Achondroplasia in children. Causes of achondroplasia and features of genetics

– congenital disease, in which the growth of the bones of the skeleton and the base of the skull is disturbed. The disease was first described under this name in 1878, in 1900 expanded clinical characteristic was given by Pierre Marie. Therefore, achondroplasia is sometimes called parro-marie disease.

Most of the causes of dwarfism are achondroplasia. The incidence of the disease is one case per twenty thousand newborns. The disease is independent of gender and race. Every fifth patient suffering from achondroplasia gets the disease by inheritance, in the rest of the patients it is associated with primary mutations of the FGFR3 gene. If the achondroplasia gene is present in both parents, then such children most often die in the womb.

According to geneticists, achondroplasia is most often diagnosed in children born to fathers over forty years old. However, it is impossible to foresee the possibility of the birth of such a child due to the fact that genes can mutate even in healthy parents. Genetic counseling may only be useful for parents who have signs of achondroplasia in order to plan a family in the future.

Today, doctors continue research in the field of the FGFR3 gene, the “culprit” of achondroplasia. As it turned out, this gene belongs to the group responsible for the formation of fibroblast growth receptor proteins. Normally, this protein provides the passage of signals from chemical compounds and thereby stimulates the growth and maturation of cells. In people suffering from achondroplasia, signaling mechanisms are impaired, which causes problems with normal bone formation. At the moment, scientists are investigating the mechanism of achondroplasia, which can take a significant step forward in the treatment of the disease.

Today, medicine knows several forms of the disease:

• Hyperplastic achondroplasia (characterized by accelerated but disordered growth of the epiphyses);
• Gelatinous softening of the cartilage of the epiphysis (it is this form of the disease that is the main cause of intrauterine death);
• Hypoplastic achondroplasia (this form of the disease is characterized by underdevelopment of cartilage tissue).

The reasons

The main cause of achondroplasia is a mutation in the FGFR3 gene, which leads to dystrophy of the epiphyseal cartilage. The cells of the growth zone are arranged randomly, as a result of which the physiological process of ossification is disturbed. Because of this, the bones begin to lag behind in development. At the age when cartilage ossifies in children, patients with achondroplasia have still unformed bone tissue with a predominance of cartilage. Mostly bones that grow in the endochondral type are affected, i.e. ossification comes from within the cartilaginous bone. These are the bones of the base of the skull, tubular bones.

Symptoms

The symptomatology of the disease manifests itself already at the birth of a child - an increase in the circumference of the head above the norm, shortened limbs can be noted. The forehead is convex, the occiput and crown protrude. Often in children with achondroplasia, doctors diagnose hydrocephalus. Due to the incorrect formation of the bones of the skull, the facial skeleton also suffers - the eyes of the child are widely spaced, deeply set in orbits, the brow ridges hang. Nose has irregular shape- it is flattened, the upper part is wide, the wings of the nose are significantly removed on the sides. Due to the fact that the nasal passages are narrowed, patients often suffer from sinusitis, otitis media.

The proximal segments of the limbs - hips and shoulders - are shortened, curvature is noted. The hands of a newborn barely reach the navel. Feet are wide and short. The fingers of such babies are almost the same length, however, they are also short. In most cases, this symptom retains its severity - in adults suffering from achondroplasia, middle finger in the position of a straightened hand, it barely reaches the inguinal fold. The trunk of children suffering from achondroplasia is little changed, the chest is developed normally. Due to the curvature of the spine, the stomach protrudes forward, the buttocks, on the contrary, protrude backward more than in healthy babies.

Patients with achondroplasia early age have breathing problems, which in turn is associated with structural features of the face, enlarged tonsils, high sky. Doctors often pay attention to the increase in the level of sudden death in children with this pathology. It is assumed that compression of the medulla oblongata due to the irregular size and shape of the foramen magnum plays a key role here.

Often, children with achondroplasia are developmentally retarded, later they begin to hold their heads, sit down and walk, but at the same time, intellectual development does not suffer. In some cases, children may have trouble adjusting to the world around them because most services are not adapted to people with special needs.

As the child grows, his bones take on an increasingly irregular shape - they thicken and bend, tubercles form. Excessive elasticity in the epiphyseal and metaphyseal sections provokes bone deformities, which are aggravated by the appearance of a load on them, an increase in body weight.

