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.

Grainyhead-like 2 interacts with noggin to regulate tissue fusion in mouse.

Defective tissue fusion during mammalian embryogenesis results in congenital anomalies, such as exencephaly, spina bifida and cleft lip and/or palate. The highly conserved transcription factor grainyhead-like 2 (Grhl2) is a crucial regulator of tissue fusion, with mouse models lacking GRHL2 function presenting with a fully penetrant open cranial neural tube, facial and abdominal clefting (abdominoschisis), and an open posterior neuropore. Here, we show that GRHL2 interacts with the soluble morphogen protein and bone morphogenetic protein (BMP) inhibitor noggin (NOG) to impact tissue fusion during development. The maxillary prominence epithelium in embryos lacking Grhl2 shows substantial morphological abnormalities and significant upregulation of NOG expression, together with aberrantly distributed pSMAD5-positive cells within the neural crest cell-derived maxillary prominence mesenchyme, indicative of disrupted BMP signalling. Reducing this elevated NOG expression (by generating Grhl2-/-;Nog+/- embryos) results in delayed embryonic lethality, partial tissue fusion rescue, and restoration of tissue form within the craniofacial epithelia. These data suggest that aberrant epithelial maintenance, partially regulated by noggin-mediated regulation of BMP-SMAD pathways, may underpin tissue fusion defects in Grhl2-/- mice.

Genome-wide analysis of copy-number variation in humans with cleft lip and/or cleft palate identifies COBLL1, RIC1, and ARHGEF38 as clefting genes.

Cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex, heterogeneous etiology. It is well established that common and rare sequence variants contribute to the formation of CL/P, but the contribution of copy-number variants (CNVs) to cleft formation remains relatively understudied. To fill this knowledge gap, we conducted a large-scale comparative analysis of genome-wide CNV profiles of 869 individuals from the Philippines and 233 individuals of European ancestry with CL/P with three primary goals: first, to evaluate whether differences in CNV number, amount of genomic content, or amount of coding genomic content existed within clefting subtypes; second, to assess whether CNVs in our cohort overlapped with known Mendelian clefting loci; and third, to identify unestablished Mendelian clefting genes. Significant differences in CNVs across cleft types or in individuals with non-syndromic versus syndromic clefts were not observed; however, several CNVs in our cohort overlapped with known syndromic and non-syndromic Mendelian clefting loci. Moreover, employing a filtering strategy relying on population genetics data that rare variants are on the whole more deleterious than common variants, we identify several CNV-associated gene losses likely driving non-syndromic clefting phenotypes. By prioritizing genes deleted at a rare frequency across multiple individuals with clefts yet enriched in our cohort of individuals with clefts compared to control subjects, we identify COBLL1, RIC1, and ARHGEF38 as clefting genes. CRISPR-Cas9 mutagenesis of these genes in Xenopus laevis and Danio rerio yielded craniofacial dysmorphologies, including clefts analogous to those seen in human clefting disorders.

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.

Divergent growth of the transient brain compartments in fetuses with nonsyndromic isolated clefts involving the primary and secondary palate.

Cleft lip/palate is a common orofacial malformation that often leads to speech/language difficulties as well as developmental delays in affected children, despite surgical repair. Our understanding of brain development in these children is limited. This study aimed to analyze prenatal brain development in fetuses with cleft lip/palate and controls. We examined in utero MRIs of 30 controls and 42 cleft lip/palate fetal cases and measured regional brain volumes. Cleft lip/palate was categorized into groups A (cleft lip or alveolus) and B (any combination of clefts involving the primary and secondary palates). Using a repeated-measures regression model with relative brain hemisphere volumes (%), and after adjusting for multiple comparisons, we did not identify significant differences in regional brain growth between group A and controls. Group B clefts had significantly slower weekly cerebellar growth compared with controls. We also observed divergent brain growth in transient brain structures (cortical plate, subplate, ganglionic eminence) within group B clefts, depending on severity (unilateral or bilateral) and defect location (hemisphere ipsilateral or contralateral to the defect). Further research is needed to explore the association between regional fetal brain growth and cleft lip/palate severity, with the potential to inform early neurodevelopmental biomarkers and personalized diagnostics.

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.

