Congenital spondyloepiphyseal dysplasia translates into German roughly as “congenital malformation of the long tubular bones and vertebral bodies” and describes a form of dwarfism that is genetically caused. Other synonyms for congenital spondyloepiphyseal dsyplasia are SEDC and SED congenital type. The disease was first described by German pediatricians Jürgen W. Spranger and Hans-Rudolf Wiedemann in 1966, and for this reason, SEDC is also referred to as SED type Spranger-Wiedemann.
What is congenital spondyloepiphyseal dysplasia?
Congenital spondyloepiphyseal dysplasia is a skeletal dysplasia and is defined by abnormal development of the vertebral bodies and epiphysis of the long bones. It represents a rare form of SED and is inherited in an autosomal dominant manner.
Causes
The cause of the disease is a mutation in the COL2A1- gene, which is responsible for coding the protein collagen type II. The mutation causes incorrect substitution of the responsible amino acid, leading to the present clinical picture. The mutation is inherited in an autosomal dominant manner. Thus, one affected allele is sufficient to cause congenital SED. In the case of one parent affected heterozygously, i.e. with one allele, the rate of transmission to the offspring is 50 percent. In the case of two heterozygous affected parents, it is 75 percent. In the case of one or both homozygous affected parents, a transmission of the disease is 100 percent.
Symptoms, complaints, and signs
Collagen type II is an important structural protein for hyaline and elastic cartilage in mammals, and a mutation therefore results in extensive symptomatology. The orthopedic symptomatology is initially in the foreground:
People with congenital spondyloepiphyseal dysplasia are small in stature from birth. The shortened torso and the short limbs are particularly noticeable. In contrast, the hands, feet and face do not show any conspicuous growth defects. The backbone has a normal size in relation to the thigh bones. Individuals with congenital SED grow to be 0.9 to 1.4 meters tall. A pathologic curvature of the spine exists and develops from an initial hollow back (hyperlordosis) to a hunchback (kyphosis) and/or a lateral twist (lateral deviation/scoliosis) of the spine. Flattening of the vertebral bones and other deformities, especially in the neck, increase the risk of spinal cord damage. Other orthopedic deformities such as coxa vara, malalignment of the femur, or clubfoot are also common. Decreasing mobility of the limbs very often develops in early childhood. In addition, arthritic complaints are often present. Deformity of the facial bones has not been confirmed, but the cheekbones are often described as flattened. However, this observation could not be substantiated by statistics. Instability of the dens axis, the spine of the second cervical vertebra, may occur and continue to cause extraskeletal complaints. It can lead to respiratory disorders after birth as well as in the further course of childhood, which manifest themselves in short pauses in breathing up to respiratory arrest. Collagen type II is required not only for bone formation but also in the vitreous body of the eye, which is why complaints are also frequently present here. Nearsightedness (myopia) and retinal detachment (retinal detachment) are therefore further consequences of the COL2A1 mutation. Another affected area is the inner ear, which is why those affected tend to suffer from hearing loss. There is also an increased risk of cleft lip and palate. Thus, due to the mutation, sufferers are affected not only orthopedically but also extraskeletally.
Diagnosis and course of the disease
Diagnosis is made by human genetic testing. A targeted mutation search in the COL2A1 gene allows laboratory testing to confirm the suspicion. All 54 exons of the COL2A1 gene, including splice sites, are sequenced from genomic DNA. Written informed consent for this procedure is required from the patient or the patient’s parents, respectively, because the guidelines of the Genetic Diagnostics Act apply.
Complications
This disease results in various malformations and deformities on the patient’s body.The patients suffer from a strong dwarfism and also from growth disturbances of the other body regions. Deformities of the face or of the hands and ears may also occur. The back is also severely curved and a so-called clubfoot develops. The quality of life of the affected person is considerably limited and reduced by this disease. Likewise, the facial deformities can lead to severe inferiority complexes or reduced self-esteem. Likewise, many patients not infrequently suffer from respiratory problems, and in the worst case, complete respiratory failure can occur. The eyes are also affected by this disease, resulting in visual difficulties or complete blindness. The ears are also affected by hearing loss. Often, those affected can no longer cope with everyday life on their own and are dependent on the help of other people. Treatment can be carried out with the help of therapies or through various interventions. However, not all complaints can be alleviated. If necessary, the life expectancy of the affected person is reduced. Furthermore, it is not uncommon for the patient’s parents to require psychological care.
When should one go to the doctor?
