Childhood progeria. Early aging - causes, features and methods of prevention

What is progeria, what are its signs and consequences? 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 and affects one in 8 million children worldwide. The name of the syndrome comes from the Greek word and means “premature aging.” Although there are various shapes progeria, classic type Hutchinson-Gilford syndrome Progeria is named after the doctors who first described the disease, Dr. Jonathan Hutchinson in 1886, and Dr. Hastings Guilford in 1897.

Today it is known that CSGP is caused by a mutation in the LMNA (Lamin) gene. The LMNA gene produces the protein lamin, which holds the cell nucleus together. Researchers believe that a 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 illnesses can occur at the age of one and a half to two years. This cessation of growth, loss of weight and hair, protruding veins, wrinkled skin - all this is accompanied by complications more typical for older people - joint stiffness, generalized atherosclerosis, osteoporosis, cardiovascular diseases, stroke. Children with this disease are remarkably similar appearance, despite different ethnic backgrounds. Most often, children with progeria die from (heart disease) at an average age of thirteen years (range from about 8 to 21 years).

There is also “adult” progeria (Werner syndrome), which begins in adolescence(15-20 years old). The life expectancy of patients is reduced to 40-50 years. Most common reasons fatal outcome are myocardial infarction, stroke and malignant tumors. Exact reason Scientists cannot determine the development of the disease.

Who is at risk?

Although progeria is genetic disease, in the classical sense of Hutchinson-Gilford syndrome, but not hereditary, i.e. None of the parents are either carriers or affected. Each case is thought to represent a sporadic (random) mutation that occurs in either the egg or sperm before conception.

The disease affects all races and both sexes equally. If a couple of parents have one child with CSGP, 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 on from generation to generation, but not classic CSGP.

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 the specific genetic changes or mutations in a gene that lead to CSGP. After the initial clinical assessment(child's appearance and medical documentation), a blood sample is taken from the child for testing. A definitive scientific method for diagnosing children is currently being developed. This will lead to more accurate and more early diagnosis , which will help ensure that children with this mutation receive proper care.

What treatment is available for children with progeria?

A seemingly ordinary form psychological state- phobic anxiety, causes cell damage and leads to premature aging.

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

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

26 children took part in drug trials—that’s a third of all known cases progeria. Children taking the drug showed a 50% increase in annual weight gain. 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 emphasize that thanks to new development Damage to blood vessels is not only reduced, but also partially restored over the period.

Progeria is a genetic disease in which premature, rapid aging of the body occurs: the skin, internal organs and systems. The disease has two forms: childhood (Hutchinson-Gilford syndrome) and adult (Werner syndrome). It should be noted that it occurs most often 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 occurs in the body accelerates the aging process by approximately 8-10 times. A child with this disease, when he turns 8 years old, looks 80. And not only in appearance. The condition of his internal organs also corresponds to his age. old age. Therefore, such children live for a very short time, approximately 13–20 years.

Today on the www.site we will talk in more detail about premature aging of the human body - this is progeria disease, 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 of 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 stability, triggers the process of rapid aging in the body.

Note that, unlike many other genetic diseases, progeria is not hereditary and 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. Manifestations of the disease begin closer to 2 years of age, when parents notice that the child has stopped developing. Already from 9 months of age, growth retardation is observed. The baby is not gaining weight well, the skin loses its elasticity, looks aging, and keratinized areas appear on it. Joints lose elasticity, subcutaneous tissue becomes thinner adipose tissue. These children often experience hip dislocations.

The shape of the child's head and face takes on a characteristic appearance. The head becomes much more face, lower jaw small, smaller than the top one. Veins are clearly visible on the scalp and eyelids. Eyelashes fall out, eyebrows thin, hair falls out rapidly. The child’s baby teeth are growing poorly, they are noted to be irregular shape. Teeth that have grown to replace baby teeth begin to fall out.

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

At further development disease, the elasticity of the arteries is impaired, atherosclerosis develops, cardiovascular diseases occur, and a stroke may occur.

