Hypochondrogenesis is a very rare hereditary disease that manifests itself by multiform deformities of the human skeleton. To date, only a few cases are known. It was first described in 1921, when physicians associated it with dwarfism. After that, hypochondrogenesis received little attention in medical literature and research. In 1977, the disease was redefined and distinguished from achondrogenesis, whose carriers have no viability. Because the chances of neonatal survival are very low, it is termed lethal.
What is hypochondrogenesis?
Hypochondrogenesis is inherited in an autosomal dominant manner. The mutated genes come from either the mother or the father. Since a gene is always duplicated -one comes from the mother, one from the father, mutated genes are usually inactivated by the other, healthy gene. However, in hypochondrogenesis, the diseased gene is dominant and turns off the healthy one (autosomal). Thus, the disease is fully expressed. It is called collagen II disease together with other diseases of similar type. In hypochondrogenesis, an important gene fails, so that bone formation is disturbed. Most children suffering from hypochondrogenesis die very early; many are stillborn or suffocate after birth. However, this is a statistical fallacy, because surviving children are called carriers of Congenital Spondyloepiphyseal Dysplasia, a disease that bears a strong resemblance to hypochondrogenesis.
Causes
The cause of hypochondrogenesia is a genetic alteration. In this disease, there is a failure of the gene COL2A1. This gene is located on the 17th chromosome and controls the formation of collagen II. Genes are responsible for various construction and control functions. In the case of a mutation, these functions can no longer be fulfilled. COL2A1 controls the composition of collagen at the ribosomes. The genetic information is read out, but is defective. The collagen molecule produced in this way is unable to perform the normal functions of a collagen. The cells incorporate it into the growing bones, but the collagen molecule cannot ensure the internal and external cohesion of the bones. This leads to severe deformities in the entire skeletal structure of the human body. Children with this disease have little or no viability. Because of the disturbed skeletal structure, many children cannot breathe properly and die shortly after birth.
Symptoms, complaints, and signs
Collagen II is instrumental in building bones. Bones become deformed when collagen is disrupted. Collagen II is a protein that makes bones grow together and gives them stability. Without this protein, the bones literally melt away. Without stabilization of the body by the skeleton, a person is not fit to live. Hypochondrogenesis is manifested by very short extremities and a shortened trunk. The chest is malformed and the ribs are very shortened. The spine is completely deformed and cannot fulfill its functions. In contrast, the head appears disproportionately large. The face is flattened, from which the eyes protrude strongly. The abdominal area is extremely distended, indicating a defect in water regulation. Some stillbirths also showed other malformations of internal organs. Medical experts disagree on the relevance of these.
Diagnosis and course of the disease
Diagnosis for hypochondrogenesis may occur in the womb. During pregnancy tests, the doctor takes amniotic fluid from the mother. This is examined in the laboratory. If the findings are positive, counseling is given to the parents. The extent to which an abortion is possible is not medically relevant, but must be clarified by the parents within the framework of the legal possibilities. The viability of fetuses with hypochrogenesis is very low. Most children with these symptoms are stillborn. Few children are born alive, but die during the first years of life. In a more advanced pregnancy, the doctor can make the diagnosis by means of ultrasound in the womb. He examines the development of the skeletal structure of the embryo. If this reveals abnormalities, he can arrange for genetic testing.
Complications
Hypochondrogenesis usually causes very severe short stature and in most cases leads directly to the death of the patient. For this reason, no special treatment is usually possible. The bones of the affected person are extremely deformed, so that an adhesion of the bones occurs. The stability of the bones decreases and fractures occur. If the affected person is born directly without stabilization of the skeleton, he cannot survive and dies. Furthermore, stillbirths are not rare. The head of the patient is sometimes larger than in ordinary babies and the internal organs are also deformed. Due to the death of the child, in most cases there are severe psychological complaints and complications. Patients suffer from depression, and partners are usually affected as well. If early diagnosis occurs, abortion may also be considered if desired by the parents. The life expectancy of the mother is usually not affected by hypochondrogenesis. Furthermore, no particular complications for the mother occur.
When should one go to the doctor?
Since hypochondrogenesia does not heal itself and in most cases the symptoms worsen, a doctor must be consulted in any case with this condition. In this way, further complications can be avoided. The sooner the doctor is consulted, the higher the probability of a cure. The affected person should see a doctor if the child suffers from growth disorders and restricted bone structure. The bones often fuse with each other, so that movement restrictions and, in many cases, severe pain can occur. Likewise, very short extremities may indicate hypochondrogenesis and should always be examined by a physician. Hypochondrogenesis can also lead to stillbirth in some cases. If the condition is diagnosed before birth, an abortion may occur. In many cases, the condition can also lead to psychological distress in the mother or parents, so a visit to a psychologist is advisable.
Treatment and therapy
In the case of a genetic disease, therapies are not possible so far. On the one hand, a therapy would have to start with the parents or the carrier of the autosomal dominant gene, but on the other hand, it would also have to start with the fetus in the womb. Doctors are trying to develop a gene therapy in which mutated genes are replaced by healthy ones, but this method is so far only in the experimental phase. Whether it will find an application in the near future remains to be seen. The development of the fetus and embryo in the womb could be controlled from the outside by adding important vitamins and proteins, but collagen II is produced exclusively in the cell by the defective gene itself. It is not possible to supply and process artificial collagen II (such as insulin for diabetes).
Prevention
Because it is a genetic mutation, there is no prevention for this disease. However, during pregnancy tests, the parents’ genes are checked for mutations. If a change is found, the doctor informs the parents. However, such genetic testing can be done outside of pregnancy. This gives parents the opportunity to discuss the extent to which they want to enter into a high-risk pregnancy. Geneticists, as well as physicians, provide intensive counseling to parents at risk and inform them about all possible disorders. Alternatives to having their own pregnancy may also be considered here, such as adoption or artificial insemination.
Follow-up care
There are no clear preventive or aftercare measures against the hereditary disease hypochondrogenesis. However, in connection with a pregnancy examination, the physician checks the genes of the parents for any mutations. In the event of a change, comprehensive information is immediately provided to the parents. They can then consider whether or not they wish to enter into such a high-risk pregnancy. Through intensive consultation with doctors and geneticists, the affected parents learn all the important facts about the disease and the associated disorders. Possibly, an alternative such as artificial insemination or adoption is discussed. Targeted self-help for those affected is basically not available.During pregnancy, it is possible to specifically control the development of the fetus. This is achieved with protein and vitamin supplements. However, a cure for the hereditary disease is not possible. Since the affected children are often born dead, the parents consider abortion. The accompanying upsets and discomforts can trigger depression. That is why psychotherapeutic support is very important. Contacting other parents helps to cope with the situation and process the grief. To prevent recurrence, those affected should take advantage of comprehensive genetic counseling if they are planning another pregnancy.
Here’s what you can do yourself
Hypochondrogenesis cannot be prevented directly in most cases. Parents can have various tests performed during pregnancy to detect the condition at an early stage. Alternatively, artificial insemination can be performed to prevent the disease with insertion of foreign genetic material. Methods of self-help are also usually not available to the affected person. During pregnancy, the development of the child can be controlled to a limited extent by the addition of proteins and vitamins, although this does not provide a complete cure for the disease. In many cases, the children are stillborn, so parents may have to consider abortion. Furthermore, hypochondrogenesis can lead to severe psychological discomfort or depression in parents and relatives. For this reason, psychological counseling and treatment by a psychologist should always be carried out in the case of the disease. Contact with other affected persons can also answer questions and solve possible psychological upsets. Genetic counseling should be done before another pregnancy to avoid the recurrence of hypochondrogenesis.