How is Pfeiffer syndrome inherited?

Pfeiffer syndrome follows an autosomal dominant inheritance pattern. This means inheriting just one copy of the altered gene from either parent can cause the condition.

How rare is Pfeiffer syndrome?

Pfeiffer syndrome is classified as not well established. The estimated prevalence is approximately Unknown. Because rare disease data can be limited, actual numbers may differ from published estimates.

How is Pfeiffer syndrome diagnosed?

Information about diagnosis is currently limited for this condition.

Are there treatments for Pfeiffer syndrome?

Information about treatment is currently limited for this condition.

What complications can arise from Pfeiffer syndrome?

Pfeiffer syndrome can lead to complications due to the early fusion of skull bones, which may affect brain development and increase pressure inside the skull. Additionally, malformations in the hands and feet can impact mobility and daily activities. Each person with Pfeiffer syndrome may experience different complications, so it's important to monitor for any changes.

How does Pfeiffer syndrome affect daily life and activities?

Living with Pfeiffer syndrome can present challenges, especially with physical activities due to hand and foot malformations. Some individuals may need assistance with tasks that require fine motor skills or mobility. Support from family, friends, and healthcare providers can help improve daily life and encourage independence.

What is the life expectancy for someone with Pfeiffer syndrome?

The life expectancy for individuals with Pfeiffer syndrome can vary widely depending on the severity of their symptoms and any associated complications. While specific data on life expectancy is limited, many people with this condition can lead fulfilling lives with appropriate medical care and support. Regular check-ups with healthcare providers are important for monitoring health.

What specialists should be involved in the care of someone with Pfeiffer syndrome?

Individuals with Pfeiffer syndrome may benefit from a team of specialists to address their unique needs. This can include geneticists, orthopedic surgeons, and neurosurgeons, among others. Working with a healthcare team ensures that all aspects of the condition are managed effectively, helping to improve quality of life.

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Pfeiffer syndrome (ACS5) - Clinical Profile, Genes & Research | Kisho | Kisho

Features include always present findings: Tracheal cartilaginous sleeve; and sometimes findings: Cloverleaf skull and 3-4 toe cutaneous syndactyly. 29 total HPO annotations.

Organ System	Phenotype Count	Example Features
Arms and legs	4	Short middle phalanx of toe, Shortening of all middle phalanges of the fingers, 3-4 toe cutaneous syndactyly
Head and neck	4	Coronal craniosynostosis, High palate, Hypoplasia of the maxilla
Brain and nerves	3	Hydrocephalus, Intellectual disability, Depressed nasal bridge
Eyes	1	Strabismus
Lungs and breathing	1	Bronchomalacia

GeneReviews

Clinical Guidance

Apert syndrome shows substantial overlap with the clinical characteristics seen in other FGFR2-associated craniosynostosis syndromes (e.g., craniosynostosis, midface retrusion, vertebral fusions). In most individuals, Apert syndrome can be readily distinguished from other syndromic craniosynostosis syndromes (e.g., Crouzon, Pfeiffer, Jackson-Weiss, Beare-Stevenson) at or before birth due to the presence of syndactyly. However, several other important distinguishing features have implications for surveillance and medical management . Craniosynostosis is a near-universal finding in individuals with Apert syndrome, though some affected individuals with other typical manifestations (e.g., midface retrusion and syndactyly) without craniosynostosis have been reported.

Source: GeneReviews — "Apert Syndrome"

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

FGFR1

FGFR1 encodes fibroblast growth factor receptor 1 (822 aa). Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Highest expression in Artery Aorta (144.8 TPM) and Ovary (142.9 TPM).

Pfeiffer syndrome is associated with mutations in the FGFR1 gene on chromosome 8.

The FGFR1 protein participates in p-8Y- FGFR1 R576W, p-8Y-FGFR1 N546K, and p-8Y-FGFR1 K656E pathways.

FGFR1 is classified as a druggable target (Clinically Actionable, Drug Resistance, Druggable Genome, Kinase, and Tyrosine Kinase categories) with score 1.1.

