Achondroplasia (Parrot-Marie disease, diaphyseal aplasia, congenital chondrodystrophy, dwarfism). Metaphyseal dysplasia - Pyle's syndrome

No one can be protected from the birth of a sick child. This is a big blow not only for parents, but also for medical staff. This is especially true for pathologies that cannot be prevented or prevented. Achondroplasia is one of these diseases.

Achondroplasia is a genetic disease, the main characteristic of which is short limbs, while the body length remains normal. The average height of the patient is 130 centimeters, and in some cases even less. The spine of 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, and this affects girls more often than boys.

This pathology cannot be cured, and methods for completely restoring growth are currently unknown. All methods of therapy are aimed at reducing all negative manifestations of the disease to a minimum.

Causes

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

Only those bones that grow according to the enchondral type take part in this process. Since the bones located in the area of ​​the cranial vault are formed from connective tissue, they grow according to age and this provokes an imbalance in proportion and the formation of a specific shape of the patient’s skull.

Symptoms

Anatomical abnormalities become noticeable after the baby is born. Doctors note such external manifestations in the newborn as:

• large volume head;
• limbs are very short.

It is clearly visible on the baby’s head that the forehead has a convex shape, and the occipital and parietal protuberances are protruding. In some cases, hydrocephalus is diagnosed. The eyeballs are set deep and the distance between them is wide. 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 a newborn's hands can only reach the navel. The baby's body has normal development, there are no changes in the chest, the stomach is protruded forward.

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

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

As the patient gets older, flatfoot 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

Since the patient’s appearance has characteristic features, 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 out regularly, and the results are compared with the norm data developed for patients with achondroplasia.

It is also important to conduct research on different organs. For this purpose the following specialists are involved:

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

Each patient is required to bring the doctor X-ray results, from 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 cerebral parts is determined. The hole in the back of the head has a reduced diameter, and the size of the lower jaw and bones of the cranial vault is larger than in healthy patients.

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

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

An X-ray of the pelvis shows a changed shape of the iliac wing. It is rectangular, unfolded and significantly shortened.

By taking X-rays of the joint, doctors can determine fibular lengthening, deformity, and incongruity.

Treatment

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

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

If the patient's arms and legs are very deformed, and the spinal cord 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, surgical intervention is performed crosswise in several stages. This means that in the first stage the thigh of the right leg and the shin of the left are operated on, and in the second - vice versa.

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

Increase in height (video)

Achondroplasia is the most common birth defect that is characterized by abnormal body proportions: people suffering from this disease have signs of relative macrocephaly (the forehead protrudes forward and the bridge of the nose is flat), the arms and legs are very short, while the legs and spine are deformed, the shoulders and hips the bones are shortened more than the radii, and the torso is of almost normal size.

Sometimes a large head is a reflection of hydrocephalus - the presence of excess fluid in the brain - and requires surgical intervention. The palms of patients with achondroplasia are small with short, thick fingers. There is some distance between the middle and ring fingers (trident hand). In most cases, people, having reached adulthood, have a height of no more than 120-130 cm.

What it is?

Achondroplasia is a genetic disease that results in impaired bone growth. This is one of the most common types of dwarfism. It is possible to judge whether a child has this pathology from the moment of birth.

Pathogenesis and genetics

Achondroplasia is caused by mutations in the FGFR3 gene, and is located on the fourth chromosome. At the same time, the growth of cartilage is inhibited. FGFR3 encodes a protein called Fibroblast Growth Factor 3. This protein is responsible for the growth of bones in the body. In achondroplasia, FGFR3 cannot function properly, and bone and cartilage growth slows down. This results in short bones, abnormal bone shape, and short stature.

FGFR3 is a transmembrane tyrosine kinase receptor that binds to FGF. The binding of FGF to the extracellular region of FGFR3 activates the intracellular domain of the receptor and triggers a signal sequence. In endochondral bone, FGFR3 activation inhibits chondrocyte proliferation in the growth plate, thereby helping to coordinate chondrocyte growth and differentiation with the growth and differentiation of bone progenitor cells.

Achondroplasia-associated FGFR3 mutations are gain-of-function mutations that cause ligand-independent activation of the FGFR3 protein. This constant upregulation of the FGFR3 protein improperly inhibits the proliferation of chondrocytes in the growth plate and leads to shortening of long bones, as well as abnormal formation of other bones.

