surgical treatment

Surgical treatment for Russell-Silver syndrome is not always used, but only in cases where certain symptoms cause discomfort or affect the patient's quality of life. Indications for surgery may include:

• cleft palate;
• incorrect positioning of teeth and developmental anomalies of the lower jaw;
• clinodactyly – curvature or abnormal development of the fingers;
• capmtodactyly is a congenital variant of contracture;
• syndactyly - fusion of fingers;
• developmental defects of the genitals.

The question of the optimal age for surgery is decided individually: some anomalies require faster elimination, and such disorders as defects in the structure and development of the genitals are best operated upon when the patient reaches puberty.

Prevention

Nowadays, planning a healthy pregnancy necessarily includes periconceptional prophylaxis, which can significantly reduce the risk of having a child with genetic abnormalities, including Russell-Silver syndrome. This type of prophylaxis includes:

• conducting a full examination of the couple at the planning stage, which allows for the detection and treatment of many pathologies in advance - these are various infectious, hormonal or endocrine disorders that can have a negative effect on the development and formation of the fetus;
• taking vitamin supplements for several months before the start of the planning stage (vitamins B, vitamin C, retinol, folic acid);
• Genetic tests at the planning stage will help to detect developmental defects in the embryo already in the first trimester of pregnancy.
• It is recommended to refrain from consanguineous marriages, as it has been proven that close kinship between the baby's parents significantly increases the risk of developing genetic pathologies.

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Forecast

Parents of children with Russell-Silver syndrome never stop asking themselves and doctors: what is the prognosis for treatment? Will the result be favorable? No doctor will give a clear answer: although statistics are constantly changing, no one will undertake to claim that treatment will rid the child of this disease. But there is another answer, supported by real figures: both the well-being and appearance of a patient diagnosed with Russell-Silver syndrome change dramatically for the better. And this is only on condition that the parents themselves resisted the disease in tandem with an experienced endocrinologist and other specialists.

In most cases, patients diagnosed with Russell-Silver syndrome acquire a normal appearance with timely and competent treatment. Patients adapt to the conditions quite successfully and can lead a completely full life.

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