Congenital Craniofacial Defects Research Articles

Perspectives on the state of cleft lip and cleft palate patient care in Africa.

As the most common congenital craniofacial defect, patients with cleft lip -palate (CLP) experience morbidity and social stigma, particularly in low-income and middle-income countries (LMICs) such as those of sub-Saharan Africa (SSA). Delays in treatment secondary either to lack of awareness, skills, equipment and consumables; poor health infrastructure, limited resources or a combination of them, has led to SSA having the highest rates of death and second highest rates of disability-adjusted life years in patients with CLP globally. Here we review current perspectives on the state of comprehensive cleft lip and palate repair in Africa. To bridge gaps in government health services, nongovernmental organizations (NGOs) have emerged to provide care through short-term surgical interventions (STSIs). These groups can effect change through direct provision of care, whereas others strengthen internal system. However, sustainability is lacking as there continue to be barriers to achieving comprehensive and longitudinal cleft care in SSA, including a lack of awareness of CLP as a treatable condition, prohibitive costs, poor follow-up, and insufficient surgical infrastructure. With dedicated local champions, a comprehensive approach, and reliable partners, establishing sustainable CLP services is possible in countries with limited resources. The replacement of CLP 'missions' with locally initiated, internationally supported capacity building initiatives, integrated into local healthcare systems will prove sustainable in the long-term.

A Randomised Controlled Trial on the Effect of Hamulectomy on Hearing Outcomes in Cleft Palate Patients - A Comparative Study

Abstract Introduction: Cleft palate, a common congenital craniofacial defect, requires surgical repair and many surgical approaches have been employed for the same to reduce the risk of post-operative complications and improve outcomes. In order to achieve tension free closure, fracture of pterygoid hamulus has been advised. However, the effect of this manoeuvre on auditory functions remains debatable. The study was designed to evaluate the effect of hamulectomy on auditory function during the post-operative period after palatoplasty. Materials and Methods: The present study enrolled 100 participants aged 10 months–2 years with isolated cleft palate defect. They were randomly divided into two groups: palatoplasty with hamulectomy (n = 50) and palatoplasty without hamulectomy (n = 50). Hearing outcomes were evaluated using objective measures (otoscopy, tympanometry, and otoacoustic emission [OAE] tests) at 1-month and 6-month post-operative follow-up visits. The Chi-square test was used to analyse the data and significance level was kept at P ≤ 0.05. Results: The findings of otoscopy, tympanometry and OAE tests were statistically similar between the two study groups (P > 0.05; Chi-square test) at both one month and six months follow-up visits. Another noteworthy observation was improvement in auditory function during follow-up period indicating recovery of middle ear function following palatoplasty. Discussion: The addition of hamulectomy to the palatoplasty treatment may improve the hearing outcomes for cleft palate patients and can be adopted to achieve tension free closure.

A BMP-controlled metabolic/epigenetic signaling cascade directs midfacial morphogenesis.

Craniofacial anomalies, especially midline facial defects, are among the most common birth defects in patients and are associated with increased mortality or require lifelong treatment. During mammalian embryogenesis, specific instructions arising at genetic, signaling, and metabolic levels are important for stem cell behaviors and fate determination, but how these functionally relevant mechanisms are coordinated to regulate craniofacial morphogenesis remain unknown. Here, we report that bone morphogenetic protein (BMP) signaling in cranial neural crest cells (CNCCs) is critical for glycolytic lactate production and subsequent epigenetic histone lactylation, thereby dictating craniofacial morphogenesis. Elevated BMP signaling in CNCCs through constitutively activated ACVR1 (ca-ACVR1) suppressed glycolytic activity and blocked lactate production via a p53-dependent process that resulted in severe midline facial defects. By modulating epigenetic remodeling, BMP signaling-dependent lactate generation drove histone lactylation levels to alter essential genes of Pdgfra, thus regulating CNCC behavior in vitro as well as in vivo. These findings define an axis wherein BMP signaling controls a metabolic/epigenetic cascade to direct craniofacial morphogenesis, thus providing a conceptual framework for understanding the interaction between genetic and metabolic cues operative during embryonic development. These findings indicate potential preventive strategies of congenital craniofacial birth defects via modulating metabolic-driven histone lactylation.

