Osteoonychodysplasia is a mutation-related malformation syndrome with predominant involvement of the limbs. In addition to skeletal abnormalities, involvement of the kidneys and eyes is often present. Symptomatic treatment is aimed primarily at delaying terminal renal failure.
What is osteoonychodysplasia?
Malformation syndromes are characterized by dysplasia of various structures of the anatomy. In medicine, dysplasia is the malformation of tissues or organs. Dysplastic phenomena are present, for example, with underdevelopment or overdevelopment. Osteoonychodysplasia is a congenital malformation syndrome with predominant involvement of the extremities. It is associated with various malformations and functional disorders of different organs. For example, a well-known disorder from this group is nail-patella syndrome, which is associated with deformities of the fingernails and bones. As a subgroup of osteoonchyodysplasias, nail-patella syndrome occurs in about one case in every 50,000 newborns around the world. Girls are affected as often as boys. The age of manifestation is considered to be infancy. Osteoonychodysplasia is also known as Turner-Kieser syndrome and is associated with heredity. The hereditary disease was first documented in the 1920s to 1930s. The US American Turner, the German Kieser, and the Austrians Trauner and Rieger are primarily considered the first describers.
Causes
Osteoonychodysplasia is a hereditary disease. Inheritance of the symptom complex occurs in the autosomal dominant mode of inheritance. Therefore, the agreements of a diseased parent suffer from the malformation syndrome with a risk of 50 percent. In most cases, therefore, familial clustering has been observed. However, sporadic cases have also been observed. The primary cause for both variants is a genetic mutation, which corresponds to a new mutation in sporadic occurrence. The mutation appears to affect the LMX1B gene on the longer arm of chromosome 9, and the gene locus is 9q34. Previous studies of osteoonychodysplasia suggest more than 80 different mutations of the same gene as the cause of the disease. The LMX1B gene is a limb transcription factor belonging to the LIM homeodomain protein group. These proteins are involved in the in limb development as well as kidney and eye development. Depending on renal involvement, nail-patella syndrome is causally associated with different alleles. Mutation of the LMX1B gene results in loss of function of the transcription factor such that development is impaired. The disorder is associated with the AB0 system of blood groups.
Symptoms, complaints, and signs
Patients of osteoonychodysplasia suffer lead symptomatically from deformed skeletal structures. The deformities of their bones and joints are most prominent on radiographs as an underdeveloped patella. Bony exostosis is often present on the right iliac crest or posterior horn of the pelvis. Involvement of the patella affects more than 90 percent of patients. Complete nonunion of the structure occurs in nearly one-fourth of all cases. The underdeveloped and partially luxated patella makes the patients’ knees partially unstable, so that motor development is delayed and falls are favored. Patients have limited ability to bring the elbows to pronation or supination. The radial head is often subluxated. In the majority of cases, the condition is associated with arthrodysplasia of the elbows. The joints of the limbs are usually capable of hyperextension. Other case reports have documented bone changes for the syndrome such as scoliosis, the development of cervical ribs, and underdevelopment of the nails. In individual cases, these symptoms may be associated with renal problems that can cause proteinuria or nephritis. Other associated symptoms may include hypothyroidism, irritable bowel syndrome, attention deficit disorder, or thin tooth enamel. Ocular symptoms and sensory-neural hearing loss often round out the symptomatic picture.
Diagnosis and disease course
The first tentative diagnosis of osteoonychodysplasia is made to the physician by radiographic imaging, which shows characteristic changes in the skeleton. Electron-optic imaging also often reveals characteristic changes in the glomerular basement membrane.Molecular genetic analysis is not necessary in most cases, since the clinically typical picture alone substantiates the initial tentative diagnosis. The prognosis of patients depends on the severity in each individual case. In cases of severe organ involvement, the syndrome may be lethal.
Complications
Because osteoonychodysplasia is a symptom complex of various hereditary disorders, the risk of complications varies for affected patients. For example, life expectancy is not reduced in the so-called nail-patella syndrome, which is characterized by deformities of the fingernails and bones. In the other forms of osteoonychodysplasia, however, internal organs are often still involved. For example, more than 50 percent of patients suffer from renal insufficiency. The course of the kidney disease in particular determines the prognosis of the disease. Often, renal insufficiency progresses and leads to the patient requiring dialysis. In these cases, curative therapy is only possible through kidney transplantation. This is especially true if there is a risk of total failure of both kidneys. Further complications of osteoonychodysplasia are scoliosis, clubfeet, exotoses (overlegs) or malformed elbow joints. In these cases orthopedic treatments are necessary. Sometimes cardiac arrhythmias or glaucomas occur as complications. The prognosis of cardiac arrhythmias varies among individuals. To avoid long-term heart disease, treatment by a cardiologist is important. Glaucoma can cause blindness later in life if intraocular pressure is not reduced. The deformity of the bones and fingernails themselves can have psychological effects on the patient if he or she gains the feeling of being socially excluded because of his or her appearance.
When should one go to the doctor?
