Pfeiffer Syndrome: Causes, Symptoms & Treatment

Pfeiffer syndrome is an autosomal dominant inherited disorder. This occurs very rarely and has abnormalities in the bone formation of the face and skull. Pfeiffer syndrome is caused by a mutation in certain proteins responsible for the maturation of bone cells.

What is Pfeiffer syndrome?

Pfeiffer syndrome is a rare inherited disorder that is one of the craniosynostoses. Because it is inherited in an autosomal dominant manner, individuals with this disorder have a fifty percent chance of passing it on to their children. Pfeiffer syndrome impairs 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. The failed fusion of the facial bones results in bulging and wide-set eyes, a high forehead, a flat nasal bridge, and an underdeveloped upper jaw. A clinical distinction is made between three types. The three types have features that vary in severity. Patients with types 2 or 3 are more severely affected and life expectancy is also markedly reduced. The prevalence of Pfeiffer syndrome is not precisely known and it is estimated to affect 1 in 100,000 people worldwide. The disease is caused by a mutation in the FGFR-1 and FGFR-2 genes.

Causes

Pfeiffer syndrome results from a mutation in the FGFR-1 and FGFR-2 genes, and this mutation is inherited in an autosomal dominant manner. If either parent is affected by this mutation, they will pass it on to the child with a fifty percent chance. These genes are responsible for the production of important proteins, fibroblast growth receptors 1 and 2(fibroblast growth factor receptors). Type 1 of Pfeiffer syndrome can be caused by a mutation in either receptor. 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. The 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 elongation promotes premature fusion of the bones of the skull and face. Likewise, the normal development of bones of the hands and feet is affected. This leads to the main characteristic features of Pfeiffer syndrome.

Symptoms, complaints, and signs

Premature fusion of certain skull bones leads to the characteristic facial deformities of Pfeiffer syndrome: the eyes are bulging as well as wide open and the distance between them is increased. The forehead is distinct, 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. Usually the toes and fingers are unusually short, with some fusion in the spaces between them. The thick toe and thumb are noticeably short, triangular in shape, and bend away from the other toes and fingers. Symptoms vary in severity depending on the clinical type. Type 1 is the classic form of Pfeiffer syndrome. This is milder than the other two types. The affected individual has normal intelligence, mild deformities of the fingers and toes, and mild expression of midface hypoplasia. Type 2 has more severe clinical symptoms. The skull has a cloverleaf shape and the eyeballs protrude noticeably from the orbits. Abnormalities in the fingers and toes are severe. The elbows also deform. The bones are often weak and stiffen spontaneously. Furthermore, neurological complications occur. The development of the affected child is delayed. Type 3 of Pfeiffer syndrome develops the same symptomatology as type 2, but without the cloverleaf skull.

Diagnosis and course of the disease

Pfeiffer syndrome can be diagnosed as early as the third month of pregnancy during embryonic development. Prenatal examination may reveal an abnormally large distance between the two eyes using fine ultrasound. Pathological protrusion of the eyeballs from the orbits and deformities of the cranial and facial regions can also be detected.After birth, the exact diagnosis is guaranteed with a genetic test.

Complications

In most cases, those affected with Pfeiffer syndrome suffer from various malformations and deformities. These primarily have a very negative effect on the aesthetics of the affected person, making most patients uncomfortable and suffering from inferiority complexes or lowered self-esteem. Depression can also occur due to Pfeiffer syndrome, significantly reducing the patient’s quality of life. Furthermore, Pfeiffer syndrome also leads to hearing loss, which occurs gradually. Dental problems or tooth loss may also occur, making it much more difficult to take in food and fluids. Furthermore, patients suffer from abnormalities of the toes and fingers, so that there may be restrictions in everyday life and limited movement in the patient. The child’s mental development is also significantly delayed due to Pfeiffer syndrome, so that the patient is dependent on the help of other people in adulthood. Some of the abnormalities can be removed by surgical intervention. No complications occur in this process. However, the patient is still dependent on various therapies and support measures to cope with everyday life.

When should you see a doctor?

