Pfeiffer syndrome

Pfeiffer syndrome (SP, Pfeiffer syndrome) is a rare genetic developmental disorder characterized by abnormalities in the formation of the head and face, as well as deformities of the bones of the skull and the hands and feet. The syndrome is named after German pediatrician Rudolf Pfeiffer, who first described it in 1964.

Epidemiology

Pfeiffer syndrome is a rare genetic developmental disorder and its prevalence in the population is low. There is no definitive data on the exact frequency of this syndrome because it is rare and can manifest in a variety of ways. Frequency estimates vary by source and region.

Pfeiffer syndrome is thought to be inherited in an autosomal dominant mode, meaning that it can be passed from a parent to offspring with a 50% probability. Mutations in the FGFR1 and FGFR2 genes associated with this syndrome can occur within family lines, but they can also appear randomly.

Pfeiffer syndrome is sex-independent and can occur in both boys and girls. These mutations can occur by chance during embryonic development and are not associated with a disruption of the genetic material in the parents' eggs.

Because the disease is associated with genetic mutations that occur during fetal development, its incidence may vary between populations and may depend on the presence of mutation carriers among patients' relatives.

Causes of the pfeiffer syndrome

Pfeiffer syndrome is a genetic developmental disorder that is associated with mutations in the FGFR1 and FGFR2 genes. It is generally believed that this disorder results from new (spontaneous) mutations in these genes rather than from inherited transmission from parents. Nevertheless, in rare cases, Pfeiffer syndrome can be transmitted from parent to offspring.

Mutations in the FGFR1 and FGFR2 genes lead to disruption of the normal development of the fetal skull bones and facial skeleton, resulting in characteristic features of the disease such as unusual head and face shape, high skull vault, cleft upper lip, etc.

The exact cause of mutations in the FGFR1 and FGFR2 genes is not fully understood, and research in this area is ongoing.

Pathogenesis

Pfeiffer syndrome is associated with mutations in the FGFR1 and FGFR2 genes, which encode fibroblastic growth factor receptors (FGFR) that play an important role in regulating the growth and development of cells and tissues in the body. Pathogenesis is related to abnormal development of the bones of the skull and facial skeleton during embryonic development. Here's how it occurs:

1. Mutations in the FGFR1 and FGFR2 genes: Under normal conditions, FGFR receptors regulate cell growth and development, as well as the formation of cranial and facial bones. Mutations in these genes lead to improper activation of signaling pathways, which in turn causes unusual bone development.
2. Hyperostosis: Mutations in FGFR1 and FGFR2 lead to increased activity of these receptors, resulting in hyperostosis, which is excessive bone formation. This leads to a skull and face with unusual shape and structure.
3. Structural anomalies: Hyperostosis and developmental changes in the bones of the skull and face lead to characteristic features of Pfeiffer syndrome, such as high skull vault, cleft upper lip, fusion of the skull sutures, abnormal eye position, etc.
4. Effects on other organs: In some cases, the condition may also be accompanied by other medical problems such as brain dysfunction, visual impairment, hearing impairment, etc.

Symptoms of the pfeiffer syndrome

Symptoms can vary depending on its form and severity, but typically include the following signs:

1. Anomalies of the skull and face:

   • High skull vault (turricephaly).
   • Fusion of the bony sutures of the skull, which can lead to an unnatural head shape.
   • Cleft upper lip and/or abnormal development of facial features.
   • Convex eyes (hypertelorism).
   • Narrow eye slits (hyposphenia).

2. Bone and limb anomalies:

   • Shorter and wider fingers and toes, giving them a "trefoil" appearance.
   • Fusion of the finger bones (syndactyly).
   • Abnormal development of the bones of the sternum.
   • Short neck.

3. Developmental delay: Some children may have a delay in physical and mental development.

4. Other medical problems: Some children may have additional medical problems, such as visual and hearing impairments, breathing and digestive problems, and brain dysfunction.

Forms

The major forms of Pfeiffer syndrome include the following:

1. Type I (Pfeiffer Syndrome Type I):

   • This is the mildest form.
   • Characterized by short and wide fingers and toes, and some craniofacial anomalies such as fusion of the bony sutures of the skull and cleft upper lip.
   • Developmental delay and intellectual disability are usually less severe.

2. Type II (Pfeiffer Syndrome Type II):

   • This is a more severe form of the syndrome.
   • Includes Type I features, but with more severe craniofacial and limb abnormalities.
   • Children with this form may have more severe breathing and digestive problems, as well as developmental delay and intellectual disability.

