Progeria aging beyond their years. Child or old man? Progeria - a mysterious genetic defect

Perhaps the most striking evidence of the decisive role of genes in aging is monogenic diseases with signs of accelerated aging (progeria). The causes of these diseases and their connection with natural aging will be discussed.

Progeria

One of the approaches to studying the molecular basis of human aging is to elucidate the causes of diseases premature aging- so-called partial progeria. For the most part, they are monogenic, which means they are easy to analyze. The disadvantage of this approach is that sometimes their symptoms only resemble the properties of normal aging, or not all properties are represented. For example, the symptoms of aging in progeria are more pronounced and may appear in a different sequence than in the case of “normal” aging. In particular, nail growth slows down with aging, while in progeria with short telomeres it stops completely. Thinning of the eyebrows with aging follows the loss of scalp hair, but, on the contrary, precedes it in progeria.
Thus, mutations of certain genes in humans lead to serious illnesses associated with signs of premature aging. What kind of diseases are these and what genes cause them? Let's find answers to these questions.

Werner syndrome

One of the most known diseases with signs of accelerated aging is Werner's syndrome (http://en.wikipedia.org/wiki/Werner_syndrome, adult progeria) - an autosomal recessive disease (that is, controlled by recessive alleles of an autosomal gene), characterized by the manifestation of symptoms of premature aging of the skin, vascular and reproductive system, bones. Until puberty, patients develop normally. Symptoms of aging begin in early adulthood. Already in at a young age they suffer from cataracts, sclerodermal and degenerative vascular changes, diabetes and atherosclerosis, osteoporosis, high frequency some types of cancer, graying. Patients die prematurely either from cancer or from cardiovascular pathology. Average duration Life expectancy for this disease is 40-50 years.
Gene function of this disease was characterized first among the genes of all progeria (pioneer). In Werner syndrome, an autosomal recessive mutation in the WRN gene, located on chromosome 8, leads to disruption of the function of a special DNA helicase. The main role of the WRN protein in the cell is to reinitiate blocked replication forks. As a result of the mutation, disruption of DNA replication and repair, gene expression, accelerated shortening of telomeres and increased sensitivity cells to apoptosis (review).

DNA helicases

Rothmund-Thompson syndrome (RTS)

A genetically related disease, autosomal recessive Rothmund-Thompson syndrome (http://en.wikipedia.org/wiki/Rothmund-Thompson "s_syndrome), is characterized by the presence of special hyperpigmentation of the skin (poikiloderma), hypersensitivity to sun rays, growth retardation, hypogonadotropic hypogonadism, anemia, soft tissue contractures, hypodontia, juvenile cataracts, problems with hair growth, osteosarcoma(the latter disease is hallmark and Werner's syndrome). Like the gene for the previous disease, the gene for this disease (RECQL4) belongs to the RecQ family of 3"-5" DNA helicases, which are involved in maintaining genome stability through the regulation of the replication fork.

Bloom's syndrome

In autosomal recessive Bloom syndrome, hypersensitivity to ultraviolet radiation, immunodeficiency, short stature, and osteosarcomas (which are the cause of death before age 30 in patients with this syndrome) are noted. Signs characteristic of aging are less pronounced than with previous syndromes, for example, premature menopause in women. Due to a mutation in the BLM gene, which belongs to the DNA helicase genes, the syndrome is characterized by genomic instability and increased risk carcinogenesis.

Hutchinson-Gilford syndrome

Very often, when people talk about progeria, they mean Hutchinson-Gilford syndrome, the so-called “progeria of children.” This is extremely rare disease (<1/1000000, тогда как частота предыдущих прогерий составляет в среднем < 1/100000). Еще одним отличием данной прогерии является то, что мутация, вызывающая ее, всегда возникает de novo, то есть не наследуется. Это не удивительно, поскольку носители погибают до репродуктивного возраста. Дети шестилетнего возраста при синдроме Хатчинсона-Гилфорда выглядят как уже пожилые люди и погибают от сильного атеросклероза к 13 годам. Данное заболевание отличают неспособность к росту, липоатрофия, костные нарушения, маленький клювообразный нос, срезанный подбородок, полная потеря волос, пятнистая гипопигментация кожи. С развитием заболевания возникают атеросклеротические бляшки , которые становятся проникающими, приводя к сердечным приступам и смерти.
The disease is associated with a defect in the gene for the structural nuclear envelope protein lamin A (lmna), which leads to changes in nuclear structure, genomic instability and impaired gene expression. The mutation leads to the synthesis of a shortened version of the protein and, accordingly, to a lack of wild-type lamin A.
Hutchinson-Gilford progeria is accompanied by defects in nuclear structure and function: there is dysmorphia of the nuclear surface, an increase in the level of DNA damage, and a decrease in the expression of a number of nuclear proteins, including the important heterochromatic proteins HP1 and LAP2 (from the group of lamin A-associated proteins). In addition, in the cells of patients, the pattern of modified histones is disrupted: there is a decrease in heterochromatin-specific trimethylation at the Lys9 residue in histone H3 (). Thus, the cell nuclei of patients with Hutchinson-Gilford progeria lose heterochromatin. As a result, pathological overactivation of a number of transcripts that are normally repressed occurs, for example, pericentric satellite repeat III (). Correction of lamin A splicing in patient cells restores: normal nuclear morphology, heterochromatin-specific histone modification, expression of a number of dysregulated genes ().

