Cleft Palate Cases Research Articles

Rare variants found in clinical gene panels illuminate the genetic and allelic architecture of orofacial clefting

PurposeOrofacial clefts (OFCs) are common birth defects including cleft lip, cleft lip and palate, and cleft palate. OFCs have heterogeneous etiologies, complicating clinical diagnostics because it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or sporadic OFCs; therefore, we estimated the diagnostic yield for 418 genes in 841 cases and 294 controls. MethodsWe evaluated 418 genes using genome sequencing and curated variants to assess their pathogenicity using American College of Medical Genetics criteria. Results9.04% of cases and 1.02% of controls had “likely pathogenic” variants (P < .0001), which was almost exclusively driven by heterozygous variants in autosomal genes. Cleft palate (17.6%) and cleft lip and palate (9.09%) cases had the highest yield, whereas cleft lip cases had a 2.80% yield. Out of 39 genes with likely pathogenic variants, 9 genes, including CTNND1 and IRF6, accounted for more than half of the yield (4.64% of cases). Most variants (61.8%) were “variants of uncertain significance”, occurring more frequently in cases (P = .004), but no individual gene showed a significant excess of variants of uncertain significance. ConclusionThese results underscore the etiological heterogeneity of OFCs and suggest sequencing could reduce the diagnostic gap in OFCs.

Relationship Between Cleft Lip and Palate Followed by Osteogenesis Imperfecta Accompanied by Tetralogy of Fallot in Children with a Maternal History of Catatonic Schizophrenia with Valproic Acid Therapy and Diabetes Mellitus

Researchers believe that most cases of cleft lip and cleft palate are caused by genetic and environmental factors. Nevertheless, the exact cause was not found. Nevertheless there are allegations that the condition of the cleft lip and palate has something to do with osteogenesis imperfecta with the heterozygous mutation COL1A2 and the formation of triple helix DNA accompanied by Tetralogy of Fallot in children with a maternal history of catatonic schizophrenia followed by the use of valproic acid and type II diabetes mellitus. Then, it is also found in babies with cleft lip and sky conditions usually accompanied by other congenital anomaly, but not always. This then further gives rise to speculation that there are links between the above variables and the cleft lip and palate. Therefore. Knowing the Relationship Between Cleft Lip and Palate Events with osteogenesis imperfecta with heterozygous mutation COL1A2 and triple helix DNA formation accompanied by Tetralogy of Fallot in children with a maternal history of catatonic schizophrenia followed by the use of valproic acid and type II diabetes mellitus. This research is a Systematic Review using the Preferred Reporting Items for Systematic Reviews and Meta-analyses method or commonly called PRISMA, this method is carried out systematically by following the correct research stages or protocols. The source was taken from the Google Scholar site with journals published in 2017-2023 and then screened the results of 1,870 journals. Journal clustering was carried out and the number of Q1 indexed journals was obtained in 4 journals, Q3 in 1 journal, and Q4 in 1 journal so that there were 6 journals extracted. The entire journal does not directly discuss the relationship between the research variables, but only provides an overview of the increased risk of celestial cleft conditions in babies if the expectant mother has type 2 diabetes mellitus conditions, osteogenesis imperfect, and the relationship of the two health conditions to the possibility of birth of the baby with the Tetralogy of Fallot condition, as well as the relationship of the baby to the condition of the cleft lip and palate and tetralogy of fallot

Addition of a Buccinator Musculomucosal Flap Improves Surgical Outcomes of Conventional two-Flap Palatoplasty: A Comparative Study.