FGFR2

FGFR2 encodes fibroblast growth factor receptor 2 (821 aa). Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Highest expression in Brain Spinal cord cervical c-1 (130.1 TPM) and Uterus (43.5 TPM).

Pfeiffer syndrome is caused by mutations in the FGFR2 gene on chromosome 10.

The FGFR2 protein participates in Signaling by FGFR2 and Signaling by FGFR2 in disease pathways.

FGFR2 is classified as a druggable target (Cell Surface, Clinically Actionable, Druggable Genome, Kinase, and Tyrosine Kinase categories) with score 2.0.

GeneReviews

Clinical Guidance

Reports regarding genotype-phenotype correlations in Apert syndrome are variable. Some studies suggest no clear correlations .

Pathogenic

variant

Some studies have suggested more significant hand and foot involvement in individuals with this pathogenic variant.
One study suggested better postsurgical craniofacial appearance in affected individuals with this variant, but the generalizability of this study is limited due to significant evolution of surgical techniques since the study was published .
Pathogenic

variant. Cleft palate has been reported to be more common in those with this variant.

No other features of Apert syndrome have been found to vary based on genotype .

Source: GeneReviews — "Apert Syndrome"

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Consensus clinical diagnostic criteria for Apert syndrome have not been published.

Suggestive Findings

Apert syndrome should be suspected in individuals with the following clinical features.

Head

Multisuture craniosynostosis, most commonly involving bilateral coronal sutures with variable involvement of the remaining cranial sutures
Midface retrusion with a greater degree of vertical impaction than Crouzon syndrome (See FGFR-Related Craniosynostosis Syndromes.)
Prominent eyes with downslanting palpebral fissures
Relative prognathism with malocclusion

Airway. Multilevel airway obstruction

Limbs/skeleton

Source: GeneReviews — "Apert Syndrome"

GeneReviews

Differential Diagnosis

Most children with multisuture synostosis will have a syndromic form of craniosynostosis. The presence of specific craniofacial characteristics and hand and foot anomalies allow for the clinical diagnosis of Apert syndrome in most cases. Establishing an accurate diagnosis has important implications for screening, surveillance, management, and counseling (see and ). Select syndromes to consider in the differential diagnosis of Apert syndrome include the allelic disorders listed (FGFR2-related Antley-Bixler syndrome, Beare-Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Pfeiffer syndrome types 1, 2, and 3, FGFR2-related Saethre-Chotzen syndrome) and the select syndromes listed in . Table 3. Nonallelic Craniosynostosis Syndromes to Consider in the Differential Diagnosis of Apert Syndrome

Gene	Disorder	MOI	Features of the Differential Diagnosis Disorder
POR	POR-related Antley-Bixler syndrome1

Genetic testing for FGFR1, FGFR2 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for Pfeiffer syndrome has been reported in the published literature.

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for Pfeiffer syndrome. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Apert syndrome, the evaluations summarized (if not already performed) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Apert Syndrome