A novel TTC26 variant in a patient with hexadactyly, pituitary stalk interruption, hepatopathy, nephropathy, and bilateral lip-palate cleft: A case report and expansion of the phenotype.

Biallelic pathogenic variants in the TTC26 gene are known to cause BRENS (biliary, renal, neurological, skeletal) syndrome, an ultra-rare autosomal recessive condition with only few patients published to date. BRENS syndrome is characterized by hexadactyly, severe neonatal cholestasis, and involvement of the brain, heart, and kidney, however the full phenotypic and genotypic spectrum is unknown. Here, we report on a previously undescribed homozygous intronic TTC26 variant (c.1006-5 T > C) in a patient showing some of the known TTC26-associated features like hexadactyly, hypopituitarism, hepatopathy, nephropathy, and congenital heart defect. Moreover, he presented with a suspected unilateral hearing loss and bilateral cleft lip-palate. The variant is considered to affect correct splicing by the loss of the canonical acceptor splice site and activation of a cryptic acceptor splice site. Hereby, our patient represents one additional patient with BRENS syndrome carrying a previously unreported TTC26 variant. Furthermore, we confirm the involvement of the pituitary gland to be a common clinical feature of the syndrome and broaden the clinical spectrum of TTC26 ciliopathy to include facial clefts and a probable hearing involvement.

Prevalence rates for ectodermal dysplasia syndromes.

BACKGROUND: Ectodermal dysplasias (EDs) are a heterogeneous group of genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives, including hair, teeth, nails, and certain glands. There are currently 49 recognized EDs with molecularly confirmed etiology. The EDs are very rare disorders, individually and in aggregate. Very little is published regarding the prevalence of these rare disorders. As a result of the genomics revolution, rare diseases have emerged as a global health priority. The various disabilities arising from rare disorders, as well as diagnostic and treatment uncertainty, have been demonstrated to have detrimental effects on the health, psychosocial, and economic aspects of families affected by rare disorders. Contemporary research methodologies and databases can address what have been historic challenges encountered when conducting research on rare diseases. OBJECTIVE: In this study, we aim to ascertain period prevalence rates for several of the more common ectodermal dysplasia syndromes, by querying a large multicenter database of electronic health records, Oracle Real-World Data. METHODS: For each of the included ectodermal dysplasia syndromes a clinical definition was developed by a committee of international experts with interests in EDs. The clinical definitions were based upon a combination of clinical features and designated by ICD-9 and ICD-10 codes. The January 2023 version of the Oracle Real-World Data database was queried for medical records that coincided with the clinical definitions. For our study, there were 64,523,460 individual medical records queried. RESULTS: Period prevalence rates were calculated for the following ED disorders: hypohidrotic ectodermal dysplasia, found to be 2.99 per 100,000; ectodermal dysplasia and immunodeficiency 1, 0.23 per 100,000; Clouston syndrome, 0.15 per 100,000; ectrodactyly ectodermal dysplasia and cleft lip/palate syndrome, 0.61 per 100,000; ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, 0.36 per 100,000; focal dermal hypoplasia, 0.10 per 100,000; and incontinentia pigmenti, 0.88 per 100,000. CONCLUSION: This study established estimated period prevalence rates for several of the ectodermal dysplasia syndromes, and it demonstrated the feasibility of utilizing large multicenter databases of electronic health records, such as Oracle Real World Data.

Variable phenotype of a null PPP1R13L allele in children with dilated cardiomyopathy.

Childhood-onset cardiomyopathy is a genetically heterogeneous group of conditions with several genes implicated. Recently, biallelic loss-of-function variants in PPP1R13L have been reported in association with a syndromic form of dilated cardiomyopathy (DCM). In addition, affected children manifest skin and hair abnormalities, cleft lip and palate (CLP), and eye findings. Here, we delineate the condition further by describing the phenotype associated with a homozygous frameshift variant (p.Arg330 ProfsTer76) in PPP1R13L detected in two sibships in a consanguineous family with six affected children. The index case had DCM and wooly hair, two of his siblings had DCM and CLP while three cousins had, in addition, glaucoma. Global developmental delay was observed in one child. All the children, except one, died during early childhood. Whole exome sequencing and whole genome sequencing did not reveal any other plausible variant. We provide further evidence that implicates PPP1R13L in a variable syndromic form of severe childhood-onset DCM and suggests expanding the spectrum of this condition to include glaucoma. Given the variability of the phenotype associated with PPP1R13-related DCM, a thorough evaluation of each case is highly recommended even in the presence of an apparently isolated DCM.

