KGB syndrome , also known as Hermann-Pallister syndrome, is a very rare inherited disorder that affects all body systems. Characteristics of the genetic disorder include unusual facial features, skeletal abnormalities, and delayed development.
What is KGB syndrome?
The name KGB syndrome comes from the initial letters of the family names of the first patients with the condition, which was described in the medical literature in 1975 by Jürgen Herrmann, Philip David Pallister, and John Marius Opitz. KGB syndrome is one of the rare genetic disorders. To date, it has been described to more than 200 individuals. For reasons still unknown, the disease is prevalent in male patients. Medical experts assume that the diagnosis is rarely made due to the mild course of the disease and that the symptoms are attributed to other diseases. Typical features include primarily fascial and cost-vertebral dysmorphia. The diagnosis is made clinically.
Causes
Basically, KGB syndrome is due to a mutation at the gene ANKRD11, which is located on chromosome 16. The protein produced from this gene allows other proteins to interact with each other. It is found in neurons in the brain, among other places. Besides the development of the brain, it is also involved in learning and memory processes. In addition, it can also become active in other cells, where it participates in normal bone development, among other things. Mutations at the ANKRD11 gene result in an exceptionally short protein that can hardly or not at all fulfill its function. The reduction in the effect of the protein thus underlies the symptoms of KGB syndrome. KGB syndrome is inherited in an autosomal dominant pattern. Some cases indicate direct inheritance from one parent, which is usually the mother. In others, however, the mutation appears to have formed spontaneously, affecting even those individuals whose family history did not contain evidence of genetic disorders.
Symptoms, complaints, and signs
One of the characteristic features of KGB syndrome represents the abnormally large upper central incisors (macrodontia). Other facial dysmorphic features include a broad, short skull with a triangular facial shape and a high nasal bridge. The eyes are wide apart and covered by bushy, often fused eyebrows. The space between the nose and the thin upper lip is noticeably large. The hairline may also be abnormally formed. The skeletal anomalies of the affected persons are due to a slowed mineralization of the bones. Primarily, this manifests itself in short stature. Deformation of the spine and ribs can often be observed. In addition, anomalies of the hands may occur, and here especially the little finger may be very short or bent. The mental development of affected patients is delayed. Mostly mild to moderate mental disabilities are diagnosed. Often these are accompanied by emotional disorders, such as hyperactivity or anxiety disorders. Rarely, hearing loss, strabismus or heart defects are diagnosed in the presence of KGB syndrome. Seizures, on the other hand, are relatively common (occurring in about 50% of all cases). They occur in some patients as early as 10 months of age and in this case usually manifest as flash nodding seizures.
Diagnosis and course of the disease
The diagnosis of KGB syndrome is made after a thorough clinical evaluation, a detailed patient and family history, and identification of characteristic physical findings. This is most often made clinically. Genetic testing for KGB syndrome has also been available for several years. The final diagnosis is not certain until seven to eight years of age, when the dentition has finally formed and macrodontia is clearly visible. To obtain absolute certainty, recourse can be made to gene panel analysis or a sequencing technique, by means of which the genetic malformation can be localized. KGB syndrome is not a life-threatening disease. The favorable prognosis can be further supported by close and multidisciplinary medical care.
Complications
KGB syndrome can cause the patient to experience a number of different symptoms and complaints.First and foremost, most patients suffer from relatively unusual facial features and further also from skeletal anomalies. This can lead to bullying and teasing, especially in childhood, which often results in psychological complaints and depression. Affected individuals also suffer from severely delayed mental development, resulting in retardation and underdevelopment in most cases. It is not uncommon for those affected to be dependent on the help of other people in everyday life and to no longer be able to perform various everyday tasks independently. The quality of life is considerably limited by the KGB syndrome. Furthermore, most patients suffer from short stature and a curvature of the spine. This can lead to restrictions in movement. Hyperactivity often leads to concentration disorders. Similarly, patients may suffer from hearing loss, with complete deafness occurring in the worst cases. Heart defects can also occur as a result of KGB syndrome, reducing life expectancy. There is no causal treatment for KGB syndrome. However, the individual complaints and symptoms can be corrected and treated with the help of various interventions, making everyday life easier for the affected person.
When should one go to the doctor?
