Children's progeria. Early aging - causes, features and methods of prevention

What is progeria, what are its signs and effects? How is the disease diagnosed and what treatment is available today?

Hutchinson-Gilford Progeria Syndrome (HGS) is a rare, fatal genetic disorder characterized by sudden, accelerated aging in children, affecting one in 8 million children worldwide. The name of the syndrome comes from the Greek word and means "premature aging". Although there are various forms progeria, classical type Hutchinson-Gilford Progeria Syndrome is named after the physicians who first described the disease, in 1886 Dr. Jonathan Hutchinson and in 1897 Dr. Hastings Guilford.

It is now known that SHGP is caused by a mutation in the LMNA (Lamin) gene. The LMNA gene produces the protein lamin, which holds the cell nucleus. Researchers believe that the defective lamin protein makes cell nuclei unstable. And it is this instability that triggers the process of premature aging.

Children with this syndrome appear healthy at birth, the first physical signs diseases can occur at the age of one and a half to two years. This cessation of growth, weight and hair loss, protruding veins, wrinkled skin - all this is accompanied by complications more characteristic of older people - joint stiffness, generalized atherosclerosis, osteoporosis, cardiovascular diseases, stroke. In children with this disease, remarkably similar appearance despite different ethnicity. Most often, children with progeria die of (heart disease) at an average age of thirteen (range from about 8 to 21 years).

There is also an "adult" progeria (Werner's syndrome), which begins in adolescence(15-20 years). The life expectancy of patients is reduced to 40-50 years. Most common causes lethal outcome are myocardial infarction, stroke and malignant tumors. Exact reason scientists cannot establish the development of the disease.

Who is at risk?

Although progeria is genetic disease, in the classical sense of the Hutchinson-Gilford syndrome, but not hereditary, i.e. neither parent is either a carrier or affected. Each case is thought to be a sporadic (random) mutation that occurs either in the egg or sperm prior to conception.

The disease affects all races and both sexes equally. If a couple of parents have one child with SHGP, the chance that a second child will be born with the same condition is 1 in 4 to 8 million. There are other progeric syndromes that can be passed down from generation to generation, but not classic SHPS.

How is progeria diagnosed?

Now that this gene mutation identified, the Progeria Research Foundation has developed diagnostic testing programs. It is now possible to confirm specific genetic changes or mutations in a gene that lead to SHGP. After initial clinical evaluation(appearance of the child and medical documentation), a blood sample is taken from the child for testing. The definitive scientific method for diagnosing children is currently being developed. This will result in more accurate and more early diagnosis , which will help ensure that children with this mutation are properly cared for.

What treatments are available for children with progeria?

The usual, at first glance, form psychological state- phobic anxiety, causes cell damage and leads to premature aging.

To date, only a few ways are available to optimize the quality of life of children with Progeria. Treatment includes ongoing care, cardiac care, special meals and physical therapy.

Over the past few years, encouraging research data have been published that describe the potential drug treatment for children with progeria. Scientists believe that farnesyl transferase inhibitors (FTIs), originally developed to treat cancer, may reverse the structural abnormalities that cause progeria in children.

26 children took part in trials of the drug - this is a third of all known cases progeria. Children who took the drug showed a 50% increase in annual weight gain. The density also improved in children. bone tissue before normal level, and a 35% reduction in arterial stiffness, which is associated with high risk heart attack. The researchers point out that thanks to new development damage to blood vessels is not only reduced, but also partially restored over a period.

Progeria is a genetic disease in which premature, rapid aging of the body occurs: skin, internal organs and systems. The disease has two forms: childhood (Hatchinson-Gilford syndrome) and adult (Werner syndrome). It should be noted that most often occurs in boys. Girls get sick much less often. The disease is rare. To date, only eighty cases of progeria are known worldwide.

A genetic failure that has occurred in the body accelerates the aging process by about 8-10 times. A child with such a disease, when he turns 8, looks 80. And not only externally. The condition of his internal organs also corresponds to his age. old age. Therefore, such children live for a very short time, about 13 - 20 years.

Today on www.site we will talk in more detail about premature aging of the human body - this is a disease of progeria, the symptoms, causes and treatment of which will essentially interest us further ... Let's start with the causes of this pathology:

Why does progeria disease occur, what are the causes leading to it?

The disease is caused by a genetic mutation in lamin A (LMNA). This is a gene that is directly involved in the process of cell division. Its mutation causes a malfunction in genetic system, which deprives cells of their resistance, starts the process of rapid aging in the body.

Note that unlike many other genetic diseases, progeria is not hereditary, it is not transmitted from parents to children. The mechanism of sudden genetic mutation has not yet been studied by scientists.