The surgical outcomes of novel two-flap palatoplasty adding a buccinator musculomucosal flap were compared with those of conventional two-flap palatoplasty to clarify the effects of lengthening the nasal mucosa of the soft palate using a BMMF in cleft lip and palate or cleft palate cases. Retrospective, comparative study. Tertiary, cleft team. Non-syndromic patients undergoing primary cleft palate repair using two-flap palatoplasty with BMMF (BMMF group) or conventional two-flap palatoplasty (non-BMMF group). Palatoplasty between January 2012 and March 2020. Perceptual Japanese speech evaluation, rate of an indication for additional speech surgery (AS), rate of incidence of oronasal fistula (IF) including spontaneously closing fistula, and rate of occurrence of oronasal fistula (OF) present for more than 3 months. Of 92 analyzed patients, 70 received two-flap palatoplasty with BMMF and 22 received two-flap palatoplasty. In the BMMF and non-BMMF groups, the respective percentage of hypernasality (no, mild) was 91.4% and 77.2%, no nasal emission was 71.4% and 63.6%, velopharyngeal function (competent, borderline competent) was 83.7% and 77.4%, intelligibility (very good, good) was 93.7% and 86.4%, AS was 1.4% and 13.6%, IF was 7.1% and 36.4%, and OF was 1.4% and 9.1%. Significant improvements were observed for AS (p = 0.0412) and IF (p = 0.00195) in the BMMF group, with no recorded major adverse effects. Adding a BMMF on the nasal side of the soft palate to conventional two-flap palatoplasty significantly improved postoperative outcomes. This approach may therefore be a good option for cleft palate treatment.

A multi-program analysis of cleft lip with cleft palate prevalence and mortality using data from 22 International Clearinghouse for Birth Defects Surveillance and Research programs, 1974-2014.

Cleft lip with cleft palate (CLP) is a congenital condition that affects both the oral cavity and the lips. This study estimated the prevalence and mortality of CLP using surveillance data collected from birth defect registries around the world. Data from 22 population- and hospital-based surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) in 18 countries on live births (LB), stillbirths (SB), and elective terminations of pregnancy for fetal anomaly (ETOPFA) for CLP from 1974 to 2014 were analyzed. Prevalence and survival (survival for LB only) estimates were calculated for total and subclassifications of CLP and by pregnancy outcome. The pooled prevalence of total CLP cases was 6.4 CLP per 10,000 births. The prevalence of CLP and all of the pregnancy outcomes varied across programs. Higher ETOPFA rates were recorded in most European programs compared to programs in other continents. In programs reporting low ETOPFA rates or where there was no ascertainment of ETOPFA, the rate of CLP among LB and SB was higher compared to those where ETOPFA rates were ascertained. Overall survival for total CLP was 91%. For isolated CLP, the survival was 97.7%. CLP associated with multiple congenital anomalies had an overall survival of 77.1%, and for CLP associated with genetic/chromosomal syndromes, overall survival was 40.9%. Total CLP prevalence reported in this study is lower than estimates from prior studies, with variation by pregnancy outcomes between programs. Survival was lower when CLP was associated with other congenital anomalies or syndromes compared to isolated CLP.

Prevalence of Dental Anomalies in Non-syndromic Cleft Lip And Palate Patients in Erbil City (an Orthopantomogramic Study)

Background and objectives: Cleft lip and palate deformity is one of the highly frequent and most difficult problems arising in the orthodontic clinics, one of the problems associated with these deformities is the dental anomalies presented as defect in the number and eruption process, this study aimed to find the prevalence of these dental anomalies in the cleft lip and palate patients in Erbil city. Method: One hundred orthopantomograms out of 167 cleft lip and palate patients examined by a well-trained orthodontist for the presence of hypodontia, supernumerary teeth and any impactions and arranged according to the age, gender and the grouping of the deformity whether involving the alveolus or its unilateral or bilateral clefts then analyzed using statistical packages. Results: Prevalence of dental anomalies involved a total of 271 dental anomalies distributed between the most frequent anomaly, starting with hypodontia (139) teeth missed, Impactions (103) teeth impacted and Supernumerary of a total (29) teeth, (96%) of the cases examined has at least one dental anomaly. Conclusion: Dental anomalies commonly present with cleft lip and palate cases in Erbil city, orthodontists should consider these anomalies for managing such cases

Using a New Deep Learning Method for 3D Cephalometry in Patients With Cleft Lip and Palate.

