Pfeiffer Syndrome

Pfeiffer Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Pfeiffer Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • acrocephalosyndactyly, type V
  • ACSV
  • Noack syndrome
  • craniofacial-skeletal-dermatologic syndrome

Disorder Subdivisions

  • Pfeiffer syndrome type I
  • Pfeiffer syndrome type II
  • Pfeiffer syndrome type III

General Discussion

Pfeiffer syndrome is a rare genetic disorder characterized by premature fusion of certain skull bones (craniosynostosis), and abnormally broad and medially deviated thumbs and great toes. Most affected individuals also have an abnormal midface, with protruding eyes and conductive hearing loss. Three forms of Pfeiffer syndrome are recognized, of which types II and III are the more serious.



Pfeiffer syndrome is an autosomal dominant condition associated with mutations in the fibroblast growth factor receptor-2 (FGFR2) gene and the fibroblast growth factor receptor-1 (FGFR1) gene.



Pfeiffer syndrome is now known to be a member of a group of conditions caused by mutations in the FGFR genes including Apert syndrome, Crouzon syndrome, Beare-Stevenson syndrome, FGFR2-related isolated coronal synostosis, Jackson-Weiss syndrome, Crouzon syndrome with acanthosis nigricans and Muenke syndrome. (For more information on these conditions, please see the Related Disorders section below.)

Symptoms

Infants with Pfeiffer syndrome type I have craniosynostosis that causes the head to appear short in the AP diameter and tall (turribrachycephaly). Additional craniofacial abnormalities may include a high, full forehead; underdeveloped midfacial regions (midface hypoplasia); widely spaced eyes (ocular hypertelorism); an underdeveloped upper jaw (hypoplastic maxilla), with a prominent lower jaw; and dental abnormalities. Intelligence is usually normal.



Pfeiffer syndrome type II is characterized by a more severe form of craniosynostosis (Cloverleaf skull), and more severe hand and foot anomalies, as well as additional malformations of the limbs. In infants with Pfeiffer syndrome type II, premature closure of the fibrous joints (cranial sutures) between several bones in the skull causes the skull to have a "tri-lobed" appearance (cloverleaf skull deformity, or (Kleeblattschadel type craniosynostosis). In addition, this form of craniosynostosis is often associated with hydrocephalus, a condition in which inhibition of the normal flow of cerebrospinal fluid (CSF) and abnormal widening (dilatation) of the spaces around the brain (ventricles) may cause accumulation of CSF in the skull and increased pressure on the brain. Characteristic craniofacial abnormalities associated with Pfeiffer syndrome type II may include an abnormally high, broad forehead; severe protrusion of the eyes (ocular proptosis); an unusually flat middle portion of the face (midface hypoplasia); a "beak-shaped" nose; and downwardly displaced ears. Affected infants may also exhibit abnormal fixation and lack of mobility (ankylosis) of the elbow joints and/or, in some cases, various malformations of certain internal organs in the abdominal area (visceral anomalies). In addition, infants with Pfeiffer syndrome type II often experience impaired mental development and neurological problems due to severe involvement of the brain, and/or hypoxia due to airway problems. Without appropriate treatment, the physical abnormalities associated with the disorder may lead to life-threatening complications during infancy.



Individuals with Pfeiffer syndrome type III have symptoms and findings similar to those present in Pfeiffer syndrome type II, with the exception of the cloverleaf skull deformity. Additional characteristics associated with Pfeiffer syndrome type III include a shortened base of the skull (anterior cranial base); the abnormal presence of certain teeth at birth (natal teeth); severe protrusion of the eyes (ocular proptosis) due to abnormal shallowness of the bony cavities that accommodate the eyeballs (orbit); and/or various malformations of certain internal organs in the abdominal area (visceral anomalies). As in type II, individuals with Pfeiffer syndrome type III often experience impaired mental development and severe neurological problems and may develop potentially life-threatening complications early in life without appropriate treatment.