In general, patients with achondroplasia are characterized by the following disorders:

• curvature of the femur;
• "looseness" of the knee joints;
• the formation of a flat foot;
• decreased muscle tone;
• incorrect relationship between the fibula and tibia;
• curvature of the upper limbs in the forearm;
• growth deficit;
• change in the shape of the skull, malocclusion;
• a number of diseases accompanying achondroplasia;
• excess body weight.

Diagnostics

Usually, it is not difficult for a doctor to diagnose the disease. The appearance of the patient and the proportions of his body primarily indicate achondroplasia. AT childhood the study is done more carefully to see the degree of deviation of the parameters from the norm. For children with achondroplasia, there is a special table of height and weight, with which the obtained data of children with suspected disease are compared. Thus, doctors can assess the child's tendency to achondroplasia, observe the dynamics of his indicators. In case of significant deviations, consultations of other specialists are appointed. The neurosurgeon examines the patient for hydrocephalus, magnetic resonance and CT scan brain. The otolaryngologist examines the structure of the patient's throat and nasal passages to confirm or refute the diagnosis. In some cases, you may need to consult a pulmonologist.

To diagnose achondroplasia, patients undergo an X-ray examination of the skull, chest and pelvis. According to its results, the proportions of the brain and facial parts of the skull, the size of the foramen magnum, the thickness of the ribs, their deformation, the presence of anatomical bends, the thickness and shape ilium.

Particular attention is paid to tubular bones, which, in achondroplasia, have a shortened thin diaphysis and expansion of the metaphyses. Joints in patients with achondroplasia are deformed, especially pronounced deformation in the knee and wrist joints.

Treatment

Treatment of the disease is currently not possible. Doctors can only minimize the consequences in order to improve the quality of life of patients. In childhood, for such babies, conservative therapy is carried out - massage, physiotherapy. This helps to strengthen the muscular corset and prevent severe deformation. lower extremities. Patients are advised to wear special shoes that reduce pressure on the bones. It is also important to follow a diet to prevent burdening the skeleton with excess weight. Defects in the jaw area are corrected by wearing special plates.

There are cases when hormone therapy is prescribed in childhood, which makes it possible to slightly compensate for the lack of growth. For adults, hormone therapy is not used.

If the parents decided on a surgical solution to the problem, then in that case it is necessary to contact a specialized clinic that has sufficient experience in performing such operations.

Surgical intervention is performed if the disease brings obvious discomfort to the patient. An unequivocal decision in favor of the operation is made when there is a threat of infringement spinal cord, the occurrence of kyphosis of the middle part of the back, "o"-shaped legs.

It is also possible to lengthen the bones, for which several surgical interventions are performed in stages. At the age of four to six years, children undergo surgery to lengthen the legs (up to six cm), hips (up to approximately seven to eight cm) and shoulders (possible result - up to five centimeters). The duration of such stages is about five months with a break of two to three months. The next series of intervention is carried out at the age of fourteen to fifteen years. Here the patient also goes through three stages, the expected result is the same as the first time.

However, such actions do not completely eliminate the disease and its symptoms, since with small stature, bone lengthening even up to ten centimeters does not make patients look like ordinary people. In addition, not all patients are ready to go through a series of operations and painful rehabilitation periods.

The disease is not hidden, thus, doctors monitor a minor patient from birth and as achondroplasia manifests itself. Most often, the reason congenital pathology is a mutation in the FGFR3 gene. It is he who is responsible for the process of ossification and development of cartilaginous tissues, and violations of this process are what can cause dwarfism. In the presence of "failures", the cartilage in the child's body ceases to grow in length. A mutation may appear spontaneously or be caused by a hereditary factor. Experts believe that achondroplasia can cause conception after the age of 40 by the father of the child. In some cases, this is also true for mothers.

The disease is inextricably linked with the genetic factor. In the event that dwarfism is recorded in one of the parents or both in the father and in the mother, the risks of inheriting the disease increase to 50-75 percent, respectively. It is important to note that the risk of pathology as a result of a new mutation is much higher than the risk of its inheritance. Violations at the level of eggs and sperm lead to achondroplasia in 80 percent of cases. If we consider the total number of children with dwarfism, then most of them have parents normal growth.

