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Nature Reviews. Genetics Mar 2011Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP can occur in isolation or as part of a broad range of chromosomal, Mendelian or... (Review)
Review
Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP can occur in isolation or as part of a broad range of chromosomal, Mendelian or teratogenic syndromes. Although there has been marked progress in identifying genetic and environmental triggers for syndromic CLP, the aetiology of the more common non-syndromic (isolated) forms remains poorly characterized. Recently, using a combination of epidemiology, careful phenotyping, genome-wide association studies and analysis of animal models, several distinct genetic and environmental risk factors have been identified and confirmed for non-syndromic CLP. These findings have advanced our understanding of developmental biology and created new opportunities for clinical translational research.
Topics: Animals; Cleft Lip; Cleft Palate; Environment; Female; Gene Expression Regulation; Genome-Wide Association Study; Humans; Male; Mice; Mutation
PubMed: 21331089
DOI: 10.1038/nrg2933 -
American Journal of Medical Genetics.... Nov 2013Orofacial clefts are common birth defects and can occur as isolated, nonsyndromic events or as part of Mendelian syndromes. There is substantial phenotypic diversity in... (Review)
Review
Orofacial clefts are common birth defects and can occur as isolated, nonsyndromic events or as part of Mendelian syndromes. There is substantial phenotypic diversity in individuals with these birth defects and their family members: from subclinical phenotypes to associated syndromic features that is mirrored by the many genes that contribute to the etiology of these disorders. Identification of these genes and loci has been the result of decades of research using multiple genetic approaches. Significant progress has been made recently due to advances in sequencing and genotyping technologies, primarily through the use of whole exome sequencing and genome-wide association studies. Future progress will hinge on identifying functional variants, investigation of pathway and other interactions, and inclusion of phenotypic and ethnic diversity in studies.
Topics: Brain; Cleft Lip; Cleft Palate; Exome; Genome-Wide Association Study; Genotype; Humans; Phenotype; Sequence Analysis, DNA
PubMed: 24124047
DOI: 10.1002/ajmg.c.31381 -
Plastic and Reconstructive Surgery Jul 2021Secondary cleft rhinoplasty presents some of the most challenging cases of both cosmetic and functional nasal deformities. Understanding the anatomy and growth... (Review)
Review
BACKGROUND
Secondary cleft rhinoplasty presents some of the most challenging cases of both cosmetic and functional nasal deformities. Understanding the anatomy and growth abnormality seen with the cleft nasal deformity helps to tailor surgical management. This article seeks to expand on the application of current concepts in secondary rhinoplasty for unilateral cleft lip nasal deformity.
METHODS
The authors review nasal analysis in the cleft rhinoplasty patient and provide the surgical management for each aspect in the secondary cleft rhinoplasty.
RESULTS
The secondary rhinoplasty was divided into seven areas: piriform hypoplasia, septal reconstruction, dorsal reshaping, tip reshaping, tip projection, alar reshaping, and alar repositioning. Surgical management for each is provided.
CONCLUSION
Secondary cleft rhinoplasty requires an understanding of the structural dysmorphology, and the use of cosmetic, functional, and secondary rhinoplasty techniques for its successful management.
Topics: Cleft Lip; Esthetics; Humans; Nasal Cartilages; Nasal Septum; Reoperation; Rhinoplasty; Treatment Outcome
PubMed: 34076624
DOI: 10.1097/PRS.0000000000008124 -
International Journal of Molecular... May 2019Craniofacial bone defect anomalies affect both soft and hard tissues and can be caused by trauma, bone recessions from tumors and cysts, or even from congenital... (Review)
Review
Craniofacial bone defect anomalies affect both soft and hard tissues and can be caused by trauma, bone recessions from tumors and cysts, or even from congenital disorders. On this note, cleft/lip palate is the most prevalent congenital craniofacial defect caused by disturbed embryonic development of soft and hard tissues around the oral cavity and face area, resulting in most cases, of severe limitations with chewing, swallowing, and talking as well as problems of insufficient space for teeth, proper breathing, and self-esteem problems as a consequence of facial appearance. Spectacular advances in regenerative medicine have arrived, giving new hope to patients that can benefit from new tissue engineering therapies based on the supportive action of 3D biomaterials together with the synergic action of osteo-inductive molecules and recruited stem cells that can be driven to the process of bone regeneration. However, few studies have focused on the application of tissue engineering to the regeneration of the cleft/lip and only a few have reported significant advances to offer real clinical solutions. This review provides an updated and deep analysis of the studies that have reported on the use of advanced biomaterials and cell therapies for the regeneration of cleft lip and palate regeneration.
