Rai Rabjot, Iwanaga Joe, Dupont Graham, Oskouian Rod J, Loukas Marios, Oakes W Jerry, Tubbs R Shane
Seattle Science Foundation, 550 17th Ave, James Tower, Suite 600, Seattle, WA, 98122, USA.
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA, USA.
Childs Nerv Syst. 2019 Feb 11. doi: 10.1007/s00381-019-04082-7.
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.
法伊弗综合征是一种罕见的常染色体显性遗传性疾病，与颅缝早闭、面中部发育不全以及宽阔的拇指和脚趾有关。根据临床发现，该综合征已分为三种临床亚型。
本综述将特别研究最严重的类型，即法伊弗综合征2型，重点关注其遗传学和分子生物学。
该综合征的这一亚型由新发散发性突变引起，其中大多数发生在成纤维细胞生长因子受体1型和2型（FGFR1/2）基因中。然而，并没有一种特定的突变。这种疾病在遗传上具有异质性，可能有不同的表型表达，在各种情况下与其他类似的颅缝早闭有重叠。已鉴定出一种导致法伊弗综合征和克鲁宗综合征的FGFR2特异性错义突变，研究结果表明基因表达可能受同一基因内多态性的影响。与其他与颅缝早闭相关的疾病相比，法伊弗综合征是最极端的表型，因为潜在的突变对二级和三级蛋白质结构有更广泛的影响，并表现出更严重的临床症状。