Symptoms

The disease manifests itself in the form of obvious dwarfism, accompanied by violations of the proportions of the body, head and limbs. Other defects in the physique or lag in the intellectual development of the child are not noted.

While maintaining the relatively natural size of the head and torso in children with achondroplasia, it is possible to determine a significant shortening of the limbs by eye. The first signs of the disease are insufficient separation of the index finger from the middle fingers, which causes a visual deformation of the hand. The length of the fingers is also different from the norm. The palm of the child has the shape of a square. Legs may be crooked, feet too wide and not long enough.

A frequent manifestation of the disease is a protruding forehead and a flat back of the nose. If the child begins a significant increase in the size of the head, then the risk of hydrocephalus is high. In such cases, it is necessary to recognize the pathology in a timely manner and eliminate the concomitant disease with the help of surgery.

In most cases, achondroplasia is accompanied by transient kyphosis in the upper spine. This is due to weak muscle tone. As the child learns to walk, the kyphosis disappears without outside intervention. At this stage, it is important to ensure proper back support. Otherwise, there is a possibility of a hump formation. The dwarfism of this form can be recognized by lordosis in lumbar expressed by a strong bend. In view of the presence of these symptoms, getting up, crawling and walking in a child begins later than in peers.

Diagnosis of achondroplasia in a child

It is possible to diagnose the disease already with a visual examination of a minor patient. In some cases, an additional general examination is required. This is necessary for an objective assessment of the degree of non-compliance of real indicators with the norm. So, when making a diagnosis, a specialist works with a table of height and weight standards for a specific age. If the diagnosis is confirmed, the pediatrician refers the child to a neurosurgeon, an otolaryngologist, and other specialized specialists. Consultation of a neurosurgeon is carried out in order to exclude hydrocephalus. For this, the doctor performs CT and MRI. The task of the otolaryngologist is to study the structure of the nasopharynx and, if necessary, prescribe therapy that prevents characteristic complications. Laboratory tests are not used in the diagnosis of achondroplasia.

Complications

All parents want to know how dangerous achondroilia is for their children. Possible Complications diseases are expressed in the narrowing of the channels of the spinal cord, as a result - squeezing the spinal cord and nerves. If measures are not taken in time, this can lead to limited movements, incontinence, and sexual dysfunction in boys.

Treatment

Since the disease is congenital, it is not possible to cure it completely. Longevity data positive impact hormone therapy with the use of growth hormone do not exist. As additional method an increase in the growth of the child by 20-30 centimeters can be considered surgical operation using a compression-distraction apparatus. Doctors do not recommend treating dwarfism in this way. Artificial lengthening of bones entails serious complications.

What can you do

Parents of children with dwarfism should remember that a child with achondroplasia can do absolutely everything that his peers can do. In the absence of complications and concomitant diseases, intellectual development corresponds to the norms. Minor patients can fully serve themselves on their own and are ready for successful social adaptation. Psychological trauma can be the only difficulty. In this case, the first help of a child psychologist is needed, who will take care of preventing the development of an inferiority complex.

What does a doctor do

Basically, doctors perform the following types of treatment:

• Medication - to eliminate the symptoms that cause discomfort to the child.
• Surgical - in the presence of hydrocephalus.
• Physiotherapy - to develop muscles and prevent the appearance of a hump.

Prevention

Genetic consultations and prenatal diagnostics make it possible to detect pathology in time, but not prevent it. This also applies to hereditary achondroplasia.

No one can be insured against the birth of a sick child. This is a big blow not only for parents, but also for medical staff. This is especially true of pathologies that cannot be prevented and prevented. One such condition is achondroplasia.

Achondroplasia is a genetic disorder whose main characteristic is short limbs, while the body length remains normal. The average value of the patient's height is at the level of 130 centimeters, and in some cases even less. The spine in such a patient has a curved shape, the head is large, and the frontal tubercles protrude significantly.

The incidence of pathology among all newborns is 1: 10,000, while girls are affected more often than boys.

This pathology cannot be cured, and methods for complete restoration of growth are currently unknown. All methods of therapy are aimed at minimizing all negative manifestations of the disease.

