Craniofacial Birth Defects Research Articles

Haplotype-based gene-gene interaction of bone morphogenetic protein 4 and interferon regulatory factor 6 in the etiology of non-syndromic cleft lip with or without cleft palate in a Chilean population.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans, the etiology of which can be dependent on the interactions of multiple genes. We previously reported haplotype associations for polymorphic variants of interferon regulatory factor 6 (IRF6), msh homeobox 1 (MSX1), bone morphogenetic protein 4 (BMP4), and transforming growth factor beta 3 (TGFB3) in Chile. Here, we analyzed the haplotype-based gene-gene interaction for markers of these genes and NSCL/P risk in the Chilean population. We genotyped 15 single nucleoptide polymorphisms (SNPs) in 152 Chilean patients and 164 controls. Linkage disequilibrium (LD) blocks were determined using the Haploview software, and phase reconstruction was performed by the Phase program. Haplotype-based interactions were evaluated using the multifactor dimensionality reduction (MDR) method. We detected two LD blocks composed of two SNPs from BMP4 (Block 1) and three SNPs from IRF6 (Block 2). Although MDR showed no statistical significance for the global interaction model involving these blocks, we found four combinations conferring a statistically significantly increased NSCL/P risk (Block 1-Block 2): T-T/T-G C-G-T/G-A-T; T-T/T-G C-G-C/C-G-C; T-T/T-G G-A-T/G-A-T; and T-T/C-G G-A-T/G-A-T. These findings may reflect the presence of a genomic region containing potential causal variants interacting in the etiology of NSCL/P and may contribute to disentangling the complex etiology of this birth defect.

Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate.

Nonsyndromic orofacial clefts (OFCs) are a heterogeneous group of common craniofacial birth defects with complex etiologies that include genetic and environmental risk factors. OFCs are commonly categorized as cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP), which have historically been analyzed as distinct entities. Genes for both CL/P and CP have been identified via multiple genome-wide linkage and association studies (GWAS); however, altogether, known variants account for a minority of the estimated heritability in risk to these craniofacial birth defects. We performed genome-wide meta-analyses of CL/P, CP, and all OFCs across two large, multiethnic studies. We then performed population-specific meta-analyses in sub-samples of Asian and European ancestry. In addition to observing associations with known variants, we identified a novel genome-wide significant association between SNPs located in an intronic TP63 enhancer and CL/P (p=1.16×10-8). Several novel loci with compelling candidate genes approached genome-wide significance on 4q21.1 (SHROOM3), 12q13.13 (KRT18), and 8p21 (NRG1). In the analysis of all OFCs combined, SNPs near FOXE1 reached genome-wide significance (p=1.33×10-9). Our results support the highly heterogeneous nature of OFCs and illustrate the utility of meta-analysis for discovering new genetic risk factors.

Combined ultrasound and exome sequencing approach recognizes Opitz G/BBB syndrome in two malformed fetuses.

Orofacial clefts are the most common congenital craniofacial anomalies and can occur as an isolated defect or be associated with other anomalies such as posterior fossa anomalies as a part of several genetic syndromes. We report two consecutive voluntary pregnancy interruptions in a nonconsanguineous couple following the fetal ultrasound finding of cleft lip and palate and posterior fossa anomalies confirmed by means of post-termination examination on the second fetus. The quantitative fluorescent PCR, the karyotype, and the comparative genomic hybridization-array analysis after amniocentesis were normal. Exome sequencing on abortive material from both fetuses detected a missense mutation in MID1, resulting in a clinical diagnosis of Opitz G/BBB syndrome. The same mutation was found in the mother and in her brother, who both revealed cerebellar anomalies at an MRI examination. Our study supports the efficacy of exome sequencing in the presence of both a family history suggestive of an inherited disorder and well-documented ultrasound findings. It reveals the importance of a synergistic effort between gynecologists and geneticists aimed at the integration of the most sophisticated ultrasound techniques with the next-generation sequencing tools to provide a definite diagnosis essential to orient the final decision and to estimate a proper recurrence risk.