Guanine at position 1138 in the FGFR3 gene is one of the most mutable nucleotides identified in all human genes. A mutation of this nucleotide occurs in almost 100% of cases of achondroplasia; more than 80% of patients have a new mutation. New guanine mutations at position 1138 of the FGFR3 gene occur exclusively in paternal germ cells and their frequency increases with paternal age (>35 years).

Symptoms of achondroplasia

Immediately after birth, you can detect the most obvious signs of achondroplasia in a newborn:

1. Deep location of the eye orbits,
2. The presence of additional folds on the inner corners of the eyes,
3. Saddle-shaped flattened nose shape,
4. Enlarged head
5. Convex forehead
6. Noticeably protruding parietal and occipital tubercles,
7. Wide-set eyes
8. Hydrocephalus,
9. Strong protrusion of the buttocks due to the posterior position of the pelvis,
10. Small chest
11. Enlarged tonsils,
12. Breathing problems
13. Violation of muscle tone,
14. Significant protrusion of the upper jaw,
15. High sky
16. Rough tongue
17. Short arms and legs of the baby,
18. Wide palms and feet with short toes,
19. Retarded physical development
20. Possible torticollis
21. Hearing and vision impairments.

As they grow, all of these symptoms progress, leading to multiple complications, many of which can be fatal.

Diagnosis of achondroplasia

To assess the condition of organs and systems, a comprehensive examination is carried out. To exclude hydrocephalus in children with achondroplasia, MRI and CT scans of the brain are performed.

1. When radiography of the skull in patients with achondroplasia, there is a disproportion between the brain and facial parts, the foramen magnum is reduced in size, the bones of the cranial vault and the lower jaw are enlarged. The Turkish saddle is characteristically shoe-shaped and flat, the base is elongated.
2. X-rays of the spine usually do not reveal gross changes. Physiological curves are less pronounced than normal.
3. X-ray of the chest is usually unchanged, in some cases the sternum protrudes forward and is slightly curved. Deformations and thickening of the ribs are possible. Sometimes the anatomical bends of the clavicle are absent.
4. X-rays of tubular bones reveal shortening, thinning of the diaphyses, goblet expansion and thickening of the metaphyses.
5. X-rays of the joints reveal deformation of the articular surfaces, disruption of the shape of the epiphyses, and widening of the joint spaces.
6. X-ray of the pelvis reveals changes in the size and shape of the wings of the iliac bones. The horizontal location of the roof of the acetabulum is determined.

As a rule, making a diagnosis does not cause difficulties due to the characteristic appearance and proportions of the patient’s body.

Achondroplasia - treatment

Effective treatment of achondroplasia is not currently possible. Doctors can only minimize the consequences to improve the quality of life of patients.

In childhood, conservative therapy is carried out for such children - massage, physical therapy. This helps strengthen the muscle corset and prevent severe deformation of the lower extremities. Patients are advised to wear special shoes that reduce pressure on the bones. It is also important to follow a diet to avoid 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 helps to slightly compensate for the lack of growth. Hormone therapy is not used for adults. If the parents decide to surgically solve the problem, then it is necessary to contact a specialized clinic that has sufficient experience in performing such operations.

• Surgery is performed if the disease causes obvious discomfort to the patient. An unambiguous decision in favor of surgery is made when there is a threat of spinal cord entrapment, kyphosis of the middle part of the back, or an “o”-shaped leg.
• It is also possible to lengthen the bones, for which several surgical interventions are performed in stages. At four to six years of age, children undergo surgery to lengthen their legs (up to six cm), hips (up to about seven to eight cm) and shoulders (possibly 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 interventions 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 short stature, elongation of bones even up to ten centimeters does not make patients look like ordinary people. In addition, not all patients are ready to undergo a series of operations and painful rehabilitation periods.

Inheritance of achondroplasia

For healthy parents of a child with achondroplasia, the risk of recurrence in future children is low, but probably somewhat higher than for the general population, since the possibility of sexual mosaicism, although extremely rare in achondroplasia, has been proven.

In a marriage where one partner has achondroplasia, the risk of recurrence in each child is 50%, since achondroplasia is an autosomal dominant disease with complete penetrance. In a marriage of two affected individuals, each child has a 50% risk of having achondroplasia, a 25% risk of lethal homozygous achondroplasia, and a 25% chance of normal growth.

When a mother with achondroplasia is pregnant, a fetus of normal size requires delivery by cesarean section.