The reasons

At the heart of this pathology are the problems of bone formation processes due to a genetic failure in the formation of epiphyseal cartilage. The cells of the growth zone are arranged randomly, which provokes a violation of normal ossification, and the patient's growth slows down.

Only those bones that grow according to the endochondral type take part in this process. Since the bones located in the region of the cranial vault are formed from connective tissue, they grow according to age and this provokes a violation of the proportion and the formation of a specific shape of the patient's skull.

Symptoms

Anatomical anomalies become noticeable after the birth of the baby. Doctors note in a newborn such external manifestations as:

• large volume head;
• limbs are very short.

On the baby's head, it is clearly visible that the forehead has a convex shape, and the occipital and parietal tubercle are protruding. In some cases, hydrocephalus is diagnosed. eyeballs set deep and wide apart. The shape of the nose is saddle-shaped, and the upper part is wide. The forehead, like the upper jaw, has a protrusion forward.

The arms and legs of patients with achondroplasia are shortened at the expense of the hips and shoulders. Doctors notice that the handles of a newborn can only reach the navel. The body of the baby has a normal development, there are no changes in the chest, the stomach is protruded forward.

Children diagnosed with achondroplasia are more likely than other babies to experience sudden death in their sleep. Doctors explain this by the fact that in such patients it is compressed medulla and the upper part of the spinal cord due to the small diameter of the opening in the occipital region.

In the first two years of life, the child develops kyphosis in the cervicothoracic region, which may disappear after the child begins to walk. All children with achondroplasia have lags in physical development, but mental and intellectual development does not suffer.

As the patient grows older, flat-valgus feet begin to form, and the knee joints lose their stability. Adult women reach a height of 124 centimeters, and men - 131 centimeters. It is worth noting that most patients with this diagnosis tend to gain excess weight and suffer from obesity.

Diagnostics

Because the appearance the patient has character traits, then it is not difficult for doctors to make a diagnosis. All children should be examined to assess the severity of the pathology, and the data obtained should be recorded in a summary table. It is important to fill it regularly, and the results are compared with the data of the norm developed for patients with achondroplasia.

It is also important to conduct a study of different organs. For this, the following specialists are involved:

• neurosurgeon (he recommends MRI and CT);
• otolaryngologist;
• pulmonologist.

Each patient is obliged to bring the results of the x-ray to the doctor, according to which the doctor can confirm or refute the diagnosis.

On an x-ray of a patient with a history of achondroplasia, a violation of the proportions between such parts of the skull as the facial and brain is determined. The hole in the back of the head has a reduced diameter, and the dimensions mandible and there are more bones of the cranial vault than in healthy patients.

The chest x-ray shows that the sternum is curved, the ribs are thickened and deformed. In some cases, the absence of a normal anatomical curvature of the clavicle is determined.

The patient's spine in the picture does not have any special changes, but its physiological curves are weakly expressed, which can lead to the development of lumbar hyperlordosis.

An x-ray of the pelvis shows the altered shape of the iliac wing. It is rectangular, deployed and significantly shortened.

When taking x-rays of the joint, doctors can see fibula lengthening, deformity, and incongruity.

Treatment

To date, there are no methods for the complete cure of patients from achondroplasia in orthopedics. Clinical studies have been conducted on the use of growth hormone, but this method has not been proven effective.

• use special orthopedic shoes;
• engage in physical therapy;
• take a course of massage;
• lose weight.

If the patient's arms and legs are very deformed, and the spinal canal is narrowed, then he is recommended to undergo surgery. In order to correct the deformity, doctors perform an osteotomy, and if necessary, to eliminate the narrowing, a laminectomy.

In the case of leg lengthening to increase height, surgery is performed crosswise in several stages. This means that the hip is operated on in the first stage. right foot and the lower leg of the left, and in the second - vice versa.

For the entire course of operations, the child can grow up to 28 centimeters. Therapy begins at 4 years of age. During this period, the first three stages of intervention are carried out. Rehabilitation after each operation is about 5 months, and the interval between manipulations should not be less than 2-3 months.

For repeated stages, a child is invited at the age of 14–15 years. During this period, the teenager must again go through all the stages of painful procedures.

