Progeria Hutchinson Guilford causes. Symptoms of early aging of the body

Dr. Leslie Gordon is a renowned American expert on progeria, director of the Progeria Research Foundation, and researcher.

Dr. Gordon has a personal battle with this disease - five years ago her son was diagnosed with progeria.

Dr. Gordon teaches pediatrics at Brown University School of Medicine in Providence, Rhode Island.

He is a researcher at Tufts University in Boston, where he is actively conducting research in the field of Hutchinson-Gilford syndrome (HGPS).

Thanks to Dr. Gordon Western medical science has made significant progress in this area. In particular, Dr. Gordon discovered the progeria gene and made many other important discoveries regarding the pathogenesis of this rare disease.

The researcher often appeared on television, her articles on progeria were published in the New York Times, The Boston Globe, People Magazine, The Boston Herald, Science News, USA Today, and The Journal of the American Medical Association (JAMA).

In this article, Dr. Gordon responds to NHMHB representatives on FAQ about progeria.

- What is Hutchinson-Gilford syndrome, or progeria, and what causes this disease?

- When we talk about progeria, I refer to Hutchinson-Gilford syndrome because there are other progeric syndromes.

Progeria is what we call "syndrome premature aging", which affects the child’s body in the most in different ways, especially aging their cardiovascular system.

All children with progeria die prematurely, suffering from severe atherosclerosis, between the ages of 8 and 20 years. The main cause of death for such children is cardiovascular diseases, which are typical for old people. Progeria occurs on average in one child in 4 million people, but in some populations the figure varies from 1 to 8 million.

Most children with progeria appear completely normal at birth. At about 9 months of age they begin to develop classic symptoms progeria, including skin changes, baldness, etc. Such children grow to a maximum of 3.5 feet, which is slightly more than half the height of a normal adult.

The nervous system and brain of such children are spared the disease, so they function in accordance with biological age. Social skills and intelligence are completely preserved in children with progeria.

In other words, these are happy children, first and second graders, who want to enjoy life and play around with their peers, but very quickly become decrepit and leave us. Understanding what happens in a child's body with progeria should help us find a cure for this terrible disease.

- When and why did you decide to found the Foundation for the Study of Progeria?

- When our son Sam was almost 2 years old, he was diagnosed with progeria. My husband is a doctor, and I myself am a doctor and scientist. Of course, we perfectly understood the essence of the problem and did everything possible to stop this disease.

In a few days we collected all the available modern science material - it turned out that these were less than 200 published articles. That's all. There was not even an organization that would raise funds for further research, there was practically nothing.

So my husband and I decided to found the Progeria Research Foundation, PRF. My sister Audrey is a lawyer, and we asked her, as a legal savvy person, to become the first president and CEO of the foundation.

We now have a large and very qualified board of directors, a wonderful committee of volunteers and many other people who help in the fight against progeria.

The Progeria Research Foundation is non-profit organization, which is constantly growing.

- What does the Progeria Research Foundation do?

- The Foundation for the Study of Progeria was created at a time when there was practically nothing for children with this syndrome in our country. We founded this organization with a clear understanding of what it takes to fight the disease.

This is what we kept hearing: “There is no money to do research in this area, so we have nothing to help these patients.” Then we raised money and gave researchers grants to conduct special important works, and we continue to do so today.

They told us: “There is no equipment and tools. No cell cultures. Researchers need something to work with.” Therefore, we created our own bank of cells and tissues taken from progeria patients. All children with this syndrome can donate their cells to our bank so that scientists have enough material for research. Now they have everything, and the results were not long in coming.

We wanted to lure researchers from other fields and convince them to study progeria. We held scientific meetings that helped disseminate information, we offered substantial grants for key research, and this helped attract scientists to our field not only from different parts of America, but even from other countries.

We also created the Progeria Research Genetics Consortium, which today includes 20 scientists, including me. Six of us took part in historical research, which culminated in the discovery of the progeria gene.

- Is it possible to diagnose progeria before the birth of a child?

- Yes, this can be done. This became possible thanks to the recent discovery of the progeria gene. But since progeria is not transmitted through generations (it is a sporadic mutation), it is extremely unlikely that two children with this rare disease will be born in one family.

After the discovery of the progeria gene, diagnosis of this syndrome became quick and reliable. Doctors from all over the world send us samples of their patients' cells to test for Hutchinson-Gilford syndrome, and we do it completely free of charge. For all.

- What is the prognosis for children with progeria?

- The disease is fatal in 100% of cases. The child dies at a young age as a result of a heart attack or stroke. What kills him is the same thing that kills most older people, only it happens in childhood or adolescence. Blocked brain and coronary arteries, angina pectoris, strokes - this is what to expect from this disease.

- What difficulties do patients with progeria face?