Prevention

Prevention of achondroplasia consists of medical genetic consultation and prenatal diagnosis, which makes it possible to detect pathologies even at the stage of intrauterine development. Consultation with a geneticist is especially required for those who already have a history of dwarfism in their family. A special examination will allow you to assess the risk of having a sick child.

If parents already have achondroplasia, the disease cannot be prevented, as it is inherited.

is a congenital disease in which the growth process of the bones of the skeleton and the base of the skull is disrupted. The cause of the development of pathology is a genetic mutation. Some fetuses die in utero. At birth, abnormalities are noticeable from the first days of life: the head is enlarged, the limbs are shortened. Subsequently, there is a pronounced lag in the growth of arms and legs with a normal body size, valgus and varus deformities of the limbs, and spinal deformities occur. Achondroplasia is diagnosed based on examination, special measurements and radiography. Treatment is symptomatic, aimed at preventing and eliminating severe deformities.

ICD-10

Q77.4

General information

Achondroplasia (congenital chondrodystrophy, Parrot-Marie disease, diaphyseal aplasia) is a genetic disease in which shortening of the limbs is observed in combination with normal body length. Characteristic features are short stature (130 cm or less), a forward curved spine, a saddle nose and a relatively large head with prominent frontal tubercles. According to specialists in the field of traumatology and orthopedics, achondroplasia occurs in one out of 10 thousand newborns, women suffer more often than men. There are currently no ways to completely cure achondroplasia by restoring height and body proportions. Treatment is aimed at minimizing the negative consequences of the disease.

Causes of achondroplasia

The pathology is based on impaired bone development due to genetically determined degeneration of epiphyseal cartilage. The cause of the disease is a mutation in the FGFR3 gene. In 20% of cases, achondroplasia is inherited, in 80% it develops as a result of a mutation that occurs for the first time. Due to the chaotic arrangement of cells in the growth zone, the normal ossification process is disrupted. As a result, bone growth slows down. In this case, only bones that grow according to the enchondral type are affected: tubular bones, bones of the base of the skull, etc. The bones of the cranial vault, growing from connective tissue, reach the required size, which leads to a discrepancy in proportions between the head and body, causing a characteristic change in shape skulls

Symptoms of achondroplasia

The violation of anatomical proportions is noticeable already at birth: the child has a relatively large head, short arms and legs. The forehead is convex, the brain part of the skull is enlarged, the occipital and parietal tubercles protrude. In some cases, hydrocephalus is possible. There are disturbances in the structure of the facial skeleton resulting from improper development of the bones of the base of the skull. The eyes of patients with achondroplasia are widely spaced, located deep in the orbits, and there are additional folds near the inner corners of the eyes. The nose is saddle-shaped, flattened, with a wide upper part, the frontal bones protrude noticeably forward, the upper jaw also protrudes significantly forward over the lower jaw. The language is rough, the palate is high.

The lower and upper limbs of patients with achondroplasia are uniformly shortened, mainly due to the proximal segments (hips and shoulders). The hands of a newborn baby only reach the navel. All segments of the limbs are somewhat curved. The feet are wide and short. The palms are wide, the II-V fingers are short, almost the same length, the first finger is longer than the others. In the first months of life, patients with achondroplasia have visible fat pads and skin folds on the extremities. The torso is normally developed, the chest is not changed, the stomach is protruded forward, and the pelvis is tilted posteriorly, so the buttocks protrude more than in healthy children.

Infants with achondroplasia are more likely than their healthy peers to develop sudden death during sleep. It is assumed that the cause of death in such cases is compression of the medulla oblongata and the upper part of the spinal cord due to an abnormality in the shape and size of the foramen magnum. In addition, children suffering from achondroplasia are characterized by breathing problems due to the structural features of the face, large tonsils and small chest.

At 1-2 years of life, due to impaired muscle tone, patients with achondroplasia may develop cervicothoracic kyphosis, which disappears after they start walking. All children have some delay in physical development. They begin to hold their heads only after 3-4 months, learn to sit at 8-9 months and later, and begin to walk at 1.5-2 years. At the same time, the intellectual development of patients with achondroplasia usually remains within normal limits, and there are no mental abnormalities.

As we grow older, due to the distortion of epiphyseal bone growth, with normal periosteal growth, the bones become increasingly thicker, curved, and become lumpy. Due to the increased elasticity of the epiphyseal and metaphyseal sections of the tubular bones, varus deformities of the limbs occur, rapidly progressing with early loading. The curvature is further aggravated by the excessive traction of well-developed muscles and the significant mass of a normally developing torso. Due to a violation of the normal axis of the limbs, patients with achondroplasia develop planovalgus feet, and the knee joints become loose.

