The heterogeneous genetic architectures of orofacial clefts

Kelsey Robinson; Sarah W Curtis; Elizabeth J Leslie

doi:10.1016/j.tig.2024.02.004

The heterogeneous genetic architectures of orofacial clefts

Trends Genet. 2024 May;40(5):410-421. doi: 10.1016/j.tig.2024.02.004. Epub 2024 Mar 13.

Authors

Kelsey Robinson¹, Sarah W Curtis¹, Elizabeth J Leslie²

Affiliations

¹ Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
² Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: ejlesli@emory.edu.

PMID: 38480105
DOI: 10.1016/j.tig.2024.02.004

Abstract

Orofacial clefts (OFCs) are common, affecting 1:1000 live births. OFCs occur across a phenotypic spectrum - including cleft lip (CL), cleft lip and palate (CLP), or cleft palate (CP) - and can be further subdivided based on laterality, severity, or specific structures affected. Herein we review what is known about the genetic architecture underlying each of these subtypes, considering both shared and subtype-specific risks. While there are more known genetic similarities between CL and CLP than CP, recent research supports both shared and subtype-specific genetic risk factors within and between phenotypic classifications of OFCs. Larger sample sizes and deeper phenotyping data will be of increasing importance for the discovery of novel genetic risk factors for OFCs and various subtypes going forward.

Keywords: cleft lip; cleft palate; genetic heterogeneity; orofacial clefts; phenotypic heterogeneity.

Publication types

Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Cleft Lip* / genetics
Cleft Palate* / genetics
Genetic Predisposition to Disease
Humans
Phenotype
Risk Factors