If visual irregularities or malformations of the skeletal system are noticed immediately after birth, a health check should be performed without delay. If the birth takes place in the circle of a team of obstetricians, the parents normally do not have to take any further measures. Midwives and doctors independently record the infant’s state of health and document any abnormalities. Imaging procedures and other examinations are used to identify any abnormalities and a diagnosis is made. If health deviations, delays or underdevelopment occur in the further development and growth process, the observations are to be discussed with a physician. If there is hearing loss, the possibility of hyperextension of the joints or a visual blemish of the nail shape, a doctor is needed. Often there is an abnormal sequence of movements in everyday life, which can be interpreted as an indication of a disease. A thin enamel, disturbances of attention or a low physical as well as mental resilience should be presented to a doctor. Irregularities in urination or kidney activity must also be examined and treated by a doctor. If deficiency symptoms appear despite an adequate and balanced diet, this can be a warning signal from the organism. A control visit to a doctor is necessary so that the cause of the complaints can be found. Noticeable in osteoonychodysplasia are disturbances of the elbow activity as well as a visual change of the joint.
Treatment and therapy
Causal treatment is not currently available for patients with osteoonychodysplasia. The disease is not curable until gene therapy approaches reach the clinical stage. Gene therapy may make the complex of symptoms a curable disease in the future, but at the current time, patients are treated symptomatically only. When the kidneys are involved, treatment focuses on proteinuria. This symptom may progress to renal failure. Therefore, to treat nephropathy, a reduction in proteinuria must be aimed for. In most patients, renal failure still occurs around the age of 30. Kidney transplantation is the treatment of choice at this stage. The skeletal dysplasias of osteoonychodysplasia can also be corrected with reconstructive surgery. This applies, for example, to non-union of the patella. Physiotherapy may be required to stabilize the skeleton.The targeted development of muscles provides support for the mostly hypoplastic bones and joints. In addition, physiotherapy promotes normal motor development. Symptoms such as nail hypoplasia are more of a cosmetic problem and do not necessarily need to be corrected immediately. If treatment of nail hypoplasia is still desired, nail bed transplantation usually takes place.
Outlook and prognosis
As a rule, it is recommended to see a doctor already at the appearance of the first symptoms of osteoonychodysplasia, as this may favor the further course of the disease. Since there is no cure for this genetic disease, affected individuals rely on purely symptomatic treatment aimed at reducing proteinuria and thus delaying terminal renal failure. It is particularly important to strictly adhere to the instructions of the treating physician. This usually includes taking diuretics and corticosteroids, avoiding alcohol consumption, regular monitoring of kidney function, a balanced diet and a healthy lifestyle. Attending physiotherapy with accompanying home exercises is also advisable, as the skeleton and motor function can benefit from stronger muscles, thus positively influencing the course of the disease. If all these medical recommendations are followed consistently, the time of kidney failure can be delayed to the age peak of 30 years in one third of patients. Since patients very often feel excluded due to their clearly visible deformities, psychotherapeutic treatment or attendance at self-help groups can be of great help in improving the quality of life. However, the patient’s life expectancy is often significantly reduced due to kidney failure. This can only be counteracted by a kidney transplant as the final treatment option, which is usually performed shortly before the patient reaches the age of 30. This can completely exclude the recurrence of the disease in the transplant and thus offer a very good outlook for further life. If the patient has a desire to have children, genetic testing and counseling would be recommended, which can rule out the inherited occurrence of the disease.
Prevention
At best, osteoonychodysplasia can be prevented in the form of genetic counseling during the family planning phase.
Follow-up care
In most cases, there are no special or direct aftercare measures available to the person affected by osteoonychodysplasia, so the person affected by this condition should definitely see a doctor at a very early stage. The earlier a doctor is consulted, the better the further course of the disease usually is. A doctor should therefore be contacted at the first signs and symptoms. Since this is a genetic disease, the affected person should in any case have a genetic examination and counseling if he or she wishes to have children, in order to prevent the recurrence of the disease. Most of the affected persons are dependent on the permanent examination of the kidney. Drinking alcohol should also be avoided as much as possible. In general, a healthy lifestyle with a balanced diet has a positive effect on the further course of the disease. Furthermore, physiotherapy measures are also very important, although the affected person can also perform many of the exercises themselves in their own home. However, it is not uncommon for osteoonychodysplasia to reduce the life expectancy of the affected person, as this often leads to kidney failure.
What you can do yourself
Osteoonychodysplasia cannot be cured, but its negative influences can be mitigated by certain methods. In symptomatic therapy, it is important to follow the doctor’s recommendations closely. Treatment includes regular intake of corticosteroids and diuretics. Depending on the severity of the genetic defect, dialysis therapy is often given as early as infancy. Especially in severe cases with malformations of the spine or extremities, a lot of patience is required. With assistance in everyday life, problems with locomotion and various activities can be reduced. In the case of a foot deformity, special insoles or shoes are used to make things easier for those affected. If the pelvic bone is also damaged, further assistance may be necessary.The psychological consequences for the patients play a very important role. They often feel marginalized, especially in the case of clearly visible malformations. For a better quality of life, attendance of self-help groups is recommended. It is also useful to talk about the problem in the family and look for practical solutions. A special diet can help in connection with kidney weakness. In addition, the skeleton strengthens with stronger muscles. So, with regular physiotherapy, the body gets more strength, moreover, motor skills develop normally.