A number of deformities characteristic of achondroplasia occur. The hip bones bend and twist inward in the lower sections. Due to the uneven growth of the bones of the lower leg, the fibula in the upper part “pushes” upward and ceases to articulate with the tibia, and in the lower part it “distorts” the ankle joint. As a result, the ankle joint rotates 10-15 degrees inward, the foot goes into a supination position at an angle of 10-20 degrees. The upper limbs are also twisted, especially in the forearms. The shortening of the upper limbs remains, however, in adult patients with achondroplasia, the fingers no longer reach the navel, but the inguinal fold.

In adult patients, growth deficiency is observed, mainly due to shortening of the lower extremities. The average height of women is 124 cm, men - 131 cm. Changes in the head and facial skeleton persist and even become more pronounced: an enlarged cerebral part of the skull, a protruding and overhanging forehead, a deep bridge of the nose, a visible malocclusion. Possible squint.

Complications

Patients with achondroplasia are prone to obesity. Due to narrowed nasal passages, they often develop otitis media and conductive hearing loss. Due to upper airway obstruction, signs of respiratory distress may occur. With achondroplasia, narrowing of the spinal canal is quite often observed. It usually occurs in the lumbar, less often in the cervical or thoracic spine. May manifest as sensory disturbances, paresthesias and leg pain. In severe cases, dysfunction of the pelvic organs, paresis and paralysis is possible.

Diagnostics

The diagnosis of achondroplasia is made by a pediatric orthopedist; it does not cause difficulties due to the characteristic appearance and proportions of the patient’s body. All children are examined in detail to assess the degree of deviations from normal skeletal development, the data is entered into a table. This table is regularly updated as the child grows, and the data entered into it is compared with a standard table specially compiled for patients with achondroplasia.

To assess the condition of various organs and systems, a comprehensive examination is carried out, and consultations with various specialists are prescribed. To exclude hydrocephalus, newborn children with achondroplasia are examined by a neurosurgeon; if hydrocephalus is suspected, an MRI of the brain or a more accessible computed tomography is prescribed. To study the condition of the nasal passages and ENT organs, patients with achondroplasia are referred for consultation to an otolaryngologist. You may also need to consult a pulmonologist.

An X-ray of the skull reveals a disproportion between the facial and brain parts. The foramen magnum is reduced in size, the lower jaw and bones of the cranial vault are enlarged. The Turkish saddle has a characteristic shoe-shaped shape and a flat, elongated base. Chest X-ray with achondroplasia is usually unchanged; in some cases, the sternum protrudes forward and is somewhat curved. Possible thickening of the ribs and their deformation in the area of ​​​​the transition to the cartilaginous arches. Sometimes the normal anatomical curves of the clavicle are absent.

In photographs of the spine of patients with achondroplasia, gross changes, as a rule, are also not detected; physiological curves are less pronounced than in healthy people, and lumbar hyperlordosis may be detected. X-ray of the pelvis indicates a change in the size and shape of the wings of the iliac bones - they are rectangular in shape, expanded and shortened. The horizontal location of the roof of the acetabulum is also determined.

X-rays of tubular bones in patients with achondroplasia reveal shortening and thinning of the diaphyses, thickening and goblet-shaped expansion of the metaphyses. The epiphyses are immersed in the metaphyses like hinges. X-rays of the joints show deformation and incongruence of the articular surfaces, widening of the joint spaces and disruption of the shape of the epiphyses. X-rays of the knee joint of patients with achondroplasia indicate elongation of the fibula; X-rays of the ankle joint reveal rotation and supination.

Treatment of achondroplasia

It is not yet possible to completely cure patients using modern orthopedics. Attempts have been made to treat with growth hormone, but reliable evidence of the effectiveness of this technique in achondroplasia has not been obtained. At an early age, conservative therapy is carried out aimed at strengthening muscles and preventing limb deformation. Patients with achondroplasia are prescribed exercise therapy, massage, recommended to wear special orthopedic shoes, etc. Obesity prevention is carried out.

Surgical interventions for achondroplasia are indicated for severe deformities of the limbs and narrowing of the spinal canal. An osteotomy is performed to correct deformities, and a laminectomy is performed to eliminate spinal stenosis. In some cases, surgeries are also performed to increase height. Limb lengthening for achondroplasia is usually carried out crosswise, in two stages: first, the thigh is lengthened on one side and the lower leg on the other, then surgical interventions are performed on the remaining segments.

