Review

Authors: Michael J Dixon, Mary L Marazita, Terri H Beaty...

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

Review

Authors: Mario A Aycart, Edward J Caterson

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

Authors: Pablo Antonio Ysunza, Maria Carmen Pamplona, Gabriela Repetto...

Topics: Cleft Palate; Humans

PubMed: 26290872
DOI: 10.1155/2015/701850

Review

Authors: Marcela Martín-Del-Campo, Raúl Rosales-Ibañez, Luis Rojo...

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

Review

Authors: Elizabeth Gershater, Yuan Liu, Binglan Xue...

Orofacial cleft disorders, including cleft lip and/or palate (CL/P), are one of the most frequently-occurring congenital disorders worldwide. The health issues of patients with CL/P encompass far more than just their anatomic anomaly, as patients with CL/P are prone to having a high incidence of infectious diseases. While it has been previously established that the oral microbiome of patients with CL/P differs from that of unaffected patients, the exact nature of this variance, including the relevant bacterial species, has not been fully elucidated; likewise, examination of anatomic locations besides the cleft site has been neglected. Here, we intended to provide a comprehensive review to highlight the significant microbiota differences between CL/P patients and healthy subjects in various anatomic locations, including the teeth inside and adjacent to the cleft, oral cavity, nasal cavity, pharynx, and ear, as well as bodily fluids, secretions, and excretions. A number of bacterial and fungal species that have been proven to be pathogenic were found to be prevalently and/or specifically detected in CL/P patients, which can benefit the development of CL/P-specific microbiota management strategies.

Topics: Humans; Cleft Lip; Cleft Palate; Nasal Cavity

PubMed: 37143743
DOI: 10.3389/fcimb.2023.1159455

Review

Authors: Jeremie D Oliver, Shihai Jia, Leslie R Halpern...

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

Meta-Analysis

Authors: Matthew Fell, Kyle Dack, Shaheel Chummun...

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

Review

Authors: Pablo Antonio Ysunza, Gabriela M Repetto, Maria Carmen Pamplona...

BACKGROUND

One of the most controversial topics concerning cleft palate is the diagnosis and treatment of velopharyngeal insufficiency (VPI).

OBJECTIVE

This paper reviews current genetic aspects of cleft palate, imaging diagnosis of VPI, the planning of operations for restoring velopharyngeal function during speech, and strategies for speech pathology treatment of articulation disorders in patients with cleft palate.

MATERIALS AND METHODS

An updated review of the scientific literature concerning genetic aspects of cleft palate was carried out. Current strategies for assessing and treating articulation disorders associated with cleft palate were analyzed. Imaging procedures for assessing velopharyngeal closure during speech were reviewed, including a recent method for performing intraoperative videonasopharyngoscopy.

RESULTS

Conclusions from the analysis of genetic aspects of syndromic and nonsyndromic cleft palate and their use in its diagnosis and management are presented. Strategies for classifying and treating articulation disorders in patients with cleft palate are presented. Preliminary results of the use of multiplanar videofluoroscopy as an outpatient procedure and intraoperative endoscopy for the planning of operations which aimed to correct VPI are presented.

CONCLUSION

This paper presents current aspects of the diagnosis and management of patients with cleft palate and VPI including 3 main aspects: genetics and genomics, speech pathology and imaging diagnosis, and surgical management.

Topics: Cleft Palate; Diagnosis, Differential; Diagnostic Errors; Humans; Speech Disorders; Symptom Assessment; Velopharyngeal Insufficiency

PubMed: 26273595
DOI: 10.1155/2015/196240

Authors: Seong Hoon Bae, Jun-Young Kim, Mincheol Jeong...

Although the cleft palate is regarded as a contraindication for Eustachian tube ballooning, the presence of submucosal cleft palate may be overlooked while diagnosing Eustachian tube dysfunction. Therefore, we aimed to determine the incidence of the presence of a hard palate bony notch and vomer defect, which indicate the presence of submucosal cleft palate in patients with Eustachian tube dysfunction. In the Eustachian tube dysfunction group (n = 28), 4 patients (14.3%) exhibited a hard palate bony notch and a concurrent vomer defect. Three of them exhibited the presence of occult submucosal cleft palate, which had not been diagnosed previously. None of the control group (n = 39) showed any of these findings. The hard palate length of patients in the Eustachian tube dysfunction group was significantly lesser than that of those in the control group (34.2 ± 5.6 mm vs. 37.2 ± 2.1 mm, P = 0.016). Patients with Eustachian tube dysfunction have a high incidence of submucosal cleft palate and its occult variant, which are challenging to diagnose without any preexisting suspicion. Clinicians should evaluate the hard palate and vomer to exclude the presence of occult submucosal cleft palate while diagnosing Eustachian tube dysfunction.

Topics: Cleft Palate; Ear Diseases; Eustachian Tube; Humans; Incidence; Palate, Hard; Vomer

PubMed: 35710691
DOI: 10.1038/s41598-022-14011-5

Authors: Omri Emodi, Tal Capucha, Dekel Shilo...

BACKGROUND

The effect of improvement in prenatal identification of cleft lip or palate (CL/P) on termination of pregnancy (TOP) worldwide is scarcely reported. Our aim was to assess changes in the prevalence of cleft palate attributed to the high access and availability of prenatal advanced screening and pregnancy termination in Israel.

METHODS

A retrospective study was conducted on CL/P patients which were treated in our institute and born between January 2000 and December 2018. Clinical and demographic data were extracted from medical records. Data on TOP were collected based on accessible information from the Ministry of Health. Cleft palate severity was evaluated using the Veau Classification.

RESULTS

The study was conducted on 258 patients. Higher incidence of Veau II and III was evident throughout the examined period (2000-2018). However, when evaluating the incidence per year, we found that the incidence of severe cases (Veau III and IV) decreased every year showing a major decline of 60% in the last decade, whereas mild cases (Veau type I and II) demonstrated a marked increase of 90%. Regarding the incidence of abortions in Israel, a decrease of 30% was observed in the last two decades, meanwhile a substantial increase was detected in the rate of abortions related to physical malformations of the fetus. Additionally, the number of late terminations due to physical malformations significantly increased in the last decade.

CONCLUSIONS

Significant decrease was observed in the incidence of severe cleft palate cases in the last decade. Concurrently, we found a substantial increase in percentage of abortions performed due to physical malformations. We suggest that these changes might be attributed to the accessibility of advanced prenatal screening and pregnancy termination in Israel under the social healthcare system.

Topics: Pregnancy; Female; Humans; Cleft Palate; Cleft Lip; Incidence; Retrospective Studies; Ultrasonography, Prenatal; Abortion, Spontaneous

PubMed: 35129039
DOI: 10.1080/14767058.2022.2032635