Embryogenesis and Adult Life in the Absence of Intrinsic Apoptosis Effectors BAX, BAK, and BOK.

Intrinsic apoptosis, reliant on BAX and BAK, has been postulated to be fundamental for morphogenesis, but its precise contribution to this process has not been fully explored in mammals. Our structural analysis of BOK suggests close resemblance to BAX and BAK structures. Notably, Bok-/-Bax-/-Bak-/- animals exhibited more severe defects and died earlier than Bax-/-Bak-/- mice, implying that BOK has overlapping roles with BAX and BAK during developmental cell death. By analyzing Bok-/-Bax-/-Bak-/- triple-knockout mice whose cells are incapable of undergoing intrinsic apoptosis, we identified tissues that formed well without this process. We provide evidence that necroptosis, pyroptosis, or autophagy does not substantially substitute for the loss of apoptosis. Albeit very rare, unexpected attainment of adult Bok-/-Bax-/-Bak-/- mice suggests that morphogenesis can proceed entirely without apoptosis mediated by these proteins and possibly without cell death in general.

The heterogeneous genetic architectures of orofacial clefts.

Orofacial clefts (OFCs) are common, affecting 1:1000 live births. OFCs occur across a phenotypic spectrum - including cleft lip (CL), cleft lip and palate (CLP), or cleft palate (CP) - and can be further subdivided based on laterality, severity, or specific structures affected. Herein we review what is known about the genetic architecture underlying each of these subtypes, considering both shared and subtype-specific risks. While there are more known genetic similarities between CL and CLP than CP, recent research supports both shared and subtype-specific genetic risk factors within and between phenotypic classifications of OFCs. Larger sample sizes and deeper phenotyping data will be of increasing importance for the discovery of novel genetic risk factors for OFCs and various subtypes going forward.

Suppression of microRNA 124-3p and microRNA 340-5p ameliorates retinoic acid-induced cleft palate in mice.

The etiology of cleft lip with or without cleft palate (CL/P), a common congenital birth defect, is complex, with genetic and epigenetic, as well as environmental, contributing factors. Recent studies suggest that fetal development is affected by maternal conditions through microRNAs (miRNAs), a group of short noncoding RNAs. Here, we show that miR-129-5p and miR-340-5p suppress cell proliferation in both primary mouse embryonic palatal mesenchymal cells and O9-1 cells, a neural crest cell line, through the regulation of Sox5 and Trp53 by miR-129-5p, and the regulation of Chd7, Fign and Tgfbr1 by miR-340-5p. Notably, miR-340-5p, but not miR-129-5p, was upregulated following all-trans retinoic acid (atRA; tretinoin) administration, and a miR-340-5p inhibitor rescued the cleft palate (CP) phenotype in 47% of atRA-induced CP mice. We have previously reported that a miR-124-3p inhibitor can also partially rescue the CP phenotype in atRA-induced CP mouse model. In this study, we found that a cocktail of miR-124-3p and miR-340-5p inhibitors rescued atRA-induced CP with almost complete penetrance. Taken together, our results suggest that normalization of pathological miRNA expression can be a preventive intervention for CP.

A unique form of collective epithelial migration is crucial for tissue fusion in the secondary palate and can overcome loss of epithelial apoptosis.

Tissue fusion frequently requires the removal of an epithelium that intervenes distinct primordia to form one continuous structure. In the mammalian secondary palate, a midline epithelial seam (MES) forms between two palatal shelves and must be removed to allow mesenchymal confluence. Abundant apoptosis and cell extrusion support their importance in MES removal. However, genetically disrupting the intrinsic apoptotic regulators BAX and BAK within the MES results in complete loss of cell death and cell extrusion, but successful removal of the MES. Novel static- and live-imaging approaches reveal that the MES is removed through streaming migration of epithelial trails and islands to reach the oral and nasal epithelial surfaces. Epithelial trail cells that express the basal epithelial marker ΔNp63 begin to express periderm markers, suggesting that migration is concomitant with differentiation. Live imaging reveals anisotropic actomyosin contractility within epithelial trails, and genetic ablation of actomyosin contractility results in dispersion of epithelial collectives and failure of normal MES migration. These findings demonstrate redundancy between cellular mechanisms of morphogenesis, and reveal a crucial and unique form of collective epithelial migration during tissue fusion.

foxe1 mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations.

