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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 -
BioMed Research International 2015
Topics: Cleft Palate; Humans
PubMed: 26290872
DOI: 10.1155/2015/701850 -
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 -
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 -
Tissue Engineering. Part B, Reviews Jun 2021Clefts of the lip and/or palate are the most prevalent orofacial birth defects occurring in about 1:700 live human births worldwide. Early postnatal surgical... (Review)
Review
Clefts of the lip and/or palate are the most prevalent orofacial birth defects occurring in about 1:700 live human births worldwide. Early postnatal surgical interventions are extensive and staged to bring about optimal growth and fusion of palatal shelves. Severe cleft defects pose a challenge to correct with surgery alone, resulting in complications and sequelae requiring life-long, multidisciplinary care. Advances made in materials science innovation, including scaffold-based delivery systems for precision tissue engineering, now offer new avenues for stimulating bone formation at the site of surgical correction for palatal clefts. In this study, we review the present scientific literature on key developmental events that can go awry in palate development and the common surgical practices and challenges faced in correcting cleft defects. How key osteoinductive pathways implicated in palatogenesis inform the design and optimization of constructs for cleft palate correction is discussed within the context of translation to humans. Finally, we highlight new osteogenic agents and innovative delivery systems with the potential to be adopted in engineering-based therapeutic approaches for the correction of palatal defects. Impact statement Tissue-engineered scaffolds supplemented with osteogenic growth factors have attractive, largely unexplored possibilities to modulate molecular signaling networks relevant to driving palatogenesis in the context of congenital anomalies (e.g., cleft palate). Constructs that address this need may obviate current use of autologous bone grafts, thereby avoiding donor-site morbidity and other regenerative challenges in patients afflicted with palatal clefts. Combinations of biomaterials and drug delivery of diverse regenerative cues and biologics are currently transforming strategies exploited by engineers, scientists, and clinicians for palatal cleft repair.
Topics: Cleft Palate; Humans; Signal Transduction; Tissue Engineering; Tissue Scaffolds
PubMed: 32873216
DOI: 10.1089/ten.TEB.2020.0181 -
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 -
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 -
Oral Diseases Jul 2022Clefts of the lip and palate (CLP), the major causes of congenital facial malformation globally, result from failure of fusion of the facial processes during... (Review)
Review
Clefts of the lip and palate (CLP), the major causes of congenital facial malformation globally, result from failure of fusion of the facial processes during embryogenesis. With a prevalence of 1 in 500-2500 live births, CLP causes major morbidity throughout life as a result of problems with facial appearance, feeding, speaking, obstructive apnoea, hearing and social adjustment and requires complex, multi-disciplinary care at considerable cost to healthcare systems worldwide. Long-term outcomes for affected individuals include increased mortality compared with their unaffected siblings. The frequent occurrence and major healthcare burden imposed by CLP highlight the importance of dissecting the molecular mechanisms driving facial development. Identification of the genetic mutations underlying syndromic forms of CLP, where CLP occurs in association with non-cleft clinical features, allied to developmental studies using appropriate animal models is central to our understanding of the molecular events underlying development of the lip and palate and, ultimately, how these are disturbed in CLP.
Topics: Cleft Lip; Cleft Palate; Embryonic Development; Face; Humans
PubMed: 35226783
DOI: 10.1111/odi.14174 -
Journal of Dental Research Oct 2017Development of the mammalian secondary palate involves highly dynamic morphogenetic processes, including outgrowth of palatal shelves from the oral side of the embryonic... (Review)
Review
Development of the mammalian secondary palate involves highly dynamic morphogenetic processes, including outgrowth of palatal shelves from the oral side of the embryonic maxillary prominences, elevation of the initially vertically oriented palatal shelves to the horizontal position above the embryonic tongue, and subsequently adhesion and fusion of the paired palatal shelves at the midline to separate the oral cavity from the nasal cavity. Perturbation of any of these processes could cause cleft palate, a common birth defect that significantly affects patients' quality of life even after surgical treatment. In addition to identifying a large number of genes required for palate development, recent studies have begun to unravel the extensive cross-regulation of multiple signaling pathways, including Sonic hedgehog, bone morphogenetic protein, fibroblast growth factor, transforming growth factor β, and Wnt signaling, and multiple transcription factors during palatal shelf growth and patterning. Multiple studies also provide new insights into the gene regulatory networks and/or dynamic cellular processes underlying palatal shelf elevation, adhesion, and fusion. Here we summarize major recent advances and integrate the genes and molecular pathways with the cellular and morphogenetic processes of palatal shelf growth, patterning, elevation, adhesion, and fusion.
Topics: Animals; Cleft Palate; Gene Expression Regulation, Developmental; Humans; Mammals; Morphogenesis; Palate; Signal Transduction; Transcription Factors
PubMed: 28745929
DOI: 10.1177/0022034517703580