Child's Nervous System

, Volume 35, Issue 9, pp 1451–1455 | Cite as

Pfeiffer type 2 syndrome: review with updates on its genetics and molecular biology

  • Rabjot Rai
  • Joe IwanagaEmail author
  • Graham Dupont
  • Rod J. Oskouian
  • Marios Loukas
  • W. Jerry Oakes
  • R. Shane Tubbs



Pfeiffer syndrome is a rare autosomal dominant inherited disorder associated with craniosynostosis, midfacial hypoplasia, and broad thumbs and toes. The syndrome has been divided into three clinical subtypes based on clinical findings.


This review will specifically examine the most severe type, Pfeiffer syndrome type 2, focusing on its genetics and molecular biology.


This subtype of the syndrome is caused by de novo sporadic mutations, the majority of which occur in the fibroblast growth factor receptor type 1 and 2 (FGFR1/2) genes. There is not one specific mutation, however. This disorder is genetically heterogeneous and may have varying phenotypic expressions that in various cases have overlapped with other similar craniosynostoses. A specific missense mutation of FGFR2 causing both Pfeiffer and Crouzon syndromes has been identified, with findings suggesting that gene expression may be affected by polymorphism within the same gene. Compared to other craniosynostosis-related disorders, Pfeiffer syndrome is the most extreme phenotype, as the underlying mutations cause wider effects on the secondary and tertiary protein structures and exhibit harsher clinical findings.


Pfeiffer syndrome Acrocephalosyndactyly Craniosynostosis Cloverleaf skull Fibroblast growth factor receptor (FGFR) 


Compliance with ethical standards

The authors have nothing to disclose.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Rabjot Rai
    • 1
  • Joe Iwanaga
    • 1
    Email author
  • Graham Dupont
    • 1
  • Rod J. Oskouian
    • 1
    • 2
  • Marios Loukas
    • 3
  • W. Jerry Oakes
    • 4
  • R. Shane Tubbs
    • 1
    • 3
  1. 1.Seattle Science FoundationSeattleUSA
  2. 2.Swedish Neuroscience Institute, Swedish Medical CenterSeattleUSA
  3. 3.Department of Anatomical SciencesSt. George’s UniversitySt. George’sGrenada
  4. 4.Children’s of AlabamaBirminghamUSA

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