Causes

Pfeiffer syndrome is an autosomal dominant genetic disorder. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. Essentially all cases of Pfeiffer syndrome type II and type III have resulted from new mutations. Advanced paternal age is associated with an increased risk for new mutations for Pfeiffer syndrome. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.



Pfeiffer syndrome type I is associated with mutations in the FGFR1 gene and the FGFR2 gene. Pfeiffer syndrome type II and type III are associated with mutations in the FGFR2 gene.

Affected Populations

The incidence of all types of Pfeiffer syndrome is approximately 1/100,000.

Standard Therapies

Diagnosis

The diagnosis of Pfeiffer syndrome is based on clinical findings. Molecular genetic testing for the FGFR1 and FGFR2 genes is available if the diagnosis is uncertain.



Treatment

The treatment of Pfeiffer syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians; surgeons; physicians who diagnose and treat disorders of the ears, nose, and throat (otolaryngologists); neurologists; specialists who assess and treat hearing problems (audiologists); and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.



Specific therapies for Pfeiffer syndrome are symptomatic and supportive. Because craniosynostosis and, in some cases, associated hydrocephalus may result in abnormally increased pressure within the skull (intracranial pressure) and on the brain, early surgery may be advised to correct craniosynostosis and, in the case of hydrocephalus, to insert a tube (shunt) to drain excess cerebrospinal fluid (CSF) away from the brain and into another part of the body where the CSF can be absorbed. Early corrective and reconstructive surgery may also be performed in infants with Pfeiffer syndrome to help correct certain associated craniofacial abnormalities (e.g., midface hypoplasia, facial asymmetry, nasal abnormalities, ocular proptosis due to shallow orbits). According to the medical literature, the results of such craniofacial surgery may vary.



Airway compromise can also occur, especially in very young children. This causes low oxygen levels that can, if unrecognized and untreated, result in brain damage.



In addition, in some cases, reconstructive surgery may be performed to help correct ear malformations and/or specialized hearing aids may be used to improve conductive hearing loss.



In some individuals with Pfeiffer syndrome, surgery may also be conducted to help correct syndactyly and/or other skeletal malformations and improve function and mobility. Physical therapy and additional orthopedic and supportive measures may also be used to help further improve an affected individual's mobility. The surgical procedure(s) performed to correct certain craniofacial, audiological, digital, and/or skeletal abnormalities associated with the disorder will depend upon the severity and location of the anatomical abnormalities and their associated symptoms.



Early intervention may be important to ensure that children with Pfeiffer syndrome reach their potential. Special services that may be beneficial to affected children include special social support, physical therapy, and other medical, social, and/or vocational services.



Genetic counseling is recommended for affected individuals and their families. In addition, thorough clinical evaluations may be important in family members of diagnosed individuals to detect any symptoms and physical characteristics that may be potentially associated with Pfeiffer syndrome.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Muenke M, Wilkie AOM. Craniosynostosis Syndromes. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Vogelstein B (eds) The Metabolic and Molecular Bases of Inherited Disease (OMMBID). New York, NY: McGraw-Hill; 2002:245.



JOURNAL ARTICLES

Hackett A, Rowe L. FGFR1 Pfeiffer syndrome without craniosynostosis: an additional case report. Clin Dysmorphol. 2006;15:207-10.



Stevens CA, Roeder ER. Ser351Cys mutation in the fibroblast growth factor receptor 2 gene results in severe Pfeiffer syndrome. Clin Dysmorphol. 2006;15:187-8.



Oliveira NA, Alonso LG, Fanganiello RD, Passos-Bueno MR. Further evidence of association between mutations in FGFR2 and syndromic craniosynostosis with sacrococcygeal eversion. Birth Defects Res A Clin Mol Teratol. 2006;76:629-33.



Quintero-Rivera F, Robson CD, Reiss RE, et al. Apert syndrome: what prenatal radiographic findings should prompt its consideration? Prenat Diagn. 2006;26966-72.



Itoh S, Nojima M, Yoshida K. Usefulness of magnetic resonance imaging for accurate diagnosis of Pfeiffer syndrome type II in utero. Fetal Diagn Ther. 2006;21:168-71.



