Pfeiffer syndrome is an autosomal dominant hereditary disease. This occurs very rarely and shows abnormalities in the bone formation of the face and skull. Pfeiffer syndrome is caused by a mutation in certain proteins that are responsible for the maturation of bone cells.

What is Pfeiffer Syndrome?

Pfeiffer syndrome is a rare hereditary disease that belongs to the craniosynostosis. Because it is inherited in an autosomal dominant manner, people with the condition have a 50 percent chance of passing it on to their children. Pfeiffer syndrome interferes with the normal growth of the bones of the skull and face, resulting in craniofacial abnormalities. The bones fuse early and affect the shape. The bones of both hands and feet are also affected by the abnormal growth. See AbbreviationFinder for abbreviations related to Pfeiffer Syndrome.

The failed fusion of the facial bones results in bulging and wide eyes, a high forehead, a flat bridge of the nose, and an underdeveloped upper jaw. Clinically, three types are distinguished. The three types have different characteristics. Patients with types 2 or 3 are more affected and life expectancy is also noticeably reduced. The prevalence of Pfeiffer syndrome is not known exactly and is estimated to affect 1 in 100,000 people worldwide. This disease is caused by a mutation in the genes FGFR-1 and FGFR-2.

Causes

Pfeiffer syndrome results from a mutation in the FGFR-1 and FGFR-2 genes. This mutation is inherited in an autosomal dominant manner. If either parent has this mutation, they have a 50 percent chance of passing it on to the child. These genes are responsible for the production of important proteins, the fibroblast growth receptors 1 and 2 (fibroblast growth factor receptors). Type 1 Pfeiffer syndrome can be caused by a mutation in either of the two receptors. Types 2 and 3 are caused by a mutation in the FGFR-2 gene and are not associated with a change in the FGFR-2 gene.

Proteins perform many important functions. During embryonic development, they signal immature cells to develop into mature bone cells. A mutation in one of these genes alters protein function and causes prolonged signaling. This lengthening promotes the premature fusion of the skull and facial bones. The normal development of bones in the hands and feet is also affected. This leads to the main characteristic features of Pfeiffer syndrome.

Symptoms, Ailments & Signs

The premature fusion of certain skull bones leads to the characteristic facial deformities of Pfeiffer syndrome: the eyes are bulging and wide open, and the distance between them is increased. The forehead is prominent, the ears are low-set and the midface is underdeveloped. The skull is flattened and short. More than half of all patients complain of hearing loss and dental problems.

Mostly the toes and fingers are unusually short, with some fusions in the interstices. The thick toe and thumb are noticeably short, triangular in shape, and curve away from the other toes and fingers. Depending on the clinical type, the symptoms vary in severity. Type 1 is the classic form of Pfeiffer syndrome. This is milder than the other two types. The patient has normal intelligence, slight deformities of the fingers and toes, and mild midface hypoplasia.

Type 2 has more severe clinical symptoms. The skull is in the shape of a shamrock and the eyeballs protrude noticeably from the eye sockets. Anomalies in fingers and toes are severe. Also deform the elbows. The bones are often weak and spontaneously stiffen. There are also neurological complications. The development of the affected child is delayed. Type 3 Pfeiffer syndrome develops the same symptoms as type 2, but without the cloverleaf skull.

Diagnosis & course of disease

Pfeiffer syndrome can be diagnosed as early as the third month of pregnancy of embryonic development. A prenatal examination using fine ultrasound can reveal an abnormally large distance between the two eyes. The pathological protrusion of the eyeballs from the orbits as well as deformations of the skull and face area can also be determined. After birth, the exact diagnosis is guaranteed with a genetic test.

Complications

In most cases, those affected by Pfeiffer syndrome suffer from various malformations and malformations. These primarily have a very negative effect on the aesthetics of those affected, so that most patients feel uncomfortable with them and suffer from inferiority complexes or reduced self-esteem. Depression can also occur due to Pfeiffer syndrome and significantly reduce the patient’s quality of life.

Furthermore, Pfeiffer syndrome also leads to hearing loss that occurs gradually. Tooth problems or tooth loss can also occur and make eating and drinking much more difficult. Furthermore, the patients suffer from anomalies in the toes and fingers, so that there may be limitations in everyday life and restricted movement in the patient.

The mental development of the child is also significantly delayed due to Pfeiffer syndrome, so that in adulthood the patient is dependent on the help of other people. Some of the abnormalities can be removed through surgery. There are no complications. However, the patient is still dependent on various therapies and support measures in order to be able to cope with everyday life.

When should you go to the doctor?

Children suffering from Pfeiffer syndrome require intensive medical care from birth. The malformations on the head and limbs must be surgically corrected. In addition, the affected children usually need painkillers, anti-inflammatory drugs and other drugs. Parents should contact a specialist immediately after delivery so that a comprehensive diagnosis can be carried out. The actual treatment takes place in special centers.