BACKGROUND: FOXE1 mutations in humans are associated with cleft palate and hypothyroidism. We previously developed a foxe1 mutant zebrafish demonstrating mineralization defects in larvae. In the present study, we investigate the thyroid status and skeletal phenotype of adult foxe1 mutants. RESULTS: Mutant fish have increased expression of tshß in the pituitary, and of hepatic dio1 and dio2. In plasma, we found higher Mg levels. Together these findings are indicative of hypothyroidism. We further observed mineralization defects in scales due to enhanced osteoclast activity as measured by increased expression levels of tracp, ctsk, and rankl. Gene-environment interactions in the etiology of FOXE1-related craniofacial abnormalities remain elusive, which prompts the need for models to investigate genotype-phenotype associations. We here investigated whether ethanol exposure increases the risk of developing craniofacial malformations in foxe1 mutant larvae that we compared to wild types. We found in ethanol-exposed mutants an increased incidence of developmental malformations and marked changes in gene expression patterns of cartilage markers (sox9a), apoptotic markers (casp3b), retinoic acid metabolism (cyp26c1), and tissue hypoxia markers (hifaa, hifab). CONCLUSION: Taken together, this study shows that the foxe1 mutant zebrafish recapitulates phenotypes associated with FOXE1 mutations in human patients and a clear foxe1-ethanol interaction.

Let-7c-5p associate with inhibition of phenobarbital-induced cell proliferation in human palate cells.

Cleft palate (CP) is one of the most common congenital diseases, and is accompanied by a complicated etiology. Medical exposure in women is among one of the reasons leading to CP. Recently, it has been reported that microRNA (miRNA) plays a crucial role in palate formation and the disruption of miRNA that influence the development of CP. Although association with pharmaceuticals and miRNAs were suggested, it has remained largely unknow. The aim of the current investigation is to elucidate upon the miRNA associated with the inhibition of phenobarbital (PB)-induced cell proliferation in human embryonic palatal mesenchymal (HEPM) cells. We showed that PB inhibited HEPM cell viability in a dose-dependent manner. We demonstrated that PB treatment suppressed cyclin-D1 expression in HEPM cells. Furthermore, PB upregulated let-7c-5p expression and downregulated the expression of two downstream genes (BACH1 and PAX3). Finally, we demonstrated that the let-7c-5p inhibitor alleviated PB-induced inhibition of cell proliferation and altered BACH1 and PAX3 expression levels. These results suggest that PB suppresses cell viability by modulating let-7c-5p expression.

Spectrum of Disease in Hospitalized Newborns with Congenital Micrognathia: A Cohort of 3,236 Infants at North American Tertiary-Care Intensive Care Units.

OBJECTIVE: To describe the spectrum of disease and burden of care in infants with congenital micrognathia from a multicenter cohort hospitalized at tertiary care centers. STUDY DESIGN: The Children's Hospitals Neonatal Database was queried from 2010 through 2020 for infants diagnosed with micrognathia. Demographics, presence of genetic syndromes, and cleft status were summarized. Outcomes included death, length of hospitalization, neonatal surgery, and feeding and respiratory support at discharge. RESULTS: Analysis included 3,236 infants with congenital micrognathia. Cleft palate was identified in 1266 (39.1%). A genetic syndrome associated with micrognathia was diagnosed during the neonatal hospitalization in 256 (7.9%). Median (IQR) length of hospitalization was 35 (16, 63) days. Death during the hospitalization (n = 228, 6.8%) was associated with absence of cleft palate (4.4%, P < .001) and maternal Black race (11.6%, P < .001). During the neonatal hospitalization, 1289 (39.7%) underwent surgery to correct airway obstruction and 1059 (32.7%) underwent gastrostomy tube placement. At the time of discharge, 1035 (40.3%) were exclusively feeding orally. There was significant variability between centers related to length of stay and presence of a feeding tube at discharge (P < .001 for both). CONCLUSIONS: Infants hospitalized with congenital micrognathia have a significant burden of disease, commonly receive surgical intervention, and most often require tube feedings at hospital discharge. We identified disparities based on race and among centers. Development of evidence-based guidelines could improve neonatal care.

