PFEIFFER SYNDROME

Pfeiffer Syndrome is a rare genetic disorder characterized by abnormalities in the shape of the head and face, as well as malformations in the hands and feet. This condition affects the growth of bones, particularly in the skull, leading to distinct facial features and potential complications.

Typically, a newborn’s skull isn’t a single solid piece. Instead, it consists of several bones with specialized joints between them. This design allows the skull to grow and expand as the brain develops. Normally, the bones of the skull fuse together only once the head has reached its full size.

However, in Pfeiffer syndrome, these skull bones fuse prematurely, before the brain has finished growing. As a result, the skull cannot expand properly, leading to abnormalities in the shape of the head and face.

Treatment for Pfeiffer syndrome typically begins shortly after birth. Since the condition can vary greatly from person to person, the appropriate care plan depends on the specific symptoms exhibited by the child.

Causes

Pfeiffer syndrome stems from a mutation in genes responsible for regulating the growth and death of specific cells. While it can be hereditary, most cases occur due to spontaneous mutations in the baby’s genes, rather than being passed down from parents who typically do not have the syndrome.

This genetic mutation disrupts the production and function of certain proteins during pregnancy. Consequently, these proteins may signal premature fusion of the baby’s skull bones before the brain has fully developed, exerting pressure on the brain and causing alterations in skull shape, along with other bodily issues. Premature fusion of bones in the hands and feet is also common.

Prevalence

Pfeiffer Syndrome is considered rare, with an estimated incidence of 1 in 100,000 live births. However, the actual prevalence may vary due to underdiagnosis or misdiagnosis.

Types of Pfeiffer syndrome

Pfeiffer syndrome manifests in three distinct types, each affecting a child’s appearance, with types 2 and 3 being more severe and potentially causing developmental delays, learning differences, and various issues related to the brain, mobility, and nervous system.

Pfeiffer Syndrome Type 1:
- Referred to as classic Pfeiffer syndrome, this is the mildest form of the condition.
- Symptoms include sunken cheekbones, facial deformities, and larger thumbs and big toes.
- Individuals with type 1 typically have an average life expectancy with proper treatment but may experience complications such as fluid buildup in the brain (hydrocephalus) and hearing loss.
Pfeiffer Syndrome Type 2:
- This type is more severe and can be life-threatening if left untreated.
- Babies with type 2 Pfeiffer syndrome exhibit extensive fusion of their skull bones, leading to complex bone growth issues, joint stiffness, and abnormalities in their hands and feet.
- Their skulls often take on a cloverleaf shape, bulging at the front and sides, with a high, wide forehead and a sunken midface.
- Other distinctive features include a “beak-like” nose, wide-set and protruding eyes (ocular proptosis), and downward-angled ears.
- Type 2 also presents with fluid buildup in the brain, neurological complications, and developmental disabilities.
Pfeiffer Syndrome Type 3:
- Similar to type 2 but with some variations, type 3 Pfeiffer syndrome does not exhibit bulging at the sides and front of the skull.
- Additional symptoms may include the presence of teeth at birth and a shortened base of the skull.
- Without proper treatment, type 3 can also be fatal.

Symptoms of Pfeiffer Syndrome

Symptoms of Pfeiffer syndrome vary in type and severity from one child to another, affecting various parts of the body:

Head and Face:

The condition prominently affects the head and face due to impaired skull expansion and mid-face bone growth.
Observable signs include:
- A broad, flattened nose with a downturned tip
- Irregularly spaced or crooked teeth
- Wide-set, protruding eyes
- Shortened head length from front to back
- Elevated forehead
- Sunken midface
- Underdeveloped upper jaw

Fingers and Toes:

Children often exhibit:
- Shortened fingers and toes
- Widened thumbs and big toes that angle away from the other digits
- Webbing between fingers and toes

Other Associated Problems:

More than half of affected children experience hearing loss, along with additional issues such as:
- Dental abnormalities
- Feeding difficulties
- Cleft palate
- Joint stiffness, notably in elbows
- Acid reflux
- Speech impairments
- Sleep apnea
- Vision impairments
- Developmental delays
- Nervous system and brain development issues

Risk Factors

The primary risk factor for Pfeiffer Syndrome is having a family history of the condition or inheriting a mutated gene from one or both parents.

Diagnosis for Pfeiffer Syndrome

Pfeiffer syndrome can be diagnosed both during pregnancy and after birth through various diagnostic methods.

During Pregnancy:

Doctors may use ultrasound or magnetic resonance imaging (MRI) to detect signs of Pfeiffer syndrome in the fetus.
These imaging techniques allow visualization of the baby’s skull and other relevant structures, aiding in early detection.

After Birth:

Following delivery, doctors often perform a physical examination to assess the newborn’s skull, thumbs, and big toes, which can provide clues suggestive of Pfeiffer syndrome.

