Atelosteogenesis is a rare, incurable skeletal malformation caused by a genetic defect. Affected individuals usually die in the first few days after birth; a favorable course results in numerous physical malformations.
What is atelosteogenesis?
Atelosteogenesis is a so-called dysplasia, a congenital malformation of the skeleton. The term is composed 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. Three types of atelosteogenesis are known, which differ in cause and course. What they all have in common, however, is that the disease is triggered by a defect in one of two specific genes. In types I and III, the formation of filamin B is disturbed, while in type II there are errors in the coding of a so-called sulfate transporter. Both are proteins that perform numerous functions in the body, which is why their absence or incorrect formation causes severe damage. The disease already occurs in the unborn child and is usually fatal. With less than one affected person in one million, it is one of the rare diseases.
Causes
Atelosteogenesis occurs when a mutation occurs in either of the two genes in question. Such a defect in the genetic material can be triggered by environmental toxins or radiation, for example; however, many mutations happen without external influences. The probability of developing type II is much lower than for the other two types. This is due to the fact that atelosteogenesis types I and III are autosomal dominant, i.e. a mutation on one of the chromosomes present in duplicate in humans is already sufficient to trigger the malformation, even if the same DNA section on the other chromosome is free of errors. However, this also means that the mutation usually reappears in the affected child without one of the parents already 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, complaints, and signs
Numerous deformities and malformations of the skeleton occur in all forms of the course. The limbs, especially upper arms and thighs, are severely shortened. Many children have joint deformities up to completely dislocated hip, knee and elbow joints, club feet and cleft palate. The spine, especially in the thoracic region, is severely deformed (scoliosis). Children suffering from atelosteogenesis type II show a clearly protruding abdomen and typical facial features already in the womb: The nasal bone is flat and the midface and upper jaw are atrophied, making the lower jaw appear to protrude. The reduced chest causes difficulty in breathing. Collapse of the trachea or lungs is often the actual cause of death. Because of the child’s deformed limbs, childbirth can also be difficult unless a cesarean section is performed.
Diagnosis and course
Bone deformity is usually apparent on ultrasound in the first trimester of pregnancy, especially from 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 performed during pregnancy. This reveals to what extent one of the parents is known to be a carrier of a mutation of the affected gene. In the case of the other two forms, the disease can only be reliably differentiated from other diseases after birth, by means of X-rays and cell examinations of bone and cartilage. Children suffering from type I or II usually die in the womb or shortly after birth, while type III is somewhat milder. However, these patients also suffer throughout their lives from breathing difficulties, progressive deformation of the spine, side effects of the numerous operations required, and the resulting pain.
Complications
Unfortunately, death is very common in atelosteogenesis.Death occurs already a few days after birth. If this can be prevented, there are some malformations on the body, with which the affected person must live. As a rule, the skeleton is affected by malformations. These can look different in atelosteogenesis, mostly the joints are incorrectly positioned and some joints are dislocated. Affected individuals suffer from shortened upper arms and a deformed spine. Due to atelosteogenesis, an ordinary life is not possible. Locomotion is severely restricted. The face is also affected by malformations, with the nasal bone and the upper jaw being particularly affected. Due to the malformations of the lungs, breathing may be restricted. Due to this restriction, death often occurs. For the mother, the birth of a child with atelosteogenesis is usually difficult and a cesarean section must be performed. It is not possible to cure atelosteogenesis. Affected individuals must live with the symptoms, and life expectancy is reduced. In order for the joints to move, surgeries are performed. However, after these operations, disabilities cannot be ruled out. Mental disabilities do not occur, as long as they are not acquired during the patient’s life.
When should you see a doctor?
As a rule, atelosteogenesis does not require direct consultation with a doctor, since the complaint can be diagnosed before birth or immediately after birth. Unfortunately, this disease also cannot be treated, so most patients die after only a few days after birth. In most cases, the child dies directly in the hospital, so that a visit of the affected person 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 necessary in any case to avoid further complications. As a rule, a psychologist can be consulted directly in this case, who can carry out the treatment. If the child survives the atelosteogenesis and does not die from the symptoms, the affected person is dependent on permanent therapies. In this case, the treatment is carried out by different physicians. Due to the extremely pronounced deformities, the patients are dependent on the help of other people in their daily lives. In many cases, only the pain until death can be alleviated by palliative care measures.