Topics: Animals; Biocompatible Materials; Cleft Lip; Cleft Palate; Folic Acid; Humans; Intercellular Signaling Peptides and Proteins; Osteogenesis; Regenerative Medicine; Stem Cell Transplantation; Tissue Engineering
PubMed: 31052503
DOI: 10.3390/ijms20092176 -
Medicina (Kaunas, Lithuania) Nov 2023Cleft lip with or without cleft palate is one of the most common congenital malformations, with an average prevalence of 1 in 1000 live births. Cleft lip and/or palate... (Review)
Review
Cleft lip with or without cleft palate is one of the most common congenital malformations, with an average prevalence of 1 in 1000 live births. Cleft lip and/or palate is incredibly phenotypically diverse, with constant advancements and refinements in how we care for patients. This article presents an in-depth review of the latest advances and current evidence in cleft lip and palate surgery. This includes presurgical infant orthopedics, perioperative practice patterns including use of enhanced recovery after surgery (ERAS) protocols, patient-reported outcome measures, and the latest adjuncts in cheiloplasty and palatoplasty.
Topics: Infant; Humans; Cleft Lip; Cleft Palate; Plastic Surgery Procedures; Orthopedic Procedures
PubMed: 38003981
DOI: 10.3390/medicina59111932 -
Oral Diseases Jul 2022This systematic review compared children's primary dentition caries experience for those with cleft lip and/or palate (CL/P) and without. Four databases were searched... (Meta-Analysis)
Meta-Analysis Review
This systematic review compared children's primary dentition caries experience for those with cleft lip and/or palate (CL/P) and without. Four databases were searched without date restriction for; cross-sectional studies comparing caries experience for children with CL/P to those without. Screening, data extraction and risk assessment were carried out independently (in duplicate). Meta-analyses used a random-effects model. Twenty studies (21 reports) fitting the inclusion criteria comprised 4647 children in primary dentition from 12 countries. For dmft (n = 3016 children; 15 groups), CL/P mean = 3.2; standard deviation = 2.22 and no CL/P mean dmft = 2.5; sd 1.53. For dmfs (n = 1095 children; 6 groups), CL/P mean = 4; sd = 3.5 and no CL/P mean = 3; sd = 2.8. For % caries experience (n = 1094 children; 7 groups), CL/P mean = 65%; sd = 20.8 and no CL/P mean = 52%; sd = 28.1. Meta-analysis showed higher caries experience in children with CL/P, standardised mean difference = 0.46; 95% CI = 0.15, 0.77. Studies' risk of bias was high (n = 7), medium (n-10) and low (n = 3). Children with CL/P had higher caries experience compared to those without CLP.
Topics: Child; Cleft Lip; Cleft Palate; Cross-Sectional Studies; Dental Caries; Dental Caries Susceptibility; Humans
PubMed: 35263806
DOI: 10.1111/odi.14183 -
Journal of the World Federation of... Oct 2020A child born with a cleft lip and palate will face 20 years or more of hospital care and surgery. This is a global problem with approximately 10 million people affected...
A child born with a cleft lip and palate will face 20 years or more of hospital care and surgery. This is a global problem with approximately 10 million people affected worldwide. Various models of care exist around the condition, and the best configurations of services within an economy need to be optimized. We provide examples of how centralized care can improve outcomes and provide an opportunity to establish national registries, and then emphasize the opportunities for building research platforms of relevance. The default of any cleft service should be to centralize care and enable cleft teams with a sufficient volume of patients to develop proficiency and measure the quality of outcomes. The latter needs to be benchmarked against the better centers in Europe. Two areas of concern for those with cleft are morbidity/mortality and educational attainment. These two issues are placed in context within the literature and wider approaches using population genetics. Orthodontists have always played a key role in developing these initiatives and are core members of cleft teams with major responsibilities for these children and their families.
Topics: Child; Cleft Lip; Cleft Palate; Europe; Humans; Research Design
PubMed: 33023731
DOI: 10.1016/j.ejwf.2020.09.003 -
International Journal of Molecular... Oct 2022Orofacial clefts are among the most common craniofacial anomalies with multifactorial etiologies, including genetics and environments. DNA methylation, one of the most... (Review)
Review
Orofacial clefts are among the most common craniofacial anomalies with multifactorial etiologies, including genetics and environments. DNA methylation, one of the most acknowledged mechanisms of epigenetics, is involved in the development of orofacial clefts. DNA methylation has been examined in patients with non-syndromic cleft lip with cleft palate (nsCL/P) from multiple specimens, including blood, saliva, lip, and palate, as well as experimental studies in mice. The results can be reported in two different trends: hypomethylation and hypermethylation. Both hypomethylation and hypermethylation can potentially increase the risk of nsCL/P depending on the types of specimens and the specific regions on each gene and chromosome. This is the most up-to-date review, intending to summarize evidence of the alterations of DNA methylation in association with the occurrence of orofacial clefts. To make things straightforward to understand, we have systematically categorized the data into four main groups: human blood, human tissues, animal models, and the factors associated with DNA methylation. With this review, we are moving closer to the core of DNA methylation associated with nsCL/P development; we hope this is the initial step to find a genetic tool for early detection and prevention of the occurrence of nsCL/P.