New insights in orofacial cleft: epidemiological and genetic studies on italian samples.

Cleft of the lip and/or palate (CL±P) is the most common congenital craniofacial anomaly affecting around 1 in 700 live births worldwide. Clefts of the human face can be classified anatomically as cleft lip only (CL), cleft palate only (CP), cleft lip and palate (CLP) or a combined group of cleft lip with or without cleft palate (CL±P), based on differences in embryologic development. CL±P has a genetic base and several linkage and association analyses have been performed in order to obtain important information about the role of candidate genes in its onset; not less important are gene-environment interactions that play an increasing role in its aetiology. In CL±P, several loci have been seen associated with the malformation, and, in some cases, a specific gene mapping in a locus has also been identified as susceptibility factor. In CP, one gene has been found, but many more are probably involved. In this short review the genetic studies carried out on CL±P, and the interaction with environmental factors (alcohol, smoking, drugs) are discussed.

Evidence for SNP-SNP interaction identified through targeted sequencing of cleft case-parent trios.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans, affecting 1 in 700 live births. This malformation has a complex etiology where multiple genes and several environmental factors influence risk. At least a dozen different genes have been confirmed to be associated with risk of NSCL/P in previous studies. However, all the known genetic risk factors cannot fully explain the observed heritability of NSCL/P, and several authors have suggested gene-gene (G × G) interaction may be important in the etiology of this complex and heterogeneous malformation. We tested for G × G interactions using common single nucleotide polymorphic (SNP) markers from targeted sequencing in 13 regions identified by previous studies spanning 6.3 Mb of the genome in a study of 1,498 NSCL/P case-parent trios. We used the R-package trio to assess interactions between polymorphic markers in different genes, using a 1 degree of freedom (1df) test for screening, and a 4 degree of freedom (4df) test to assess statistical significance of epistatic interactions. To adjust for multiple comparisons, we performed permutation tests. The most significant interaction was observed between rs6029315 in MAFB and rs6681355 in IRF6 (4df P = 3.8 × 10-8 ) in case-parent trios of European ancestry, which remained significant after correcting for multiple comparisons. However, no significant interaction was detected in trios of Asian ancestry.

Psychological adjustment to craniofacial conditions (excluding oral clefts): A review of the literature

Objective: A congenital craniofacial anomaly (CFA) is expected to impact upon several domains of psychological, emotional and social functioning, yet no recent reviews have comprehensively summarised the available literature. Further, existing reviews tend to draw upon literature in the field of cleft lip and palate, and do not give substantive attention to other types of CFAs.Design: A review of 41 papers published between January 2000 and March 2016 pertaining to psychological adjustment to CFAs.Main outcome measures: Findings are presented according to key psychological domains: General Psychological Well-being, Quality of Life, Behaviour, Emotional Well-being, Social Experiences, Appearance, and Treatment-Related Experiences.Results: Current literature offers a contradictory picture of adjustment to CFAs. Psychological adjustment appeared to be comparable to norms and reference groups in approximately half of the papers related to non-syndromic CFAs, while more variation was found across domains among samples with syndromic CFAs. Associations were found between adjustment, physical health and cognitive function in several papers. The review identified a number of gaps in the literature, such as the inclusion of a wide range of diagnoses within research samples.Conclusions: This review demonstrates the complexity of findings, both within and across domains, and highlights a number of methodological challenges.

