The Atelosteogenesis is a rare incurable skeletal deformity caused by a gene defect. Affected people usually die in the first few days after birth; if the course goes well, there are numerous physical undesirable developments.
What is an atelosteogenesis?
Abbreviated as AO by AbbreviationFinder, Atelosteogenesis is a so-called dysplasia, a congenital malformation of the skeleton. The term is made up of the ancient Greek words “atelos” (incomplete) and “osteogenesis” (bone formation). Since it is a fundamental malformation of bone and cartilage tissue, the disease is not limited to individual parts of the body, but affects the entire organism.
There are three known types of atelosteogenesis, which differ in cause and form. What they all have in common, however, is that the disease is triggered by a defect in one of two special genes. With types I and III the formation of filamin B is disturbed, with type II errors occur in the coding of a so-called sulfate transporter.
Both are proteins that fulfill numerous functions in the body, which is why their lack or incorrect structure causes severe damage. The disease occurs in the unborn and is usually fatal. With less than one affected person in a million, it is a rare disease.
Atelosteogenesis occurs when a mutation occurs in one of the two genes in question. Such an error in the genetic material can be triggered, for example, by environmental toxins or radiation; however, many mutations also occur without external influences. The probability of developing type II is much lower than with the other two types.
This is because atelosteogenesis types I and III are autosomal dominant, i.e. the mutation on one of the duplicate chromosomes in humans is sufficient to trigger the malformation, even if the same DNA section is free of defects in the other chromosome. However, this also means that the mutation usually occurs again in the sick child without either of the parents being affected, since most patients do not survive infancy.
Atelosteogenesis type II, on the other hand, is inherited recessively. This means that the damage only occurs if the genetic defect is present on both partner chromosomes. Therefore, healthy people can be carriers of the mutation and pass it on.
Symptoms, ailments & signs
Numerous deformations and malformations of the skeleton occur with all forms of progression. The limbs, especially the upper arms and thighs, are severely shortened. Many children have joint misalignments up to and including completely dislocated hip, knee and elbow joints, club feet and cleft palates. The spine, especially in the chest area, is badly deformed (scoliosis).
Children with atelosteogenesis type II already have a clearly protruding abdomen and typical facial features in the womb: the nasal bone is flat and the midface and upper jaw are atrophied, which means that the lower jaw appears to protrude. The reduced rib cage makes breathing difficult.
A collapse of the windpipe or lungs is often the real cause of death. Due to the deformed limbs of the child, childbirth can also be difficult unless a caesarean section is performed.
Diagnosis & course
The deformation of the bones can usually already be seen in the first trimester of pregnancy in the ultrasound, especially on the basis of shortened limbs with a normal sized skull (“short stature”), dislocated joints and underdeveloped thorax. In atelosteogenesis type II, the typical signs always appear on the face. If this form is suspected, a genetic test can also be carried out during pregnancy.
This makes it clear to what extent one of the parents is known to be a carrier of a mutation in the affected gene. With the other two forms, the safe differentiation from other diseases is only carried out after birth, through x-rays and cell examinations on bones and cartilage.
Children with type I or II usually die in the womb or shortly after birth, while type III is somewhat milder. However, these patients also suffer from breathing difficulties, progressive deformation of the spine, side effects of the numerous necessary operations and the resulting pain.
Unfortunately, death is very common in atelosteogenesis. Death occurs a few days after birth. If this can be prevented, there will be some malformations on the body with which the person concerned has to live. Usually the skeleton is affected by malformations. These can look different in atelosteogenesis, usually the joints are incorrectly positioned and some joints are dislocated.
Those affected suffer from shortened upper arms and a deformed spine. Atelosteogenesis makes an ordinary life impossible. Movement is severely restricted. The face is also affected by malformations, particularly the nasal bone and the upper jaw. Breathing may be restricted due to the malformation of the lungs.
This limitation often leads to death. For the mother, having a child with atelosteogenesis is usually difficult and requires a caesarean section. It is not possible to cure atelosteogenesis. Those affected have to live with the symptoms, reducing life expectancy.
Operations are performed so that the joints can be moved. After these operations, however, disabilities cannot be ruled out. Intellectual disabilities do not arise as long as they are not acquired in the course of the patient’s life.
When should you go to the doctor?
As a rule, atelosteogenesis does not have to go to a doctor directly, as the complaint can be diagnosed before birth or immediately after birth. Unfortunately, this disease cannot be treated either, so that most patients die just a few days after giving birth.
