Craniofacial syndromes and class III phenotype: common genotype fingerprints? A scoping review and meta-analysis

• Published in: Pediatric research 2024-05, Vol.95 (6), p.1455-1475
• Main Authors: Faria-Teixeira, Maria Cristina, Tordera, Cristina, Salvado e Silva, Francisco, Vaz-Carneiro, António, Iglesias-Linares, Alejandro
• Format: Article
• Language: English
• Subjects: Craniofacial Abnormalities - genetics; Down syndrome; Genotype; Genotype & phenotype; Humans; Malocclusion, Angle Class III - genetics; Medical databases; Medicine; Medicine & Public Health; Pediatric Surgery; Pediatrics; Phenotype; Review; Review Article; Syndrome
• ISSN: 0031-3998; 1530-0447; 1530-0447
• DOI: 10.1038/s41390-023-02907-5

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