System/Concern	Evaluation	Comment
Craniofacial	Physical exam to identify cleft palate, ear anomalies, face shape, fontanelles, suture ridging, skull base symmetry	Assessing degree of maxillary hypoplasia is important for determining risk for airway compromise.
Eyes	Consultation w/pediatric ophthalmologist1	Incl assessment of eye surfaces, eye alignment, optic nerves
Ears	Ear-specific hearing eval	—
Respiratory	Assess for airway symptoms (snoring, stridor, apnea, respiratory distress).	Consider consultation w/otolaryngologist sleep medicine
Cardiovascular	Cardiac assessment	Echocardiogram if a murmur is present or if clinical cardiac concerns
Gastrointestinal	Upper GI w/small bowel follow-through if symptomatic or during preoperative eval for gastrostomy tube	To evaluate for intestinal malrotation
Genitourinary	Assessment for cryptorchidism in males	Referral to urologist Renal ultrasound
Musculoskeletal	CT scan of head/skull/sutures	CT w/3D reconstruction will delineate degree of suture involvement help w/preoperative planning. Cervical spine imaging to evaluate for vertebral fusions instability
Neurologic	CT scan or MRI of the head to evaluate for hydrocephalus CNS anomalies	If concern for hydrocephalus or Chiari malformation, consider brain MRI.
Other	Assessment for developmental disabilities	Consider referral to a neurodevelopmental specialist/ early intervention services Consultation w/clinical geneticist genetic counselor
Treatment of Manifestations in Individuals with Apert Syndrome Manifestation/Concern	Treatment	Considerations/Other
Craniosynostosis	In general, multisuture craniosynostosis should be surgically repaired in 1st yr of life.1,2,3,4	Specific timing guided by child's anatomy, risk for intracranial pressure, respiratory status5 Midface
retrusion	Jaw surgery to advance the midface	Typically in childhood or adolescence6,7
Cleft palate	Palate surgery is typically performed prior to development of pressure consonants.	To improve speech production intelligibility Feeding/
swallowing difficulties8	Feeding therapy is helpful to evaluate swallowing safety support eating by mouth.	—
Dental	Pediatric dental care eval by craniofacial orthodontist as part of coordinated craniofacial team care	Orthodontist plays an important role in determining type timing of orofacial interventions.
Strabismus	Strabismus should be treated by ophthalmologist w/expertise in eye alignment in children w/craniosynostosis.	Amblyopia is a major cause of visual impairment.
Hearing loss	Placement of tympanostomy tubes	If chronic middle ear effusions are present Hearing aids, bone conduction sound processors, tympanoplasties, aural atresia/stenosis repair
obstruction	Awareness of potential airway compromise proactive airway mgmt are crucial in infants children.	Specific airway mgmt in Apert syndrome will depend on level severity of obstruction. Temporizing measures to bypass airway obstruction:; Placement of nasal stents; Endotracheal intubation

Source: GeneReviews — "Apert Syndrome"

GeneReviews

Clinical Guidance

Contact sports and activities that involve neck hyperflexion or extension should be avoided, unless the individual has had the cervical spine assessed and cleared. Avoid factors that potentiate hearing loss (ototoxic medications, overly loud stimuli). Use of CPAP/BiPAP for long-term treatment of sleep apnea should be avoided when possible because pressure on the midface will exacerbate midfacial retrusion.

Source: GeneReviews — "Apert Syndrome"

GeneReviews

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Apert Syndrome"

Clinical Trials

1 trial found

Explore Trials

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

A craniofacial team made up of the appropriate specialties allows for proper planning and coordination so that the affected individual may receive the best possible care . Ideally, the composition of the multidisciplinary team caring for a child with Apert syndrome should include the following specialists: • Audiologist • Dentist • Dermatologist • Feeding specialist • Geneticist • Neurodevelopmental and behavioral pediatrician • Neurosurgeon • Nurse • Nutritionist • Ophthalmologist • Oral surgeon • Orthodontist • Orthopedist (hand and foot surgery) • Otolaryngologist • Pediatrician • Plastic surgeon • Psychologist • Pulmonologist/ sleep medicine • Social worker • Speech pathologist • Spine surgeon Table 7. Recommended Surveillance for Individuals with Apert Syndrome

System/Concern	Evaluation	Frequency
Oropharynx	Assessment for velopharyngeal insufficiency1,2	After emergence of language Speech assessment to monitor for speech disorders
Dental	Assessments w/primary dentist to caries support dental health3	Every 6 mos
Eyes	Ophthalmologic eval to incl vision, eye alignment, dilated fundoscopy to assess optic nerves4	Annually
Ears	Audiologic otologic assessements	At least annually
Musculoskeletal	Monitor for development of scoliosis by clinical exam w/surveillance spine radiographs if recommended by spine surgeon.	Annually in childhood adolescence

Source: GeneReviews — "Apert Syndrome"

Phenotype severity distribution: 1 always present feature.

Estimated prevalence: Unknown (Unknown prevalence).

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

1 clinical trial registered, 1 recruiting. Interventions under study include gene therapy. Research is primarily sponsored by academic and government institutions.

60 publications have been identified in PubMed for Pfeiffer syndrome. Research spans Case Report / Case Series (43%), Review / Meta-Analysis (14%), and Epidemiology / Natural History (14%).