Core structure

Thus, the molecular cause of this syndrome is disturbances in the structure of the nucleus. The cell nucleus of higher organisms is a complex, highly organized repository of individual genetic information. A typical nucleus contains specific functional regions, represented by ordered chromosomes and protein subcompartments, in which specific processes, including gene expression, occur. The nuclear lamina plays an important role in the structural organization of the nucleus. It consists of lamin A and B type proteins. These intermediate filament proteins form an interwoven network located at the periphery of the nucleus and underlying the nuclear membrane. Lamina plays a regulatory role in gene expression, since lamina proteins interact with chromatin and can participate in the fixation and organization of genome regions in space. The lamina provides the mechanical and surface properties of the nucleus and is the site of docking with peripheral heterochromatin. Lamins are also distributed in the nucleoplasm, where they participate in DNA replication and transcription with the participation of the enzyme RNA polymerase II. Thus, disruption of the nuclear lamina, which interacts with chromatin, can lead to disruption of gene expression.

Restrictive dermopathy

Trichothiodystrophy

Cockayne syndrome

Ataxia-telangiectasia

Patients with the autosomal recessive disease ataxia telangiectasia suffer from neuronal degeneration, premature aging and an increased incidence of tumors. In vitro, cells from patients with this syndrome rapidly lose telomeres due to oxidative damage. Patients with ataxia telangiectasia carry a mutation in the Atm gene (ataxia teleangiectasia mutated), which encodes ATM kinase, the main sensor of DNA damage in the cell. Recognizing DNA damage at cell cycle checkpoints, ATM phosphorylates target proteins such as p53, Chk1, Chk2, BRCA1, NBS1, FANCD2, histone H2AX, which, in turn, induce cell cycle arrest and DNA repair. Mutations in the genes of some ATM targets also lead to accelerated aging.

Nijmejen breakdown syndrome (NBS)

Such mutations also include the cause of Nijmegen breakage syndrome. Patients are distinguished by microcephaly, a special facial shape, short stature, immunodeficiency, radiosensitivity, and a predisposition to lymphoid types of cancer. In the case of a mutation in the NBS1 gene, chromosomal instability occurs as a result of a defect in Holliday structures formed during the post-replicative recombination repair of double-stranded DNA breaks.

Fanconi anemia

Symptoms of Fanconi anemia include developmental defects (for example, missing fingers), red bone marrow dysfunction, acute myelogenous leukemia and other forms of cancer, often preventing survival into adulthood. In total, 7 genes are known that can lead to Fanconi anemia: FancA, FancB, FancC, FancD, FancE, FancF and FancG. The products of these genes are phosphorylated by ATM and are involved in DNA repair and S-phase arrest of the cell cycle.

The connection between progeria and telomeres

Many of the listed partial progerias are associated with short telomeres: Werner syndrome, RTS, Hutchinson-Gilford progeria, ataxia telangiectasia, NBS. In turn, accelerated telomere shortening in progeria, causing replicative aging of differentiated somatic cells and stem cell dysfunction, causes symptoms that are largely reminiscent of normal aging, such as hair loss, graying, nail dystrophy, decreased bone mass, hematological diseases, and immunodeficiencies.

Congenital dyskeratosis

An even more convincing example of the role of telomeres in progeria and aging in general is the disease dyskeratosis congenita (

Progeria is a premature aging syndrome manifested by characteristic changes in the skin and internal organs. This is a rare genetic abnormality detected 1 person in 4 million. There are no more than eighty observed cases of this disease in the world. The etiopathogenetic factors of progeria have not been fully studied.

