The medical profession defines Wolf-Hirschhorn syndrome as a symptom complex consisting of various malformations. The syndrome occurs due to a structural abnormality of chromosome four, which usually corresponds to a new mutation. The disease is incurable and can therefore only be treated symptomatically.
What is Wolf-Hirschhorn syndrome?
Wolf-Hirschhorn syndrome or Wolf syndrome is a genetically caused symptom complex of malformations. The clinical picture corresponds to a structural chromosomal aberration, that is, a structural abnormality of the chromosome set. The leading symptom of the syndrome is short stature. The physical and mental development of affected children is severely delayed and accompanied by various malformations. The prevalence of the disease is estimated to be one in 50000, and within Germany there are slightly more than ten newly diagnosed cases per year. Girls are affected by the complex of symptoms slightly more often than boys. Ulrich Wolf and Kurt Hirschhorn first described the disease independently in the 20th century. By 1998, U.S. researchers speak of only 120 documented cases. Consequently, until the 21st century, many cases of Wolf syndrome have gone undiagnosed.
Causes
The cause of Wolf-Hirschhorn syndrome is a chromosomal abnormality on the short p arm of chromosome four. Affected individuals are missing sections of varying size in this region. A deletion of about 165 kilobase pairs in band 4p 16.3 is the smallest abnormality that can cause the symptoms of Wolf syndrome. In about 90 percent of cases, the chromosome four mutation occurs entirely new. This means that Wolf-Hirschhorn syndrome is usually not inherited, but arises anew in the paternal chromosome. In ten percent of cases, a balanced translocation from the chromosomes of one parent causes the malformation complex. A section of chromosome four is thereby relocated to another chromosome. If such a repositioning of chromosome segments caused the disease, then a second child of the parents also has about a 50 percent chance of developing Wolf-Hirschhorn syndrome.
Symptoms, complaints, and signs
Malformations in the facial region occur in all patients with Wolf syndrome. These include, in particular, enlarged eye segments with drooping eyelid axes and a broad nose or small jaw. A high forehead or a long skull are equally common. The same is true for protruding or widely spaced eyes, upper lip furrows, cleft jaw and palate, downturned corners of the mouth and scalp defects or a chin that turns backward. Affected individuals often have short necks and low-set ears, some of which are deaf. The eyes often tremble or are affected from birth by glaucoma or cataracts. Also iris clefts, strabismus or corneal deformities occur. In connection with the brain, there is often a narrowing of the brain due to premature hardening of all cranial sutures, underdevelopment of the cerebellum or an epileptic disposition. In addition to malformations of the kidneys, malformations of the heart with cardiac arrhythmias or valvular defects often occur. Sometimes the genitals and extremities are also malformed, for example in the form of a doubled thumb.
Diagnosis and course of the disease
Low birth weight, in combination with susceptibility to infection, small size, and developmental abnormalities, may give a physician the first signs of the disease. A definitive diagnosis can rarely be made, or only with uncertainty, by examination. Therefore, the physician is more likely to use fluorescence in situ hybridization to confirm the initial suspicion. This is a cytogenetic procedure that detects numerical and structural chromosomal abnormalities. Fluorescence-labeled DNA probes are used as markers. The prognosis for patients with Wolf-Hirschhorn syndrome is poor. About one third of all affected patients die within the first year of life. The prognosis is slightly better for girls than for male patients. Of the patients who survive the first year of life, for example, about two-thirds are female.
Complications
Because of Wolf-Hirschhorn syndrome, affected individuals suffer from a number of malformations and deformities that have a very negative impact on the quality of life and on the daily life of the affected individual.As a rule, this results in a very wide nose and a relatively no jaw. The ingestion of food and liquids can also be significantly impeded due to Wolf-Hirschhorn syndrome. Particularly in children, bullying or teasing therefore also occurs, so that the patients often suffer from psychological complaints or depression. Parents and relatives are also frequently affected by these complaints. The syndrome also leads to permanent strabismus and possibly other visual problems. There are also disorders of the heart or even a heart valve defect, which can be fatal for the affected person. Some patients also present with a double thumb. The treatment of Wolf-Hirschhorn syndrome is usually purely symptomatic, so that there is no completely positive course of the disease. Whether there is a reduction in life expectancy due to the syndrome cannot be generally predicted.