Utilizing Infant Cry Acoustics to Determine Gestational Age

The date of last menstruation period and ultrasonography are the most commonly used methods to determine gestational age (GA). However, if these data are not clear, some scoring systems performed after birth can be used. New Ballard Score (NBS) is a commonly used method in estimation of GA. Cry sound may reflect the developmental integrity of the infant. The aim of this study was to evaluate the connection between the infants' GA and some acoustic parameters of the infant cry. A prospective single-blind study was carried out. In this prospective study, medically stable infants without any congenital craniofacial anomalies were evaluated. During routine blood sampling, cry sounds were recorded and acoustic analysis was performed. Step-by-step multiple linear regression analysis was performed. The data of 116 infants (57 female, 59 male) with the known GA (34.6 ± 3.8 weeks) were evaluated and with Apgar score of higher than 5. The real GA was significantly and well correlated with the estimated GA according to the NBS, F0, Int, Jitt, and latency parameters. The obtained stepwise linear regression analysis model was formulized as GA=(31.169) - (0.020 × F0)+(0.286 × GA according to NBS) - (0.003 × Latency)+(0.108 × Int) - (0.367 × Jitt). The real GA could be determined with a ratio of 91.7% using this model. We have determined that after addition of F0, Int, Jitt, and latency to NBS, the power of GA estimation would be increased. This simple formula can be used to determine GA in clinical practice but validity of such prediction formulas needs to be further tested.

A Qualitative Study of Children's Perspectives on Their Peer Relationships in the Context of Living With a Craniofacial Anomaly.

To gain understanding of perspectives on peer relationships from children with congenital craniofacial anomalies (CFA). This was qualitative research based in a phenomenological approach, using narratives that captured children's responses to open-ended and objective questions about peer relations and life with a CFA. Interviews were audio recorded and transcribed. Transcripts were coded according to thematic categories. Children were patients at a reconstructive plastic surgery center in an urban hospital and medical school and were recruited from a regional support organization for families of children with CFA that was associated with the hospital. Nine children with congenital CFA aged 9 to 14 years. Thematic coding categories were developed from the narratives using an open coding strategy; these categories focused on aspects of children's interactions with peers and their appraisals of the role of their CFA in their lives. Children reported satisfaction with most aspects of their peer relationships and expressed confidence in their ability to manage challenges. They acknowledged some difficulties with living with a CFA but tended to hold a balanced perspective on the impact of a CFA on their lives, and they expressed optimism about their future lives. This sample of children with CFA exhibited much resilience. Although they may not be representative of all children with CFA, they provide examples that can be used to generate hypotheses for future research.

Subphenotyping and Classification of Orofacial Clefts: Need for Orofacial Cleft Subphenotyping Calls for Revised Classification.

Nonsyndromic orofacial clefting (OFC) describes a range of phenotypes that represent the most common craniofacial birth defects in humans, with an overall birth prevalence of 1:700 live births. Because of the lifelong negative implications on health and well-being associated with OFC and the numbers of people affected, quality research into its etiology, diagnosis, treatment outcomes, and preventative strategies is essential. A range of different methods is used for recording and classifying OFC subphenotypes, one of which is the International Classification of Diseases (ICD) system. However, there is a general perception that research is being hampered by a lack of sensitivity and specificity in grouping those with OFC into subphenotypes, with potential heterogeneity and confounding in epidemiologic, genetic, and genotype-phenotype correlation studies. This article provides a background to the necessity of OFC research, discusses current controversies within cleft subphenotyping, and provides a brief overview of current OFC classifications as well as their limitations. The LAHSHAL classification is described in the context of a potentially useful tool for OFC that could complement the ICD-10/ICD-11 Beta coding systems to become a simply understood, universally accepted, clinically friendly, and research-sensitive instrument. Empowering registries, clinicians, and researchers to use a common classification system would have significant implications for OFC research across the world at a time when accurate subphenotyping is crucial and health care research is becoming increasingly tailored toward the individual.

Indications for Computer-Aided Design and Manufacturing in Congenital Craniofacial Reconstruction

The complex three-dimensional relationships in congenital craniofacial reconstruction uniquely lend themselves to the ability to accurately plan and model the result provided by computer-aided design and manufacturing (CAD/CAM). The goal of this study was to illustrate indications where CAD/CAM would be helpful in the treatment of congenital craniofacial anomalies reconstruction and to discuss the application of this technology and its outcomes. A retrospective review was performed of all congenital craniofacial cases performed by the senior author between 2010 and 2014. Cases where CAD/CAM was used were identified, and illustrative cases to demonstrate the benefits of CAD/CAM were selected. Preoperative appearance, computerized plan, intraoperative course, and final outcome were analyzed. Preoperative planning enabled efficient execution of the operative plan with predictable results. Risk factors which made these patients good candidates for CAD/CAM were identified and compiled. Several indications, including multisuture and revisional craniosynostosis, facial bipartition, four-wall box osteotomy, reduction cranioplasty, and distraction osteogenesis could benefit most from this technology. We illustrate the use of CAD/CAM for these applications and describe the decision-making process both before and during surgery. We explore why we believe that CAD/CAM is indicated in these scenarios as well as the disadvantages and risks.