3. Type III (Pfeiffer Syndrome Type III):

   • This is the most severe form.
   • Characterized by severe skull and facial abnormalities, including more severe fusion of the bony sutures of the skull, which can limit brain growth.
   • Limb anomalies are more pronounced, and children often have short, wide fingers and extra toes (polydactyly).
   • Developmental delay and intellectual disability are also more serious.

Diagnostics of the pfeiffer syndrome

Diagnosis is usually based on clinical signs and may include the following steps:

1. Clinical examination: The physician performs a visual examination of the patient to look for characteristic craniofacial abnormalities, limb abnormalities, and other signs. This step helps to determine if the syndrome is suspected.
2. Immunohistochemical analysis: In some cases, a biopsy of the skin or other tissues may be needed to examine mutations in the FGFR1 and FGFR2 genes. This molecular study may confirm the diagnosis.
3. Heredity testing: If there is a family history of Pfeiffer syndrome, genetic testing may be useful to determine if the parents have a mutation in the FGFR1 and FGFR2 genes. This may help in planning a pregnancy and assessing the risk of passing the mutation to offspring.
4. Instrumental diagnosis: Additional examinations may include skull and limb radiographs and other imaging to evaluate bone and tissue abnormalities.
5. Specialist consultations: Because the disease can affect various body systems, patients may be referred for consultations with a variety of specialists such as a geneticist, neurosurgeon, orthopedist, and cranial and facial anomaly specialists.

Differential diagnosis

Differential diagnosis involves identifying the differences between this syndrome and other medical conditions that may have similar features. Some of the conditions that may be similar to Pfeiffer syndrome include:

1. Crouzon syndrome: This genetic disorder is also characterized by abnormalities of the skull and facial bone. However, unlike JS, Crouzon syndrome does not have abnormalities of the arms and legs.
2. Apert syndrome: This is another genetic disorder that can lead to similar skull and facial bone abnormalities, including a "falcon nose" appearance. However, Apert syndrome usually lacks the limb abnormalities that characterize SP.
3. Saethre-Chotzen syndrome: This syndrome can also manifest with abnormalities of the skull and facial bone. It has some similarities to SP, but is characterized by other genetic mutations and special features.
4. Trisomy 21 syndrome (Down syndrome): This syndrome has its own characteristics, including a face with distinctive features, but it is different from Pfeiffer syndrome and other genetic disorders.

Treatment of the pfeiffer syndrome

Treatment for this syndrome is usually multifaceted and requires coordination between specialists from different fields. Here are some aspects of treatment for Pfeiffer syndrome:

1. Surgery: Surgery may be required to correct abnormalities of the skull, facial bones and limbs. This may include surgeries to correct the aperture of the skull, shaping the correct shape of the face, and surgeries on the arms and legs to improve functionality.
2. Orthodontics: Patients with SP may have problems with their bite and the alignment of their teeth. Orthodontic treatment, such as wearing braces, may be necessary to correct these problems.
3. Speechand physical therapy: Children may have delays in speech and motor skills. Speech and physical therapy can help develop these skills.
4. Support and rehabilitation: This is an important aspect of treatment for patients and their families. Psychological support and help in learning to adapt to the features of the syndrome can help to improve quality of life.
5. Medication: Sometimes medications may be prescribed to relieve pain and reduce inflammation if patients experience discomfort.

Forecast

The prognosis of Pfeiffer syndrome can be varied and depends on the severity of symptoms and the effectiveness of treatment. It is important to note that Pfeiffer syndrome is a serious genetic disorder, and its severity can vary greatly from patient to patient. Here are some common aspects of prognosis:

1. Individuality of prognosis: Each case of SP is unique. Some children may have more severe physical abnormalities and medical problems than others.
2. Impact of treatment: Prognosis can be improved with surgery and rehabilitation. Early initiation of treatment and a comprehensive approach can significantly improve the patient's quality of life.
3. Role of genetic mutations: The type and mutations in the genes responsible for SP can also affect prognosis. Some mutations may be more severe than others.
4. Support and rehabilitation: Psychological and physical rehabilitation, as well as family support, can play an important role in the patient's adjustment to SP.
5. Prognosis for long-term survivors: Some patients with SP who have undergone surgery and received appropriate treatment have a chance for a long life. However, medical and psychological support may be required throughout life.

The overall prognosis for Pfeiffer syndrome can be unpredictable due to its diversity and complexity. Therefore, it is important that the patient's treatment and support be individualized and based on their unique needs. Regular consultation with physicians and specialists will help the patient's family make informed decisions and ensure the best quality of life for the child.

Literature used

Ginter, Puzyrev, Skoblov: Medical Genetics. A national manual. GEOTAR-Media, 2022.