Deep learning algorithms based on automatic 3-dimensional (D) cephalometric marking points about people without craniomaxillofacial deformities has achieved good results. However, there has been no previous report about cleft lip and palate. The purpose of this study is to apply a new deep learning method based on a 3D point cloud graph convolutional neural network to predict and locate landmarks in patients with cleft lip and palate based on the relationships between points. The authors used the PointNet++ model to investigate the automatic 3D cephalometric marking points. And the mean distance error of the center coordinate position and the success detection rate (SDR) were used to evaluate the accuracy of systematic labeling. A total of 150 patients were enrolled. The mean distance error for all 27 landmarks was 1.33mm, and 9 landmarks (30%) showed SDRs at 2mm over 90%, and 3 landmarks (35%) showed SDRs at 2mm under 70%. The automatic 3D cephalometric marking points take 16 seconds per dataset. In summary, our training sets were derived from the cleft lip with/without palate computed tomography to achieve accurate results. The 3D cephalometry system based on the graph convolutional neural network algorithm may be suitable for 3D cephalometry system in cleft lip and palate cases. More accurate results may be obtained if the cleft lip and palate training set is expanded in the future.

Radiographic Evaluation of Position and Angulation of Impacted Maxillary Canines in Cleft Palate Cases

Objective: To evaluate the position and angulation of impacted maxillary canines in unilateral and bilateral cleft lip and palate cases and compare them to noncleft cases. Material and method: In this study 60 patients OPGs were taken out of which 20 (12 males, 8 females) presented with unilateral cleft lip and palate (UCLP) (Group I), 20 (15 males, 5 females) had bilateral cleft lip and palate (BCLP) (Group II) and 20 (13 males, 7 females) had no clefts (Group III). All the subjects had impacted maxillary canines (bilateral or unilateral). Cases with 2/3rd canine root completion were selected. Intruis suite R2 software was used to determine the position and angulation of the canine. Results: A total of 63% (37) of the canines were in Sector 1, and 31% (18) were in Sector 2. In-depth of canine impaction relative to the root of the incisor maximum canines were in Grade II and Grade III at 45% (27) and 36% (22) respectively. Angulation of the canine relative to the intercondylar line was seen most in Group II (75%) and (19%) in Group I as compared to the noncleft group (Group III). No difference was seen in the position of canine impaction for buccally and palatally canines and for the unilateral and bilateral cleft groups or the noncleft and cleft groups. Conclusions: The majority of the impacted canines had cusp tips located in sectors II and III. In almost all cases, angulation did not increase the prediction of eventual impaction, although it may have contributed slightly in Sector II.

Initiation to the management of a case of cleft lip and palate in Madagascar: Naso-Alveolar Molding

Introduction: Cleft lip and palate represent the most common facial anomaly in the world, with a prevalence of 4.66‰ in Madagascar in 2016. These malformations constitute aesthetic, functional and social damage. Pre-surgical orthodontic management has not yet been applied in Madagascar. The objective of our study was to report the case of a patient with a cleft lip and palate treated pre-surgically by "Naso-Alveolar Molding". Observation: This is a 3-month-old male child with a bilateral nasolabio-alveolar cleft associated with a total secondary cleft. The initial exo-buccal examination revealed 15mm (left) and 16mm (right) nasal cleft widths, 6mm (left) and 5mm (right) lip cleft widths. The intraoral examination showed 3mm (left) and 4mm (right) of alveolar cleft widths. The treatment consisted of the placement of “Naso-Alveolar Molding”. The evolution having been favorable after a month marked by the reduction of the width of the slits and an aesthetic improvement exo-buccal. Discussion: Pre-surgical orthodontics is performed in infancy to facilitate feeding, reduce cleft width, and reposition deformed nasal cartilages and alveolar processes; to lengthen the deficient columella in the neonatal period. The main objective being to minimize the extent of surgery that would have to be performed. The malleability of the nasal cartilage at the infantile stage indicates the orthodontist to its conception and to ensure a favorable prognosis. Conclusion: The treatment of cleft lip and palate consists of a multidisciplinary approach including Dento-Facial Orthopedics.