Compound heterozygous variants in RAB34 in a rare skeletal ciliopathy syndrome.

Skeletal ciliopathies are a heterogenous group of congenital disorders characterized by multiple internal abnormalities, and distinct radiographic presentation. Pathogenic variants in at least 30 cilia genes are known to cause skeletal ciliopathies. Here we report a fetus with an atypical skeletal ciliopathy phenotype and compound heterozygous variants in the RAB34 gene. The affected fetus had multiple malformations, including posterior neck edema, micrognathia, low-set and small ears, auricular hypoplasia, cleft lip and palate, short extremities, and a combination of rarely occurring pre- and postaxial polydactyly. Genome sequencing identified compound heterozygous variants in the RAB34 gene: maternal c.254T>C, p.(Ile85Thr), and paternal c.691C>T, p.(Arg231*) variants. Only the paternal variant was present in the unaffected sibling. Evidence in the literature indicated that Rab34-/- mice displayed a ciliopathy phenotype with cleft palate and polydactyly. These features were consistent with malformations detected in our patient supporting the pathogenicity of the identified RAB34 variants. Overall, this case report further expands genetic landscape of human ciliopathy syndromes and suggests RAB34 as a candidate gene for skeletal ciliopathies.

Research Trends in the Relationship Between Orofacial Cleft and Cancer: A Bibliometric and Network Visualization Study.

OBJECTIVE: To use the bibliographic data of publications regarding the association between orofacial cleft (OC) and cancer to examine the implications of publication growth, co-citation, co-words, and authorship networks using bibliometric indicators and network visualization. METHODS: Bibliometric study analyzed documents related to the association between OC and cancer. Data were obtained in October 2023 from the Scopus, Pubmed, Web of Science. The search strategy was developed, and data obtained were imported into R ("bibliometrix") for analysis. Results: 70 documents were found from 1977 to 2023. Most were journal articles (90.0%) designed as case-control studies (42.8%). American Journal of Epidemiology was the most relevant source. The most cited document was Frebourg T, et al. (2006). Vieira A, Martelli-Junior were the most cited author. Most authors were affiliated to Brazil (University of Montes Claros) and United States (University of Pittsburgh). Research in this thematic has included children and adults of both sexes. Research trend points to gastric cancer, leukemia and breast cancer as the most investigated cancers in association to OC. CONCLUSION: This bibliometric analysis helps fill research gaps regarding the knowledge of the relationship between OC and cancer, providing some clues for selecting future research in this topic.

Analysis of publications regarding the association between orofacial cleft and cancer highlighted: The majority of publications as journal articles (90.0%) designed as case­control studies (42.8%).American Journal of Epidemiology was the most relevant source.The most global cited documents were Frebourg T, et al. (2006).Vieira A, Martelli-Junior was the top author of the published literature and the most local cited author.Most of the authors were mainly affiliated to Universities from Brazil (University of Montes Claros) and United States (University of Pittsburgh).Motor themes of study include genetic association studies, investigating single nucleotides polymorphisms shared by OC and cancer types.Research in this thematic has included children and adults of both sexes. Research trend points to gastric cancer, leukemia and breast cancer as the most investigated cancers in association to OC.

Cleft palate and minor metabolic disturbances in a mouse global Arl15 gene knockout.