Cystathionine β-synthase genetic variant rs2124459 is associated with a reduced risk of cleft palate in French and Belgian populations

BackgroundOrofacial cleft (OFC) is the most prevalent craniofacial birth defect. Genes involved in one-carbon, folate and vitamin B12 metabolisms have been associated with OFC but no study performed a concomitant...

Congenital and acquired mandibular asymmetry: Mapping growth and remodeling in 3 dimensions.

Disordered craniofacial development frequently results in definitive facial asymmetries that can significantly impact a person's social and functional well-being. The mandible plays a prominent role in defining facial symmetry and, as an active region of growth, commonly acquires asymmetric features. Additionally, syndromic mandibular asymmetry characterizes craniofacial microsomia (CFM), the second most prevalent congenital craniofacial anomaly (1:3000 to 1:5000 live births) after cleft lip and palate. We hypothesized that asymmetric rates of mandibular growth occur in the context of syndromic and acquired facial asymmetries. To test this hypothesis, a spherical harmonic-based shape correspondence algorithm was applied to quantify and characterize asymmetries in mandibular growth and remodeling in 3 groups during adolescence. Longitudinal time points were automatically registered, and regions of the condyle and posterior ramus were selected for growth quantification. The first group (n=9) had a diagnosis of CFM, limited to Pruzansky-Kaban type I or IIA mandibular deformities. The second group (n=10) consisted of subjects with asymmetric, nonsyndromic dentofacial asymmetry requiring surgical intervention. A control group (n=10) of symmetric patients was selected for comparison. A linear mixed model was used for the statistical comparison of growth asymmetry between the groups. Initial mandibular shape and symmetry displayed distinct signatures in the 3 groups (P<0.001), with the greatest asymmetries in the condyle and ramus. Similarly, mandibular growth had unique patterns in the groups. The dentofacial asymmetry group was characterized by significant asymmetry in condylar and posterior ramal remodeling with growth (P<0.001). The CFM group was characterized by asymmetric growth of the posterior ramus (P<0.001) but relatively symmetric growth of the condyles (P=0.47). Forms of CFM are characterized by active and variable growth of the dysplastic side, which has a distinct pattern from other disorders of mandibular growth.

Gene Interactions Provide Evidence for Signaling Pathways Involved in Cleft Lip/Palate in Humans

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common craniofacial birth defect that has a complex etiology. Genome-wide association studies have recently identified new loci associated with NSCL/P, but these loci have not been analyzed in a Mexican Mestizo population. A complex etiology implies the presence of genetic interactions, but there is little available information regarding this in NSCL/P, and no signaling pathway has been clearly implicated in humans. Here, we analyzed the associations of 24 single nucleotide polymorphisms (SNPs) with NSCL/P in a Mexican Mestizo population (133 cases, 263 controls). The multifactorial dimensionality reduction method was used to examine gene–gene and gene–folic acid consumption interactions for the 24 SNPs analyzed in this study and for 2 additional SNPs that had previously been genotyped in the same study population. Six SNPs located in paired box 7, ventral anterior homeobox 1, sprouty RTK signaling antagonist 2, bone morphogenetic protein 4, and tropomyosin 1 genes were associated with higher risks of NSCL/P (P = 0.0001 to 0.04); 2 SNPs, 1 each in netrin 1 and V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B, were associated with a lower risk of NSCL/P (P = 0.013 to 0.03); and 2 SNPs, 1 each in ATP binding cassette subfamily A member 4 (ABCA4) and noggin, showed associations with NSCL/P that approached the threshold of significance (P = 0.056 to 0.07). In addition, 6 gene–gene interactions (P = 0.0001 to 0.001) and an ABCA4–folic acid consumption interaction (P < 0.0001) were identified. On the basis of these results, combined with those of previous association studies in the literature and biological characterizations of murine models, we propose an interaction network in which interferon regulatory factor 6 plays a central role in the etiology of NSCL/P.