Updated Evidence in Management of Cleft Lip and Palate: Simple Review Article

The most common oro-facial congenital deformity reported in live newborns is a cleft of the lip, palate, or both. The objective of this study was to&nbsp;the&nbsp;updates in management, and outcomes of cases of cleft lip and/or palate. PubMed and EBSCO Information Services&nbsp;will be&nbsp;chosen as the search databases for the publications used within the study. Topics concerning&nbsp;the&nbsp;updates in management, and outcomes of cases of cleft lip and/or palate, published in English around

A retrospective study on clinical and epidemiological profile of nonsyndromic cleft lip and palate patients admitted in a large Comprehensive Cleft Care Centre in West Bengal, India

Aim: The aim of this study is to observe the clinical and epidemiological profile of nonsyndromic cleft lip (CL) and/or palate patients admitted to a cleft care center in West Bengal from May 2021 to April 2022. Materials and Methods: A retrospective epidemiological study had been done by preparing a master data sheet to record the patient's data from a Comprehensive Cleft Care Centre in West Bengal. The study variables included were patient's age reporting at the hospital, type of cleft, sex distribution of patients, residential address of the parents, socioeconomic status through parents' education, occupation, and monthly income, and consanguineous marriage history of the family. Results: A total of 276 nonsyndromic cleft patients during the time period (May 2021 to April 2022) were considered. Among these, 164 were male and 112 were female patients. The mean age of patients reporting to this hospital on average was 13–18 months. CL with palate patients (62%) predominated than any other type and was mostly seen in male patients (69.59%); isolated CL (22%) cases were more in females (56.25%), whereas isolated cleft palate (16%) cases were seen more in males (62.79%); unilateral (77%) and left-sided cleft (67%) were found predominantly than bilateral cases (23%) and seen mostly in females, whereas bilateral cleft cases were more in males. Most of the patients belonged to North 24 Parganas District which is an adjacent district of Kolkata, and most of the families belonged to a low socioeconomic group, and interestingly, most of them had consanguineous marriage history (61%) with at least one generation. Conclusion: The results of this study provided that CL with palate type is more common among all types of clefts and predominantly found in males than females in West Bengal. The unilateral left-sided cleft is predominant among all other varieties. Most of the parents belonged to low socioeconomic status and are having consanguineous marriage history. We need to spread awareness among the public through ads and banners, social media, and medical free camps about the deformity of CL and/or palate and also possible preventive measures, make arrangements for free treatment among the CL and/or CL and palate population for better life of cleft patients and their parents.

Clinical Characteristics of the Cleft Lip and/or Palate: Association with Congenital Anomalies, Syndromes, and Chromosomal Anomalies.

Cleft lip and/or palate (CL/P) can be accompanied by other congenital anomalies. We conducted a long-term evaluation of the associations between cleft patterns, sex distribution, and accompanying congenital anomalies of patients with CL/P. The medical records of 739 patients with CL/P, seen between January 1967 and December 2020, were retrospectively reviewed. Fisher's exact test was used for statistical analysis. Among the 739 patients with CL/P, the male-to-female ratio was 1.1. Regarding the cleft pattern, 121 (16.4%), 104 (14.1%), 280 (37.9%), 198 (26.8%), and 36 (4.9%) patients had cleft lip (CL), cleft lip and alveolus (CLA), cleft lip and palate (CLP), cleft palate (CP), and submucous cleft palate (SMCP), respectively. Congenital anomalies were identified in 107 (14.5%) cases, of which 53 (49.5%) had congenital heart disease. The frequencies of congenital anomalies patients with in CL/P were 14/225 (6.2%), 36/280 (12.9%), 43/198 (21.7%), and 14/36 (38.9%) for a combination of CL and CLA, CLP, CP, and SMCP, respectively. Accompanying syndromes and chromosomal anomalies were identified in 40 (5.4%) cases, in which Pierre Robin sequence (16 cases of CP and 4 cases of SMCP) was the most frequent. No sex differences were observed in CL/P, and CLP and CP were the most common cleft patterns. Congenital anomalies associated with CL/P were dominated by congenital heart disease and were most frequently identified in CP and SMCP cases. Notably, the Pierre Robin sequence, a complex syndrome characterized by micrognathia, glossoptosis, respiratory obstruction, and a U- or V-shaped CP, was found in cases of both CP and SMCP, and accounted for the symptoms in most cases.