There are two morphological forms of pathology:

Childhood progeria – Hutchinson-Gilford syndrome,
Adult progeria - Werner's syndrome.

The term “progeria” translated from ancient Greek means “early aging”. The unnatural depletion of all life support systems is due to a genetic failure. At the same time, the aging process accelerates tenfold.

For Hutchinson-Gilford syndrome Children with delayed physical development show signs of aging: baldness, wrinkles, a specific appearance. Their body changes greatly: the structure of the skin is disrupted, secondary sexual characteristics are absent, and internal organs lag behind in development. Then age-related ailments quickly develop: hearing loss, arthrosis-arthritis, atherosclerosis, stroke or heart attack, bone demineralization. An eight-year-old child with this disease looks and feels 80 years old. In mental development, sick children remain absolutely adequate. Their intellectual development does not suffer. They rarely live past 13 years of age. Boys suffer from progeria somewhat more often than girls.

example of the development of a child with childhood progeria (Hutchinson-Gilford syndrome) from 1 year to 12 years

Werner syndrome usually begins to manifest clinically in young people aged 16-20 years. Progeria in adults is accelerated aging with damage to all systems and a high risk of developing cancer of various localizations. The genomic instability that drives the normal aging process leads to a variety of pathological changes. Such patients die by the age of 30-40, having all the symptoms of extreme old age.

a patient with adult progeria (Werner syndrome) - before the onset of the disease at 15 years old and with a developed form at 48 years old

Progeria is an incurable disease that “takes away” childhood from sick children and “turns” them into real old people. Regular and adequate medical care can slow down the irreversible aging process and reduce the severity of clinical symptoms. For this purpose, medications, nutritional supplements, surgical and physiotherapeutic techniques are used.

Etiology

The main cause of progeria is a single genetic mutation, the mechanism of which is currently unknown. Some scientists believe that the true cause of the mutation lies in the heredity of the parents, others - in the impact of radiation on the embryo during X-rays of a pregnant woman.

In Werner syndrome, the process of reproduction of DNA molecules is disrupted, and in Hutchinson-Gilford syndrome, the biosynthesis of the protein that determines the shape of cell nuclei is disrupted. Genetic disorders make cells unstable, which leads to the launch of unexpected mechanisms of aging. A large amount of protein accumulates in cells that stop dividing. In this case, the shell of the nucleus becomes unstable, and the cells of the body become unusable and die prematurely. The mutation results in the production of a truncated progerin protein, which is unstable and rapidly degrades within the cell. Unlike the whole protein, it does not integrate into the nuclear lamina, which is located under the nuclear membrane and is involved in chromatin organization. The nuclear substrate is destroyed, resulting in serious problems. Progerin accumulates in the smooth muscle cells of the vascular wall. Degeneration of these cells is one of the leading manifestations of the disease.

Progeria in adults is inherited in an autosomal recessive manner. In children, the mutation is not inherited, but occurs directly in the patient’s body. This is not surprising, since carriers die before reproductive age.

Non-genetic factors influencing the development of the disease:

Lifestyle,
accompanying illnesses,
climate,
nutrition,
state of the environment,
excess sun exposure,
smoking,
hypovitaminosis,
psycho-emotional factors.

Symptoms

In children (Hutchinson-Gilford syndrome)

At birth, a sick child appears to be a normal baby. Clinical signs of progeria appear already in the first year of life. Some children develop correctly up to 2-3 years of age, and then begin to lag behind their peers in terms of height and weight. Children with progeria have a specific appearance, since the signs of the disease are characteristic and unique. All patients are strikingly similar to each other.

typical children with Hutchinson-Gilford syndrome from different families)

A 4-year-old boy with a less typical form of Hutchinson-Gilford syndrome

Sick children have a disproportionate skull with a large brain part and a small facial part. Their nose resembles the beak of a bird: it is thin and pointed. The lower jaw is poorly developed, the chin is small, the lips are thin, the ears are protruding, and the eyes are unnaturally large. The teeth grow in two rows, they are deflated and begin to fall out early. It is this set of specific features that makes sick children look like old people.
Skeletal abnormalities are the main symptom of the pathology. Sick children are characterized by short stature, underdeveloped collarbones and hips. The bones of patients are very fragile, they often break, and joint mobility is limited. Hip dislocations are common. The manifestation of the disease is dwarfism. Skeletal and nail defects are observed. The nails are yellow and convex, resembling “watch glasses.” Sick children begin to sit and walk late, their posture changes. Some are unable to walk without assistance.
The skin and subcutaneous fat become thin. Early aging in patients manifests itself in different ways: the skin becomes covered with wrinkles, its turgor decreases, the eyelids swell, and the corners of the mouth droop. Dry and wrinkled skin is especially noticeable on the face and limbs. The hair on the head falls out, becomes sparse and vellus, and there are no eyelashes or eyebrows. A venous network is visible through the thinned skin on the head. Due to the lack of subcutaneous fat, the child looks like a skeleton covered with skin. Dry and wrinkled skin atrophies in places, large areas of hyperpigmentation, thickening and keratinization appear on it.
Other symptoms: infantilism, shrill voice, muscle wasting, short arms, narrow and protruding chest.