Risk behaviors among adolescents with complex diseases

Adolescents with complex diseases may have a higher frequency of risk behaviors than their healthy peers. To characterize risk behaviors in adolescents with complex chronic diseases. Risk behaviors were assessed by means of a self-administered questionnaire designed for this purpose, in adolescents aged 10 to 19 years, who attended a pediatrics specialties clinic due to cystic fibrosis, congenital craniofacial anomalies, liver transplantation, kidney transplantation and spinal dysraphism. We assessed 98 patients with a mean age of 14.1 years (59% women). The most common behaviors were those related to accidents and violence, physical inactivity and unhealthy eating. Tobacco, alcohol and drug use, and sexual risk behaviors were observed in patients older than 15 years. Adolescents with congenital craniofacial anomaly followed by those with cystic fibrosis, showed a greater tendency towards some risk behaviors. Less physical activity and early onset of tobacco use predominated in women. Males had more physical violence. Eighteen percent of patients had more than 3 risk behaviors; 52% had two or three and 30% had one risk behavior. Risk behaviors in these adolescents with complex diseases varied according to the type of disease, gender and age.

Population-Based Study of Prevalence of Cleft Lip/Palate in Southern Thailand.

Oral cleft is a common craniofacial birth defect that leads to long-lasting adverse outcomes. In Thailand, there have been two studies of the prevalence of oral clefts using data from university hospitals during 1969 through 1978 and 1988 through 1999, which found prevalence rates of 1.23 and 1.22 per 1000 live births, respectively. The primary outcome was to assess the prevalence of oral clefts from the birth defects registry during 2009 through 2013 in three provinces in southern Thailand. The secondary outcomes were to correlate the risk of oral cleft and maternal age. Population-based study. Four hundred sixty-seven hospitals in three provinces in southern Thailand. Oral cleft cases and maternal data-including live births, stillbirths, and termination of pregnancy following a prenatal diagnosis-were collected from the birth defects registry. Of the total 186,393 births, there were 269 oral cleft cases, giving an average prevalence of 1.44 per 1000 births (95% CI, 1.22-1.63). The most common cleft type was cleft lip and palate (45.0%), followed by cleft palate (29.0%), with 15.6% syndromic cleft. The mean maternal age was 28.0 ± 6.4 years. There were no differences in prevalence of oral clefts among the different maternal age groups. However, advanced maternal age 35+ years was associated with syndromic cleft children. The prevalence of oral clefts was 1.44 per 1000 live births, with 15% of cases having an associated congenital anomaly or a recognized syndrome. Increased maternal age was associated with a higher prevalence of syndromic cleft.

Infraorbital nerve block for postoperative pain following cleft lip repair in children.