CSD is hereditary and is therefore usually diagnosed immediately after birth. Parents who notice short stature, growth disturbances or malpositions in their child should involve the pediatrician. Arthritic complaints or a general feeling of illness are also clear warning signs that should be clarified immediately. Treatment usually takes place in a specialized clinic and includes various medicinal and surgical measures. During treatment, the patient must be closely monitored by a physician and regularly examined. If no medical treatment is given, KSD takes a serious course. To prevent the deformities and organ dysfunctions from significantly affecting the quality of life, the disease must be treated at an early stage. If symptoms of congenital spondyloepiphyseal dysplasia appear later in life, a visit to the doctor is recommended. In this case, the underlying condition may be only mild CSD, which, however, also requires medical treatment. The right contact person is the family doctor, an orthopedist and various internists. The individual symptoms are treated by speech therapists, ear and eye specialists and therapists.
Treatment and therapy
Orthopedic problems are the main focus of treatment for sufferers. Regular exercise sessions in the form of physiotherapy to stabilize the spine are recommended. The other extraskeletal symptoms should also not be neglected, as they can cause serious consequential damage. Especially since a worsening of the extraskeletal symptoms can be expected over time, regular ophthalmologic and ENT check-ups are an important part of the care of children with SEDC. A cervical spine radiograph to verify or rule out suspected SED is urgently needed within the first six months of the infant’s life. Furthermore, functional imaging, especially an MRI of the craniocervical junction, i.e., the junction of the upper cervical vertebrae to the skull, is recommended. In the case of emergency and trauma surgery, the anesthesiologist in particular should be informed as early as possible about possible atlantoaxial instability, i.e., instability between the first two cervical vertebrae, atlas and axis. Because severe complications can occur, especially during intubation of congenital SED- patients, advance consultation is essential.
Outlook and prognosis
Congenital spondyloepiphyseal dysplasia is characterized by an unfavorable prognosis. The disease develops because of a gene mutation in the process of human development. Legal regulations prevent doctors and physicians from altering the genetic material of the human organism. Therefore, the main focus of researchers is on the development of treatment methods that lead to the alleviation of symptoms. The malformations are corrected by doctors in surgical interventions in the best possible way. Despite all efforts and multiple corrections, a natural state of health of the patient cannot be achieved. The goal is to alleviate discomfort and restore optimal functioning of the body. Each operation is associated with various risks and side effects.These must be taken into account when making a prognosis. In addition, the dysplasia leads to a strong emotional burden in many people. In the case of an unfavorable course of the disease, it can lead to the development of mental illnesses. These further worsen the quality of life as well as the general health of the affected person. The symptoms of dysplasia are expressed in a different intensity in each patient. The more symptoms occur, the worse the prognosis. In addition, in severe cases, respiratory failure may occur, leading to premature death of the patient. In cases of complete blindness, affected individuals are dependent on the daily assistance of other people.
Prevention
Because significant orthopedic discomfort occurs during the course of the disease, regular medical treatment is essential. In particular, the frequently occurring severe misalignment of the spine can often be counteracted with competent physiotherapy. Instruction in self-help, i.e. regular and correct gymnastic exercises, is indispensable for a self-determined life of the sick person. In other areas of treatment, such as hearing loss and myopia, the extent of the disease varies greatly. Therefore, the extent to which ongoing treatment is worthwhile or life-limiting for the patient must be weighed individually for those affected.
Follow-up care
In most cases, patients with this disease have either no or only very few aftercare measures available to them. First and foremost, a physician should be consulted and a diagnosis made early in the course of this disease, as this may also not result in an independent cure. If the patient wishes to have children, genetic testing and counseling can also be performed to prevent the recurrence of the disease. However, a complete cure is not possible. Due to the disease, most of those affected are dependent on the measures of physiotherapy or physical therapy. Many of the exercises can be repeated at home, which speeds up the treatment. Regular checks by a doctor are also very useful and important in order to detect and treat other damage at an early stage. Some of those affected are also dependent on the help and support of their own family in their everyday lives, whereby loving conversations can also have a positive effect on the course of the disease and also on the psychological state of the person affected. As a rule, the life expectancy of the affected person is not reduced by this disease.
What you can do yourself
Patients with congenital spondyloepiphyseal dysplasia work with their treating physicians to develop a plan for helping themselves in everyday life. Due to their dwarfism, patients suffer from limitations in their ability to move around, making it difficult to perform certain daily activities. The patients’ homes can be modified to meet their needs and requirements so that they do not suffer from severe movement restrictions, at least at home. Due to the deformities of the spine and the associated strain on the back, it is enormously important that those affected regularly perform physiotherapeutic exercises with a physiotherapist. Certain training sessions can also be performed at home if desired by the patient. In this way, the affected person strengthens the muscles and, at best, counteracts further deterioration of the ability to move. Patients regularly attend routine medical examinations, even if no new complaints arise. This is because sufferers are predisposed to eye diseases and hearing loss. The respiratory tract may also be affected by congenital spondyloepiphyseal dysplasia, making checkups necessary. Some patients suffer from inferiority complexes that need to be managed by a psychologist. Parents may also need psychotherapeutic treatment in some cases.