In adults (Werner syndrome)

The first clinical signs of Werner syndrome appear by the age of 14-18 years. Until puberty, patients develop normally. Then they begin to lag behind their peers in physical development, go bald, and turn gray. Their skin becomes thinner, wrinkles and becomes unhealthy pale. The arms and legs look very thin due to atrophy of subcutaneous fat and muscles.

37-year-old man with Werner syndrome

After 30 years, the following pathological processes develop in the body of patients:

cataracts in both eyes,
hoarseness of voice,
calluses on the feet,
ulcerative-necrotic processes in the skin,
dysfunction of the sweat and sebaceous glands,
heart dysfunction,
osteoporosis, metastatic soft tissue calcification, osteomyelitis,
erosive osteoarthritis,
“scleroderma mask” on the face,
short stature, dense and short body, thin and dry limbs,
decreased intelligence,
nail deformation,
the appearance of large pigment spots on the skin,
hump on the back
exophthalmos due to thyroid dysfunction,
moon-shaped face due to pituitary dysfunction,
testicular atrophy in men, menstrual irregularities in women, early menopause.

The skin epidermis is flattened, connective tissue fibers are sclerosed, subcutaneous tissue atrophies and is partially replaced by connective tissue. Limitation of passive movements in the joints of the arms and legs is manifested by the inability to fully flex and extend the limb. This is due to cicatricial tightening of the tendons and pain.

By the age of 40, patients develop senile ailments: heart problems, diabetes mellitus, frequent fractures of arms and legs, joint pain, benign and malignant skin tumors, dysfunction of the parathyroid glands. Cancer, heart attack and stroke, internal hemorrhages are the main causes of death in progeria.

Symptoms of pathology only resemble the process of normal aging. Signs of aging in progeria vary in severity or appear in a different order. With natural aging, nail growth slows down, and with progeria, it stops completely. In older people, eyebrows become thinner after hair loss on the head, and in patients with progeria, the opposite is true.

Diagnostics

Hutchinson-Gilford syndrome

Werner's syndrome

Diagnosis of progeria does not require specific techniques and studies. The external signs of the disease are so eloquent that the diagnosis is made based only on symptoms and visual examination data. Specialists study personal and family history.

Additional studies are indicated to identify concomitant diseases. Patients are prescribed a general blood test, biochemical examination, x-ray of the osteoarticular apparatus, histological examination of the skin, and medical genetic counseling.

Treatment

Currently, there is no panacea for progeria. All treatments that have ever been used have proven ineffective. Doctors, using modern methods, are trying to stop the disease and prevent it from getting worse. Patients are jointly treated by specialists in the field of endocrinology, therapy, and cardiology.

To alleviate the condition of patients, doctors prescribe:

"Aspirin" for the prevention of acute cardiac and vascular failure - heart attack and stroke.
Statins for lowering blood cholesterol levels and preventing atherosclerosis - “Lipostat”, “Choletar”, “Liptonorm”.
Anticoagulants to prevent or slow down the process of thrombosis - “Warfarex”, “Sincumarin”.
Preparations containing growth hormone - “Getropin”, “Neotropin”, “Dinatrope”. They allow you to correct delays in physical development.
Preparations that heal wounds and stimulate blood circulation during the formation of ulcers - “Mefanat”, “Bepanten”.
Hypoglycemic drugs for diabetes mellitus - “Diabeton”, “Maninil”, “Gliformin”.

Physiotherapeutic procedures are carried out to influence stiff and stiff joints. Patients are prescribed electrophoresis, reflexology, exercise therapy, infrared rays, water procedures, mud therapy, UHF therapy, and magnetic therapy. Patients with progeria are advised to eat proper nutrition, enriched with vitamins and microelements, moderate physical activity, long walks in the fresh air, and proper rest.

