Wiedemann-Rautenstrauch syndrome is a congenital disease characterized by premature aging and manifests itself from the neonatal period. The development of the disease is associated with genetic mutations POLR3A, LMNA, ERCC8. The disease manifests itself in the newborn period, manifests itself in senile appearance, multiple congenital malformations, lag in growth and psychomotor development. For the diagnosis of pathology, karyotyping, neuroimaging, ECG and ultrasound of the heart are prescribed. Specific treatment of the syndrome is under development, so patients are prescribed symptomatic drugs, reconstructive operations are performed.
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Wiedemann-Rautenstrauch disease is named after two German pediatricians who independently described the typical clinical picture of the syndrome in 1977-1979. In the medical literature, pathology is also called neonatal progeroid syndrome. The disease is extremely rare: today there are only 15 cases with a confirmed diagnosis and 36 more patients with suspected Wiedemann-Rautenstrauch syndrome (SVR). The statistics of the prevalence of pathology per 100 thousand population is unknown.
The etiology and pathogenesis of the disease have not yet been precisely established. An extended genetic study reveals mutations of the POLR3A, LMNA and ERCC8 genes in sick children. The syndrome is not strictly a hereditary disease. However, in modern genetics, it is believed that the risk of recurrence of diseases in the family is about 25% – this indicates a possible autosomal recessive type of transmission of mutant genes.
Scientists have not been able to identify the mechanisms of the disease. Some experts associate its progression with disorders of hormonal and lipid metabolism, in particular with high levels of prolactin and triglycerides at cholesterol concentrations at the upper limit of normal. Physical development disorders are caused by a low content of growth hormone and insulin-like growth factor. The defeat of the central nervous system is associated with the processes of demyelination.
The external signs of Wiedemann-Rautenstrauch syndrome are noticeable from the moment of birth. The baby has a low body weight, delayed antenatal development, pseudohydrocephaly. A characteristic sign of the disease is dry wrinkled skin and pronounced veins on the skull, which in combination with a triangular face creates an old man’s appearance. The chin protrudes, the eyes are deep-set, the eyebrows and eyelashes are sparse. The hair on the head is sparse and dull. With age, the appearance of the child practically does not change.
Wideman-Rautenstrauch syndrome is characterized by a wide-open large fontanel, hypotension of skeletal muscles, lack of fatty tissue on the face and limbs. Lipoatrophy does not affect the lateral surfaces of the trunk and buttocks, which have a normal volume and baby plumpness. 70% of newborns have baby teeth. Often there is underdevelopment and shortening of the distal phalanges of the fingers and toes.
Some children with Wiedemann-Rautenstrauch syndrome have umbilical hernias, ventriculomegaly, cryptorchidism. Pathologies of the musculoskeletal system are manifested by osteopenia, articular contractures, hip dysplasia. The defeat of the respiratory system is represented by a weak cry, softening of the cartilage of the trachea, attacks of suffocation. Involvement in the process of the digestive system is manifested by gastroesophageal reflux and chronic constipation.
The most dangerous in Wiedemann-Rautenstrauch syndrome is heart damage. Infarctions at an early age and decompensation of congenital malformations are the main causes of death. Patients have vision problems caused by corneal opacity, congenital glaucoma, and retinal damage. The pathology of the basal ganglia is a great danger, which is manifested by dysregulation of autonomic functions, muscle tone, and higher nervous activity.
With Wiedemann-Rautenstrauch syndrome, there is a delay in psychomotor development, its intensity varies from compliance with the lower limit of the age norm to mental retardation. As the child grows, there is a strong deficit in length and body weight, which makes the senile facial features stand out even more. Some patients have neurological deficits in the form of ataxia, tremor, and cranial nerve damage.
Examination of a child with a typical phenotype and malformations is carried out by a pediatrician together with a geneticist. Diagnosis begins with a detailed examination of the patient, identification of external signs of underdevelopment and stigmas of embryogenesis, after which they proceed to the analysis of pregnancy and childbirth, the study of family history. The following research methods are used in the diagnostic process:
- MRI of the brain. With its help, it is possible to determine the lesion of the basal nuclei, signs of hydrocephalus, the consequences of an intracerebral hemorrhage, the study is also prescribed if a stroke is suspected. Neurosonography is actively used in newborn children as a faster and more affordable option for neuroimaging.
- Radiography of skeletal bones. Diagnosis is carried out with visible bone and joint deformities to determine the type and degree of the disorder. Echosonography, CT and MRI are used for targeted examination of affected joints.
- Ultrasound of the heart. With the help of echocardiography, congenital heart defects and major vessels are determined, the speed and nature of blood flow are assessed, and the ejection fraction is measured. Diagnosis is supplemented by electrocardiography, CT of the heart, angiography.
- Blood test. Wiedemann-Rautenstrauch syndrome is characterized by an increase in fasting glucose levels, dyslipidemia with an increase in the number of atherogenic lipoprotein fractions. In hormonal diagnostics, a decrease in insulin-like growth factor and somatotropic hormone is determined.
- Karyotyping. Genetic diagnosis is necessary to exclude other hereditary diseases caused by abnormalities in the number or shape of chromosomes. With Wiedemann-Rautenstrauch syndrome, a normal male or female karyotype is determined without pronounced chromosomal abnormalities.
Diagnosis of Wiedemann-Rautenstrauch syndrome is difficult due to its rare occurrence and unclear etiological picture. When making a diagnosis, differentiation with other syndromes accompanied by progeria is carried out. It is necessary to exclude Hutchinson-Guilford disease, the signs of which appear only in the second year of life, and Werner syndrome, manifesting in adolescence.
Today, there are no drugs in medicine that could cure the disease. Patients are prescribed symptomatic medications. Statins, anticoagulants and antihypertensive drugs are used to prevent cardiovascular crises. Low body weight and poor physical development of children remain a big problem, so recombinant growth hormone drugs are prescribed. In case of joint stiffness, physiotherapy is performed.
The help of pediatric surgeons is required for severe congenital malformations that disrupt the vital activity of the child. Most often, the operation is performed to correct cardiovascular abnormalities and is performed in the first year of the patient’s life. Timely implementation of coronary bypass surgery or angioplasty can slow down the development of cardiovascular pathology and prolong the patient’s life.
Since 2006, drugs based on farnesyltransferase inhibitors have been developed in the USA. Initially, they were intended for cancer patients to slow down the aging process of cells and return them to their normal shape. Later, the ability of drugs to act on the mechanism of progeria and slow down its development was revealed. While the development is at the stage of laboratory studies, the drugs are not used in humans as part of clinical trials.
Prognosis and prevention
The average life expectancy of a child with SVR does not exceed 6 years. The literature describes the case of death in infancy, there is also information about 3 patients who survived to adolescence. The cause of death is mainly heart attacks and strokes. Etiopathogenetic treatment of the disease has not yet been developed, so the prognosis for life is unfavorable. There are no preventive measures due to the extreme rarity of the disease and difficulties in determining its etiology.