Postoperative pain is a barrier to the quality of paediatric care, the proper management of which is a challenge. Acute postoperative pain often leads to adverse functional and organic consequences that may compromise surgical outcome. Cleft lip is one of the most common craniofacial birth defects and requires surgical correction early in life. As expected after a surgical intervention in such a sensitive and delicate area, the immediate postoperative period of cleft lip repair may be associated with moderate to severe pain. Infraorbital nerve block associated with general anaesthesia has been used to reduce postoperative pain after cleft lip repair. To assess the effects of infraorbital nerve block for postoperative pain following cleft lip repair in children. We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, Issue 6, 2015), MEDLINE, EMBASE, and Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) from inception to 17 June 2015. There were no language restrictions. We searched for ongoing trials in the following platforms: the metaRegister of Controlled Trials; ClinicalTrials.gov (the US National Institutes of Health Ongoing Trials Register), and the World Health Organization International Clinical Trials Registry Platform (on 17 June 2015). We checked reference lists of the included studies to identify any additional studies. We contacted specialists in the field and authors of the included trials for unpublished data. We included randomised controlled clinical trials that tested perioperative infraorbital nerve block for cleft lip repair in children, compared with other types of analgesia procedure, no intervention, or placebo (sham nerve block). We considered the type of drug, dosage, and route of administration used in each study. For the purposes of this review, the term 'perioperative' refers to the three phases of surgery, that is preoperative, intraoperative, and postoperative, and commonly includes ward admission, anaesthesia, surgery, and recovery. Two review authors (GF and EH) independently identified, screened, and selected the studies, assessed trial quality, and performed data extraction using the Cochrane Pain, Palliative and Supportive Care Review Group criteria. In case of disagreements, a third review author (EMKS) was consulted. We assessed the evidence using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). We included eight studies involving 353 children in the review. These studies reported different types of interventions (lignocaine or bupivacaine), observation times, and forms of measuring and describing the outcomes, making it difficult to conduct meta-analyses. In the comparison of infraorbital nerve block versus placebo, there was a large effect in mean postoperative pain scores (our first primary outcome) favouring the intervention group (standardised mean difference (SMD) -3.54, 95% confidence interval (CI) -6.13 to -0.95; very low-quality evidence; 3 studies; 120 children). Only one study reported the duration of analgesia (in hours) (second primary outcome) with a difference favouring the intervention group (mean difference (MD) 8.26 hours, 95% CI 5.41 to 11.11; very low-quality evidence) and less supplemental analgesic requirements in the intervention group (risk ratio (RR) 0.05, 95% CI 0.01 to 0.18; low-quality evidence). In the comparison of infraorbital nerve block versus intravenous analgesia, there was a difference favouring the intervention group in mean postoperative pain scores (SMD -1.50, 95% CI -2.40 to -0.60; very low-quality evidence; 2 studies; 107 children) and in the time to feeding (MD -9.45 minutes, 95% CI -17.37 to -1.53; moderate-quality evidence; 2 studies; 128 children). No significant adverse events (third primary outcome) were associated with the intervention, although three studies did not report this outcome. Five out of eight studies found no unwanted side effects after the nerve blocks. Overall, the included studies were at low or unclear risk of bias. The reasons for downgrading the quality of the evidence using GRADE related to the lack of information about randomisation methods and allocation concealment in the studies, very small sample sizes, and heterogeneity of outcome reporting. There is low- to very low-quality evidence that infraorbital nerve block with lignocaine or bupivacaine may reduce postoperative pain more than placebo and intravenous analgesia in children undergoing cleft lip repair. Further studies with larger samples are needed. Future studies should standardise the observation time and the instruments used to measure outcomes, and stratify children by age group.

Secondary Alveolar Bone Grafting in Orofacial Cleft: A Survey of a Portuguese Tertiary Hospital

Orofacial clefts are the most frequent craniofacial birth defects. In the presence of bone defect, the secondary alveolar bone grafting is the correction method most commonly accepted by clinicians. This study evaluates the result of this technique in a tertiary hospital. Analysis of the secondary alveolar bone grafting performed between 2007 and 2014, with inclusion of cases in which the iliac crest was the donor site for the graft and the clinical and imaging information was complete. The success of the intervention was assessed radiographically using the Bergland scale (type I-IV) and correlated to variables associated with pathology and/or surgical correction. Of the 32 secondary alveolar bone grafting performed, 29 met the inclusion criteria: 13 cases (44.8%) corresponded to complete unilateral pre-foramen clefts; four (13.8%) to complete bilateral pre-foramen clefts; eight (27.6%) to transforamen unilateral clefts and four (13.8%) to bilateral transforamen clefts. According to the scale of Bergland (applied with a mean follow-up of 8 ± 5 months) six were classified as type I, 15 as type II, five as type III and three as type IV. No association was found between the effectiveness of the surgery and the type of orofacial clefts, the presence of the incisor and the canine eruption phase. Five patients were re-operated (three of type II and two of type III at baseline). In this series, the secondary alveolar bone grafting was effective in most patients (72% type I and II) regardless of the type of orofacial clefts. The relatively high proportion of failures (10.3%) and subsequent need for re-intervention (17%) justify long-term follow up and the continuation of this study. It is important to highlight the multidisciplinary involvement in order to identify previously the ideal timing for each intervention and to optimize results.