Infants are fed through a tube with special milk formulas containing additives for weight gain. Milk teeth are removed to make room for permanent teeth, which erupt quickly in sick children. Specialists monitor the state of the cardiovascular system, which allows early detection of emerging ailments. Surgical treatment is also indicated for patients with early aging syndrome. With the help of angioplasty or coronary artery bypass grafting, the patency of blood vessels is restored.

Progeria is an incurable pathology whose development cannot be stopped. Experimental treatment of adults using stem cells and farnesyltransferase inhibitors makes it possible to restore subcutaneous fat, overall weight, and reduce bone fragility. The prognosis of the disease is always unfavorable. Patients die from acute coronary insufficiency or cancer. Prevention of progeria is impossible due to the fact that the disease is genetic. Lifelong therapy can only make it easier and prolong the life of patients. Continuing care, cardiac care and physical therapy are the main directions in the treatment of the disease.

Video: examples of people with premature aging syndrome

Video: TV show about people with progeria

Humanity has not yet learned to fight all illnesses. Progeria, or premature aging syndrome, should also be considered an incurable disease.

What is premature aging syndrome

People started talking about progeria for the first time relatively recently. This is not surprising, because the disease is extremely rare - 1 time in 4–8 million people. The disease occurs at the genetic level. The aging process accelerates approximately 8–10 times. There are no more than 350 examples of the development of progeria in the world.

The disease affects males more than females (1.2:1).

The disease is characterized by severe growth retardation (manifests from an early age), changes in the structure of the skin, absence of hair and secondary sexual characteristics, as well as cachexia (depletion of the body). Internal organs are often not fully developed, and the person looks much older than his actual age.

Progeria is a genetic disease that manifests itself as underdevelopment and premature aging of the body.

The mental state of an individual suffering from progeria corresponds to biological age.

Progeria cannot be cured and causes the development of atherosclerosis (chronic artery disease), which ultimately leads to heart attacks and strokes. The result of the pathology is death.

Forms of the disease

Progeria is characterized by premature withering of the body or its underdevelopment. The disease involves:

childhood form (Hutchinson-Gilford syndrome);
adult form (Werner's syndrome).

Progeria in children can be congenital, but most often the first signs of the disease appear in the second or third year of life.

Progeria in adults occurs differently. The disease can suddenly overtake an individual at the age of 14–18 years. The prognosis in this case is also unfavorable and leads to death.

Video: progeria, or young old people

Reasons for the development of progeria

The exact causes of progeria have not yet been discovered. There is an assumption that the etiology of the development of the disease is directly related to the disruption of metabolic processes in connective tissue. Fibroblasts begin to grow through cell division and the appearance of excess collagen with low glycosaminoglycan levels. Slow formation of fibroblasts is an indicator of the pathology of intercellular matter.

Causes of progeria in children

The cause of the development of progeria syndrome in children is changes in the LMNA gene. It is he who is responsible for encoding lamin A. We are talking about a human protein from which one of the layers of the cell nucleus is created.

Often progeria is expressed sporadically (randomly). Sometimes the disease is observed in siblings (descendants from the same parents), especially in blood-related marriages. This fact indicates a potential autosomal recessive form of inheritance (manifests exclusively in homozygotes who received one recessive gene from each parent).

When studying the skin of carriers of the disease, cells were recorded in which the ability to correct damage in DNA was impaired, as well as to reproduce genetically homogeneous fibroblasts and change the depleted dermis. As a result, subcutaneous tissue tends to disappear without a trace.

Progeria is not inherited

It has also been recorded that the Hutchinson-Gilford syndrome being studied is related to pathologies in carrier cells. The latter are simply unable to fully free themselves from DNA compounds caused by chemical agents. When cells with the described syndrome were detected, experts determined that they were not capable of full division.

There are also suggestions that childhood progeria is an autosomal dominant mutation that occurs de novo, or without signs of inheritance. It was considered one of the indirect signs of the development of the disease, the basis of which included measurements of telomeres (the ends of chromosomes) in the owners of the syndrome, their close relatives and donors. In this case, an autosomal recessive form of inheritance is also seen. There is a theory that the process provokes a violation of DNA repair (the ability of cells to correct chemical damage, as well as breaks in molecules).

Reasons for the formation of progeria in adults

Progeria in an adult organism is characterized by autosomal recessive inheritance with the mutation gene ATP-dependent helicase or WRN. There is a hypothesis that in the unifying chain there are failures between DNA repair and metabolic processes in the connective tissue.