Progeria in adults:

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

There is thinning and dryness of the skin, it becomes pale and takes on an unhealthy tint. Under the skin, visible 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, his skin becomes rough, his skin becomes ulcerated, there is a dysfunction of the sweat glands, sebaceous glands. The patient’s body experiences a calcium deficiency, which causes the development of osteoporosis, erosive osteoarthritis, and the development of diseases 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 characteristic features also includes a thin chin, sharply protruding forward, dense, short body and thin, dry limbs, heavily covered with pigmentation.

A large number of patients, by about 40 years of age, become ill oncological diseases, diabetes mellitus. They are diagnosed with a 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, how its treatment will help improve well-being and slow down the processes that have begun.

Treatment for progeria

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

For example, a patient is prescribed daily intake small doses of aspirin, which helps reduce the risk of heart attacks and prevent stroke.

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

Anticoagulants are used to reduce the risk of blood clots. Also, during therapy, growth hormone is used, which helps the patient’s body restore weight gain and promotes normal growth.

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

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

Treatment for progeria requires individual approach to each patient, depending on his condition and age. Currently being carried out clinical researches drugs created by scientists to treat this genetic disease. Perhaps effective therapeutic techniques will soon appear. Be healthy!

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 “premature aging syndrome”, 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 By 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

People first started talking about premature aging syndrome 100 years ago. And it’s not surprising: such cases occur once in 4-8 million babies. Progeria (from the Greek pro - earlier, gerontos - old man) - or Hudchinson Guilford syndrome. This disease is also called childhood old age. This is an extremely rare genetic disease that accelerates the aging process by approximately 8-10 times. Simply put, a child ages 10-15 years in one year.

Children with progeria appear normal for 6 to 12 months after birth. After this, 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 and 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. People call this disease “canine old age.”

There are now about 60 known cases of progeria in people around the world. Of these, 14 people live in the United States, 5 in Russia, and the rest in Europe. Features of such patients include dwarf stature, 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 a person bird-like features. Due to the loss of subcutaneous fat, all blood vessels are visible. The voice is usually high. Mental development appropriate for age. And all these sick children are strikingly similar to each other.

Until recently, doctors were unable to determine the cause of the disease. And only recently, American researchers discovered that the cause of “childhood old age” is a single mutation. Progeria is caused by a mutated form of the LMNA gene. According to the director of the National Genome Research Institute, Francis Collins, who led the study, the 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 large protruding ears, bulging eyes and swollen veins on his bald skull - turns into a one hundred and sixteen year old man.

Hussein Khan and his family are unique in their own way: 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. Neither of them has progeria, nor do their two children, 14-year-old Sangeeta and two-year-old Gulavsa. Their 19-year-old daughter Rehena and two sons: 7-year-old Ali Hussein and 17-year-old Ikramul suffer from this disease. None of them have practically any chance of living even to 25, and this is probably the saddest thing.

Adult progeria (Werner syndrome) is a hereditary or family disease. Manifests 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. Slowly developing juvenile cataract. The skin of the feet, legs, to a lesser extent, hands and forearms, as well as the face, gradually becomes thinner, the subcutaneous tissue and muscles in these areas atrophy. On lower limbs 90% of patients experience trophic ulcers, hyperkeratosis and nail dystrophy.

Atrophy of the facial skin ends with the formation of a beak-shaped nose (“bird nose”), narrowing of the mouth and a sharpening of the chin, reminiscent of a “scleroderma mask.” From endocrine disorders hypogenitalism is noted, late appearance or absence of secondary sexual characteristics, dysfunction of the superior and inferior parathyroid glands (disorder calcium metabolism), thyroid gland(exophthalmos) and pituitary gland (moon face, high voice). Osteoporosis is often observed. Changes in the fingers resemble those seen in sclerodactyly. Most patients with Werner syndrome die before age 40. Trials are currently underway to treat the disease with stem cells.