Lajeunie E, Heuertz S, El Ghouzzi V, et al. Mutation screening in patients with syndromic craniosynostoses indicates that a limited number of recurrent FGFR2 mutations accounts for severe forms of Pfeiffer syndrome. Eur J Hum Genet. 2006;14:289-8.



Glaser RL, Jiang W, Boyadjiev SA, et al. Paternal origin of FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome. Am J Hum Genet. 2000;66:768-77.



Kress W, Collmann H, Busse M, Halliger-Keller B, Mueller CR. Clustering of FGFR2 gene mutations in patients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses). Cytogenet Cell Genet. 2000;91:134-7.



Robin NH, Scott JA, Arnold JE, et al. Favorable prognosis for children with Pfeiffer syndrome types 2 and 3: implications for classification. Am J Med Genet. 1998;75:240-4.



Tartaglia M, Di Rocco C, Lajeunie E, Valeri S, Velardi F, Battaglia PA. Jackson-Weiss syndrome: identification of two novel FGFR2 missense mutations shared with Crouzon and Pfeiffer craniosynostotic disorders. Hum Genet. 1997;101:47-50.



Winter RM, Reardon W. Lumpers, splitters, and FGFRs. Am J Med Genet. 1996;63(3):501-2.

Moore MH, Cantrell SB, Trott JA, David DJ. Pfeiffer syndrome: a clinical review. Cleft Palate Craniofac J. 1995;32:62-70.



Muenke M, Schell U, Robin NH. et al. Variable clinical spectrum in Pfeiffer syndrome: correlation between phenotype and genotype. Proc Green Genet Ctr. 1995;15:126.



Cohen MM Jr. Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis. Am J Med Genet. 1993;45:300-7.



INTERNET

Robin NH, Falk MJ, Haldeman-Englert CR. (Updated June 7, 2011). FGFR-Related Craniosynostosis Syndromes. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1993-2012. Available at http://www.genetests.org. Accessed April 5, 2012.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. http://omim.org/geneMap/8/158?start=-3&limit=10&highlight=158Pfeiffer Syndrome. Entry No: 101600. Last Edited June 10, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed April 5, 2012.



Vogels A and Fryns J-P. Pfeiffer Syndrome. In: Orphanet Journal of Rare Diseases. http://www.ojrd.com/content/1/1/19. June 1, 2006. Accessed April 5, 2012.

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



FACES: The National Craniofacial Association

PO Box 11082

Chattanooga, TN 37401

Tel: (423)266-1632

Fax: (423)267-3124

Tel: (800)332-2373

Email: faces@faces-cranio.org

Internet: http://www.faces-cranio.org



National Hydrocephalus Foundation

12413 Centralia Rd.

Lakewood, CA 90715-1653

USA

Tel: (562)924-6666

Fax: (562)924-6666

Tel: (888)857-3434

Email: nhf@earthlink.net

Internet: http://www.nhfonline.org



Let's Face It

University of Michigan, School of Dentistry / Dentistry Library

1011 N. University

Ann Arbor, MI 48109-1078

USA

Tel: (360)676-7325

Email: faceit@umich.edu

Internet: http://www.dent.umich.edu/faceit



NIH/National Institute on Deafness and Other Communication Disorders

31 Center Drive, MSC 2320

Communication Avenue

Bethesda, MD 20892-3456

Tel: (301)402-0900

Fax: (301)907-8830

Tel: (800)241-1044

TDD: (800)241-1105

Email: nidcdinfo@nidcd.nih.gov

Internet: http://www.nidcd.nih.gov



Headlines - Craniofacial Support Group

128 Beesmoor Road

Frampton Cotterell

Bristol, BS36 2JP

United Kingdom

Tel: 01454850557

Email: info@headlines.org.uk

Internet: http://www.headlines.org.uk



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



Cleft Lip and Palate Foundation of Smiles

2044 Michael Ave SW

Wyoming, MI 49509

Tel: (616)329-1335

Email: Rachelmancuso09@comcast.net

Internet: http://www.cleftsmile.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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