Height increase (video)

Genes play an important role in the development of an organism. Only a small part falls on various diseases of an infectious nature. If mutation codes are passed on to a child through the genes, then diseases that cannot be cured develop. One of them is achondroplasia, which manifests itself in specific symptoms and has genetic causes of its development.

Achondroplasia is a combination of dwarfism with disproportionate development of the limbs. This is a genetic disorder where a mutation in the child's gene is seen in FGFR3. It is this gene that is responsible for bone and cartilage development. With achondroplasia, signs of the disease are noted from birth. The child grows more slowly than others, and he also has disproportionate limbs.

The disease occurs in 1 case per 25,000 people. It is noted in the deformity of the spine, short stature, normal torso, but with short limbs. Does not depend on gender, affects both the male part and the female part.

Achondroplasia translates as "no cartilage". However, people with this diagnosis have cartilage tissue. Just unlike a healthy person, certain anomalies are observed. Healthy man during the intrauterine period and in childhood, it gradually becomes ossified. His cartilage is replaced by bones, except for the area of ​​his nose and ears. In people with achondroplasia, this process is impaired, especially in the shoulder girdle and hips. Because of this, the tubular bones become short, which provokes slow growth.

Achondroplasia has its own varieties:

• The form is divided into:

1. Hyperplastic - a disordered and rapid increase in cartilage tissue, where the growth bone is located, and the growth of an organ that is part of the endocrine system.
2. Hypoplastic - underdevelopment of cartilaginous tissue and growth retardation of the endocrine system organ.
3. Gelatinous softening of cartilaginous tissue. With this form, children usually do not survive. If they are born, then during the sexual period of maturation, their vitality increases.

• For reasons of occurrence:

1. Hereditary - when a mutated gene is passed from parents. If both parents have it, then the child is definitely born sick.
2. Sporadic - mutation of a gene in the process of life. Here heredity does not play a role. Noted for the following reasons:

• Radiation.
• High temperatures.
• The production of organic substances in the body that provoke changes.

Other names of the disease are called Parro-Marie's disease, congenital chondrodystrophy, diaphyseal aplasia, dwarfism.

Causes of achondroplasia

The website site notes genetic inheritance as main reason achondroplasia. If at least one parent has a mutated gene, then the risk of developing the disease in a child is 50%. If the corresponding gene is observed in both parents, then the disease develops in 75%. Only 25% of the child can be born healthy, but at the same time carry a mutated gene, which is why it is passed on to subsequent generations.

If the child is inherited the appropriate gene that affects the development of his skeleton, then he goes through severe torment. Usually such children do not live long and die quickly. Only in the absence of a mutated gene will a child be born healthy and will not pass it on to the next generation.

Another cause of achondroplasia may be mutations not in genes, but in sperm or eggs. Parents of a sick child can be absolutely healthy and of normal growth. However, when the baby was conceived, a sperm or an egg was involved, which were mutated. Such parents may have other healthy children. However, often the disease in question is rarely manifested for such a reason, which minimizes the risks.

The older the parents get, the more likely they are to pass on the wrong genes to their children when they conceive. So, men after 40 years (like women) can give birth to unhealthy children in whom genes are transmitted in an autosomal dominant manner.

The considered factors influence the change in the development of cartilage tissue. Chondrocytes are randomly arranged, which interferes with normal ossification. This provokes a decrease in bone growth. The result is a child with a disproportionate growth of the limbs.

Symptoms of achondroplasia

It is very easy to recognize a person with achondroplasia by his short stature and disproportionate limbs with the torso or head. At the same time, the intellect and physique are not violated. Symptoms of achondroplasia are:

1. Small stature in men up to 130 cm. in women up to 125 cm.
2. lower and upper limbs are short due to underdevelopment of the shoulder and femoral girdle. Over time, the limbs thicken, which leads to their curvature and tuberosity. These deformations become visible, especially under loads.
3. Curvature of the legs to X- or O-shape.
4. Wide and short feet.
5. Fingers on the hands of the same length and shortened. The middle and index fingers are closely spaced, which resembles the appearance of a trident. The brushes are square in shape.
6. Arched and high hard palate.
7. Protruding forehead.
8. Limited elbow and knee extension.
9. Wide nose with a depressed, low bridge of nose.
10. Lagging behind in physical development.
11. Curvature of the spine in some cases, which manifests itself in excessive bending. This is noted on the gait. The development of kyphosis is possible, which is associated with poor muscle tone. Over time, kyphosis can improve if you keep your back straight while walking to prevent a hump. The lumbar region often suffers - the development of lordosis.
12. Additional fold with inside eyes.
13. The body and head are of relatively normal size.
14. Possible hydrocephalus.
15. Incorrect bite of teeth due to a small jaw.
16. Tendency to infectious ENT diseases due to narrowed nasal passages.
17. Small and wrinkled face.

