Achondroplasia or Parro-Marie disease is an autosomal dominant disease that is transmitted from parent to child and is characterized by a disruption in the growth of bone tissue of the skeleton and base of the skull. The disease may occur due to genetic predisposition or certain factors that affect the fetus during pregnancy. In rare cases, the mutation leads to the death of the fetus in the initial stages of gestation.
After birth, the clinical picture is clearly visible: shortened limbs and a disproportionately large head. In some cases, the disease is accompanied by diseases of internal organs and functional systems. In this case, the patient has a normal length torso and shortening of the limbs. The height of an adult does not exceed 130 cm. As a rule, pathology occurs more often in women than in men.
Causes
Achondroplasia is also called congenital chondrodystrophy. The patient has a disproportionately large head with convex frontal lobes, a nose with a depression in the middle part of the back, and a forward curved spine. The cause of these characteristic symptoms is a mutation in the FGFR3 gene, which stimulates the growth of bones, cartilage and joints.
A change in genotype affects the development of cartilage tissue, which, in turn, causes disruption of proper bone growth. As a result, uneven, modified bones are detected in the child using diagnostic methods. Normally, the FGFR3 gene slightly stops the growth of fibroblasts and chondrocytes, which controls the proper development of bones and cartilage.
During genetic changes, the gene is susceptible to functional disorders, which causes disruptions in the growth of bone tissue and structural changes in the entire musculoskeletal system. A specific gene responsible for the appearance of achondroplasia is passed on from one generation to the next. Therefore, the probability that a child will be born with a genetic pathology is 50% if his parents also had this autosomal disease.
More than 70% of cases of mutagen in children are caused by spontaneous mutation, which can be influenced by the following factors:
- presence of parents with this disease;
- newborns who have had a change in the FGFR3 genotype;
- the age of the child's father; the older the parent, the higher the risk of congenital chondrodystrophy.
Genetics plays a key role in the birth of a sick child. If achondroplasia is observed in only one parent, then the probability of the disease developing in the child is 50%. If both parents have this disease, there is more than a 70% chance that a sick baby will be born.
The most common mutation in achondroplasia occurs in the protein chain of the receptor responsible for fibroblast growth, where an amino acid (arginine) is placed instead of the necessary glycine.
Achondroplasia-like disorders
Symptoms of the following disorders may be similar to those of achondroplasia. Comparisons can be useful for differential diagnosis:
Hypochondroplasia is a genetic disorder characterized by short stature and disproportionately short arms, legs, hands, and feet (i.e. short limb dwarfism). In those who suffer from this disorder, short stature is often not recognized until early or middle age or, in some cases, adulthood. Affected individuals may also develop bowing of the legs in early childhood, which often improves spontaneously with age. In some cases, additional abnormalities may be present, such as an unusually large head (macrocephaly), a relatively prominent forehead, limited elbow extension and rotation, and/or other physical abnormalities.
In addition, mild mental retardation may occur in about 10 percent of cases. In some cases, hypochondroplasia appears to occur randomly for unknown reasons (sporadic) without an obvious family history. In other cases, it is a familial disorder with autosomal dominant inheritance. As noted above (see Causes), hypochondroplasia and achondroplasia can result from different mutations of the same gene (ie, FGFR3).
Achondroplasia can be distinguished from other forms of short limb dwarfism by careful clinical examination, radiological examination and/or additional diagnostic methods.
Classifications
The disease is classified into certain types depending on the structural changes and the nature of the development of the disease. If we take into account the peculiarities of pathogenesis, the following types of pathology are distinguished:
Symptoms of Forestier's disease
- Genetically determined. This type of disease occurs in children whose parents had achondroplasmia. This could be the child's mother, father, or both parents. The mutated gene is passed on to the fetus during conception or development.
- Sporadic appearance. This form of the disease occurs in children whose bodies produce certain substances that affect the mutation of the FGFR3 gene. The appearance of pathology in this case does not depend on the genetic predisposition of the newborn. Achondroplasia in this case can occur under the influence of radioactive substances, elevated temperatures and substances produced by the body, which are the main factor of genetic changes.
Depending on the morphological characteristics, pathology is divided into the following groups:
- hypoplastic - people with this type of pathology have underdeveloped cartilage tissue and an underdeveloped organ responsible for endocrine function;
- hyperplastic - in contrast to the hypoplastic form of pathology, this type is characterized by an excessive and disproportionate increase in the plates of cartilage tissue, which contains fibroblasts and chondrocytes, as well as the rapid growth of the organ responsible for the functionality of the endocrine glands;
- gelatinous softening of cartilage - with this form of mutation, the fetus dies in the womb.
There have been isolated cases where a child was born with gelatinous softening of cartilage tissue. After reaching sexual maturity, a characteristic increase in viability was observed.
Regardless of the type and form of mutation, doctors cannot completely cure the patient. Modern medicine can correct complications of the diagnosis and improve the patient’s condition
Symptoms
The symptoms of the disease are similar to those of hypochondroplasia, a hereditary disease characterized by a pathological disorder in the development of cartilage and bone tissue, resulting in dwarfism. The main signs of achondroplasia include the following factors:
- height not exceeding 130 cm;
- disproportionately short limbs and torso of normal length (the formation of limbs is a rather long process due to underdeveloped shoulder and hip joints);
- short and straight fingers (adjacent fingers are quite close);
- curved shape of the legs;
- difficulty moving and bending;
- a large head disproportionate to the body with pronounced frontal lobes, which is why the face itself appears small;
- saddle nose;
- a forward curved spine in the lumbar region, as a result of which a person’s gait changes;
- mental and physical developmental delays are possible.