Prosthetic Rehabilitation of Completely Edentulous Unrepaired Cleft Palate Patient with Implant Supported Hader Bar and Clips: A Case Report

Prosthetic rehabilitation of an edentulous cleft lip and palate patient with a combined hard and soft palate defect is a great challenge, due to the lack of retention of the obturator prosthesis as a result of its weight and the inability to obtain a border seal. Dental implants improve the retention, stability, and occlusal function of prostheses when used in carefully selected cleft lip and palate cases. This clinical report presents an edentulous unilateral cleft lip and palate patient who has hard and soft palate defects and an atrophied maxilla, treated with an implant-supported speech-aid prosthesis Prosthetic rehabilitation of an edentulous cleft lip and palate patient with a combined hard and soft palate defect is a great challenge, due to the lack of retention of the obturator prosthesis as a result of its weight and the inability to obtain a border seal. Dental implants improve the retention, stability, and occlusal function of prostheses when used in carefully selected cleft lip and palate cases. The prosthetic rehabilitation of edentulous patient with unrepaired cleft palate poses a great challenge due to both hard and soft tissue defect compromising retention, support and stability of the obturator due to inability to obtain border seal and heavy weight. In carefully selected patient use of osseointegrated implant along with the bars and clips supporting and retaining maxillary overdentures on implants play a significant role in their efficacy. This clinical report presents an edentulous unilateral cleft palate patient treated with an implant-supported Hader bar and clips.

Prevalence of Simonart's band in cleft children at a cleft center in Indonesia: A nine-year retrospective study.

Simonart's band is a soft tissue band that connects the cleft gap of the base of the nostril or the margin of the alveolus. While research on the prevalence of Simonart's band in cleft lip and palate cases has been carried out in various countries, research on Simonart's band in Indonesia has yet to be conducted. This study aimed to determine the prevalence of different types of Simonart's band at a cleft center in Indonesia. The data of cleft patients were reviewed retrospectively over a 9-year period at the Cleft Lip and Palate Center Center, Harapan Kita Women and Children Hospital, Jakarta, Indonesia. The patients were divided based on the type of cleft and the type of Simonart's band. The results were analyzed by means of descriptive statistics. Out of 638 cleft patients from the period 2008-2016, 77 patients had Simonart's band. The liptolip band was most commonly found (52 cases, 67.5%). The lip-to-alveolus band was found in 20 cases (26.0%) and the alveolus-to-alveolus band had the lowest prevalence of 5 cases (6.5%). Associations between the cleft type (unilateral cleft lip and palate (UCLP), unilateral cleft lip and alveolus (UCLA), and bilateral cleft lip and palate (BCLP)) and Simonart's band type were all significant (p = 0.001, according to Fisher's exact test), which indicates significant differences in the distribution of the bands with regard to different cleft types. There was a significant difference in the distribution of the bands between the UCLP and UCLA groups (p = 0.000). On the other hand, the distribution of the bands in the UCLP group did not differ much from that in the BCLP group (p = 0.065). The prevalence of Simonart's band was significantly higher in the patients with the unilateral complete cleft of the primary and secondary palate than in the subjects with the cleft of the primary palate. In the UCLP group, most patients had the lip-to-lip band type. In the BCLP group, the majority also had the lip-to-lip band type. In contrast, in the UCLA group, the majority showed the lip-to-alveolus band type.

Analysis of Variations in Maxillary Second Molar Buccopalatal Inclination in Angle's Class I, Angle's Class III Malocclusion, and Unilateral Cleft Lip and Palate (UCLP) Cases: A Comparative Observational Study.

Introduction Cleft of the lip and/or the palate iscommonly inheriteddefect which involves cleft of lip and palate. Maxillary second molar inclination has been studied in various malocclusion. Every abnormality in body is compensated to some extend by compensation. Our objectives were to evaluate maxillary second molar inclination in Angle's Class I, Class III malocclusion, and unilateral cleft lip and palate (UCLP) patients in transverse plane and to compare variation in maxillary second molar inclination in Angle's Class I, Class III malocclusion, and UCLP cases buccopalatally in transverse plane. Material and method Model of 45 subjects were analyzed.The maxillary second molar inclination was measured using aid of protractor fixed on the surveyor. Axis under consideration was the axis along the long axis of the central fossa of maxillary second molar. Various standardization regarding measurement of second molar inclination were set. The maxillary second molar inclination was compared among 3 groups Angle's Class I, Class III malocclusion, and UCLP cases. Results Data was analyzed using one-way analysis of variance (ANOVA) and post-hoc Tukey test. There was a significant difference between inclination of maxillary second molar when Angle's Class I malocclusion was compared with Angle's Class III malocclusion and UCLP cases (p = 0.003 and p = 0.011, respectively). There was not a significantdifference betweenAngle's Class III malocclusion and UCLP cases (p = 0.87). Conclusion Amongst Class III patients and UCLP patients the inclination of maxillary second molar had greater buccal inclination. Maxillary second molar correction would alleviate the effect of deleterious force on periodontium and bone generated by malpositioned teeth.