Premature aging symptoms:

In children:

Immediately after birth, the baby looks completely normal. The manifestations of the disease begin closer to the age of 2, when parents notice that the child has stopped developing. Growth retardation has been observed since 9 months. The baby is not gaining weight well, the skin loses elasticity, looks aging, keratinized areas appear on it. The joints lose their elasticity, the subcutaneous adipose tissue. These children often have hip dislocations.

A characteristic appearance takes the shape of the head and face of the child. The head becomes much more face, lower jaw small, smaller than the top. On the scalp, eyelids, veins are clearly visible. Eyelashes fall out, eyebrows thin out, hair falls out intensely. The child's milk teeth do not grow well, they are noted irregular shape. Teeth that have grown in place of milk teeth begin to fall out.

When a child reaches three years old, his growth stops completely, it is noted. mental retardation. The nose takes on a beak-like shape, the skin becomes thinner. Skin undergo typical aging changes.

At further development diseases, the elasticity of the arteries is disturbed, atherosclerosis develops, cardiovascular diseases occur, and a stroke can occur.

Progeria in adults:

The disease in adults begins to develop suddenly in adolescence (14-18 years). It all starts with unreasonable weight loss, growth stops. A characteristic sign of the onset of the disease is early graying, increased prolapse hair, baldness.

Thinning, dryness of the skin is observed, it becomes pale, acquires an unhealthy shade. blood vessels, the subcutaneous fat layer of the extremities is rapidly lost, why hands and the patient's legs look very thin.

After 30 years of life, the patient's eyes are affected by cataracts. His voice becomes weak, the skin becomes coarse, ulcerated, there is a violation of the function of sweat, sebaceous glands. The patient's body is deficient in calcium, which causes the development of osteoporosis, erosive osteoarthritis, diseases develop of cardio-vascular system, intellectual abilities decrease.

Premature aging of the human body is also manifested by other characteristic symptoms: short stature, round, moon-shaped face, nose like a bird's beak, thin, narrow lips. TO characteristics also includes a thin chin, sharply protruding forward, dense, short body and thin, dry limbs, profusely covered with pigmentation.

A large number of patients, by about 40 years, fall ill oncological diseases, diabetes. They are diagnosed with dysfunction parathyroid glands, severe cardiovascular pathologies. It is these serious diseases that cause early death patients with progeria. Which is unlikely to suit anyone ... Therefore, let's talk about how progeria is corrected, what treatment will help in improving well-being and slowing down the processes that have begun.

treatment for progeria

Modern medicine does not yet have methods for treating and preventing this genetic disease. The help of doctors is to slow down its progression, reduce, minimize symptoms.

For example, the patient is given daily intake small doses of aspirin, which helps reduce the risk of heart attacks, preventing stroke.

Use drugs from the group of statins, which reduce cholesterol levels.

Use drugs - anticoagulants, which reduce the risk of blood clots. Also, during therapy, growth hormone is used, which helps the patient's body to restore weight gain, promotes normal growth.

Physiotherapeutic methods are used to help restore the elasticity of the joints, allowing the patient not to lose physical activity. These techniques are very important, in particular for young patients.

In addition, in children with progeria, milk teeth are removed. With this disease, adult teeth erupt very early, while milk teeth deteriorate rapidly. Therefore, they need to be removed in a timely manner.

Progeria treatment requires individual approach to each patient, depending on his condition and age. Currently underway clinical researches drugs created by scientists to treat this genetic disease. Perhaps, effective therapeutic methods will soon appear. Be healthy!

Dr. Leslie Gordon is a well-known American expert on progeria, director of the Progeria Research Foundation, researcher.

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

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

He is a research fellow at Tufts University in Boston, where he is active in research on Hutchinson-Gilford Syndrome (HGPS).

Thanks to Dr. Gordon Western medical science 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 has been featured on television frequently, and her articles on progeria have appeared 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 the Hutchinson-Gilford syndrome, because there are other progeric syndromes.

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

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

Most children with progeria look completely normal at birth. At about 9 months of age, they begin to develop classic symptoms progeria, including skin changes, baldness, and others. 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 bypass the disease, so they function in accordance with biological age. Social skills and intelligence in children with progeria are completely preserved.

In other words, these are happy children, first-graders, second-graders who want to enjoy life and play 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 establish the Progeria Research Foundation?

- When our son Sam was almost 2 years old, he was diagnosed with progeria. My husband is a doctor and I am a doctor myself. 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 this is less than 200 published articles. And that's it. There was not even an organization that would raise funds for further research, there was practically nothing.

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

We now have a large and highly qualified board of directors in the organization, an excellent 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 constantly heard: “There is no money for research in this area, so we have nothing to help such patients.” Then we raised money and gave researchers grants to conduct special important works and we continue to do so today.

