Complutense University of Madrid, School of Dentistry, 28040, Madrid, Spain.
University of Lisbon, School of Medicine, University Clinic of Stomatology, 1200, Lisbon, Portugal.
Pediatr Res. 2024 May;95(6):1455-1475. doi: 10.1038/s41390-023-02907-5. Epub 2024 Feb 12.
Skeletal Class III (SCIII) is among the most challenging craniofacial dysmorphologies to treat. There is, however, a knowledge gap regarding which syndromes share this clinical phenotype. The aims of this study were to: (i) identify the syndromes affected by the SCIII phenotype; (ii) clarify the involvement of maxillary and/or mandibular structures; (iii) explore shared genetic/molecular mechanisms. A two-step strategy was designed: [Step#1] OMIM, MHDD, HPO, GeneReviews and MedGen databases were explored; [Step#2]: Syndromic conditions indexed in [Step#1] were explored in Medline, Pubmed, Scopus, Cochrane Library, WOS and OpenGrey. Eligibility criteria were defined. Individual studies were assessed for risk of bias using the New Ottawa Scale. For quantitative analysis, a meta-analysis was conducted. This scoping review is a hypothesis-generating research. Twenty-two studies met the eligibility criteria. Eight syndromes affected by the SCIII were targeted: Apert syndrome, Crouzon syndrome, achondroplasia, X-linked hypohidrotic ectodermal dysplasia (XLED), tricho-dento-osseous syndrome, cleidocranial dysplasia, Klinefelter and Down syndromes. Despite heterogeneity between studies [p < 0.05], overall effects showed that midface components were affected in Apert and Down Syndromes, lower face in Klinefelter Syndrome and midface and lower face components in XLED. Our review provides new evidence on the craniofacial characteristics of genetically confirmed syndromes exhibiting the SCIII phenotype. Four major regulatory pathways might have a modulatory effect on this phenotype. IMPACT: What does this review add to the existing literature? To date, there is no literature exploring which particular syndromes exhibit mandibular prognathism as a common trait. Through this research, it was possibly to identify the particular syndromes that share the skeletal Class III phenotype (mandibular prognathism) as a common trait highlighting the common genetic and molecular pathways between different syndromes acknowledging their impact in craniofacial development.
III 类骨骼（SCIII）是最具挑战性的颅面畸形之一。然而，对于哪些综合征具有这种临床表型，目前还存在知识空白。本研究的目的是：（i）确定受 SCIII 表型影响的综合征；（ii）阐明上颌和/或下颌结构的参与；（iii）探索共同的遗传/分子机制。设计了两步策略：[步骤#1] 探索 OMIM、MHDD、HPO、GeneReviews 和 MedGen 数据库；[步骤#2]：在 [步骤#1] 中索引的综合征条件在 Medline、Pubmed、Scopus、Cochrane Library、WOS 和 OpenGrey 中进行了探索。定义了入选标准。使用新渥太华量表评估个体研究的偏倚风险。对于定量分析，进行了荟萃分析。这是一项生成假说的研究。有 22 项研究符合入选标准。针对受 SCIII 影响的 8 种综合征进行了研究：Apert 综合征、Crouzon 综合征、软骨发育不全、X 连锁低汗性外胚层发育不良（XLED）、毛发-牙齿-骨综合征、锁骨颅骨发育不全、克莱恩费尔特综合征和唐氏综合征。尽管研究之间存在异质性[ p < 0.05]，但总体效应表明，Apert 和唐氏综合征的中面部成分受到影响，克莱恩费尔特综合征的下脸受到影响，XLED 的中脸和下脸成分受到影响。本综述提供了关于表现出 SCIII 表型的遗传证实综合征的颅面特征的新证据。四个主要的调节途径可能对这种表型具有调节作用。影响：这篇综述对现有文献有何补充？迄今为止，尚无文献探讨哪些特定综合征表现出下颌前突作为共同特征。通过这项研究，有可能确定具有骨骼 III 类表型（下颌前突）共同特征的特定综合征，突出不同综合征之间的共同遗传和分子途径，承认它们对颅面发育的影响。