Treatment and therapy
It is not possible to cure the underlying disease or its cause. Therefore, treatment of affected children is limited to symptom relief. Because type I and II sufferers survive their birth by only a few days, only palliative measures such as artificial respiration and pain-relieving drugs are available. Surgical measures are primarily used to treat type III sufferers. Even in the first months of life, several operations are necessary to achieve the lowest possible degree of disability and the highest possible quality of life. For example, joints are stiffened shortly after birth where necessary, especially in the spine. These operations often lead to further complications later on, such as pseudarthrosis, which in turn require treatment. Clubfeet can be surgically corrected around the age of three months. Cleft palate in particular requires a series of procedures: For the first few weeks of life, infants receive an artificial palate plate; later, the palate is surgically closed, and often, after a few years, oral surgery follow-up is necessary. In order to learn to speak, the children usually need logopedic support. Because of the numerous consequential damages, patients must be closely monitored by doctors throughout their lives and receive a range of accompanying treatments such as pain therapy and physiotherapy.
Outlook and prognosis
Atelosteogenesis has an extremely poor prognosis. Most patients die a short time after birth. In most cases, death occurs after only a few days. The disease is considered incurable with current medical options. It is a genetic predisposition in which no intervention is possible. For legal reasons, changes to human genetics are generally not permitted. Therefore, the available options for scientists and researchers are limited.With the existing and proven medicines or surgical interventions, a relief of the complaints or a cure is not possible to the necessary extent. Numerous malformations are present, 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 beyond the first days after birth. However, due to the natural growth and development process of the child, severe complications occur after the first weeks or months. Ultimately, they also lead to the premature death of the patient. If medical treatment is possible, doctors decide to use life-prolonging measures. These are always performed after an ethical justifiability review and are only possible to a manageable extent.
Prevention
Random mutations of individual genes cannot be prevented. Therefore, there are no ways to prevent the cause of atelosteogenesis.
Follow-up
Scheduled follow-up examinations have specific goals. Among other things, physicians want to use them to prevent the recurrence of disease. However, this turns out to be impossible in atelosteogenesis. It is a hereditary disease that is already present in young children. A cure is impossible. Interfering with human genetics before birth has been prohibited until now. Children born with the diagnosis of atelosteogenesis statistically live very short lives. X-rays and genetic tests provide information about the extent of the disease. Doctors tend to perform operations already in the first months. This is to reduce the degree of disability. If the infants survive the first years of life, permanent medical treatment becomes necessary. In addition to further surgical interventions, follow-up care consists of therapies such as speech therapy and physiotherapy. However, any growth spurt can lead to life-threatening complications. Affected individuals are dependent on outside help for the rest of their lives. It is crucial to tie a close-meshed nursing net around the sufferer. From school age onwards, psychological support is often necessary. The patients suffer from their social role as disabled persons. The physical limitations are a burden and inhibit development.
What you can do yourself
Atelosteogenesis is already noticeable in the embryonic stage. The deformation of the bones is usually visible on ultrasound during the first twelve weeks of pregnancy. Women who are pregnant with an embryo affected by atelosteogenesis should consider very carefully whether they want to carry the pregnancy to term, with due regard for their own physical well-being. Natural childbirth is usually not possible with severely deformed embryos and is in no way advisable due to the numerous complications and extreme pain involved. In such pregnancies, a cesarean section is always required. Parents must also be prepared for the fact that the infant is very likely to die shortly after birth, unless there is already a miscarriage. Psychological care is therefore already advisable during pregnancy. In addition, in the event of survival, organizational measures must be taken to ensure the care of a severely physically disabled infant. Care spaces for physically disabled infants are extremely scarce. At least one parent will therefore have to adjust to a severely delayed return to work. Psychological care is also needed for the growing children themselves, who usually develop normally intellectually. As a rule, they suffer mentally very much both from their physical limitations themselves and from the reaction of their social environment to their conspicuous external appearance.