Prenatal diagnostic approaches diagnosed craniosynostosis and identified a novel nonsense variant in SMAD6 in a Chinese fetus

Craniosynostosis is one of the most common congenital craniofacial birth defects. The genetic etiology is complex, involving syndromic developmental diseases, chromosomal abnormalities, and monogenic non-syndromic diseases. Herein, we presented a proband of craniosynostosis, who firstly displayed structural abnormalities. This research conducted dynamic ultrasound monitoring a fetus with gradually developing intrauterine growth retardation (IUGR). A novel de novo variant c.41G > A: p.W14* in SMAD6 was identified by pedigree analysis and genetic examination approaches. Recombinant plasmid carrying wild-type sequence and mutant that carries c.41G > A in SMAD6 were constructed and transfected into HEK293T cells. mRNA and protein expression of SMAD6 were reduced in SMAD6 mutants compared to the wild type. Cycloheximide (CHX) treatment and si-UPF1 transfection rescued the SMAD6 mRNA expression in the mutant construct, indicating that c.41G > A: p.W14* in SMAD6 triggered nonsense-mediated mRNA degradation (NMD) process and thus led to haploinsufficiency of the protein product. Our study demonstrated that whole-exome sequencing (WES) was a powerful tool for further diagnosis and etiological identification once fetal malformation was detected by ultrasound. Novel de novo c.41G > A: p.W14* in SMAD6 is pathogenic and potentially leads to craniosynostosis via NMD process.

A392V and R945X mutations cause orofacial clefts via impairing PTCH1 function

The Hedgehog (HH) signaling plays key roles in embryogenesis and organogenesis, and its dysfunction causes a variety of human birth defects. Orofacial cleft (OFC) is one of the most common congenital craniofacial defects, and its etiology is closely related to mutations in multiple components in the HH pathway, including the PTCH1 receptor. A quantity of PTCH1 variants have been associated with OFC, but the pathogenicity and underlying mechanism of these variants have not been functionally validated. In our previous studies, we identified two PTCH1 variants (A392V and R945X) in two families with hereditary OFC. Here we explore the functional consequences of these two variants. In zebrafish embryos, microinjection of wild type PTCH1 mRNA causes curved body axis and craniofacial anomalies. In contrast, microinjection of A392V and R945X PTCH1 mRNAs results in much milder phenotypes, suggesting these two variants are loss-of-function mutations. In mammalian cells, A392V and R945X mutations reverse the inhibitory effect of PTCH1 on HH signaling. Biochemically, the two mutants PTCH1 show lower expression levels and shortened half-life, indicting these mutations decrease the stability of PTCH1. A392V and R945X mutations also appear to cause PTCH1 to localize away from vesicles. Taken together, our findings indicate that A392V and R945X variants are loss-of-function mutations that disrupt the function of PTCH1 and thus cause dysregulation of HH signaling, leading to the pathogenesis of OFC.

Ras signaling and RREB1 are required for the dissociation of medial edge epithelial cells in murine palatogenesis

ABSTRACTCleft palate is one of the major congenital craniofacial birth defects. The etiology underlying the pathogenesis of cleft palate has yet to be fully elucidated. Dissociation of the medial edge epithelium (MEE) at the contacting region of palatal shelves and subsequent migration or apoptosis of MEE cells is required for proper MEE removal. Ras-responsive element-binding protein 1 (RREB1), a RAS transcriptional effector, has recently been shown to play a crucial role in developmental epithelial–mesenchymal transition (EMT), in which loss of epithelial characteristics is an initial step, during mid-gastrulation of embryonic development. Interestingly, the involvement of RREB1 in cleft palate has been indicated in humans. Here, we demonstrated that pan-Ras inhibitor prevents the dissociation of MEE during murine palatal fusion. Rreb1 is expressed in the palatal epithelium during palatal fusion, and knockdown of Rreb1 in palatal organ culture resulted in palatal fusion defects by inhibiting the dissociation of MEE cells. Our present findings provide evidence that RREB1-mediated Ras signaling is required during palatal fusion. Aberrant RREB1-mediated Ras signaling might be involved in the pathogenesis of cleft palate.

Altered regulation of cell migration in IRF6-mutated orofacial cleft patients-derived primary cells reveals a novel role of Rho GTPases in cleft/lip palate development.