- I would divide these difficulties into two main categories.

First, daily health maintenance. Our foundation very quickly found out that doctors do not have complete information on proper organization examinations, preventive measures in rapidly aging children.

Families constantly need information and professional help. Therefore, we organized a third program - a database of medical and scientific data ( Medical and Research Database). Our scientists analyze and systematize all incoming information about patients with progeria, drawing up special protocols on nutrition, physical therapy, etc. In addition, doctors and parents of patients can call us around the clock and receive advice.

We strongly recommend special physical and occupational therapy for these children. Our consultants ask parents about this, and it turns out that in most cases nothing like this is done. A child with progeria who is passing good course physical therapy, lives a completely different life. Remember this.

Secondly, there are psychological and social difficulties. Children with progeria are very different in appearance from healthy children, although intellectual development they have exactly the same.

Children with this syndrome want to be like everyone else, to lead ordinary life, play with other children, have fun. They can have a wonderful childhood relationship. They don't want to think about progeria, and progeria shouldn't eat up their already short life.

I have found that families with progeria tend to connect with other families who have suffered the same affliction. Therefore, our foundation often brings such families together, giving them the opportunity to share experiences and support each other morally. This is very important for everyone.

Konstantin Mokanov

Progeria

Progeria

Patients with progeria often have a characteristic appearance: short stature, relatively big head and reduced facial part of the skull
ICD-10	E 34.8 34.8
ICD-9	259.8 259.8
OMIM		176670
DiseasesDB		10704
eMedicine	derm/731	derm/731
MeSH	D011371	D011371

In children

Although childhood progeria can be congenital, most patients with Clinical signs usually appear in the 2-3rd year of life. The child's growth slows down sharply, atrophic changes dermis, subcutaneous tissue, especially on the face and limbs. The skin becomes thinner, becomes dry, wrinkled, and there may be scleroderma-like lesions and areas of hyperpigmentation on the body. Veins are visible through thin skin. Appearance patient: large head, frontal tubercles protrude above a small, pointed (“bird-like”) face with a beak-like nose, lower jaw underdeveloped. Muscle atrophy is also observed, dystrophic processes in teeth, hair and nails; changes in the osteoarticular apparatus, myocardium, hypoplasia of the genital organs, disturbance fat metabolism, lens opacification, atherosclerosis.

Average duration life with childhood progeria - 13 years. Most sources give ages of death between 7 and 27 years, with cases of adulthood being very rare. There is only one known case of a patient who survived the 27-year mark - a Japanese man described by Ogihara and others in 1986 who lived for 45 years.

In adults

Adult progeria has an autosomal recessive pattern of inheritance. The defective gene is WRN (ATP-dependent helicase gene). It is assumed that the process is related to a violation of DNA repair, metabolism connective tissue.

Histological picture: flattening of the epidermis, homogenization and sclerosis of connective tissue, atrophy of subcutaneous tissue with its replacement by connective tissue fibers. Clinically, the disease manifests itself during puberty. Slow growth and symptoms of hypogonadism are noted. Typically, in the third decade of life, the patient's hair turns gray and falls out, cataracts develop, and the skin gradually thins and atrophies subcutaneous tissue on the face and limbs, as a result of which the arms and especially the legs become thin. Foci of scleroderma-like compaction and dyschromia appear, most pronounced in the distal parts of the limbs and on the face, which, along with a thin beak-shaped nose and narrowed oral opening, gives it a mask-like appearance. In areas exposed to pressure, hyperkeratosis and chronic poorly healing trophic ulcers develop. Osteoporosis, metastatic calcification of soft tissues, and, less commonly, osteomyelitis are found. Diabetes mellitus is often observed, the signs of which, like the symptoms of early generalized atherosclerosis, are usually detected in patients aged 30-40 years; malignant neoplasms are possible (for example, skin cancer, sarcoma, adenocarcinoma).

The diagnosis is made based on clinical picture. Differential diagnosis carried out with congenital poikiloderma, scleroderma. Treatment is symptomatic, mainly aimed at preventing atherosclerotic complications, eliminating diabetes mellitus, trophic ulcers. It is carried out by a therapist, endocrinologist or other specialist, depending on the prevailing clinical symptoms. The prognosis for recovery is poor; Most patients die from atherosclerotic complications and malignant neoplasms. Prevention has not been developed.

Aging

A severe form of human progeria, Hutchinson-Gilford syndrome, has been found to be associated with molecular changes that are characteristic of normal aging, such as genomic instability, decreased telomere length, and disruption of stem cell homeostasis. This data along with genetic research life expectancy have led to the hypothesis that progeria syndromes accelerate a number of pathological changes which usually control the normal aging process.