ARL15, a small GTPase protein, was linked to metabolic traits in association studies. We aimed to test the Arl15 gene as a functional candidate for metabolic traits in the mouse. CRISPR/Cas9 germline knockout (KO) of Arl15 showed that homozygotes were postnatal lethal and exhibited a complete cleft palate (CP). Also, decreased cell migration was observed from Arl15 KO mouse embryonic fibroblasts (MEFs). Metabolic phenotyping of heterozygotes showed that females had reduced fat mass on a chow diet from 14 weeks of age. Mild body composition phenotypes were also observed in heterozygous mice on a high-fat diet (HFD)/low-fat diet (LFD). Females on a HFD showed reduced body weight, gonadal fat depot weight and brown adipose tissue (BAT) weight. In contrast, in the LFD group, females showed increased bone mineral density (BMD), while males showed a trend toward reduced BMD. Clinical biochemistry analysis of plasma on HFD showed transient lower adiponectin at 20 weeks of age in females. Urinary and plasma Mg2+ concentrations were not significantly different. Our phenotyping data showed that Arl15 is essential for craniofacial development. Adult metabolic phenotyping revealed potential roles in brown adipose tissue and bone development.

Monodactyly in a patient with CHARGE syndrome: An additional case report.

CHARGE syndrome is a rare autosomal dominant syndrome characterized by multiple congenital anomalies including coloboma, heart defects, ear anomalies, and developmental delay, caused by pathogenic variants in the CHD7 gene. The discovery of the molecular basis of this syndrome increased the number of cases reported and expanded the phenotype and clinical variability. Limb anomalies are occasional clinical findings in this syndrome, present in about 30% of reported cases. The occurrence of limb anomalies in this syndrome suggests that it should be considered as part of the phenotypic spectrum. Here, we describe an individual with CHARGE syndrome presenting unilateral monodactyly.

The society for craniofacial genetics and developmental biology 46th annual meeting.

The Society for Craniofacial Genetics and Developmental Biology (SCGDB) held its 46th Annual Meeting at Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio on October 10th-12th, 2023. On the first day of the meeting, Drs. Sally Moody and Justin Cotney were each honored with the SCGDB Distinguished Scientist Awards for their exceptional contributions to the field of craniofacial biology. The following two days of the meeting featured five sessions that highlighted new discoveries in signaling and genomic mechanisms regulating craniofacial development, human genetics, translational and regenerative approaches, and clinical management of craniofacial differences. Interactive workshops on spatial transcriptomics and scientific communication, as well as a poster session facilitated meaningful interactions among the 122 attendees representing diverse career stages and research backgrounds in developmental biology and genetics, strengthened the SCGDB community.

The Hard Palate Sweep: a multiplanar 2-dimensional sonographic method for the prenatal detection of cleft palate.

BACKGROUND: Prenatal diagnosis of cleft palate is challenging. Numerous 2-dimensional and 3-dimensional methods have been proposed to assess the integrity of the fetal palate, yet detection rates remain relatively low. We propose the "Hard Palate Sweep," a novel 2-dimensional method that enables clear demonstration of the entire fetal palate throughout pregnancy, in a single sweep, avoiding acoustic shadows cast by surrounding bones. OBJECTIVE: This study aimed to assess the feasibility and performance of the Hard Palate Sweep, performed throughout pregnancy. STUDY DESIGN: This was a prospective cross-sectional study performed between 2018 and 2022 in pregnant patients referred for a routine or targeted anomaly scan between 13 and 40 weeks of gestation. The presence or absence of a cleft palate was determined using the "Hard Palate Sweep." This was compared with the postnatal palate integrity assessment. Test feasibility and performance indices, including sensitivity, specificity, and positive and negative predictive values were calculated. Offline clips were reviewed by 2 investigators for the assessment of inter- and intraoperator agreement, using Cohen's kappa formula. The study protocol was approved by the institutional ethics committee. All participating patients were informed and provided consent. RESULTS: A total of 676 fetuses were included in the study. The Hard Palate Sweep was successfully performed in all cases, and 19 cases were determined to have a cleft palate. Of these, 13 cases were excluded because postmortem confirmation was not performed, leaving 663 cases available for analysis. Six cases determined to have a cleft palate were confirmed postnatally. In 655 of 657 cases prenatally determined to have an intact palate, this was confirmed postnatally. In the 2 remaining cases, rare forms of cleft palate were diagnosed postnatally, rendering 75% sensitivity, 100% specificity, 100% positive predictive value, and 99.7% negative predictive value for the Hard Palate Sweep (P<.001). There was complete intra- and interoperator agreement (kappa=1; P<.0001). CONCLUSION: The Hard Palate Sweep is a feasible and accurate method for prenatally detecting a cleft palate. It was successfully performed in all attempted cases between 13 and 40 weeks of gestation. This method is reproducible, offering high sensitivity and specificity. Implemented routinely, the Hard Palate Sweep is expected to increase the prenatal detection of cleft palate.