Cleft lip and palate based on birth order and family history at Mitra Sejati General Hospital, Indonesia

Background: Cleft lip and palate is one of the most common congenital abnormalities in infants and is caused by more than one factors, which can be genetic and environmental. Defects in a family gene can result in cleft lip and palate. The study found a high family history relationship with the incidence of cleft lip and palate. Birth order studied by several researchers also has different results, which were influenced by folic acid consumption, maternal knowledge, lack of antenatal care visits and maternal age. To determine the cases of cleft lip and palate based on the birth order of the children and family history of the patients at Mitra Sejati General Hospital. Purpose: The study aimed to investigate cleft lip and cleft palate patients by birth order and family history. Methods: This research was a retrospective descriptive study using survey method. Researchers gave 13 questions through a questionnaire and data were collected and counted manually. Results: The results showed that based on the birth, the cleft case in the first birth order amounted to 25 people, the second 30 people, the third 19 people, and the fourth or more as many as 20 people. Based on family history, 27 patients had a family history of cleft lip and palate, while 67 patients did not have family history. Conclusion: The cases of clefts at Mitra Sejati General Hospital happened more frequently in the second child and most incidence did not have family history.

Frenotomy procedure of a cleft lip and palate case

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease can be transmitted through direct or indirect contact with droplets from the infected person’s respiratory system. The aim of this study was a rapid review of the use of personal protective equipment against coronavirus in the field of dentistry.Methods: This study was a rapid cross-sectional review and research. A search was performed in Scopus and PubMed. The key words were PPE) personal protective equipment) with “Corona virus” OR “Coronavirus” OR “Covid 19” as well as thecombination of “oral health” and “dent” with “Corona virus” OR “Covid 19” OR “coronavirus.” Finally, we selected nine articles and excluded 545 irrelevant articles. We reviewed these nine studies in full text and excluded two of them as they were unrelated to the review of personal protective equipment.Results: One study showed that patients with COVID-19 who do not yet have symptoms might seek emergency dental treatment. Two researchers concluded that dentists had good information about how the virus was transmitted but did not know its symptoms well. One study concluded that the use of filtering facepiece respirators (FFRs) during the COVID-19 pandemic is essential to preventing exposure to aerosols and droplets, as it is more fluid-resistant and functions better than surgical masks, which cause flooding around the mouth and nose.Conclusion: This study shows that many dentists do not have enough information about the disease and proper personal protective equipment. This may be due to a lack of precise operating instructions.

Cayler Syndrome with Isolated Cleft Palate: Case Report

Published on:August 2022 Journal of Young Pharmacists, 2022; 14(3):337-338 Case Report | doi:10.5530/jyp.2022.14.66 Authors: Elizabeth Jacob*, Cyril Sajan Department of Pharmacy, Sumandeep Vidyapeeth (Deemed to Be University), Vadodara, Gujarat, INDIA. Abstract: The present study was focused on assessing the clinical Isolated cleft palate is the term used when a cleft occurs only within the palate. In clinical terms it is differentiated from other clefts, affecting the primary palate because it as such doesn’t affect either the alveolar ridge or the perioral musculature. This makes the diagnosis of the cleft, by facial analysis, more challenging, since it is concealed in the palate. Cayler syndrome is an abnormal condition at birth represented by hypoplasia of the depressor angular oris muscle (HDAOM) in an addition to cardiac birth defects. A considerable range of multiple organ system anomalies are also to predicted to be present. Paediatrician must make awareness regarding this minor facial anomaly as it can be related to multiple, cardiac and internal organs abnormalities. I present to you a paediatric rare case of cleft palate which appears to be isolated, along with cayler syndrome. To my knowledge no previous report on situs inverse totalis was reported. Additionally, the patient does not have any major cardiac anomalies associated with the cayler complications.Keywords: Isolated cleft palate, Cayler syndrome, Palatoplasty, Palatogenesis, Clefting.

