Kampomele dysplasia is a mutation-related malformation syndrome. Skeletal dysplasias, short stature, and respiratory hypoplasia characterize the picture. Approximately ten percent of patients survive the first few weeks of life and receive symptomatic oeprative treatment to correct their malformations.
What is campomelic dysplasia?
Malformation syndromes are congenital combinations of malformations of different tissues and organs. Often, malformation syndromes include symptomatic skeletal dysplasias. This is true, for example, of campomelic syndrome, also known as campomelic dysplasia. Skeletal dysplasias are congenital bone or cartilage tissue defects that are referred to by the medical profession as osteochondrodysplasias. The kampomele syndrome is characterized by a bending of the upper and lower leg bones. This kampomelia is often associated with short stature and is fatal in many cases. Different forms of the syndrome are now distinguished:
- Campomelic dysplasia
- Campomelic dysplasia with autosomal sex reversal
- An Acampomelic campomelic dysplasia
- Campomelic dysplasia (long-limb form)
- Short-limb form
Short-limb form may also be associated with cloverleaf skull. The last form of the phenomenon is the mildest form and is called “Skeletal Dysplasia related to campomelic dysplasia”. It was first described in the 20th century by John Caffey. In 1971, German pediatrician Spranger and Paris pediatrician Maroteaux coined the term campomelic dysplasia.
Causes
The cause of campomelic dysplasia lies in the genetic material of the patients. The malformation syndrome is a genetic defect. Mutations in the SOX9 gene on the long arm of chromosome 17 in chromosomal region 17q24 cause the individual symptoms of the syndrome. The mutations usually occur spontaneously, but in principle they can also be inherited in the autosomal dominant mode of inheritance. The SOX9 gene encodes a protein gene transcription factor whose expression is critical for sex characteristics and skeletal development during embryogenesis. Numerous mutations have been documented involving the SOX9 gene, resulting in grid shifts and translocations, among others. Because of the multiform mutations, there is variable expressivity for the clinical picture of the disease. Presumably, chromosomal aberrations in the control regions of the gene or residual activity of the SOX9 protein are responsible for the milder forms of the disease. The sometimes mildest forms of the disease arise in translocations and inversions.
Symptoms, complaints, and signs
The leading symptom for patients with campomelic dysplasia is bending of the upper and lower leg bones. In addition to this bending, patients of the syndrome usually suffer from clinical criteria such as facial dysmorphia in terms of a flat nasal root, micrognathia, cleft palate, or dolichocephaly. In addition, short stature is present in most cases. In addition, anomalies such as clubfoot or hip dislocation may occur. An additional accompanying symptom may be polyhydramnios. Due to the involvement of the mutant protein in the expression of sexual characteristics, genital malformations may also occur in patients with the syndrome. These malformations often correspond to hypospadias, but may also manifest in intersexual genitalia or complete sex reversal. In addition, many affected individuals have only eleven pairs of ribs. In severe cases of the syndrome, the children are not viable and are accordingly stillborn or die immediately after birth. Mild cases survive and soon suffer chronic respiratory symptoms.
Diagnosis and course of the disease
To diagnose campomelic dysplasia, an x-ray is first taken, which shows characteristic signs. In addition to bending, including angulation, of the diaphyseal midline in the femur, hypoplasia of the lateral vertebral body processes or scapulae is often present. A cervical kyphosis is commonly seen, as is an absent pubic ossification, a pear-shaped os ilium, or an abnormality of the hip joint. Hypoplasia of the respiratory tract may also be indicative of the syndrome, such as pulmonary hypoplasia.By means of fine ultrasound, a suspected prenatal diagnosis is now possible. This can be confirmed by genetic diagnostics in the form of amniocentesis or chorionic villus sampling. Affected children have a rather unfavorable prognosis. Most patients die shortly after birth due to respiratory failure. Up to ten percent survive.
Complications
This disease has a relatively high mortality rate immediately after birth, so most patients die immediately afterward. However, should the affected person survive, numerous interventions are necessary to keep the patient alive. In most cases, the parents and relatives in particular also suffer from psychological complaints or depression and require psychological support. The patients themselves suffer from cleft palate and clubfoot. Other malformations and deformities of the entire body also occur, which have a significant negative impact on the daily life and aesthetics of the affected person. If the child survives the birth, breathing problems and further also respiratory insufficiency may occur even afterwards. This can also lead to the death of the affected person. Since a diagnosis can be made before birth, the pregnancy can also be terminated prematurely at the parents’ request. Psychological treatment is often necessary in this case as well. The treatment of the patient takes place with the help of surgical interventions and through therapies. Whether there is a decreased life expectancy cannot be generally predicted.
When should you see a doctor?