Severe periodontitis and congenital cytomegalovirus: Cleft lip and cleft palate.

Severe periodontitis lesions can harbor several hundred-thousand copies of active cytomegalovirus, and this paper proposes that cytomegalovirus in maternal periodontitis can infect the fetus. Cleft lips and palates may be oral examples of congenital cytomegalovirus infection. Anti-cytomegalovirus periodontal treatment is indicated for high-risk women who exhibit severe periodontitis and weakened immune system and are contemplating pregnancy or are in the first trimester of pregnancy.

Prenatal detection of orofacial clefts in Denmark from 2009 to 2018.

OBJECTIVE: To investigate the overall and type-specific prenatal detection rates (DRs) of orofacial clefts in a national cohort in Denmark. METHODS: This study was based on data from the Danish Fetal Medicine Database and included all fetuses and children from singleton pregnancies diagnosed with an orofacial cleft prenatally and/or postnatally between 2009 and 2018. The types of cleft included unilateral, bilateral or median cleft lip (CL); unilateral, bilateral or median cleft lip with secondary cleft palate (CLP); and cleft palate (CP). The clefts were grouped as cleft lip with or without cleft palate (CL(P)) or as all clefts (including CP). All cases with discordance between prenatal and postnatal diagnoses were validated in the local patient files (Astraia). Cases without prenatal validation of the postnatal diagnosis were marked as undetected. Postnatally diagnosed cases with a strong prenatal suspicion of a cleft but without an International Classification of Diseases-10 code were registered as prenatally detected. Termination of pregnancy and intrauterine death were registered as true positives even if no autopsy could be performed. Liveborn cases with a prenatal diagnosis but without a postnatal validation were excluded. RESULTS: A total of 994 cases were included in the study, of which 933 were liveborn. The prevalence of orofacial cleft was 1.6 per 1000 live births. There were no differences in the baseline characteristics between detected and undetected cases. The DR for CL(P) was 71.7% (95% CI, 64.8-78.9%), with an increase from 60.0% in 2009 to 73.0% in 2018 (P = 0.018). The type-specific DRs for the entire period were 56.4% (95% CI, 45.0-67.6%) for unilateral CL; 76.6% (95% CI, 71.7-82.9%) for unilateral CLP; 70.5% (95% CI, 52.1-87.6%) for bilateral CL; 82.3% (95% CI, 70.6-93.6%) for bilateral CLP; 0% (0/6) for median CL; 75.0% (3/4) for median CLP; and 3.3% (95% CI, 0.6-5.7%) for CP. A total of 20.9% (208/994) of the cases had associated findings, of which 33.2% (69/208) were genetic aberrations. CONCLUSIONS: The DR for CL(P) has improved in Denmark over the last decade. The DR for CLP is high, with the highest DR for bilateral CLP. However, prenatal detection of CP remains a challenge. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

An effective ultrasound fetal palate screening software based on the "sequential sector scan through the oral fissure" and three-dimensional ultrasound.