Research Type	Count	% of Total
Patient case studies	21	43%
Research summaries	7	14%
Disease patterns and progression	7	14%
Testing and diagnosis research	5	10%
Laboratory research	5	10%
Clinical study results	4	8%

Recent Publications

Lopes Cardoso I (2026). [PMID: 41751524](https://pubmed.ncbi.nlm.nih.gov/41751524/). *Genes (Basel)*. [Review / Meta-Analysis]
Elsherbini A (2026). [PMID: 41689580](https://pubmed.ncbi.nlm.nih.gov/41689580/). *J Hand Surg Am*. [Review / Meta-Analysis]
Saad R (2026). [PMID: 40843924](https://pubmed.ncbi.nlm.nih.gov/40843924/). *American journal of medical genetics. Part A*. [Case Report / Case Series]
Becerril Santos MC (2026). [PMID: 41085212](https://pubmed.ncbi.nlm.nih.gov/41085212/). *Orthodontics & craniofacial research*. [Review / Meta-Analysis]
Liu YT (2026). [PMID: 41946598](https://pubmed.ncbi.nlm.nih.gov/41946598/). *Zhonghua Yan Ke Za Zhi*. [Case Report / Case Series]
Park RK (2026). [PMID: 41637834](https://pubmed.ncbi.nlm.nih.gov/41637834/). *International journal of pediatric otorhinolaryngology*. [Epidemiology / Natural History]
Zheng L (2026). [PMID: 41232649](https://pubmed.ncbi.nlm.nih.gov/41232649/). *Journal of stomatology, oral and maxillofacial surgery*. [Diagnostic / Biomarker]
Karaman V (2026). [PMID: 41705932](https://pubmed.ncbi.nlm.nih.gov/41705932/). *Prenatal diagnosis*. [Epidemiology / Natural History]
Rashidi K (2026). [PMID: 41826279](https://pubmed.ncbi.nlm.nih.gov/41826279/). *Am J Med Genet A*. [Case Report / Case Series]
Onur H (2026). [PMID: 42084887](https://pubmed.ncbi.nlm.nih.gov/42084887/). *Turk Arch Pediatr*. [Basic Science / Preclinical]

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:101600

Orphanet

European rare disease database

Orphanet:710

GARD

Genetic and Rare Diseases Info Center

GARD:7380

Questions for Your Care Team

→Are any of the 1 active clinical trial a good fit for my situation?
→Should I pursue genetic testing for the associated genes, and what would the results mean for my family?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

FAQ

Frequently Asked Questions

Common questions about Pfeiffer syndrome

Pfeiffer syndrome is a form of congenital malformation disorder that affects the skull, hands, and feet. It is part of a group of conditions known as acrocephalosyndactyly. The syndrome is characterized by the early fusion of skull bones (bicoronal craniosynostosis), which can change the shape of the head, as well as various malformations in the hands and feet. People with this condition may also experience other associated features that vary in severity from person to person. These changes occur as part of a genetic condition that has a range of symptoms and physical signs, making each case unique in its presentation.

Common signs of Pfeiffer syndrome include the premature fusion of skull bones, which leads to an altered head shape, and malformations in the hands and feet. Other associated manifestations may also be present, although these can vary significantly among affected individuals.

Pfeiffer syndrome is linked to changes in specific genes, particularly FGFR2 and FGFR1. These genetic variations affect the normal development of bones and other tissues, leading to the range of features seen in the condition. Associated genes include FGFR1, FGFR2.

Kisho

Pfeiffer syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

FGFR1

FGFR2

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

Pfeiffer syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

FGFR1

FGFR2

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

What is Pfeiffer syndrome?

What are the symptoms of Pfeiffer syndrome?

What causes Pfeiffer syndrome?

How is Pfeiffer syndrome inherited?

How rare is Pfeiffer syndrome?

How is Pfeiffer syndrome diagnosed?

Are there treatments for Pfeiffer syndrome?

What complications can arise from Pfeiffer syndrome?

How does Pfeiffer syndrome affect daily life and activities?

What is the life expectancy for someone with Pfeiffer syndrome?

What specialists should be involved in the care of someone with Pfeiffer syndrome?