Specialists in oral and maxillofacial surgery as well as neurosurgeons and plastic surgeons are responsible. At the same time, close consultation with the paediatrician must be held. After the initial therapy, the doctor should be consulted regularly so that the medication can be discontinued and the various surgical wounds can be examined for complications. Since the Pfeiffer syndrome leads to major visual flaws, which often also put a psychological strain on the child, therapeutic advice can also be useful. If the course is positive, however, the main characteristics of the disease can be reduced to such an extent that it is possible to continue living normally without therapy and regular visits to the doctor.

Treatment & Therapy

Depending on the severity of the Pfeiffer syndrome, surgical correction of the face and skull can be carried out. This is possible through facial, oral and maxillofacial surgery as well as through plastic surgery and neurosurgery. By expanding the frontal-orbital skull area, the skull can grow properly and the size of the orbits can be increased.

The jaw and midface can also be corrected by surgical intervention. With proper treatment, sufferers can develop normal intelligence and lead normal, healthy lives. The treatment plans are carried out in stages. The right time for carrying out a reconstruction of the bone structure is very important. Accordingly, devastating effects of Pfeiffer syndrome on the ability to breathe, speak and swallow are prevented.

Because of the underdeveloped midface, children often suffer from obstructive sleep apnea. In the case of mild sleep apnea, drug treatment can significantly improve breathing. However, a severe respiratory disorder should be monitored by specialists. Surgical removal of the tonsils or a continuous airway pressure mask (CPAP) can relieve the symptoms here.

Outlook & Forecast

In order to specify a prognosis, the present type of Pfeiffer syndrome must be determined. The severity of the deformities associated with Pfeiffer syndrome has led to the classification into three types with different prognosis. In classic Pfeiffer syndrome, the deformities are only mildly pronounced. Intelligence is not diminished. The prognosis is good, especially since the existing deformities can be surgically reduced.

With Pfeiffer syndrome, the prognosis is not so optimistic. The deformities are much more serious. The so-called cloverleaf skull is typical. The deformities of the skeleton are partly operable, but mostly not correctable. Mental development is delayed. Neurological complications are to be expected.

In the case of the third Pfeiffer syndrome, the symptoms are similarly serious, only the cloverleaf skull is missing. Again, the prognosis is not particularly good due to genetic causation. The smooth transitions between the three Pfeiffer syndrome forms make clear differentiation and prognosis difficult.

It is helpful, however, that the presence of Pfeiffer syndrome can be detected before birth. The typical deformities are already noticeable during sonography. In addition, an increased risk of these genetically inheritable mutations is known in individual cases. Whether a legal abortion is then still possible or is considered by the family varies. Once the child is born, there are usually several surgeries ahead of it.

Prevention

Since Pfeiffer syndrome is an autosomal dominant inherited condition, it cannot be prevented. However, it can be diagnosed before birth.

Aftercare

In most cases, those affected with Pfeiffer syndrome have only a few or even no special options for aftercare. First and foremost, a very quick and, above all, early diagnosis of the disease is important so that no further complications can occur. Self-healing does not occur in this case, so ideally the person affected should see a doctor as soon as the first symptoms or signs of the disease appear.

Since this is also a genetic disease, if the patient wishes to have children, they should definitely have a genetic examination and counseling carried out in order to prevent the recurrence of Pfeiffer syndrome. Most patients are usually dependent on surgical interventions, which can alleviate the symptoms.

The person concerned should definitely rest after such an operation and protect his body. In any case, you should refrain from exertion or physical and stressful activities in order not to unnecessarily burden the body. Likewise, most of those affected are dependent on the help and support of their own family in their everyday life due to Pfeiffer syndrome, which can have a positive effect on the further course of the disease.

You can do that yourself

Pfeiffer syndrome is treated with a combination therapy that aims to relieve the physical symptoms and the mental and emotional side effects. The parents of sick children can support the therapy by encouraging and supporting the child.

Since the malformations can lead to bullying and teasing and, as a result, to the development of social anxiety in those affected, it is all the more important to strengthen the child’s self-confidence. Parents should also try to find a suitable kindergarten or school place at an early stage. In a facility for special children, a child with Pfeiffer syndrome can develop optimally and the parents can concentrate on having the physical symptoms treated. Since it is not possible to completely eliminate the malformations, the apartment must be made accessible for the disabled. The children also need aids such as walking aids or a wheelchair. The legal guardians should contact the respective medical specialists at an early stage and initiate the necessary measures.

Accompanying this, a therapeutic consultation for parents and child can be useful. In later life, a visit to a specialist clinic for hereditary diseases is also recommended, since sooner or later the child will ask questions about his illness. Then the relatives should be there with advice and action.