BACKGROUND: Orofacial clefts are one of the most common congenital malformations of the fetal face and ultrasound is mainly responsible for its diagnosis. It is difficult to view the fetal palate, so there is currently no unified standard for fetal palate screening, and the diagnosis of cleft palate is not included in the relevant prenatal ultrasound screening guidelines. Many prenatal diagnoses for cleft palate are missed due to the lack of effective screening methods. Therefore, it is imperative to increase the display rate of the fetal palate, which would improve the detection rate and diagnostic accuracy for cleft palate. We aim to introduce a fetal palate screening software based on the "sequential sector scan though the oral fissure", an effective method for fetal palate screening which was verified by our follow up results and three-dimensional ultrasound and to evaluate its feasibility and clinical practicability. METHODS: A software was designed and programmed based on "sequential sector scan through the oral fissure" and three-dimensional ultrasound. The three-dimensional ultrasound volume data of the fetal face were imported into the software. Then, the median sagittal plane was taken as the reference interface, the anterior upper margin of the mandibular alveolar bone was selected as the fulcrum, the interval angles, and the number of layers of the sector scan were set, after which the automatic scan was performed. Thus, the sector scan sequential planes of the mandibular alveolar bone, pharynx, soft palate, hard palate, and maxillary alveolar bone were obtained in sequence to display and evaluate the palate. In addition, the feasibility and accuracy of the software in fetal palate displaying and screening was evaluated by actual clinical cases. RESULTS: Full views of the normal fetal palates and the defective parts of the cleft palates were displayed, and relatively clear sequential tomographic images and continuous dynamic videos were formed after the three-dimensional volume data of 10 normal fetal palates and 10 cleft palates were imported into the software. CONCLUSIONS: The software can display fetal palates more directly which might allow for a new method of fetal palate screening and cleft palate diagnosis.

Effect of two different doses of nalbuphine for postoperative analgesia in children with cleft palate: a randomized controlled trial.

BACKGROUND: Cleft palate repair surgery may result in severe pain in the immediate postoperative period. The aim of this study is to compare the effects of different doses of nalbuphine for postoperative analgesia in children with cleft palate. METHODS: From November 2019 to June 2021, 90 children (45 males and 45 females, age 9-20 months old, ASA class I-II) were selected for palatoplasty. They were randomly divided into three groups: the control group (Group C), the N1 group (postoperative analgesia with 0.05 mg/kg/h nalbuphine) and the N2 group (postoperative analgesia with 0.075 mg/kg/h nalbuphine). Each group had 30 cases. Nalbuphine was not continuously infused in Group C but was continuously infused in Groups N1 and N2 at rates of 0.05 mg/kg/h and 0.075 mg/kg/h, respectively, for 24 h for postoperative analgesia. The FLACC analgesia score and Ramsay Sedation score were recorded at 10 min (T1), 30 min (T2), 2 h (T3), 12 h (T4) and 24 h (T5) after the operation. Adverse reactions such as nausea, vomiting and respiratory depression were observed and recorded. RESULTS: Compared with those in Group C, the FLACC scores in the N1 and N2 groups decreased significantly at T1-T5 (p < 0.05); the Ramsay Sedation score in the N1 group was significantly higher at T3 and T4 (p < 0.05), and that in the N2 group was significantly higher at T1-T5 (p < 0.05). Compared with that in the N1 group, the FLACC score in the N2 group was not significantly different, and the Ramsay Sedation score increased significantly at T5 (p < 0.05). CONCLUSION: Using 0.05 mg/kg/h Nalbuphine continuously for 24 h for postoperative analgesia in children with cleft palate has a better effect and fewer adverse reactions. TRIAL REGISTRATION: This study was registered at ChiCTR1900027385 (11/11/2019).

Maxillary arch dimensions in bilateral cleft lip and palate in the age 0-5 months.