When should you see a doctor?
Normally, childbirth takes place under the supervision and guidance of medical personnel. Immediately after the delivery, the members of the obstetric team automatically and independently take over the examination of the health condition of the newborn child. In this process, the first irregularities and abnormalities of health are documented. In acute cases, the first interventions are already performed at this stage. Subsequently, further medical tests are performed, which result in a clarification of the complaints. Ultimately, a diagnosis is already made within the first days or weeks of life, because of the severe health abnormalities. For this reason, parents or relatives of the child do not have to become active on their own. Wolf-Hirschhorn syndrome already shows during birth through visual irregularities, where action is required. However, if the abnormalities remain unnoticed, abnormalities in the state of health will become apparent within the first few weeks at the latest. Parents should consult a doctor with their child if they notice optical changes in the area of the face or if the eye position does not correspond to the natural posture. Disturbances of the heart rhythm or deformations of the limbs are considered signs of an existing disease. A visit to the doctor is necessary because the newborn child needs medical care at an early stage.
Treatment and therapy
To date, Wolf-Hirschhorn syndrome is incurable. This means that no causative therapies are available. Treatment of the symptoms is within the realm of possibility. However, not all of them can be treated satisfactorily. At the beginning, especially a high-caloric diet is ordered to compensate the underweight of the patients. Physical and occupational therapy are used to support motor development. Some of the patients’ malformations can be corrected surgically, such as doubled fingers or toes. For symptoms such as epilepsy, the doctor usually gives medication. In this context, the administration of valproic acid or calimbromide is most often indicated. The mental development of patients is supported by therapeutic steps. Among other things, speech therapy can serve this purpose. The goal of symptomatic treatment is especially to improve the quality of life. The child, but also the parents, are ideally intensively cared for as part of the therapy. If necessary, a psychotherapist is available to assist the parents. Although no causal therapies exist so far, Wolf-Hirschhorn syndrome may be curable in the future. Currently, medical research is looking, for example, at the replacement of defective genes, which may mitigate the malformation complex in the future through the early replacement of chromosome four.
Prevention
Like any other chromosomal mutation, Wolf-Hirschhorn syndrome cannot be prevented. However, parents who have already given birth to a child with the malformation complex can have the likelihood of the disease assessed for future offspring and, if necessary, prevent a recurrence.
Follow-up
As a rule, very few and also very limited measures of direct aftercare are available to those affected by Wolf-Hirschhorn syndrome.Therefore, they should see a doctor as early as possible in this disease and also initiate treatment so that it does not lead to complications or other complaints in the further course. Therefore, the early diagnosis and subsequent treatment of this disease is the main focus. Since Wolf-Hirschhorn syndrome is a hereditary disease, it can usually not be completely cured. Therefore, if a child is desired, genetic testing and counseling should always be performed to prevent a recurrence of the disease in the descendants. As a rule, those affected by Wolf-Hirschhorn syndrome are dependent on the measures of physiotherapy and physical therapy. This can alleviate some of the symptoms. Furthermore, support from one’s own family in everyday life is also very important. Sometimes depression and other psychological upsets can be prevented or limited by this. Frequently, contact with other people affected by the syndrome is also useful, as it leads to an exchange of information. The life expectancy of the affected person is usually not reduced by this disease.
What you can do yourself
The symptomatic therapy of Wolf-Hirschhorn syndrome can be supported by the affected persons and their relatives by a number of general measures. An adapted diet counteracts underweight. Affected children require a high-energy diet, which may need to be supplemented with nutritional supplements. The various physical malformations are treated by physiotherapy, speech therapy and occupational therapy. Physiotherapy and speech and movement exercises can be performed at home. In the event of an epileptic seizure, the emergency medical services must be called. If available, the patient will be given an emergency medication such as valproic acid. Wolf-Hirschhorn syndrome requires long-term treatment, which is best planned together with the pediatrician in charge. In addition to organizing doctor’s appointments and surgical procedures, the child must be enrolled in a special pediatric program. For this purpose, the doctor will provide the necessary contact points. Children who are already a little older can be educated about their condition. It is advisable to use age-appropriate reading material. Ideally, the treating pediatrician is also present and can answer open questions of the child. Close cooperation with the appropriate physicians is also necessary during treatment for Wolf-Hirschhorn syndrome.
