Pfeiffer syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Pfeiffer syndrome is a genetic disorder characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. Pfeiffer syndrome also affects bones in the hands and feet.

Many of the characteristic facial features of Pfeiffer syndrome result from premature fusion of the skull bones. Abnormal growth of these bones leads to bulging and wide-set eyes, a high forehead, an underdeveloped upper jaw, and a beaked nose. More than half of all children with Pfeiffer syndrome have hearing loss; dental problems are also common.

In people with Pfeiffer syndrome, the thumbs and first (big) toes are wide and bend away from the other digits. Unusually short fingers and toes (brachydactyly) are also common, and there may be some webbing or fusion between the digits (syndactyly).

Pfeiffer syndrome is divided into three subtypes. Type 1, also known as classic Pfeiffer syndrome, has symptoms as described above. Most individuals with type 1 Pfeiffer syndrome have normal intelligence and a normal life span. Types 2 and 3 are more severe forms of Pfeiffer syndrome that often involve problems with the nervous system. The premature fusion of skull bones can limit brain growth, leading to delayed development and other neurological problems. In addition, individuals with type 2 or 3 can have fusion of the bones (ankylosis) in the elbow or other joints, limiting mobility, and abnormalities of the face and airways, which can cause life-threatening breathing problems. Type 2 is distinguished from type 3 by the presence of a cloverleaf-shaped head, which is caused by more extensive fusion of bones in the skull.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Pfeiffer syndrome is most commonly caused by mutations in the FGFR2 gene. Mutations in the FGFR1 gene cause a small percentage of cases of type 1 Pfeiffer syndrome. Mutations in this gene have not been associated with type 2 or 3.

The FGFR1 and FGFR2 genes provide instructions for making proteins known as fibroblast growth factor receptors 1 and 2, respectively. Among their multiple functions, these proteins signal immature cells to become bone cells during embryonic development. A mutation in either the FGFR1 or FGFR2 gene alters the function of the respective protein, causing prolonged signaling, which can promote the premature fusion of skull bones and affect the development of bones in the hands and feet.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Pfeiffer syndrome affects about 1 in 100,000 individuals.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Broad thumb · Very frequent (99-80%)

Increased thumb width without increased dorso-ventral dimension.

Hypoplasia of the zygomatic bone · Very frequent (99-80%)

Underdevelopment of the zygomatic bone. That is, a reduction in size of the zygomatic bone, including the zygomatic process of the temporal bone of the skull, which forms part of the zygomatic arch.

Ptosis · Very frequent (99-80%)

The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Brachydactyly · Frequent (79-30%)

Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.

Clinodactyly of the 5th finger · Frequent (79-30%)

Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).

Finger syndactyly · Frequent (79-30%)

Webbing or fusion of the fingers, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers in a proximo-distal axis are referred to as "Symphalangism".

High forehead · Frequent (79-30%)

An abnormally increased height of the forehead.

Hypertelorism · Frequent (79-30%)

Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).

Turricephaly · Frequent (79-30%)

Tall head relative to width and length.

Wide nasal bridge · Frequent (79-30%)

Increased breadth of the nasal bridge (and with it, the nasal root).

Symphalangism affecting the phalanges of the hand · Frequent (79-30%)

Facial asymmetry · Occasional (29-5%)

An abnormal difference between the left and right sides of the face.

Flat face · Occasional (29-5%)

Absence of concavity or convexity of the face when viewed in profile.

High palate · Occasional (29-5%)

Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).

Other findings in the same source

From: Orphanet

Additional reported features include Hip dysplasia (Occasional (29-5%)); Hyperlordosis (Occasional (29-5%)); Mandibular prognathia (Occasional (29-5%)); Open mouth (Occasional (29-5%)); Short neck (Occasional (29-5%)); Short philtrum (Occasional (29-5%)); Short stature (Occasional (29-5%)); Synostosis of carpal bones (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Pfeiffer syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Pfeiffer syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.