INTRODUCTION: The complete bilateral cleft lip and palate (BCLP) divides the maxillary arch into three segments, separated from each other, resulting in abnormal growth of the alveolar arch. This study evaluated the maxillary arch dimensions in BCLP and compared them with neonates without craniofacial anomalies. METHODS: This retrospective study was conducted in a tertiary cleft centre. Sixty-six neonates aged 0-5 months were divided into two groups: cleft group-children with BCLP (23 boys and 18 girls) and control group-children without craniofacial deformities (15 boys and 10 girls). The dental models were processed by a 3D scanner. Landmarks were marked to achieve inter-canine distance, inter-tuberosity distance and arch length measurements. t-Tests were used for intergroup comparisons (p < .05). RESULTS: The maxillary cleft arch was demonstrated to be wider and longer in the posterior region compared to the control group. The inter-canine distance did not present differences between the cleft and controls. The inter-canine distance of the control group was the only measurement influenced by the variable sex. CONCLUSIONS: The cleft significantly interfered with the arch posterior width and arch sagittal length, making them larger. There was no statistical difference in the measurements between sex in the cleft group.

Age at primary surgery among orofacial cleft individuals in Indonesia.

OBJECTIVES: To observe the age at primary cleft surgery among charity organizations such as Smile Train in helping Indonesia manage patients with OFC. MATERIALS AND METHODS: A retrospective analysis of medical records was conducted to identify patients with orofacial clefts who underwent primary surgery between 2001 and 2021. The age at the time of surgery was recorded for each patient. Descriptive statistics were used to analyse the data and determine the average age at primary surgery. RESULTS: In the period between 2001 and 2021, a total of 34 239 individuals in Indonesia underwent primary lip surgery, while 16 768 individuals received primary palatal surgery, as recorded in the Smile Train database. Notably, a significant proportion of these surgeries were classified as delayed primary repairs. Approximately 65.3% of primary lip surgeries were performed beyond the recommended timeline of 6 months of age, indicating a delay in the surgical intervention. Similarly, 67% of primary palatal surgeries were also delayed, occurring after the recommended timeline of 18 months of life. CONCLUSIONS: This study provides insights into the age at primary surgery among individuals with orofacial clefts in Indonesia. The findings highlight the need for timely intervention and the importance of considering individualized treatment plans based on the specific type of orofacial cleft. Further research is warranted to explore factors influencing the age at primary surgery and their impact on treatment outcomes and long-term functional outcomes in this population.

Smartphone-based scans of palate models of newborns with cleft lip and palate: Outlooks for three-dimensional image capturing and machine learning plate tool.

OBJECTIVES: To evaluate the performance of smartphone scanning applications (apps) in acquiring 3D meshes of cleft palate models. Secondarily, to validate a machine learning (ML) tool for computing automated presurgical plate (PSP). MATERIALS AND METHODS: We conducted a comparative analysis of two apps on 15 cleft palate models: five unilateral cleft lip and palate (UCLP), five bilateral cleft lip and palate (BCLP) and five isolated cleft palate (ICP). The scans were performed with and without a mirror to simulate intraoral acquisition. The 3D reconstructions were compared to control reconstructions acquired using a professional intraoral scanner using open-source software. RESULTS: Thirty 3D scans were acquired by each app, totalling 60 scans. The main findings were in the UCLP sample, where the KIRI scans without a mirror (0.22 ± 0.03 mm) had a good performance with a deviation from the ground truth comparable to the control group (0.14 ± 0.13 mm) (p = .653). Scaniverse scans with a mirror showed the lowest accuracy of all the samples. The ML tool was able to predict the landmarks and automatically generate the plates, except in ICP models. KIRI scans' plates showed better performance with (0.22 ± 0.06 mm) and without mirror (0.18 ± 0.05 mm), being comparable with controls (0.16 ± 0.08 mm) (p = .954 and p = .439, respectively). CONCLUSIONS: KIRI Engine performed better in scanning UCLP models without a mirror. The ML tool showed a high capability for morphology recognition and automated PSP generation.