In art

In the "Metal Gear Solid" series of games main character Solid Snake was born under circumstances artificial insemination and interventions genetic engineering into human genetics - for the purpose of correcting DNA and cloning human genes from father to son. As a result, due to genetic interference and a violation of the genetic program (genetic defect), Solid Snake began to develop progeria by the age of 40. Quote: "Otacon: Loose skin, hardened arteries...Your symptoms of early aging are very similar to Werner's syndrome..."
In A. Reutov’s novel “Hackers of Dreams,” a team of Hackers introduces the idea of progeria to the main villain of the novel, Lord Dags.
In Chuck Palahniuk's novel Ghosts, one of the characters, Mr. Witter, is not actually an old man, as the other characters think he is, but a 13-year-old boy with progeria.
The Blade Runner character J.F. Sebastian suffers from progeria.
In the third episode of the first season of The Invisible Man, a woman named Gloria was infected with a special form of Werner's syndrome and could infect others. She infected the main character.
In the book by the Strugatsky brothers “The Beetle in the Anthill” Lev Abalkin was a progressor on a planet whose entire population was infected with a certain virus that caused rapid aging. At the time of writing the work, the authors did not even suspect the existence of progeria.
In Ruggero Deodato's film The Phantom of Death, the main character learns that he has progeria, which causes mental disorder and leads to a series of murders.
Progeria is also mentioned in the film The Curious Case of Benjamin Button. Which tells about a man who was born old, and with age he became younger.
In the episode "Candle in the Wind" of Stargate SG-1, one of the main characters was infected with microscopic robots that accelerated his aging
In episode 21 of season 2 of Bones, the victim, Chelsea Cole, suffered from progeria.
In the series X-Files Season 1 episode 16 "Young at Heart" this disease is mentioned.
In the series Smallville, in episode 6 of season 2, this disease is mentioned.
IN feature film"Jack" Robin Williams plays a teenager with progeria (premature aging).
Leon Botha, who gained popularity after the band's videos Die Antwoord

Notes

Literature

Fedorova E. V. About congenital progeria. - 1980. - T. 4. - P. 66. - (Pediatrics).

Wikimedia Foundation. 2010.

Progeria is a rare and incurable disease, with definitely not known mechanism, formed due to genetic damage. As a result of changes in genes, children, when born, begin to progressively and quickly turn into old people. With this disease, the life expectancy of all cells of the body and the entire organism as a whole is sharply reduced. Progeria is dangerous not only in children, but also in adults; the disease can progress from newborns or from adulthood.
The variant of progeria in infants is called Guilford Hutchinson syndrome; in adults it is called Werner syndrome. In essence, this is premature aging of the body.

Causes

Progeria is incurable, serious pathology, in which premature aging of the child’s body occurs, sometimes starting with prenatal period. This is a genetic breakdown in one of the regions of the genes that are responsible in the body for the processes of cell aging and their death. IN normal conditions the aging program starts slowly and in late dates, after the organism matures. With progeria, this process is accelerated hundreds of times. Children of both sexes are susceptible to it, for a short time they turn into old people, although in fact they have absolutely childhood. Progreria sometimes occurs in adolescents and adults, but this is even rarer.

The formation of progeria at an early age is called Guilford-Hutchinson syndrome; boys are usually affected somewhat more often; on average, the age of children is up to 10-13 years. IN in rare cases at special care Children with progeria live to be 18-20 years old. The disease cannot be stopped; it progresses and inexorably leads to death.

The mechanism of formation of the disease has not been thoroughly elucidated; with a high degree of probability, it has been determined that the mutation is caused by a special gene - lamin. This gene and the protein it produces are responsible for the process of proper cell division. If a malfunction occurs in the region of this gene, cells lose their resistance harmful influences environment and the body starts the aging program. Although this is genetic disease, it is not inherited, but family cases can occur - the birth of several children with progeria in a couple.

Symptoms

The manifestations of the disease are quite clear. Children from the very early age begin to lag behind their peers in terms of physical development. In addition, their body wears out too quickly, becoming what a person usually achieves after 70-90 years. The structure of the skin is disturbed, there are no signs of puberty, and the internal organs are sharply underdeveloped. Children outwardly look like old people, have childlike intelligence and suffer emotionally from similar disease. Their mental condition is not disturbed in any way, they develop in terms of the psyche according to age.

The body has the proportions of a child, with areas of cartilage where bone grows quickly overgrown, making the skeleton similar to that of an adult. The child’s body suffers from adult pathologies such as diabetes, atherosclerosis, ischemic disease hearts. Usually dies from senile pathologies.