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.

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.

Reflecting the human lip in vitro: Cleft lip skin and mucosa keratinocytes keep their identities.

OBJECTIVES: Cell models have shown great promise as tools for research, potentially providing intriguing alternatives to animal models. However, the original tissue characteristics must be maintained in culture, a fact that is often assumed, but seldom assessed. We aimed to follow the retention of the original tissue identities of cleft lip-derived skin and mucosa keratinocytes in vitro. METHODS: Cleft lip-derived keratinocytes were isolated from discarded tissue along the cleft margins during cheiloplasty. Cell identities were assessed by immunohistochemistry and quantitative real-time PCR for tissue-specific markers and compared with native lip tissue. Moreover, keratinocytes were regularly analyzed for the retention of the original tissue characteristics by the aforementioned methods as well as by differentiation assays. RESULTS: The various anatomical zones of the human lip could be distinguished using a panel of differentiation and functional-based markers. Using these markers, retention of the original tissue identities could be followed and confirmed in the corresponding primary keratinocytes in culture. CONCLUSIONS: Our findings promote patient-derived cells retaining their original identities as astonishing and clinically relevant in vitro tools. Such cells allow a better molecular understanding of various lip-associated pathologies as well as their modeling in vitro, including but not restricted to orofacial clefts.

Efficacy of intranasal administration of dexmedetomidine in combination with midazolam for sedation in infant with cleft lip and palate undergoing CT scan: a randomized controlled trial.

BACKGROUND: There is a great challenge to sedation for infants with cleft lip and palate undergoing CT scan, because there is the younger age and no consensus on the type, dosage, and route of drug administration. OBJECTIVE: This study aimed to evaluate the efficacy of intranasal administration of dexmedetomidine combined with midazolam as a sedative option for infants with cleft lip and palate under imaging procedures. METHODS: Infants scheduled for cleft lip and palate repair surgery were randomly assigned to the IND group (intranasal dexmedetomidine 2 µg/kg alone) and the INDM group (intranasal dexmedetomidine 2 µg/kg combined with midazolam 0.05 mg/kg). The primary outcome was the proportion of infants underwent successful computed tomography (CT) scans under intranasal sedation. The secondary outcomes included onset time and duration of sedation, recovery time, Ramsay sedation scale, hemodynamic parameters during sedation, and adverse events. Data analyses involved the unpaired t-test, the repeated-measures analysis of variance test, and the continuity correction χ2 test. RESULTS: One hundred five infants were included in the analysis. The proportion of infants underwent successful CT scans under sedation was significantly greater in the INDM group than in the IND group (47 [95.9%] vs. 45 [80.4%], p = 0.016). Additionally, the INDM group had a shorter onset time and a longer duration of sedation statistically (12 [8.5, 17] min vs. 16 [12, 20] min, p = 0.001; 80 [63.6, 92.5] min vs. 68.5 [38, 89] min, p = 0.014, respectively), and their recovery time was significantly longer (43 [30, 59.5] min vs. 31.5 [20.5, 53.5] min, p = 0.006). The difference in Ramsay sedation scale values 20 min after administration was statistically significant between the groups. No statistically significant difference was found between the groups in changes in heart rate and respiratory rate. CONCLUSION: Intranasal administration of dexmedetomidine in combination with midazolam resulted in higher sedation success in comparison with sole dexmedetomidine. However, it has a relatively prolonged duration of sedation and recovery time. TRIAL REGISTRATION: ChiCTR2100049122, Clinical trial first registration date: 21/07/2021.

Foreign-born 5-year-old children with cleft palate had poorer speech outcomes than their native-born peers.