Orofacial clefts are the most common congenital craniofacial birth defects. They occur from a failure in cell proliferation and fusion of neural crest cells of the lip buds and/or palatal shelves. In this study, we investigate the genetic basis and molecular mechanisms in primary cells derived from a cleft and lip palate patient presenting van der Woude syndrome (VWS). Since mutations in the integrin genes are widely correlated with VWS, Interferon Regulatory Factor 6 (IRF6) screening was conducted in a cohort of 200 participants presenting with orofacial anomalies. Primary fibroblastic cells derived from the upper right gingiva and palatal regions were isolated and two cellular populations from two participants were obtained: a control with no cleft phenotype and a patient with a cleft phenotype typical of van der Woude syndrome (VWS). IRF6 targeted sequencing revealed mutations in two distinct families. Our results showed no alteration in the viability of the CLP/VWS patient cells, suggesting the phenotype associate with the disease is not secondary to a defect in cell proliferation. We did however detect a significant decrease in the migratory ability of the CLP with Van der Woude syndrome (CLP/VWS) patient cells, which could account for the phenotype. When compared to normal cells, patient cells showed a lack of polarization, which would account for their lack of mobility. Patient cells showed protrusions all around the cells and a lack of defined leading edge. This was reflected with actin staining, WAVE2 and Arp2 around the cell, and correlated with an increase in Rac1 activation. Consistently with the increase in Rac1 activation, patient cells showed a loss in the maturation of focal adhesions needed for contractility, which also accounts for the lack in cell migration. Our findings give increased understanding of the molecular mechanisms of VWS and expands the knowledge of van der Woude syndrome (VWS) occurrence by providing a strong molecular evidence that CLP with Van der Woude syndrome (CLP/VWS) phenotype is caused by a defect in normal physiological processes of cells.

Challenges of Stem-cell-based Craniofacial Regeneration.

Oral diseases, such as dental caries, pulpitis, periodontitis, and craniofacial trauma, are common. Some individuals suffer from oral cancer or congenital craniofacial defects. The oral-systemic disease link reveals that a dental disorder is not a minor problem. Tissue loss is an inevitable consequence of most oral diseases, and repairing the tissue loss and restoring craniofacial function are highly expected by patients and are terminal targets of dental treatment. The current clinical approach for tissue loss due to dental caries, pulpitis, periodontitis, oral cancer, trauma, and developmental diseases depends on the filling of corresponding material, allograft, or autograft bone after lesion removal. Repair of the tissue volume is expectedly followed by promising functional restoration using regenerative dental tissue or tissue engineering, which has currently aroused the interest of clinicians and researchers. This review focuses on the ideas and recent findings on newly identified skeletal stem cells (SSCs) as candidates for craniofacial regeneration, signaling regulation of SSCs extended from embryonic development, and signal molecule delivery for the repair of the craniofacial defect, sincerely hoping that the hypothesis of craniofacial self-healing is true in the future.

Evaluation and Comparison of Condylar Head Inclination With Respect to Glenoid Fossa in Cleft, Class III, and Class I Individuals

Background: Cleft lip and palate are the most common congenital craniofacial defects, which need early intervention with a multidisciplinary approach including surgeons, orthodontists, speech therapists, pedodontists, etc. Craniofacial growth is affected the most, leading to marked skeletal discrepancies. Constricted maxillary arch is one of the reasons for faulty occlusal inclined planes which results in abnormal loading of condyles, thus leading to temporomandibular disorders (TMDs) in cleft. Condylar head inclination helps to evaluate the position of condyle in the glenoid fossa. Thus, changing the position of condylar head in the glenoid fossa at an early age prevents further worsening of TMD condition. The purpose of this study was to evaluate condylar inclination in individuals with cleft lip and palate and compare it with non-cleft individuals. Method: The study comprised of 40 subjects aged between 9 and 12 years, divided into 4 groups (10 in each)—unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP), and class III and class I malocclusion. Scanned three-dimensional digital volume tomography (3D-DVT) images were taken, and condylar head inclination was evaluated and compared. Result: Significant findings were obtained when group 1 was compared to group 2, group 3, and group 4 ( P-value = .001). Also, when group 2 was compared to group 3 and group 4, the values were statistically significant with P-value = .001. Conclusion: Condylar head inclination was found to be most anteriorly angulated in the class III group compared to all the other groups. Unilateral cleft lip and palate had more anteriorly angulated condyle than bilateral cleft lip and palate.