Topics: Humans; Mice; Animals; Cleft Lip; Cleft Palate; DNA Methylation; Epigenomics
PubMed: 36361518
DOI: 10.3390/ijms232112727 -
Stem Cell Research & Therapy Sep 2022Regularly discarded lip tissue obtained from corrective surgeries to close the cleft lip represents an easily accessible and rich source for the isolation of primary...
BACKGROUND
Regularly discarded lip tissue obtained from corrective surgeries to close the cleft lip represents an easily accessible and rich source for the isolation of primary fibroblasts. Primary fibroblasts have been described to show compelling similarities to mesenchymal stem cells (MSCs). Hence, cleft lip and palate (CLP) lip-derived fibroblasts could be thought as an intriguing cell source for personalized regenerative therapies in CLP-affected patients.
METHODS
Initially, we thoroughly characterized the fibroblastic nature of the lip-derived mesenchymal outgrowths by molecular and functional assays. Next, we compared their phenotype and genotype to that of bone marrow-mesenchymal stem cells (BM-MSCs) and of human lung-derived fibroblasts WI38, by assessing their morphology, surface marker expression, trilineage differentiation potential, colony-forming (CFU) capacity, and immunomodulation property. Finally, to better decipher the heterogeneity of our CLP cultures, we performed a single cell clonal analysis and tested expanded clones for surface marker expression, as well as osteogenic and CFU potential.
RESULTS
We identified intriguingly similar phenotypic and genotypic properties between CLP lip fibroblasts and BM-MSCs, which makes them distinct from WI38. Furthermore, our own data in combination with the complex anatomy of the lip tissue indicated heterogeneity in our CLP cultures. Using a clonal analysis, we discovered single cell-derived clones with increased levels of the MSC markers CD106 and CD146 and clones with variabilities in their commitment to differentiate into bone-forming cells and in their potential to form single cell-derived colonies. However, we were not able to gain clones possessing superior MSC-like capacities when compared to the heterogeneous parental CLP population. Additionally, all clones could still generate contractile forces and retained robust levels of the fibroblast specific marker FSP1, which was not detectable in BM-MSCs.
CONCLUSIONS
Our results suggest that we isolate heterogeneous populations of fibroblasts from discarded CLP lip tissue, which show a prominently multipotent character in their entirety avoiding the need for elaborate subpopulation selections in vitro. These findings suggest that CLP lip fibroblasts might be a novel potential cell source for personalized regenerative medicine of clinical benefit for CLP patients.
Topics: Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Cleft Lip; Cleft Palate; Fibroblasts; Humans; Mesenchymal Stem Cells
PubMed: 36076255
DOI: 10.1186/s13287-022-03154-x -
The Cleft Palate-craniofacial Journal :... Sep 2022A systematic review and meta-analysis to determine the association between active maternal smoking and cleft lip and palate etiology. Medline, Embase, Web of Science and... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis to determine the association between active maternal smoking and cleft lip and palate etiology. Medline, Embase, Web of Science and the Cochrane Library from inception to November, 2020. Observational studies of cigarette smoking habits in pregnant women. Outcomes included cleft lip and/or palate, cleft lip ± palate and cleft palate only. Publication bias analyses were performed and the Newcastle Ottawa scales were used to assess study quality. Fixed or random effect models were used in the meta-analysis, dependent on risk of statistical heterogeneity. Forty-five studies were eligible for inclusion of which 11 were cohort and 34 were case-control studies. Sixteen studies were of sufficient standard for inclusion in the meta-analysis. The summary odds ratio for the association between smoking and cleft lip and/or palate was 1.42 (95%CI 1.27-1.59) with a population attributable fraction of 4% (95%CI 3%-5%). There was limited evidence to show a dose-response effect of smoking. This review reports a moderate association between maternal smoking and orofacial cleft but the overall quality of the conventional observational studies included was poor. There is a need for high quality and novel research strategies to further define the role of smoking in the etiology of cleft lip and palate.
Topics: Cigarette Smoking; Cleft Lip; Cleft Palate; Female; Humans; Pregnancy; Prenatal Exposure Delayed Effects; Smoking
PubMed: 34569861
DOI: 10.1177/10556656211040015