Confirmatory Tests:

To confirm the diagnosis and rule out other conditions, additional tests may be conducted, including:
- X-rays or imaging such as a computed tomography (CT) scan, which can provide detailed information about the skull and bone structure.
- Genetic testing involving blood or saliva samples to identify the specific gene mutation responsible for Pfeiffer syndrome.

Treatments for Pfeiffer Syndrome

The treatment approach for Pfeiffer syndrome is tailored to the specific type and symptoms experienced by the child, often requiring a multidisciplinary team of specialists, including doctors, surgeons, psychologists, speech and language therapists, and others.

Skull Surgery:
- Surgery is typically a crucial component of treatment, particularly for reshaping the skull to alleviate pressure and fluid buildup.
- Most children undergo the first of several skull surgeries before 18 months of age. This procedure involves releasing the bands of tissue fusing the skull bones together, either through small openings for infants under 3 months or traditional surgery for older children.
- Subsequent surgeries may be necessary throughout the child’s life, typically totaling two to four procedures.
- Following surgery, the child may wear a special helmet to aid in the proper healing and shaping of the skull.
Midface Surgery:
- Some children may require midface surgery to address jaw abnormalities and advance midface bones. This procedure is typically performed when the child is at least 6 years old.
Treatment for Breathing Problems:
- Breathing difficulties, such as sleep apnea, may necessitate interventions to improve airflow.
- Options include wearing a continuous positive airway pressure (CPAP) mask during sleep, midface surgery to remove blockages, or surgical removal of tonsils or adenoids.
- In severe cases, a tracheostomy may be performed to create a direct opening in the child’s neck to the windpipe, facilitating easier breathing, particularly for infants too young for other corrective surgeries.
Other Treatments:
- Additional treatments may be required to address various associated issues, including:
  - Dental procedures to correct bite abnormalities and misaligned teeth.
  - Surgical interventions to address finger and toe abnormalities.
  - Surgery or hearing aids to improve hearing.
  - Vision correction treatments.
  - Speech and language therapy to aid in communication skills.
  - Physical therapy to enhance mobility.

Home Care Tips

Follow post-surgical care instructions provided by healthcare providers.
Attend regular follow-up appointments to monitor growth and development.
Provide a supportive and nurturing environment for the affected individual.

Prevention

Since Pfeiffer Syndrome is a genetic disorder, it cannot be prevented. However, genetic counseling may benefit families with a history of the condition to understand the risk of passing it on to future generations.

Complications

Children with Pfeiffer syndrome may experience various complications that require careful management:

Hydrocephalus:
- Excess fluid buildup in the brain, requiring surgical intervention to alleviate pressure.
Dental Problems:
- Changes in facial bone structure affecting tooth placement and bite, often necessitating dental work.
Hearing Loss:
- Approximately 50% of children with Pfeiffer syndrome experience hearing impairment, which may be addressed with surgery or hearing aids.
Limited Mobility:
- Difficulties in walking and movement, which can be improved through physical therapy and surgical interventions.
Sleep Apnea:
- Airway blockages due to midface bone underdevelopment, potentially leading to breathing difficulties during sleep.
- Chiari malformation, where part of the brain may protrude through the skull base, impacting oxygen flow to the brain. Treatments include medication, CPAP masks, or surgery.
Breathing Problems:
- Structural abnormalities in the airways necessitating corrective surgeries, with some cases requiring a tracheostomy to ensure adequate oxygen supply.
Vision Problems:
- Bulging eyes and incomplete eyelid closure due to shallow eye sockets, potentially resulting in dry eyes and vision loss.
Learning Differences:
- Developmental delays, learning differences, and cognitive impairment, particularly in types 2 and 3.
- Early interventions, including surgeries and therapies, can aid in improving health outcomes.

When to See a Doctor

If you notice any signs or symptoms of Pfeiffer Syndrome in yourself or your child, it’s essential to seek medical attention promptly. Early diagnosis and intervention can help manage the condition more effectively and improve outcomes.

Life Expectancy

Type 1 Pfeiffer syndrome typically has a normal life expectancy, with children able to lead fulfilling lives.
Types 2 and 3 may pose more challenges, often requiring lifelong rehabilitation, therapy, and assistance, and may have shorter lifespans due to respiratory and neurological issues if untreated.

Outlook/Prognosis

The outlook for individuals with Pfeiffer Syndrome varies depending on the severity of symptoms and complications. Many individuals with Pfeiffer Syndrome can lead fulfilling lives with appropriate medical care and support. However, they may require ongoing medical management and support to address the challenges associated with the condition.

Sources:

Photo credit: Children’s Hospital of Philadelphia
Genetics Home Reference. (2022). Pfeiffer syndrome.
National Organization for Rare Disorders. (2022). Pfeiffer syndrome.
UNC School of Medicine Division of Plastic and Reconstructive Surgery
National Library of Medicine
Boston Children’s Hospital
Children’s National Health System
Mayo Clinic
Cleveland Clinic
Medline Plus
Seattle Children’s
American Association of Neurological Surgeons
The University of Arizona Health Sciences

PFEIFFER SYNDROME TYPE I