AIM: Speech difficulties are common in children with cleft palate, but research on foreign-born children is limited. This study aimed to compare speech outcomes, surgery and speech intervention in 5-year-old foreign-born and Swedish-born children with cleft palate with or without cleft lip. METHODS: This retrospective study analysed data from the Swedish cleft lip and palate registry for children born between 2009 and 2016 using Pearson's Chi-squared test and binary logistic regression. RESULTS: Among 160 foreign-born (106 boys, 54 girls) and 847 Swedish-born (479 boys, 368 girls) 5-year-olds, foreign-born children had significantly lower rates of sufficient velopharyngeal competence (77% vs. 86%), age-appropriate consonant production (28% vs. 60%), and speech without non-oral speech errors (70% vs. 86%). Differences remained after adjustment for cleft type, gender and additional diagnosed conditions. After further adjustments for age at completed primary palatal surgery, differences in age-appropriate consonant production and speech without non-oral speech errors remained significant. Foreign-born children underwent completed primary palatal surgery at older ages and received more secondary palatal surgery and speech intervention than Swedish-born peers. CONCLUSION: Foreign-born children showed poorer speech outcomes than Swedish-born peers, despite more secondary palatal surgery and speech intervention. Age at completed primary palatal surgery could partly explain these differences.

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.

Association between sex of the individual with untreated cleft lip and social judgement made by lay persons: A cross-sectional study.

OBJECTIVE: To assess whether there is an association between an individual's sex and social judgements made by lay persons regarding untreated cleft lip. MATERIALS AND METHODS: Lay individuals over 18 years old were recruited through an application to respond online to two questionnaires: a sociodemographic survey and the Brazilian Version of Lay Persons' Social Judgements about Cleft-lip Scale (B-LSojCleft-S). B-LSojCleft-S comprises 14 items evaluating social judgements made by laypersons concerning different types of untreated cleft lips in teenagers. The 14 items are linked to 8 images featuring untreated cleft lips and 1 image without a cleft (control). Higher scores represented more favourable social judgements. Independent samples t-test, paired, and multiple linear regression were conducted (P < 0.05). The study assessed judgements of untreated cleft lips in male and female adolescents using the B-LSojCleft-S. RESULTS: The mean age of the 217 participants was 37.78 ± 12.39 years, predominantly women (72.7%), married (47.7%), with a monthly income below three minimum wages (35.6%) in the majority of cases. Significantly higher social judgement scores were observed in the control group (no cleft) compared to any type of cleft (P < 0.001), with similar scores obtained for the same types of clefts with female or male images (P > 0.05). The participant's sex is associated with social judgement scores (F [1, 214] = 6.318, P = 0.013; adjusted R2 = 0.024), with females making more favourable judgements than males (P < 0.05). CONCLUSIONS: Individuals with cleft lips receive more negative social judgement scores, regardless of their own sex. Women make better social judgements than men.

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.

Impact of protraction or orthognathic surgery for class III malocclusion on longitudinal quality of life in patients with cleft lip and palate.

OBJECTIVES: This study assessed overall quality of life (QoL) over time in youth with cleft lip and palate (CLP) undergoing maxillary protraction treatment or orthognathic surgery for class III malocclusion to identify any differences in QoL based on treatment group and outcome success. MATERIALS AND METHODS: A prospective longitudinal cohort study was conducted in two pediatric hospitals. The Short Form Health Survey (SF-12) measured physical and mental QoL prior to treatment, at maximal correction, at treatment completion, and at 1-year post treatment. Analyses included one-sample, two-sample, and paired t-tests and analyses of variance and covariance. RESULTS: Participants (N = 91) either completed protraction (n = 53) at age 11-14 or surgery (n = 38) at age 16-21. Participants were mostly Latinx (67%) males (55%) born with unilateral CLP (81%) and there were no demographic differences between the two groups other than age. The total sample's QoL was in the average range and significantly higher than national norms. No significant differences were found in QoL-based outcome success; however, the protraction group showed a gradual physical QoL improvement over time, while the surgery group experienced a temporary drop in physical QoL postoperatively. At treatment completion, higher physical QoL was associated with higher socioeconomic status. At a year post treatment, mental QoL was significantly higher for males. CONCLUSION: Both protraction and surgery appear to be acceptable treatment options in terms of overall QoL for youth with CLP. While treatment success did not impact QoL, there were some differences in physical QoL coinciding with the treatment phase as well as individual factors.