GLI1 and AXIN2 Are Distinctive Markers of Human Calvarial Mesenchymal Stromal Cells in Nonsyndromic Craniosynostosis.

All skeletal bones house osteogenic stem cell niches, in which mesenchymal stromal cells (MSC) provide progenitors for tissue growth and regeneration. They have been widely studied in long bones formed through endochondral ossification. Limited information is available on the composition of the osteogenic niche in flat bones (i.e., skull vault bones) that develop through direct membranous ossification. Craniosynostosis (CS) is a congenital craniofacial defect due to the excessive and premature ossification of skull vault sutures. This study aimed at analysing the expression of GLI1, AXIN2 and THY1 in the context of the human skull vault, using nonsyndromic forms of CS (NCS) as a model to test their functional implication in the aberrant osteogenic process. The expression of selected markers was studied in NCS patients’ calvarial bone specimens, to assess the in vivo location of cells, and in MSC isolated thereof. The marker expression profile was analysed during in vitro osteogenic differentiation to validate the functional implication. Our results show that GLI1 and AXIN2 are expressed in periosteal and endosteal locations within the osteogenic niche of human calvarial bones. Their expression is higher in MSC isolated from calvarial bones than in those isolated from long bones and tends to decrease upon osteogenic commitment and differentiation. In particular, AXIN2 expression was lower in cells isolated from prematurely fused sutures than in those derived from patent sutures of NCS patients. This suggests that AXIN2 could reasonably represent a marker for the stem cell population that undergoes depletion during the premature ossification process occurring in CS.

What Do Animal Models Teach Us About Congenital Craniofacial Defects?

The formation of the head and face is a complex process which involves many different signaling cues regulating the migration, differentiation, and proliferation of the neural crest. This highly complex process is very error-prone, resulting in craniofacial defects in nearly 10,000 births in the United States annually. Due to the highly conserved mechanisms of craniofacial development, animal models are widely used to understand the pathogenesis of various human diseases and assist in the diagnosis and generation of preventative therapies and treatments. Here, we provide a brief background of craniofacial development and discuss several rare diseases affecting craniofacial bone development. We focus on rare congenital diseases of the cranial bone, facial jaw bones, and two classes of diseases, ciliopathies and RASopathies. Studying the animal models of these rare diseases sheds light not only on the etiology and pathology of each disease, but also provides meaningful insights towards the mechanisms which regulate normal development of the head and face.

Can contamination of the environment by dioxins cause craniofacial defects?

Cleft lip and cleft palate also known as orofacial cleft is a congenital malformation involving the partial or total lack of anatomical continuity of craniofacial tissue. The most common environmental factors that may cause orofacial clefts include pharmaceuticals, alcohol, addictive drugs, and tobacco smoke. Living in the area of industrial factories, garbage, ironworks, crematoria, wastewater treatment plants, and plastic waste landfills also has a significant impact on the development of the craniofacial defects. Some of the main factors causing the formation of congenital craniofacial defects are dioxins, of which emission to the environment is an important environmental and health problem. Dioxins are a diverse group of organic chemical compounds, derivatives of oxanthrene and fumarates, which are organoleptically imperceptible. Acting mainly through induction of inflammation, they influence a number of metabolic processes, including the process of bone mineralization and embryonic development. In this work, we highlight the problem of orofacial cleft including the impact of dioxin on development of this defect and the recommended prevention.

Biomaterials for Cleft Lip and Palate Regeneration.

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.

Vascular reconstruction of congenital craniofacial defects

Background: Although craniofacial malformation are relatively common, there is some debate regarding the ideal treatment of severe mandibular or maxillary hypoplasia. Traditionally, patients with severe deficits have been treated with iliac or costochondral bone grafts followed by distraction osteogenesis, with mixed results.