Since this form of the disease is extremely rare, one can only guess what type of inheritance is inherent in it. It is similar to Cockayne syndrome (a rare neurodegenerative disorder characterized by growth failure, disorders in the development of the central nervous system, premature aging and other symptoms) and manifests itself as separate signs of early aging.

Symptoms of early aging of the body

The symptoms of progeria manifest themselves in a complex manner. The disease can be recognized at an early stage, since its symptoms are clearly expressed.

Symptoms of early aging disease in children

At birth, children who have the deadly progeria gene cannot be distinguished from healthy babies. However, by the age of 1 year, certain symptoms of the disease manifest themselves. These include:

underweight, stunted growth;
lack of hair on the body, including on the face;
lack of subcutaneous fat reserves;
insufficient tone in the skin, causing it to sag and become wrinkled;
bluish skin tone;
increased pigmentation;
strongly visible veins in the head area;
disproportionate development of the bone tissue of the skull, small lower jaw, bulging eyes, prominent ear shells, hooked nose. A child with progeria typically has a “bird-like” grimace. It is the described list of peculiar characteristics that makes children look like older people;
late teething, which lose their healthy appearance in a short time;
shrill and high-pitched voice;
a pear-shaped chest, small collarbones, tight knee joints, as well as elbow joints, which, due to insufficient mobility, force the patient to take the “rider” position;
protruding or convex yellow nails;
scleral-like formations or thickening on the skin of the buttocks, thighs and lower abdomen.

Symptoms of progeria in a child most often appear at 1 year of age.

When a small patient suffering from progeria turns 5 years old, inexorable processes of atherosclerosis formation begin to occur in his body, in which the aorta, mesenteric, and coronary arteries are severely affected. Against the background of the described failures, heart murmurs and hypertrophy (a significant increase in the mass and volume of the organ) appear in the left ventricle. The cumulative impact of these serious disorders in the body is a key reason for the low life expectancy of carriers of the syndrome. The fundamental factor that provokes the rapid death of children with progeria is considered to be myocardial infarction or ischemic stroke.

Symptoms of early aging in adults

A progeria carrier begins to quickly lose weight, be stunted in growth, turn gray and soon go bald. The patient's skin becomes thin and loses its healthy tone. Blood vessels and subcutaneous fat are clearly visible under the surface of the epidermis. With this disease, the muscles atrophy almost completely, as a result of which the legs and arms look excessively exhausted.

Progeria in adults occurs unexpectedly and develops quickly

In patients who have crossed the age limit of 30 years, both eyes are destroyed by cataracts (clouding of the lens), the voice becomes noticeably weaker, the skin over the bone tissue loses its softness, and then becomes covered with ulcerative lesions. Carriers of progeria syndrome are usually similar in appearance. They are distinguished:

small height;
moon-shaped face type;
"bird" nose;
thin lips;
a very prominent chin;
a strong, well-built body and dry, thin limbs, which are disfigured by generously manifested pigmentation.

The disease is unceremonious and interferes with the functioning of all body systems:

the activity of the sweat and sebaceous glands is disrupted;
the normal function of the cardiovascular system is distorted;
calcification occurs;
Osteoporosis (decreased bone density) and erosive osteoarthritis (irreversible processes in the joints) appear.

Unlike the child form, the adult form also has a detrimental effect on mental abilities.

Approximately 10% of patients by the age of 40 come into contact with such serious illnesses as sarcoma (malignant tissue formation), breast cancer, as well as astrocytoma (brain tumor) and melanoma (skin cancer). Oncology progresses due to high blood sugar and malfunctions of the parathyroid glands. The key causes of death in adults with progeria are most often cancer or cardiovascular abnormalities.

Diagnostics

The external signs of the disease are so obvious and vivid that the syndrome is diagnosed based on the clinical picture.

The disease can be detected even before the baby is born. This became possible thanks to the discovery of the progeria gene. However, since the disease is not transmitted through generations (it is a sporadic or single mutation), the likelihood that two children with this rare disease will be born within the same family is extremely low. After the progeria gene was discovered, detection of the syndrome became much faster and more accurate.

Changes at the gene level are now identifiable. Special programs, or electronic diagnostic tests, have been created. At the moment, it is quite possible to prove and substantiate individual mutational formations in the gene, which subsequently lead to progeria.

Science is developing rapidly, and scientists are already working on the final scientific method for diagnosing progeria in children. The described development will contribute to even earlier and more accurate diagnosis. Today, in medical institutions, children with this diagnosis are examined exclusively externally, and then tests and a blood sample are taken for testing.