Whole-genome sequencing reveals de-novo mutations associated with nonsyndromic cleft lip/palate

The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact protein-altering DNMs that contribute to the risk of nsCL/P, we conducted whole-genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs some of which are based on available evidence, contribute to the risk of nsCL/P. These include novel protein-truncating DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Many of these protein-altering DNMs were predicted to be pathogenic. Analysis using mouse transcriptomics data showed that some of these genes are expressed during the development of primary and secondary palate. Gene-set enrichment analysis of the protein-altering DNMs identified palatal development and neural crest migration among the few processes that were significantly enriched. These processes are directly involved in the etiopathogenesis of clefting. The analysis of the coding sequence in the WGS data provides more evidence of the opportunity for novel findings in the African genome.

Patterns of orofacial clefts and associated risk factors in Pakistan

Background: Orofacial clefts (OFCs) are one of the most common congenital anomalies worldwide. The purpose of the present study is to identify the incidence of different types of OFCs and the presence of known risk factors among cleft cases in the Pakistani population. Patients and Methods: A retrospective study was conducted at a comprehensive cleft care center, and data were collected from patient files from December 2018 to July 2021. Only cases of cleft lip and/or cleft palate (CL/P) that presented to center were included. SPSS was used for data analysis, and risk factors associated with OFCs were identified. Results: The study included 1269 patients with CL/P. Of the total, 677 (53.3%) patients had cleft lip with cleft palate, 211 (16.6%) had cleft lip only, and 365 (28.7%) had cleft palate only. Bilateral complete cleft lip and palate (n = 276) was most common among the participants followed by midline incomplete cleft palate (n = 215). One hundred and six (8.3%) of the cases were syndromic, and among the remaining nonsyndromic cases, 240 (18.9%) had other associated anomalies. Chi-square tests revealed the following risk factors for CL/P: consanguinity among the parents (P &lt; 0.001), a complication during pregnancy (P &lt; 0.001), medication use during pregnancy (P &lt; 0.001), maternal smoking or exposure to smoking (P = 0.002), history of miscarriage (P = 0.02), and positive family history (P &lt; 0.001). Logistic regression analysis for these factors showed maternal smoking (odds ratio [OR]: 1.99), consanguineous marriage (OR: 1.89), complication during pregnancy (OR: 1.98), and positive history of cleft (OR: 1.9) to be increasing the odds of cleft development. Conclusion: While previous studies have shown many environmental factors to be associated with development of OFCs in the child, the present study provides a quantitative estimate of the risk posed by each individual factor in the Pakistani population.

Frequency of cleft lip and cleft palate in Pakistan.

Objective: To find out the prevalence of patients with cleft lips and/or cleft palate and their association with risk factors. Study Design: Descriptive Cross-sectional study. Setting: Department of Plastic Surgery Jinnah Post-Graduate Medical Center, Karachi. Period: March 2020 to October 2021. Material &amp; Methods: The patients with any age group or gender, who had cleft lip and/or palate were included in the study. The demographic details, personal and family history and clinical examination of the patients were noted on a preformed proforma. The data was analyzed by using the Statistical Package for Social Sciences (SPSS) version 20. The p-value less than 0.05 was considered as significant. Results: The mean age and standard deviation of the study participants was 41 ± 54 months. Male gender was predominant. History of cousin marriages were positive among 92.1% of the cases and 11.1% were having positive family history with p-value ≤0.05. Majority of cases were having both deformities including cleft lip and cleft palate with frequency of 55.2% while 30.2% of the individuals were suffering from cleft lip deformity. The affected cases of cleft palate were 14.6%. Majority of the study participants were male which predominantly reported bilateral cleft lip in association with cleft palate, followed by deformity of left cleft lip and palate. Among females the cleft palate deformity was more common (10.4%) than their male counterpart but there was no significant association with gender. Conclusion: Cleft deformities are one of the most common congenital anomaly in which the cleft lip associated with cleft palate is more prevalent. Majority of the affected individuals are males and mostly their parents have cousin marriages. Family history is also one of the major contributing factor.