Orthognathic Surgeries in Patients With Congenital Craniofacial Anomalies: Profile and Hospitalization Outcomes.

To examine the occurrence of complications in patients with congenital facial anomalies who underwent orthognathic surgeries and to identify the role of patient-related factors in occurrence of complications. Retrospective analysis of hospital discharge database. Nationwide inpatient sample for the years 2004 to 2010. All patients with a diagnosis of cleft lip and/or palate or congenital craniofacial anomalies and who had an orthognathic surgery were selected. Orthognathic surgery. Occurrence of complications. During the study period, a total of 8340 patients with congenital craniofacial anomalies underwent orthognathic surgeries. The overall complication rate was 9.1%. Six different complications (bacterial infections, hemorrhage, postoperative pneumonia, iatrogenic-induced complications such as accidental punctures/lacerations or pneumothorax, other infections, and respiratory complications) occurred in at least 1% of all patients having orthognathic surgeries. Ninety-five percent of patients were discharged routinely after surgery. Patients with high comorbid burden are at a higher risk for developing complications (P < .05). The current study findings indicate that orthognathic surgeries can be safely performed in patients with congenital craniofacial anomalies. The present study results reflect the practice patterns and hospitalization outcomes across the country and could serve as benchmarks for future well-designed prospective controlled studies to examine risk factors associated with complications for not only orthognathic surgeries but also for a wider range of surgical procedures.

Risk prediction models for oral clefts allowing for phenotypic heterogeneity.

Oral clefts are common birth defects that have a major impact on the affected individual, their family and society. World-wide, the incidence of oral clefts is 1/700 live births, making them the most common craniofacial birth defects. The successful prediction of oral clefts may help identify sub-population at high risk, and promote new diagnostic and therapeutic strategies. Nevertheless, developing a clinically useful oral clefts risk prediction model remains a great challenge. Compelling evidences suggest the etiologies of oral clefts are highly heterogeneous, and the development of a risk prediction model with consideration of phenotypic heterogeneity may potentially improve the accuracy of a risk prediction model. In this study, we applied a previously developed statistical method to investigate the risk prediction on sub-phenotypes of oral clefts. Our results suggested subtypes of cleft lip (CL) and palate have similar genetic etiologies (AUC = 0.572) with subtypes of CL only (AUC = 0.589), while the subtypes of cleft palate only (CPO) have heterogeneous underlying mechanisms (AUCs for soft CPO and hard CPO are 0.617 and 0.623, respectively). This highlighted the potential that the hard and soft forms of CPO have their own mechanisms despite sharing some of the genetic risk factors. Comparing with conventional methods for risk prediction modeling, our method considers phenotypic heterogeneity of a disease, which potentially improves the accuracy for predicting each sub-phenotype of oral clefts.

SATB2 gene variants in non-syndromic cleft lip with or without cleft palate in Indian population

ObjectivesNon-syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common craniofacial birth defects and little is known about its aetiology. Initial studies of cytogenetic analysis provided the clues for possible genes involved in the pathogenesis of NSCL/P. This approach led to the identification of SATB2 gene on 2q32-q33. The aim of this study was to determine the association between SATB2 mutations and NSCL/P. Materials and methodsThe rs137853127, rs200074373 and rs1992950 mutations of the SATB2 gene were investigated in 173 patients with NSCL/P and 176 normal controls using Kbioscience KASPar chemistry, which is a competitive allele-specific PCR SNP genotyping system. ResultsThe mutations in exon 6 (rs137853127 and rs200074373) were monomorphic, the intronic variant (rs1992950) was polymorphic and genotype distribution was in agreement with Hardy–Weinberg equilibrium. The rs1992950 genotype distribution is not statistically significant between NSCL/P and controls. ConclusionOur findings suggest that the SATB2 gene variations do not contribute to the development of NSCL/P in the south Indian population.