If symptoms of progeria are detected, you must urgently seek advice from an endocrinologist and undergo a comprehensive examination.

Treatment of progeria

To date, no effective treatment for progeria has been found. The therapy is characterized by a symptomatic line, with the prevention of consequences and complications resulting from the progress of atherosclerosis, diabetes mellitus and ulcerative formations. For an anabolic effect (accelerating the process of cell renewal), a somatotropic hormone is prescribed, which is designed to increase weight and body length in patients. The therapeutic course is carried out by several specialists at once, such as an endocrinologist, cardiologist, therapist, oncologist, and others, based on the symptoms prevailing at a particular moment.

In 2006, scientists from America recorded clear progress in the fight against progeria as an untreatable disease. The researchers introduced a farnesyltransferase inhibitor (a substance that suppresses or delays the course of physiological or physicochemical processes), which had previously been tested on cancer patients, into the culture of mutating fibroblasts. As a result of the procedure, the mutation cells acquired their usual shape. The carriers of the disease tolerated the created drug well, so there is hope that in the near future it will become possible to use the drug in practice. In this way, it will be possible to exclude progeria at an early age. The effectiveness of Lonafarnib (a farnesyltransferase inhibitor) lies in the increase in the amount of subcutaneous fat in total body weight, as well as bone mineralization. The result is to reduce the number of injuries to a minimum.

There is an opinion that similar remedies can help in curing the disease as in the fight against cancer. But these are only assumptions and hypotheses, not confirmed by facts.

Therapy for patients today comes down to:

providing ongoing continuity of care;
special diet;
cardiac care;
physical support.

For progeria, treatment is exclusively supportive in nature and is focused on correcting changes occurring in the patient’s tissues or organs. The methods used are not always effective. However, doctors are doing everything they can. Patients are under continuous supervision by medical professionals.

Only by monitoring the function of the cardiovascular system is it possible to timely diagnose the development of complications and prevent their progress. All treatment methods are focused around a single goal - to stop the disease and not give it a chance to worsen, as well as to alleviate the general condition of the carrier of the syndrome, as far as the potential of modern medicine allows.

Treatment may include the following:

use of Aspirin in a minimal dosage, which can reduce the risk of developing a heart attack or stroke;
the use of other medications that are prescribed to the patient privately based on the presenting symptoms and his well-being. For example, drugs from the statin group reduce the amount of cholesterol in the blood, and anticoagulants prevent the formation of blood clots. A hormone that can increase height and weight is often used;
the use of physical therapy or procedures designed to work out joints that are difficult to bend, thereby allowing the patient to maintain activity;
elimination of milk teeth. A peculiar feature of the disease contributes to the premature appearance of molars in children, while milk teeth must be removed on time.

Based on the fact that progeria is genetic or random in nature, there are no preventive measures as such.

Treatment prognosis

The prognosis for carriers of progeria syndrome is unfavorable. Average indicators say that patients most often survive only up to 13 years, subsequently dying from hemorrhages or heart attacks, malignant neoplasms or atherosclerotic complications.

Progeria is incurable. The therapy is only in development. There is no definitive evidence of a cure yet. However, medicine is developing rapidly, so there is a high probability that patients with progeria will have a chance for a normal and long life.

No matter how incredible it may seem, progeria actually triggers premature aging mechanisms in a young body. Officially, the disease was named after the scientists who first described and studied the pathology: in children it is Hutchinson-Gilford syndrome, in adults it is Werner syndrome.

Progeria occurs several times more often in boys than in girls. On average, patients live from 10 to 13 years (in exceptional cases up to 20): a fatal disease, unfortunately, does not provide a chance for recovery and long life. Such children are noticeably behind their healthy peers in physical development, but this is not all the “charms” of progeria. Severe exhaustion of the body, a violation of the structure of the skin, the absence of secondary signs of sexual development and hair, underdeveloped internal organs and the appearance of the old man as a whole - this is the burden that falls on the shoulders of the unfortunate child.

In mental development, the child is absolutely adequate, his body retains childlike proportions, but at the same time, the epiphyseal cartilage quickly overgrows and in its place an epiphyseal line appears - everything is like in an adult. Rapidly growing children are forced to face far from childhood problems associated with progeria: atherosclerosis, stroke, and various heart diseases.

