Antley-Bixler syndrome is a genetically caused disorder whose incidence in the general population is relatively low. The commonly used abbreviation for the disorder is ABS. To date, approximately 50 cases of the disease are known and described in individuals. Basically, Antley-Bixler syndrome appears equally in men and women.
What is Antley-Bixler syndrome?
Antley-Bixler syndrome got its name from two medical doctors from the United States of America, Antley and Bixler. These two doctors first described the condition in 1975. The condition is usually associated with a typical combination of different symptoms. In the majority of cases, affected patients suffer from hypoplasia of the midface. In this context, a so-called craniosynostosis is also seen. The femur may be bent, and contractures of the joints are also present. Also, the affected patients show a certain type of synostosis. Numerous characteristic symptoms are already evident in affected children. For example, a relatively high and broad forehead is recognizable, which usually shows a strong forward curvature. In many cases, the ears are characterized by malformations, while the nose of the affected patients appears comparatively flat. In terms of intelligence as well as mental development, patients differ. Basically, two different types of Antley-Bixler syndrome are distinguished, type 1 and type 2. The malformations of the genitalia result primarily in type 2. In principle, the disease is inherited in an autosomal recessive or autosomal dominant manner.
Causes
Basically, Antley-Bixler syndrome represents a genetic disease. Two forms of the disease exist that are genetically distinct. Type 1 is based on gene mutations on the so-called POR gene, which are inherited in an autosomal recessive manner. On the other hand, type 2 is primarily caused by genetic mutations on the FGFR2 gene. In this case, an autosomal dominant mode of inheritance is present. In addition to genetic factors, other causes exist that may lead to the typical symptoms of Antley-Bixler syndrome. Pregnant women who take the medicinal substance fluconazole during the first months of pregnancy sometimes have children with the typical symptoms and signs of Antley-Bixler syndrome. Fluconazole is an antifungal drug.
Symptoms, complaints, and signs
As part of Antley-Bixler syndrome, various symptoms occur in people with the disease. In numerous cases, the sutures of the skull bone ossify too early, which is called craniosynostosis in medical terminology. In some cases, the posterior opening of the nose is missing or severely narrowed. Some patients have bent bones in the area of the thighs. Sometimes the persons also suffer from camptodactyly as well as a so-called arachnodactyly. Some affected patients have deformities in the anatomy of the heart, in the area of the vertebrae as well as the anus. In addition, some of the affected individuals have malformations around the urogenital region. Thereby, for example, intersexual sex organs are possible, because the formation of steroids does not proceed as in healthy people.
Diagnosis and course
The typical symptoms and signs of Antley-Bixler syndrome often indicate the disease relatively clearly even in young patients. Due to the rarity of the syndrome, a diagnosis is nevertheless not easy in some cases. If parents or doctors notice external malformations in newborns or infants, further examinations must be ordered immediately. First of all, a so-called anamnesis is carried out, in which the symptoms are analyzed. Since many of the symptoms of Antley-Bixler syndrome already exist and are apparent from birth, the suspicion of a hereditary disease usually falls quickly. In this context, the family history is of great importance. Similar cases in the relatives may already indicate the disease. In the course of clinical examinations, the individual symptoms of the patient are analyzed in detail. The malformations of the skeleton can be detected, for example, with the help of X-ray examinations. This reveals, for example, the bending of certain bones.Abnormalities in the facial region, such as an unusually strongly arched forehead as well as a flat nose, are easily recognizable and indicate the disease. Ultimately, a genetic test enables a comparatively reliable diagnosis of Antley-Bixler syndrome. In this way, the responsible gene mutations on the corresponding genes can be identified. It is also possible to determine which of the two types of disease the patient is suffering from.
Complications
Predominantly, patients suffer from malformation of the midface. Premature ossification of the cranial sutures is characteristic, sometimes manifesting before birth and referred to as craniosynostosis. Further complications are ossifications of the joints and a high, strongly forward arched forehead. The ears are often malformed and the nose flatter than in healthy individuals. The posterior nasal opening is absent or severely narrowed. The development of intelligence varies. Other disorders include malformations of the fingers and deformities of the vertebrae, heart anatomy, and anus. Malformations may also affect the genitourinary system, and intersexual sex organs are possible. Basically, Antley-Bixler syndrome is divided into type 1 and type 2, with female and male patients equally affected. The malformations of the genitals are attributed to type 2. Affected children show typical symptoms and complications already at birth or in the first years of life. However, since this autosomal-dominant or autosomal-recessive inherited malformation syndrome occurs extremely rarely, a conclusive diagnosis is made difficult. The causes of this hereditary disease are not treatable. However, individual therapy approaches are possible to increase the quality of life and life expectancy of patients. However, the cases of the disease known to date show that the prognosis is comparatively negative, as most patients die in childhood due to the multiple organic disorders and complications.