Patients suffering from KGB syndrome receive comprehensive medical treatment. Treatment begins in childhood and usually continues into adulthood. Parents who notice signs of the condition in their child should talk to their pediatrician promptly. This must be accompanied by treatment of the symptoms. KGB syndrome often causes chronic muscle or bone pain, which must be treated early. Many affected individuals also experience psychological symptoms that require therapeutic counseling. Parents of affected children often need the help of a psychologist as well. The physician can establish contact with a specialist and refer the relatives to a self-help group if desired. The actual medical treatment usually takes many years and involves a variety of physicians. Depending on the type and severity of KGB syndrome, cardiologists, otologists, speech therapists and neurologists may need to be involved. Affected individuals should arrange for a clinical examination if they are pregnant to detect early inheritance to the child.
Treatment and therapy
Treatment of KGB syndrome is primarily directed at the specific physical and mental symptoms, although these can diverge greatly from individual to individual. In the presence of this genetic disorder, close collaboration between pediatricians, orthodontists, neurologists, speech therapists, and many others is necessary. In the course of this collaboration, it is necessary to carefully coordinate these efforts and create a joint treatment plan as early as possible. By means of dental treatment, which corrects the macrodontia by means of maxillofacial surgery, the appearance of the affected patient can be brought closer to a normal appearance. Orthopedic surgeons correct the abnormalities of the spine, hips, and ribs to prevent later problems due to poor posture and associated incorrect weight bearing. A complete neurological evaluation helps diagnose developmental delays. Early stimulation should be provided beginning in infancy. Early speech therapy and special inclusive educational programs provide mitigation of mental defects. Psychopharmacological medications can provide relief for severe behavioral disorders.
Outlook and prognosis
The extent to which affected individuals can improve their quality of life on their own depends on their individual symptoms and complaints. If malocclusions of various degrees occur, speech quality can be improved not only by surgical treatment but also by therapy with a speech therapist. The exercises learned can also be continued in the private environment and thus intensified. In the case of slight hand anomalies and the associated difficulties in grasping or holding objects, targeted exercises can help. For example, pens or small objects can be picked up from the table and placed in a bowl to train the fine motor skills of the fingers.Intensive physiotherapy, both with a therapist and with exercises that the child can do himself, helps to minimize the symptoms of postural deformities and, ideally, to get them under control to such an extent that further aids such as crutches or wheelchairs can be dispensed with in the long term. Provided that all these therapies are already used in early childhood and are also promoted by the relatives in the private environment, there is a chance for the affected children to reduce possible late consequences as far as possible and to enable them to lead as normal a life as possible. In addition, visiting self-help groups helps. Talking to other affected people offers a variety of suggestions and tips to make life easier, and at the same time it is possible to exchange worries and hardships.
Prevention
Since the cause of the occurrence of KGB syndrome is not known and, moreover, spontaneous mutations have occurred in a number of the documented cases, it cannot be effectively prevented. However, since autosomal inheritance does occur in some cases, affected individuals should arrange for a careful clinical examination by a physician at the onset of pregnancy in order to rule out inheritance as early as possible. Unfortunately, a genetic test is not yet available for KGB syndrome.
Follow-up
Follow-up cannot aim to prevent recurrence of KGB syndrome. There are hereditary reasons for its development. Either the disease is present or it is not. Thus, scheduled follow-up examinations have different tasks than those found, for example, in cancer. Doctors are primarily concerned with keeping complications to a minimum and enabling patients to lead a symptom-free everyday life. To this end, many experts work closely together. Therapies are an essential component of aftercare. How often and how intensively treatments are used depends on the individual clinical picture. It is difficult to make general statements about intervals between appointments. In principle, the need for corrective measures decreases with age, because the body is no longer as changeable after the growth phase. Aftercare consists of lifelong continuous treatment. Patients can usually lead an independent life if therapy is started early; however, complaints remain. These often include psychosocial stress. They are best managed in regular discussion groups and therapies. It can also happen that those affected are dependent on aids such as crutches or a wheelchair for the rest of their lives. Doctors prescribe these as well as medications to manage pain.
What you can do yourself
The steps patients suffering from KGB syndrome can take themselves depend on their individual symptoms and complaints. In the case of malocclusions in the area of the teeth, speech therapy is indicated to accompany surgical treatment, which can be supported by those affected at home through regular practice. In the case of postural defects or malpositions, aids such as crutches or a wheelchair must be used. Sufferers can alleviate the discomfort by seeking physiotherapy advice and making a conscious effort to maintain a straight posture. In the case of anomalies in the hands, surgery is usually necessary. In less severe cases, targeted exercises to train grasping and holding objects can also help. If the external abnormalities are a psychological burden, it is advisable to visit a self-help group. By talking to other sufferers, they learn tips and tricks for dealing with the disease and can thus cope better with the cosmetic blemishes. These measures are always accompanied by medical monitoring. In this way, any complaints can be detected and treated at an early stage before serious complications develop.