Causes of pathology

Unfortunately, experts have not yet examined the real face of the “enemy” in detail. As a result of lengthy research, scientists were able to find out that the basis of the pathology is most likely a mutation of the lamin gene (LMNA), which is directly related to the process of cell division. A failure in the genetic system deprives cells of resistance and triggers unexpected aging mechanisms in the body.

Progeria, unlike many other diseases of genetic etiology, is not inherited, that is, it appears completely by accident, and none of the parents of a sick child can be called a carrier of the pathology.

Symptoms of the disease

Immediately after birth, children carrying the deadly progeria gene cannot be distinguished from healthy babies. Already by the first year of life, numerous symptoms of the disease make themselves felt fully. Among them:

Visible lack of body weight, very short stature.
Lack of hair on the head, eyelashes and eyebrows.
Lack of subcutaneous fat and lack of tone in the skin - it is weak and wrinkled.
A bluish tint to the skin.
Skin hyperpigmentation.
Strongly protruding veins under the skin on the head.
Disproportional development of the bones of the face and skull, a small lower jaw, bulging eyes and protruding ears, a hooked nose - the child has a “bird-like” facial expression. It is this set of specific features that makes him look like an old man.
Late appearance of teeth that quickly deteriorate.
The voice is shrill and high.
Pear-shaped chest, small collarbones, “tight” knee and elbow joints, which, due to poor mobility, force the patient to be in a “rider” position.
Yellow convex nails are “watch glasses.”
Sclera-like formations on the skin of the buttocks, thighs and lower abdomen.

After a child suffering from progeria celebrates his fifth birthday, his body begins an inexorable development process, in which the aorta, mesenteric and coronary arteries are especially affected. Against the background of these disorders, the appearance of heart murmurs and left ventricular hypertrophy is noted. The complex effect of these disorders on the body is considered one of the reasons for the short life of patients with progeria. The main factor in the sudden death of patients is also called ischemic stroke.

Progeria in adults

The disease can suddenly overtake an adult at the age of 14-15 to 18 years. The patient begins to lose weight, be stunted, turn gray and gradually go bald (progressive alopecia). The skin of a person with progeria becomes thinner, loses all its colors, acquiring an unhealthy pale tint. Underneath, a network of blood vessels is clearly visible, subcutaneous fat and muscles completely atrophy, so the arms and legs appear very thin.

In patients who have crossed the 30-year mark, both eyeballs are affected, the voice weakens, the skin over the protrusions of the bones becomes rough and covered with ulcers. Those suffering from progeria look the same: short stature, moon-shaped face, nose resembling a bird's beak, narrow mouth, sharply protruding chin, dense body and thin dry limbs, disfigured by numerous pigment spots. The disease unceremoniously interferes with various systems of the body: the work of the sweat and sebaceous glands is disrupted, the normal activity of the cardiovascular system is distorted, the body suffers from calcification, osteoporosis and erosive osteoarthritis. Unlike young patients, in adults the disease also has a detrimental effect on intellectual abilities.

About 10% of patients by the age of forty are faced with such terrible diseases as sarcoma, astrocytoma, and melanoma. Oncology develops against the background of diabetes mellitus and impaired function of the parathyroid glands. The immediate cause of death in patients with progeria in most cases is malignant tumors and cardiovascular pathologies.

Diagnosis of the disease

The external symptomatic manifestations of the pathology are so vivid and eloquent that the disease is diagnosed based on the clinical picture.

Treatment of the disease

MirSovetov is forced to admit that, unfortunately, there is no panacea for progeria. All treatment methods that are used today are also not always effective. However, doctors do everything that depends on them. Thus, all patients are under regular medical supervision, because by monitoring the state of the cardiovascular system, it is possible to timely detect the development of complications of a particular “heart” disease.

All treatment methods pursue a single, but vital goal - to “freeze” the disease, not allow it to worsen and alleviate the patient’s condition, as far as the capabilities of modern medicine allow. How can specialists help?

The use of minimum doses that can protect a person from a possible heart attack or.
The use of other medications that are prescribed individually, based on the condition of each individual patient. For example, drugs from the statin group reduce high cholesterol levels in the blood, and so-called anticoagulants block the formation of blood clots. Growth hormone is often used to “build up” height and weight.
The use of physiotherapeutic procedures that work out joints that bend with difficulty, allowing a person to remain active. What could be more important for young patients?
Removal of baby teeth. The specificity of the disease contributes to the early eruption of permanent teeth in children, while milk teeth deteriorate very quickly, so they need to be removed in a timely manner.

Prevention of the disease has not yet been developed.