Children who have Pfeiffer syndrome require intensive medical care from birth. The deformities of the head and limbs require surgical correction. In addition, affected children usually need painkillers, anti-inflammatories and other medications. Parents should contact a specialist immediately after delivery so that a comprehensive diagnosis can be made. The actual treatment takes place in specialized centers. Specialists in the fields of oral and maxillofacial surgery as well as neurosurgeons and plastic surgeons are responsible. Accompanying treatment must be closely consulted with the pediatrician. After the initial therapy, the physician should be visited regularly so that the medication can be adjusted and the various surgical wounds can be examined for complications. In addition, since Pfeiffer syndrome leads to major visual blemishes that often also affect the child psychologically, therapeutic counseling may be useful. However, if the course is positive, the main features of the disease can be reduced to such an extent that a normal continuation of life is possible without therapy and regular visits to the doctor.

Treatment and therapy

Depending on the severity of Pfeiffer syndrome, surgical correction of the face and skull may be performed. This is possible through facial, oral and maxillofacial surgery as well as plastic surgery and neurosurgery. By expanding the frontal-orbital region of the skull, the skull can be made to grow properly and the size of the eye sockets can be increased. Jaw and midface can also be corrected by surgical procedure. With just treatment, sufferers can develop normal intelligence and lead normal healthy lives. Treatment plans are carried out in stages. Very crucial is the right time to carry out reconstruction of the bone structure. Accordingly, devastating effects of Pfeiffer syndrome on the ability to breathe, speak and swallow are prevented. Due to the underdeveloped midface, children often suffer from obstructive sleep apnea. In case of mild sleep apnea, drug treatment can intensively improve breathing. However, a severe breathing disorder should be monitored by specialists. Here, surgical removal of the palatine tonsils or a continuous positive airway pressure (CPAP) mask can relieve symptoms.

Outlook and prognosis

To specify a prognosis, the presenting 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 prognoses. In classic Pfeiffer syndrome, the deformities are only mild. Intelligence is not diminished. The prognosis is good, especially since the present deformities can be mitigated surgically. In Pfeiffer syndrome, the prognosis is not so optimistic. The deformities are much more severe. Typical is the so-called cloverleaf skull. The deformities of the skeleton are partly operable, but mostly not correctable. The mental development is delayed.Neurological complications are to be expected. In the third Pfeiffer syndrome, the symptoms are similarly severe, only the cloverleaf skull is missing. Here, too, the prognosis is not particularly good due to the genetic causation. The fluid transitions between the three Pfeiffer syndrome forms make a clear differentiation and prognosis difficult. It is helpful, however, that the presence of Pfeiffer syndrome can be detected prenatally. The typical deformities are already noticeable on sonography. In addition, an increased risk for these genetically inheritable mutations is known in individual cases. Whether a legal termination of pregnancy is then still possible, or is considered on the part of the family, varies. Once the child is born, he or she usually faces several surgeries.

Prevention

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

Follow-up

In most cases, the person affected by Pfeiffer syndrome has few or even no special options for aftercare. Here, first and foremost, a very quick and, above all, an early diagnosis of the disease is important so that no further complications can occur. Self-cure does not occur, so that the affected person should ideally see a doctor at the first symptoms or signs of the disease. Since this is also a genetic disease, the patient 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 Pfeiffer syndrome. Most patients are usually dependent on surgical interventions, which can alleviate the symptoms. However, after such an operation, the affected person should in any case rest and take care of his or her body. Efforts or physical and stressful activities are to be refrained from in any case, in order not to stress the body unnecessarily. Likewise, due to Pfeiffer syndrome, most affected people are dependent on the help and support of their own family in their daily lives, which can have a positive effect on the further course of the disease.

What you can do yourself

Pfeiffer syndrome is treated as part of a combination therapy, the goal of which is to alleviate the physical symptoms and the mental and emotional accompanying symptoms. Parents of affected children can support the therapy by encouraging and supporting the child. Since the deformities can lead to bullying and teasing and subsequently to the development of social anxiety in those affected, it is all the more important to encourage the child in its self-confidence. Parents should also make early efforts to find a suitable kindergarten and school place. In an institution for special children, a child with Pfeiffer syndrome can develop optimally, and the parents can concentrate on having the physical complaints treated. Since it is not possible to completely correct the deformities, the home must be adapted for the disabled. In addition, the children will need assistive devices such as walkers or a wheelchair. The legal guardians should contact the respective specialists at an early stage and initiate the necessary measures. Accompanying therapeutic counseling can be useful for parents and child. Later in life, a visit to a specialist clinic for hereditary diseases is also recommended, as the child will sooner or later ask questions about his or her disease. At that time, family members should be available to offer advice and support.