Most of the time, the child dies directly in the hospital, so that a visit from the person concerned is no longer necessary. However, atelosteogenesis can also have a very negative effect on the psychological state of the parents or relatives and lead to various psychological complaints or depression. In this case, a visit to the doctor is definitely necessary so that there are no further complications. As a rule, a psychologist can be consulted directly who can carry out the treatment.
If the child survives the atelosteogenesis and does not die of the symptoms, then the person concerned is dependent on permanent therapy. The treatment is carried out by different doctors. Due to the extremely pronounced malformations, the patients are dependent on the help of other people in their everyday lives. In many cases, only the pain can be alleviated until death through measures of palliative medicine.
Treatment & Therapy
A cure for the underlying disease or its cause is not possible. Treatment of the affected children is therefore limited to alleviating the symptoms. Since patients of types I and II only survive their birth by a few days, only palliative measures such as artificial respiration and pain reliever medication are available. Surgical measures are primarily used to treat type III sufferers.
Several operations are necessary in the first few months of life in order to achieve the lowest possible degree of disability and the highest possible quality of life. Shortly after the birth, joints are stiffened where necessary, especially in the area of the spine. These interventions often later lead to further complications such as pseudarthrosis, which in turn require treatment.
The club feet can be surgically corrected around three months of age. The cleft palate in particular requires a number of interventions: For the first few weeks of life, the infants are given an artificial palatal plate, later the palate is surgically closed, and follow-up dental surgery is often necessary after a few years.
In order to learn to speak, the children usually need speech therapy support. Because of the numerous sequelae, patients have to be closely monitored by a doctor for the rest of their lives and have to take a number of accompanying treatments such as pain therapy and physiotherapy.
Outlook & forecast
Atelosteogenesis has an extremely poor prognosis. Most patients die soon after giving birth. Usually death occurs after a few days. With the current medical possibilities, the disease is considered incurable. It is a genetic disposition in which no intervention is possible. For legal reasons, changes in human genetics are generally not permitted. As a result, the options available to scientists and researchers are limited.
With the existing and tested medicines or surgical interventions, it is not possible to alleviate the symptoms or cure them to the necessary extent. There are numerous malformations so that the organism would not survive the multitude of necessary corrections. In exceptional cases, the malformations are present in a form that allows life for a limited time over the first few days after birth.
Due to the natural growth and development process of the child, however, serious complications arise after the first few weeks or months. Ultimately, they too lead to the premature death of the patient. If medical treatment is possible, doctors decide to use life-prolonging measures. These are always carried out after an ethical justification check and are only possible to a limited extent.
Random mutations of individual genes cannot be prevented. Therefore, there are no ways to prevent the cause of atelosteogenesis.
Scheduled follow-up examinations have specific goals. Doctors want to prevent the recurrence of a disease, among other things. In atelosteogenesis, however, this turns out to be impossible. It is a hereditary disease that is already present in small children. A cure is impossible. Interfering with human genetics before birth has so far been prohibited.
Statistically speaking, children born with a diagnosis of atelosteogenesis have a very short life. X-rays and genetic tests provide information about the extent of the disease. Doctors tend to perform operations as early as the first few months. This is intended to reduce the degree of disability.
If the toddlers survive the first few years of life, long-term medical treatment is necessary. In addition to other surgical interventions, follow-up care consists of therapies such as speech therapy and physiotherapy. However, any growth spurt can lead to life-threatening complications. Those affected are dependent on outside help for the rest of their lives.
It is crucial to put together a close-knit nursing network around the sick. From school age onwards, psychological support is often necessary. The sick suffer from their social role as disabled people. The physical limitations are a burden and inhibit development.
You can do that yourself
Atelosteogenesis is already noticeable in the embryonic stage. The deformation of the bones can usually be seen on ultrasound during the first twelve weeks of pregnancy. Women who are pregnant with an embryo suffering from atelosteogenesis should consider very carefully whether they want to carry the pregnancy out of consideration for their own physical well-being.
A natural birth is usually not possible with severely deformed embryos and, because of the numerous complications and extreme pain, it is not advisable under any circumstances. Such pregnancies always require a caesarean section.
Parents also have to be prepared for the fact that there is a high probability that the baby will die shortly after birth, unless a miscarriage has already occurred. A psychological support is therefore already recommended during pregnancy.
In addition, organizational measures must be taken in the event of survival in order to be able to guarantee the care of a severely physically handicapped infant. Childcare places for physically handicapped small children are extremely scarce. At least one parent will therefore have to be prepared for a very delayed return to work.
Psychological care is also required for the growing children themselves, who usually develop normally intellectually. As a rule, they suffer emotionally very badly both from their physical limitations themselves and from the reaction of the social environment to their conspicuous external appearance.