We were told: “There is no equipment and tools. No cell cultures. Researchers need to work with something.” Therefore, we have created our own bank of cells and tissues taken from patients with progeria. 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, to convince them to go into progeria. We held scientific meetings that helped spread the word, we offered solid grants for key research, and this helped to 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 now has 20 scientists, including myself. Six of us took part in historical research which culminated in the discovery of the progeria gene.

Can progeria be diagnosed before the baby is born?

- Yes, it can be done. This was made possible by 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 the same family.

After the discovery of the progeria gene, the diagnosis of this syndrome became fast and reliable. Doctors from all over the world send us cell samples from their patients to be tested 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. He is killed by the same thing that takes the lives of most older people, only this happens in childhood or adolescence. Clogged brain and coronary arteries, angina pectoris, strokes - that's what to expect from this disease.

- What difficulties do patients with progeria face?

- I would divide these difficulties into two main categories.

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

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

We strongly recommend special physical and occupational therapy for such 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 going through good course physical therapy, lives a completely different life. Remember this.

Secondly, there are psychological and social difficulties. Children with progeria look very different 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 wonderful childhood relationships. They don't want to think about progeria, and progeria shouldn't eat into their already short lives.

I found that families with progeria tend to communicate with other families who have suffered the same misfortune. 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

For the first time, the syndrome of premature aging was discussed 100 years ago. And no wonder: such cases occur once in 4-8 million babies. Progeria (from the Greek pro - earlier, gerontos - old man) - or Hudchinson Gilford's syndrome. This disease is also called childhood old age. This is an extremely rare genetic disease that accelerates the aging process by about 8-10 times. Simply put, a child ages 10-15 years in one year.

Babies with progeria look normal for 6 to 12 months after birth. After that, they develop symptoms characteristic of old age: wrinkled skin, baldness, brittle bones and atherosclerosis. An eight-year-old child looks 80 years old - with dry, wrinkled skin, a bald head. These children usually die at the age of 13-14 after several heart attacks and strokes against the background of progressive atherosclerosis, cataracts, glaucoma, complete loss of teeth, etc. And only a few live to 20 years or longer. In the people this disease is called "dog old age".

Now in the world about 60 cases of people with progeria are known. Of these, 14 people live in the United States, 5 - in Russia, the rest in Europe. Among the features of such patients are dwarf growth, low weight (usually not exceeding 15-20 kg), excessively thin skin, poor joint mobility, underdeveloped chin, small face in comparison with the size of the head, which gives the person as if a bird's features. Due to the loss of subcutaneous fat, all vessels are visible. The voice is usually high. Mental development age appropriate. And all these sick children are strikingly similar to each other.

Until recently, doctors could not determine the cause of the disease. And only recently, American researchers discovered that the cause of "childish old age" is a single mutation. Progeria is caused by a mutated form of the LMNA gene. According to the director of the National Institute for Genome Research Francis Collins (Francis Collins), who led the study, this disease is not hereditary. A point mutation - when only one nucleotide is changed in a DNA molecule - occurs anew in each patient. genetic mutation in the protein Lamin A causes accelerated aging of the body. And the young man - with his big protruding ears, bulging eyes and swollen veins on his bald skull - turns into a hundred and sixteen year old man.

Hussein Khan and his family are unique in their kind: this is the only case known to science when more than one family member suffers from progeria. And thanks to this family, scientists were able to make a real breakthrough in understanding the nature of the disease. Hana's husband and wife are cousins ​​to each other. None of them have progeria, and neither do their two children, 14-year-old Sangita and 2-year-old Gulavsa. This disease affects their 19-year-old daughter Rehena and two sons: 7-year-old Ali Hussein and 17-year-old Ikramul. None of them has practically no chance to live even to 25, and this is probably the saddest thing.

Adult progeria (Werner's syndrome) is a hereditary or familial disease. Manifested premature aging, starting at the age of 20-30 years, is accompanied by early graying, baldness and arteriosclerosis. Adult progeria manifests itself in the following symptoms. Slow developing juvenile cataract. The skin of the feet, legs, to a lesser extent of the hands and forearms, as well as the face gradually becomes thinner, the subcutaneous base and muscles in these areas atrophy. On lower limbs 90% of patients have trophic ulcers, hyperkeratosis and nail dystrophy.

Atrophy of the skin of the face ends with the formation of a beak-shaped nose ("bird's nose"), narrowing of the oral fissure and sharpening of the chin, resembling a "scleroderma mask". From endocrine disorders hypogenitalism is noted, late appearance or absence of secondary sexual characteristics, dysfunction of the upper and lower parathyroid glands (violation calcium metabolism), thyroid gland(exophthalmos) and pituitary (moon face, high voice). Often there is osteoporosis. Changes in the fingers resemble those in sclerodactyly. Most patients with Werner's syndrome die before the age of 40. Trials are currently underway to treat the disease with stem cells.