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

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Abstract

Introduction

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.

Methods

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

Conclusion

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.

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Authors and Affiliations

  1. Seattle Science Foundation, 550 17th Ave, James Tower, Suite 600, Seattle, WA, 98122, USA

    Rabjot Rai, Joe Iwanaga, Graham Dupont, Rod J. Oskouian & R. Shane Tubbs

  2. Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA, USA

    Rod J. Oskouian

  3. Department of Anatomical Sciences, St. George’s University, St. George’s, Grenada

    Marios Loukas & R. Shane Tubbs

  4. Children’s of Alabama, Birmingham, AL, USA

    W. Jerry Oakes

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  1. Rabjot Rai
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  2. Joe Iwanaga
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Correspondence to Joe Iwanaga.

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Rai, R., Iwanaga, J., Dupont, G. et al. Pfeiffer type 2 syndrome: review with updates on its genetics and molecular biology. Childs Nerv Syst 35, 1451–1455 (2019). https://doi.org/10.1007/s00381-019-04244-7

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  • DOI: https://doi.org/10.1007/s00381-019-04244-7

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