Sox2 regulates palate development by promoting basal cell differentiation

With a frequency of 1:500–2,500, cleft lip with or without cleft palate (CL/P) is the most common congenital craniofacial defect. In mice and humans, a complex gene regulatory network (GRN) controls the different processes required for palatogenesis. Understanding how transcription factors act as the modulators of gene expression and function in palatogenesis will lead to better genetic counseling and genetic therapies for CL/P. Our group has shown that conditionally inactivating Sox2, one of the earliest transcription factors required during embryogenesis, results in clefting of the palate and fusion of the tongue to the mandible (ankylglossia).ObjectiveTo examine the role of Sox2, a stem cell factor, in palatogenesis.MethodsUsing Pitx2cre, Sox2 was conditionally inactivated in the oral epithelial tissue of developing murine embryos. Palate development was studied during the stages of embryogenesis.ResultsThe conditional ablation of Sox2 was sufficient to generate clefting in mice. Further examination revealed that Sox2 is expressed in the P63+ basal cell population of the oral epithelium as well as the periderm, which acts to prevent oral adhesions during development. Inactivating Sox2 resulted in defective periderm formation. The loss of an intact periderm resulted in intraoral adhesions that prevented complete palate shelf extension and ankylglossia.ConclusionsSox2 is required for periderm differentiation. Inactivating Sox2 results in cleft palate and ankylglossia.Support or Funding InformationUniversity of Iowa College of DentistryNIH, NIDCRThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Birth Defects of the Craniofacial Skeleton and the Potential for Prevention

Craniofacial anomalies account for approximately one‐third of all birth defects, and common anomalies such as cleft palate, craniosynostosis, and mandibulofacial dysostosis can occur in isolation or as part of one of nearly 700 distinct syndromes. Most of the bone, cartilage and connective tissue of the head and face is derived from a stem cell and progenitor cell population called neural crest cells. Congenital craniofacial anomalies are therefore typically associated with defects in neural crest cell development. Understanding the etiology and pathogenesis of craniofacial birth defects is dependent upon knowledge of the mechanisms that govern neural crest cell formation, migration, survival and differentiation. Recently, we discovered that ribosome biogenesis, the process of making ribosomes which are essential for protein translation in all cells, plays an essential role in neural crest cell proliferation and survival during craniofacial development. Ribosome biogenesis commences with transcription of rDNA by RNA Polymerases I and III, and this event is considered a rate‐limiting step in ribosome biogenesis. Mutations in genes that encode subunits of RNA Polymerase I, or its associated factors, lead to deficiencies in ribosome biogenesis, which results in neural crest cell apoptosis, and consequently congenital craniofacial disorders such as Treacher Collins syndrome, and Acrofacial Dysostosis ‐ Cincinnati type. Inhibition of neural crest cell death is capable of ameliorating and in some cases completely preventing craniofacial malformations in mouse and zebrafish models of these syndromes. Through investigating fundamental mechanisms that regulate neural crest cell biology, our work is facilitating the development of therapeutic approaches to prevent the pathogenesis of congenital craniofacial birth defects.Support or Funding InformationStowers Institute for Medical ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Six2 regulates palate development by inhibiting palatal bone formation during development

Cleft lip with or without cleft palate (CL/P) is the most common congenital craniofacial defect, with a frequency of 1 in 500 to 1 in 2500 live births depending on the population, and lifelong care can cost more than $100,000. In mice, secondary palate development occurs from E11.5 to E17.5, and consists of outgrowth, elevation, extension and fusion processes. At any stage during palatogenesis, the disruption of these processes could cause cleft palate, and these processes are all regulated in part by palatal mesenchyme.ObjectiveTo examine Six2, a transcription factor previously shown to play a role in craniofacial and kidney development, for a role in clefting predicted by the SYSFACE tool.MethodsSix2 knockout mice were generated and examined for clefting at different embryonic stages and P0 and craniofacial developmental defects.ResultsWe demonstrate that ablation of Six2 contributes to palatogenesis. We have characterized the clefting phenotype in Six2−/− embryos, demonstrating that the palate shelves fail to extend to the midline and contain premature ossified tissue compared to wild‐type (WT) littermates. The expression of Runx2 and its target Osx were higher in Six2−/− palates and surrounding maxilla with cleft than in control littermates. Histochemistry and immunohistochemistry experiments demonstrate premature ossification by specific cells in the Six2−/− palate.ConclusionsSix2 is a regulator of palate development and it acts by negatively regulating the ossification of palatal mesenchyme. In Six2−/− mice, ectopic ossification prevents the extension of the palate shelves causing cleft.Support or Funding InformationThe University of Iowa, College of DentistryThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

MicroRNAs in Palatogenesis and Cleft Palate.

