Rabjot Rai1, Joe Iwanaga2, Graham Dupont1, Rod J Oskouian1,3, Marios Loukas4, W Jerry Oakes5, R Shane Tubbs1,4. 1. Seattle Science Foundation, 550 17th Ave, James Tower, Suite 600, Seattle, WA, 98122, USA. 2. Seattle Science Foundation, 550 17th Ave, James Tower, Suite 600, Seattle, WA, 98122, USA. joei@seattlesciencefoundation.org. 3. Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA, USA. 4. Department of Anatomical Sciences, St. George's University, St. George's, Grenada. 5. Children's of Alabama, Birmingham, AL, USA.
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.
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.
Authors: Leigh C Carmody; Hannah Blau; Daniel Danis; Xingman A Zhang; Jean-Philippe Gourdine; Nicole Vasilevsky; Peter Krawitz; Miles D Thompson; Peter N Robinson Journal: Orphanet J Rare Dis Date: 2020-02-04 Impact factor: 4.123