If the child suffers from malformations such as cleft palate, flat nasal root, or facial dysmorphia, a doctor must be consulted. Parents of affected children should immediately inform the pediatrician so that a diagnosis can be made quickly. If it is indeed campomelic dysplasia, treatment must be initiated immediately. The doctor in charge will first consult other doctors, for example an ophthalmologist or a speech therapist, and work out an individual therapy together with them and the parents. The physical treatment is usually accompanied by therapeutic counseling for parents and child. In addition, individual therapy for the child is recommended. Especially during puberty, the disease can cause emotional discomfort and lead the affected person to social withdrawal. Parents who notice such signs should talk to the child about psychological counseling. In addition, drug treatment must also be continued. Parents should regularly inform the doctor about any side effects and interactions.
Treatment and therapy
Causative therapy is not yet available for patients with campomelic dysplasia. Gene therapy approaches may eventually open new treatment avenues in the future. However, gene therapy is not yet in the clinical phase. Therefore, the malformation syndrome is treated purely symptomatically and supportively until the present time. Symptomatic treatment focuses primarily on ensuring the survival of the children for as long as possible. As a supportive measure, the parents of affected individuals are often provided with psychotherapists to help them process the situation. Invasive correction of respiratory tract hypoplasia and other malformations that affect breathing, such as rib abnormalities, is one of the most important steps in the postnatal management of surviving patients. Malformations such as hip dislocation can be corrected in a rearrangement surgery if the general condition of the patient allows it. All-important is the observation of the affected person. Any complications such as kyphoscoliosis or respiratory infections are detected as quickly as possible in this way and can possibly be corrected in time with medication or invasive surgery. In addition, observation is required due to impending hearing loss. Any learning difficulties or cognitive deficits are improved by means of early intervention.
Outlook and prognosis
In addition to symptomatic treatment of the ill child, the caring parents can also support the treatment themselves. The top priority here is to provide the children with a lot of security and love, which is an important support for the children in the face of their discomfort and pain.Depending on the severity of the disease, the individual symptoms and the instructions of the treating physicians, it is also possible to work with physhio- and ergotherapeutic exercises for home. Irrespective of this, it is advisable to use orthopedic aids and to care for the child especially lovingly after operations and to avoid any stress. Absolutely indispensable are regular check-ups at the appropriate specialized clinic and contacting the doctors in case of deterioration or previously unnoticed symptoms. In order to be able to provide sufficient support for the child, however, the parents must also take care of themselves and, if in doubt, seek help in coping with the trauma they have suffered. In addition to professional psychotherapy, it is also helpful to visit self-help groups in order to exchange ideas with other parents and, under certain circumstances, to receive tips and tricks for a better quality of life. The long-term care insurance fund also enables preventive care for up to six weeks a year, during which relatives can recharge their batteries or find time with possible siblings.
Prevention
Campomelic dysplasia can be prevented so far only in the context of fine ultrasound. Because it is usually a new mutation, the causative mutations cannot be excluded by genetic counseling during the family planning phase. If a diagnosis of the syndrome is made on the basis of fine ultrasound and subsequent molecular genetic workup, parents may decide not to have the child.
Follow-up
The measure of an aftercare are very limited in this disease in many cases or are not available to the affected person at all thereby. First and foremost, a doctor must be contacted relatively early in the process so that there is no further worsening of the symptoms or other complications. In many cases, the affected children die in the first weeks of life. The affected parents and their relatives are therefore usually dependent on intensive psychological care. In this context, loving and empathetic conversations with one’s own family have a very positive effect on the further course of the disease and can also prevent depression or other psychological upsets. In the case of a renewed desire to have children, genetic testing and counseling can also be very helpful in preventing the disease from recurring in the children. Due to the many malformations in the children, they are dependent on reb regular controls and examinations by different doctors. In the same way, a comprehensive support in the life of the children is necessary, so that they can develop well. As a rule, the disease greatly reduces the life expectancy of the affected children, although a general prediction about this can not be made.
This is what you can do yourself
Symptomatic treatment of campomelic dysplasia can be supported by the parents of a child with the disease by a number of measures. First and foremost, it is important to provide the child with a sense of security. Since the disease is often accompanied by severe pain and other discomfort, the child needs the support of relatives all the more. Whether the treatment of the individual symptoms can be supported depends on the nature of the complaints and the doctor’s instructions. In the case of malformations, orthopedic aids can be used. After an operation, it must be ensured that the child takes it easy and is not exposed to unnecessary stress. Accompanying regular control examinations in the specialized clinic are necessary. As a supportive measure, psychotherapy is offered to the parents of an affected child. In discussions with a therapist, the relatives learn how to deal with the traumatic situation and usually also have the opportunity to get in touch with other affected persons via a self-help group. Furthermore, drug treatment is often recommended, whether through medical preparations or natural sedatives such as valerian.