With this type of inheritance, the hip and shoulder joints are primarily affected, so as they grow older, these bones change their shape to a more curved one. Over time, the patient may experience severe pain in the lumbar region, which will indicate the presence of pathologies in the spinal cord.
Already in childhood, the clinical picture of achondroplasia and all the main signs are clearly visible
Epidemiology[edit]
Achondroplasia is one of several congenital conditions with similar presentations, such as osteogenesis imperfecta, tardive multiple epiphyseal dysplasia, achondrogenesis, osteopetrosis, and thanatophoric dysplasia. This makes it difficult to estimate prevalence as subjective diagnostic criteria change over time. One detailed and longitudinal study conducted in the Netherlands found that the prevalence determined at birth was only 1.3 per 100,000 live births. [27] Another study conducted at the same time found the rate to be 1 in 10,000 people. [27]
Complications
After the diagnosis is made, the patient begins to worry about how long people with this pathology live and its possible complications. With the further development of the disease, the following complications may arise: weakness in the muscles of the limbs and deterioration in their sensitivity, impaired functionality of the musculoskeletal system, pathological processes in the hip joint, which manifest themselves in the form of inflammation of the bladder, incontinence of feces and urine, as well as problems with male health.
From birth, a child may experience an excess of cerebrospinal fluid in the ventricles of the brain, which provokes strong pressure on the tissues of the skull.
Diagnosis
In order to study in detail such a concept as achondroplasia and understand what it is, it is necessary to diagnose the patient. For this purpose, a general medical examination by a doctor and instrumental research methods are used. The latter help to study in detail the nature of the pathology and the number of affected areas. Laboratory tests are not required to make a diagnosis.
During a general examination, the doctor should pay attention to the main symptoms of the disease, which manifest themselves in the structural pathologies of the patient’s body. After which one of the types of diagnostics is prescribed. These include:
- Computed tomography and radiography. Both methods are based on X-ray radiation, which is recorded in various tissues of the body, displaying detailed images of sections of the organ on a monitor. Unlike conventional radiography, CT uses more modern equipment, the scanning speed of which is much faster. This method is well suited for studying bone and cartilage formations.
- Magnetic resonance imaging. Unlike X-ray imaging, MRI uses electromagnetic waves to safely scan a patient's entire body. This allows you to reduce the risk of developing oncological tumors and obtain high-quality images of soft tissues and joints for diagnosis.
Methods are classified depending on the area of the body being studied. This can be a part of the brain, spine, chest and limbs. Radiography allows you to study the severity of the pathology and assess the occurrence of possible complications from the musculoskeletal system.
Treatment
At the moment, there are no ways to completely cure achondroplasia and restore bone growth. Treatment helps to minimize complications that arise as a result of the development of the disease. There are conservative and radical treatment.
Conservative treatment is resorted to in cases where the doctor has only identified the presence of pathology in the newborn. In such cases, there is a small chance of influencing the growth of bone and cartilage tissue with the help of special medications. These medications are growth hormones that must be injected on an ongoing basis. In some cases, such therapy eliminates all structural changes in the musculoskeletal system.
Radical treatment methods are prescribed in cases of severe skeletal deformation. Surgical operations are divided into the following types:
- Osteotomy is a serious surgical operation in which the patient's leg bones are cut, after which they are fixed in the correct position. After rehabilitation, patients are able to move normally;
- Laminectomy is a surgical operation performed on the spine. When the spinal canal is narrowed, the patient experiences severe pain and disturbances in brain activity, and in some cases there have been deaths. Therefore, doctors make an incision in the spinal canal to relieve pressure.
Osteotomy is performed for pathological development of the limbs, the knee joints of which are slightly turned to one side
Diagnostics
The clinical and radiological features of achondroplasia are well characterized. Those with typical results generally do not need molecular genetic testing to confirm the diagnosis.
When clinical features are suspicious in a newborn, radiographic findings can help confirm the diagnosis. However, if there is uncertainty, identification of a genetic variant of the FGFR3 gene using molecular genetic testing can be used to make a diagnosis.
Prevention
Preventive methods include mandatory medical consultation with a doctor regarding a genetic predisposition to gene mutation. The specialist identifies the presence of a mutagenic gene in the biological information of one of the parents and warns about possible risks, using a prenatal technique that allows us to identify the presence of pathology in the fetus, which is in the mother’s body. Diagnosis is carried out before birth. It is impossible to prevent the occurrence of the disease, since modern medicine cannot influence gene mutations.
Forecast
Most people with achondroplasia will have a normal or near-normal life expectancy. However, there is an increased risk of premature death associated not only with sudden unexpected death in infancy, but also apparently with cardiovascular complications in adulthood.
Overall, the average life expectancy is about 10 years less than the general population. A recently completed study confirms that the highest standard mortality rates occur before the age of 4 years. However, in addition, this multicenter mortality study shows that there has been a dramatic reduction in mortality, including sudden unexpected deaths, in young children with achondroplasia, most likely secondary to recognition of their special risks and aggressive assessment and intervention associated with craniocervical connection.