When should one go to the doctor?
If parents notice external malformations in their child, a doctor should be consulted immediately. In any case, the hereditary disease must be diagnosed to allow treatment of the multiple symptoms. Ideally, the diagnosis should be made before birth. Parents with a relevant medical history – for example, if there are known cases of Antley-Bixler syndrome or other hereditary diseases in the family – should bring this up during the ultrasound examination. The doctor in charge can examine the embryo specifically for malformations and, if there is a concrete suspicion, arrange for a genetic test. At the latest after birth, the external features are usually recognized by the obstetrician or the parents themselves. The diagnosis of Antley-Bixler syndrome is then made routinely. Since the condition can only be treated symptomatically to date, further visits to the doctor are usually necessary. Emergency situations arise, for example, if the child cannot breathe properly due to ossifications of the nose and mouth. Circulatory problems, digestive problems, and other health problems that can occur with Antley-Bixler syndrome also need to be treated immediately by a doctor.
Treatment and therapy
Basically, in Antley-Bixler syndrome, it is not possible to treat the causes of the disease. For this reason, only the symptoms are treated to reduce the symptoms of the diseased patient as much as possible. In the majority of cases, the affected children receive intensive medical, educational and social care in order to improve their quality of life and to relieve their guardians. However, previous cases of the disease show that the prognosis of the disease is relatively poor. A large proportion of those affected die as children. The reason for this is often significant respiratory problems.
Outlook and prognosis
Recovery from Antley-Bixler syndrome is not possible without the use of a physician. The genetic defect does not lead to relief of symptoms in its natural course, as the deformities remain for life. With medical care, individual symptoms can be treated. However, a complete cure is not possible. Furthermore, with Antley-Bixler syndrome, the normal lifespan is significantly shortened. A large number of those with the disease die in childhood.For legal reasons, it is not allowed to interfere with the genetics of humans. Only with the help of surgery as well as laser technology, corrections of individual malformations can be made if desired and required. These increase the general well-being and contribute to an improvement in the quality of life. Nevertheless, there is a risk of side effects or defensive reactions of the body due to the interventions. Inflammations occur and psychological problems can develop. Treatment of the additional conditions is associated with good prognosis prospects in most cases. Only rarely does an infestation of germs occur, which results in a minimization of the chances of cure. Since the underlying disease cannot be cured and it is already associated with a significant shortening of life, it should be thoroughly examined whether further corrections will improve the functioning of the organism.
Prevention
Antley-Bixler syndrome is a genetic disorder, so at the current time there are no options for causal prevention of the disease. Only symptomatic treatment of the disease is possible.
Follow-up
Direct follow-up is not possible in most cases of Antley-Bixler syndrome. Since this is a hereditary disease, it also cannot be treated completely and only symptomatically. A cure cannot be achieved. If affected individuals wish to have children, genetic counseling can also be performed to prevent inheritance of Antley-Bixler syndrome. Usually, patients with Antley-Bixler syndrome are dependent on taking medication. There are no further complications, although care should be taken to ensure that the medication is taken correctly and, above all, regularly. Parents in particular must ensure that their children take their medication correctly. If necessary, possible interactions with other medications should also be clarified with a doctor. Since Antley-Bixler syndrome can also cause malformations of the heart, patients should have regular heart examinations. The sexual organs can also be affected and should also be examined. Furthermore, contact with other people affected by Antley-Bixler syndrome can have a positive effect on the further course of the disease, as it leads to an exchange of information. Whether Antley-Bixler syndrome leads to decreased life expectancy cannot be universally predicted.
Here’s what you can do yourself
Patients with Antley-Bixler syndrome have their quality of life tremendously limited by the disease. Affected individuals often require intensive medical care from birth. The deformities of internal organs such as the heart vary in severity in individual cases, but corrective surgical interventions are only partially possible. In the case of possible operations, the parents stand by their sick children during their stay in the clinic. However, numerous therapeutic approaches are of a purely symptomatic nature. In addition, the disease often has a negative impact on the life expectancy of those affected and causes premature death, often in childhood. Patients suffer, for example, from severe breathing difficulties, so that strenuous physical activities are to be avoided urgently. Regular appointments with various medical specialists who monitor the health of the affected person are obligatory. If requested by the parents and if the cognitive performance of the sick child allows it, he/she attends a special educational institution. In numerous cases, palliative care is necessary for the patients, as the symptoms make survival impossible. The parents suffer enormously from the disease and therefore sometimes develop depression. It is then indicated to seek psychotherapeutic treatment immediately so that the guardians can continue to be there for their child.