Additional symptoms of the disease may include:

• Pain in the lower back.
• Dropsy in the brain.
• Strabismus.

Mental development in these children remains normal. However, they suffer from various difficulties in getting up, sitting and walking independently.

Often the death of such children occurs during sleep. Doctors explain this by squeezing the spinal cord in the neck and at the base of the skull, which interferes with the normal breathing process.

Treatment of achondroplasia

Achondroplasia is almost impossible to cure, so doctors act on the consequences of its manifestations. The main treatment is to take hormones, which should affect the overall growth of the body. There is evidence that sometimes taking hormones helped a person achieve normal growth. However, these are exceptional situations.

1. Laminectomy - cutting the spinal canal to relieve pressure.
2. Osteotomy - cutting the bone and giving it correct form. It is possible to lengthen it.

In parallel with changes in bone growth, doctors monitor changes in the trunk and head. If the head does not correspond to the age of the child, then hydrocephalus is diagnosed. Here, neurosurgeons perform an operation to remove excess fluid so that it does not put pressure on the brain.

• Kyphosis and curvature of the limbs are eliminated surgically.
• Orthodontic plates are placed on the teeth to eliminate dental defects.
• Drainage is placed in the middle ear area to exclude the development of deafness due to ENT diseases.
• Purpose proper nutrition to prevent the development of obesity.

The main complication of achondroplasia is compression of the spinal nerves and brain. This is noted in motor dysfunction, decreased sensitivity, weakness in the legs, weakening of the functions of the pelvic organs.

Forecast

Achondroplasia is a fatal disease with a poor prognosis. However, with the survival of the child, it is possible to carry out treatment that will help in eliminating the obvious signs of the disease.

If parents know about the presence of a mutated gene, then you should think about the birth of a child who will be sick. During pregnancy, it is necessary to undergo a consultation with a geneticist who will check the possibility of developing anomalies in the child.

Metaphyseal dysplasia(multiple cranial metaphyseal dysplasia, Pyle's syndrome) is a congenital systemic bone disease, manifested by large head sizes, widely spaced eyes (hypertelorism), saddle nose, bad crumbling teeth, limb deformities, disproportionately long legs. Radiologically, symmetrical bottle-shaped or club-shaped swellings of the metaphyses and the corresponding thirds of the diaphysis of the long tubular bones with thinning of the cortical layer, symmetrical hyperostosis of the bones of the cranial vault, filling of the adnexal cavities with bone tissue, narrowing of the bone holes and canals cranial nerves and vessels. There are 3 types.

1. Jansen type- characterized by generalized demineralization of bones, reduction and deformation of the epiphyseal nuclei, expansion and fragmentation of the metaphyses. The epiphyseal ossification centers are distant from the metaphyses ("free-floating epiphyses"). Shoulder heads and femur flattened, deformed joints, mobility in them is limited. varus develops and hallux valgus hips, knees and ankles. The skull is moderately enlarged, the forehead protrudes, slight supraorbital and frontonasal hyperplasia.

2. Schmid type- the disease is similar to rickets (but the mineralization of bones is not broken). It is manifested by shortening of long tubular bones, predominantly of the proximal femoral metaphysis. As a result, its varus deformity develops with bowl-shaped and jagged metaphyses, and curvature of the legs. Changes in the hands and feet are not observed.

3. Vandrager type - Peña characterized by dysplastic changes in the metaphyses of long tubular bones, radiographically having the appearance of dense longitudinal fields reaching the diaphysis. The ends of the damaged bones are expanded. The spine in the Vandrager type is not changed, in contrast to the Peña type, in which scoliosis and flattening of the cervical vertebral bodies are noted.