Palatogenesis requires a precise spatiotemporal regulation of gene expression, which is controlled by an intricate network of transcription factors and their corresponding DNA motifs. Even minor perturbations of this network may cause cleft palate, the most common congenital craniofacial defect in humans. MicroRNAs (miRNAs), a class of small regulatory non-coding RNAs, have elicited strong interest as key regulators of embryological development, and as etiological factors in disease. MiRNAs function as post-transcriptional repressors of gene expression and are therefore able to fine-tune gene regulatory networks. Several miRNAs are already identified to be involved in congenital diseases. Recent evidence from research in zebrafish and mice indicates that miRNAs are key factors in both normal palatogenesis and cleft palate formation. Here, we provide an overview of recently identified molecular mechanisms underlying palatogenesis involving specific miRNAs, and discuss how dysregulation of these miRNAs may result in cleft palate.

Embryonic defence mechanisms against glucose-dependent oxidative stress require enhanced expression of Alx3 to prevent malformations during diabetic pregnancy

Oxidative stress constitutes a major cause for increased risk of congenital malformations associated to severe hyperglycaemia during pregnancy. Mutations in the gene encoding the transcription factor ALX3 cause congenital craniofacial and neural tube defects. Since oxidative stress and lack of ALX3 favour excessive embryonic apoptosis, we investigated whether ALX3-deficiency further increases the risk of embryonic damage during gestational hyperglycaemia in mice. We found that congenital malformations associated to ALX3-deficiency are enhanced in diabetic pregnancies. Increased expression of genes encoding oxidative stress-scavenging enzymes in embryos from diabetic mothers was blunted in the absence of ALX3, leading to increased oxidative stress. Levels of ALX3 increased in response to glucose, but ALX3 did not activate oxidative stress defence genes directly. Instead, ALX3 stimulated the transcription of Foxo1, a master regulator of oxidative stress-scavenging genes, by binding to a newly identified binding site located in the Foxo1 promoter. Our data identify ALX3 as an important component of the defence mechanisms against the occurrence of developmental malformations during diabetic gestations, stimulating the expression of oxidative stress-scavenging genes in a glucose-dependent manner via Foxo1 activation. Thus, ALX3 deficiency provides a novel molecular mechanism for developmental defects arising from maternal hyperglycaemia.

Management of cleft lip and palate in Nigeria: A survey.

Clefts of the lip and/or palate are the most common congenital craniofacial defects and second only to club foot among all congenital anomalies. The management of this condition is resource intensive due to the multidimensional needs. This survey was carried out to ascertain the current state of cleft management in Nigeria with emphasis on training, scope of management, and assessment of treatment outcome. Structured questionnaires were administered to cleft surgeons based on professional and practitioners' register and the result of literature search for cleft surgeons whose names may not appear in the registers. A total of 69 returned questionnaires were analyzed. The highest number of surgeons was from southwest geopolitical region while the northeast had the least. Fifty-eight (84.1%) were specialists with the fellowships. Forty-seven had been cleft surgeons for <10 years. Majority undertook lip repair between 3 and 4 months while 50% did cleft palate at or more than 9 months. Millard rotation and advancement was used for lip repair by 91.2% and 44 employed the von Langenbeck technique for palatal repair. Forty-six respondents carried out nasal repair at the time of lip surgery with 44 doing this as closed rhinoplasty. Adhesive tapes were usually employed by 44 (63.7%) for managing the protruding premaxilla. Orthodontic evaluation was not usually part of the treatment plan of 34 respondents. Otology assessment and assessment of velopharyngeal competence were rarely done. Revision surgeries, alveolar bone grafting, rhinoplasties, and maxillary osteotomies were uncommon. Interdisciplinary team care approach was practiced by 54 (78.2%) respondents. Findings suggest an increase in the number of surgeons, but the training, scope, and standard of care remain relatively limited. Audit and assessment of the practice should also become points of emphasis.