Achondroplasia (photo) is a congenital disease that is associated with disruption of the growth and development of bones. Most often, the pathology affects the skull and skeleton. Features of the disease are low human stature (maximum 130 cm).

Why does the disease appear?

What is achondroplasia? Parrot-Marie syndrome (another name for the disease) develops due to a mutation in the FGFR3 gene. Less commonly, the pathology is inherited. Sometimes the fetus dies.

The main reasons for the development of achondroplasia are disorders of bone formation, which are a consequence of degeneration of the epiphyseal cartilages.

This leads to slower bone growth. The skull and long bones are usually affected. One of the reasons for the occurrence of pathology is the relatively late age of parents. If the father is over 40 years old, then the chances of developing a mutation increase.

Characteristic signs

Symptoms of the disease can be recognized immediately after the birth of the child. Such children have a rather large, disproportionate head, short legs and arms. Hydrocephalus is sometimes observed.

Parrot-Marie syndrome is noted in the form of disturbances in the structures of the facial skeleton, which arise due to improper development of bones. Patients with this condition have wide-set eyes that are located deep in their sockets. Additional folds form near the inner corners of the visual organs.

Signs of pathology can be recognized by the characteristic nose. It has a saddle-shaped, flattened shape with a wide upper part. The patient's tongue is rough and the palate is high. The arms and legs of patients with achondroplasia are uniformly shortened. Patients' feet also differ - they are wide and short.

Infants with this disease often die in their sleep. This occurs due to compression of the medulla oblongata and spinal cord. 1–2 years of a child’s life is accompanied by the formation of cervicothoracic kyphosis, which disappears after the baby begins to actively move.

Children with achondroplasia develop slowly. They can hold their head up 3–4 months after birth; babies learn to sit when they are one year old. Such children can move only from 2 years of age. The intelligence of patients is at the same level as that of healthy people.

Adults with Parrot-Marie disease can be recognized by the growth deficiency that occurs due to shortening of the legs. Women with this pathology reach 124 cm in height, and men grow up to 131 cm. In some patients, deformations of the head and nose remain noticeable. Strabismus often occurs. Adults with achondroplasia are often overweight. They may experience the development of conductive hearing loss and otitis media.

Carrying out diagnostics

It is not difficult to determine the diagnosis of the pathology, since Parro-Marie disease is noticeable by characteristic changes in appearance. Patients must first be carefully assessed to determine the level of deviation from normal skeletal formation and development. All data is entered into a table, which is compiled specifically for such a disease, and compared with the indications.

If a newborn needs testing for achondroplasia, the baby should first be examined by a neurosurgeon. You can also see changes on an ultrasound. Doctors recommend undergoing an MRI and CT scan of the brain. To examine the condition of the nasal passages and ENT organs, the patient is examined by an otolaryngologist. Sometimes an additional consultation with a pulmonologist is required. To diagnose pathology, radiography is used:

• skulls;
• chest;
• pelvis;
• spine;
• tubular bones.

If a child has Parrot-Marie disease, he is observed by a doctor from the moment of birth until the end of his life.

Therapy methods

The genetics of the disease is such that the pathology cannot be completely eliminated. At a young age, conservative treatment is used, which helps strengthen the muscles and stop the deformation of the limbs. It is better for patients with achondroplasia to wear only orthopedic shoes; they are prescribed a complex of exercise therapy and massage. Prevention of obesity is often recommended. To do this, patients are prescribed a special menu and exclude dishes that lead to excess weight.

Treatment of achondroplasia with surgical intervention is justified only if the patient has severe deformities of the limbs and narrowing of the spinal canal is noted. To eliminate such symptoms, it is prescribed. Sometimes surgery is performed to increase height. The limbs are stretched in 2 stages. Initially, the thigh is lengthened on one side and the lower leg on the other, and then similar actions are carried out on the remaining parts of the body.

Other operations that are often performed include:

1. Vertebral fusion. Manipulations are carried out to connect individual vertebrae. The intervention helps to cope with back kyphosis.
2. Osteotomy. An incision is made in the leg bone, through which the individual parts of the vertebrae are connected. The procedure is used for severe modification of the knee joint. Also practiced for patients who have bowed legs.

Achondroplasia is sometimes treated with the use of a special growth hormone. But the drug affects each person differently.

Life expectancy with Parro-Marie disease depends on the patient’s individual health indicators and compliance with all medical recommendations.