The main manifestations of progreria:

At birth, the child is practically no different from healthy children.
In the first year of life, height and weight gains lag sharply; children have very low height and weight.
They have a pronounced lack of body fat, and their skin tone is sharply reduced, it is wrinkled and dry.
Hair on the head, eyebrows and eyelashes, throughout the body does not grow or falls out quickly.
The skin has strong pigmentation like old people and a bluish tint.
The skull and facial bones are disproportionate, the eyes are protruding, the lower jaw is very small, the ears are protruding, and the nose is hooked.
Teeth erupt late and fall out quickly, the voice has a high pitch, shrill and hoarse.
The chest is shaped like a pear, the collarbones and limbs are small, the joints move tightly.

By the age of five, children are sharply affected by atherosclerosis, the walls of blood vessels, sclera-like formations form on the skin, especially on the buttocks, thighs and abdomen. suffer large vessels chest and abdomen, the structure and functioning of the heart changes.

Diagnosis of progeria in children

The basis of diagnosis is typical clinical manifestations. If necessary, carry out medical genetic counseling and identification of an abnormal gene. Examination and identification of pathological complications is also indicated.

Complications

The main complications of progeria are the wear and tear of all internal organs, changes in the heart, the formation of strokes and heart attacks, diabetes and atherosclerosis. Patients die from these diseases after the age of 10 years. The prognosis for the pathology is unfavorable, cases of cure are unknown.

Treatment

What can you do

There is no cure for this pathology; it is not worth spending money on empty promises cure the baby. There is no way to correct gene defects yet. Complete care and maximum social adaptation, good nutrition and baby care. No funds traditional medicine from progeria is also not available.

What does a doctor do

Drug treatment is also carried out only for the purpose of maintaining general condition health and prevention of complications. Prophylactic use of anticoagulants and drugs to lower cholesterol levels is indicated. Growth hormone can be used to help children gain weight and grow taller, and physical therapy is also indicated to improve the functioning of joints and internal organs.

Children with progeria have their baby teeth removed because their permanent teeth erupt early.

Prevention

Prevention methods have not been developed, since the pathology is genetic and is extremely difficult to influence. It is worth planning a pregnancy against the background full health, but it is impossible to completely predict the likelihood of having children with progeria.

You will also learn what can be dangerous untimely treatment progeria disease in children, and why it is so important to avoid the consequences. All about how to prevent progeria in children and prevent complications.

And caring parents will find on the pages of the service full information about the symptoms of progeria disease in children. How do the signs of the disease in children aged 1, 2 and 3 differ from the manifestations of the disease in children aged 4, 5, 6 and 7? What is the best way to treat progeria disease in children?

Take care of the health of your loved ones and stay in good shape!

Childhood progeria is a genetic disease that leads to irreversible changes in the internal organ system due to premature aging of the whole organism. First this disease was identified and described in 1889 by J. Hutchinson and independently in 1904 by H. Guilford. Despite the fact that childhood progeria is an extremely rare disease, more than 150 cases have been described since its discovery. And each of them is carefully studied a huge amount scientists.

Doctors diagnose only one in 7 million newborns with Hutchinson-Gilford syndrome. Childhood progeria develops rapidly - literally in a year the patient’s body ages by 5-9 years. In rare cases, children live to the age of 23, dying from diseases more common to older people. The first signs of “childhood old age” appear in children, starting from an early age (2-3 years).

There is no treatment as such yet, that is, medications are prescribed only for symptomatic treatment side ailments. But scientists around the world are studying the problem and looking for effective methods her decisions.

Childhood progeria is characterized by the following manifestations:

small stature;
light weight (13-22 kg);
the thinnest skin through which the vessels are visible;
inactive joints of the arms and legs;
but at the same time - a small face;
high voice.

Causes of the disease

All scientists agree that childhood progeria is not an inherited disease. The world knows only 1 family where all 3 children inherited this syndrome.

Not so long ago, it was believed that the only cause of “childhood old age” was a mutation in one gene that takes part in the formation of the lamin A protein. Cell nuclei are built on the basis of this protein. In the process of converting prelamin A into a mature protein, disruptions occur. Thus, lamin A ends up being significantly different from healthy protein. This leads to many pathological changes in the child’s body, which characterize Hutchinson-Gilford disease. Childhood progeria begins to progress, causing

But some scientists have discovered another gene in DNA, the mutation of which inevitably leads to this disease. in the BAF-1 gene, the cause of the development of defects in the cell membrane. And since BAF-1 also interacts with other proteins, a mutation in its structure causes disturbances in other proteins.

Is there a chance?

Today, scientists face difficult task a complete comprehensive study of the process. And if they succeed, then sick children will have a real chance to defeat childhood progeria, and doctors will have a chance to prevent its occurrence.

It is worth noting that many patients have little hope of salvation. US scientists have begun clinical research remedies against this disease. It is possible, however, that not every child will be able to live up to this time. But in any case, if the tests are completed successfully and childhood progeria is defeated, this will be a victory for all those who do everything in the name of saving their children from such a terrible disease.