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.

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.

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.

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.

Effects of nasoalveolar molding on nasolabial aesthetics in patients with cleft lip and palate during pre-adolescence: A systematic review and meta-analysis of retrospective studies.

This study aims to analyze long-term effects of nasoalveolar molding (NAM) as a part of cleft primary management protocols on nasolabial aesthetics for patients with non-syndromic cleft lip and palate by conducting a systematic review and meta-analysis. Six electronic databases and two journals were searched up to July 2023. Studies comparing nasolabial outcomes between NAM and non-NAM protocols were selected for further analysis. Nasolabial aesthetics were the outcome of interest. Data extraction, methodological quality assessment, risk of bias assessment, meta-analysis and subgroup analysis were performed. Seven retrospective cohort studies were selected for a qualitative review and four for a quantitative analysis. The risk of bias assessment was moderate for most studies. Only studies utilizing the Asher-McDade rating (AMR) were included for meta-analyses. The protocols with NAM exhibited a significantly lower AMR score for vermillion border than other protocols. AMR scores for nasal form and nasal symmetry from protocols with NAM were significantly lower than protocols without any pre-surgical infant orthopaedics (PSIO) but not significantly different from protocols with other PSIO techniques. The AMR score for nasolabial profile from protocols with NAM was not significantly different from other protocols. However, subgroup analysis demonstrated that protocol combining NAM and primary rhinoplasty significantly lowered AMR scores for nasal form, nasal symmetry and nasolabial profile. For patients with unilateral cleft lip with or without palate (UCLP), this study found that a protocol combining NAM and primary rhinoplasty improved nasolabial outcomes while a protocol with NAM alone offered only limited benefits. For patients with BCLP, the available evidence remains inconclusive. Performing NAM in combination with primary rhinoplasty improves nasolabial aesthetics in patients with UCLP. PROSPERO (CRD4202128384).

Nasolabial morphological changes in patients with unilateral cleft lip and palate using a Korat-modified nasoalveolar moulding appliance with primary correction.

OBJECTIVE: The objective of this study is to measure the morphological changes of the nose and lip in patients with unilateral cleft lip and palate before and after cheiloplasty with primary rhinoplasty (primary correction) in conjunction with Korat-NAM usage. DESIGN: Longitudinal cohort study. SETTING: Cleft Center Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima, Thailand. SUBJECTS: Twenty-six patients with unilateral cleft lip and palate. INTERVENTIONS: Control group: only active obturator before primary correction. Experimental group: an active obturator and Korat-NAM I before primary correction. A customized endotracheal tube was retained in the nostril for 3 weeks before switching to Korat-NAM II for 1 year. MAIN OUTCOME MEASURES: Six measurements comprising nostril rim length, nostril height, nostril sill width, columella angle, vertical lip height, and horizontal lip length were measured from the patients' photographs. All measurements, except the columella angle, were reported as the cleft side/non-cleft side value ratio. Measurements were taken at the initial appointment, immediately before, 3 weeks after, and 1 year after primary correction. RESULTS: Nostril rim length ratio, nostril height ratio, nostril sill width ratio, columella angle on the cleft side, and vertical lip height ratio were improved using Korat-NAM before and 3 weeks after primary correction. Nostril rim length and height ratios were significantly better than the control group. CONCLUSIONS: Korat-NAM improved nose and lip morphology before primary correction. An overcorrection improved the nose and lip morphology on the cleft side. The nostril rim length and vertical lip height on the cleft side also improved with Korat-NAM II 1 year after primary correction.

Prospective study of nasal growth in bilateral cleft lip and palate patients after naso-alveolar moulding and primary columella lengthening compared to controls at 5, 10 and 20 years.

INTRODUCTION: A short columella, wide nostrils and a flat nasal tip are common features in patients with bilateral complete cleft lip and palate (BCLP). The objective of this study was to evaluate nasal morphology during growth in patients treated with naso-alveolar moulding (NAM) and primary surgical columella lengthening (PCL) compared with matched non-cleft individuals. STUDY DESIGN: Prospective longitudinal case-control study. PARTICIPANTS AND METHODS: Thirty-four consecutively treated BCLP patients at 5 and 10 years and at the end of growth (19.7 ± 2.0 years) were compared through normalized photogrammetry to a control of 34 age and sex-matched non-cleft individuals. Regression Models for Panel Data assessed how nasal measurements were influenced by surgery, age and gender. RESULTS: Nasal protrusion was equal to non-cleft controls at all ages. Length of the columella was also comparable to controls at 5 and 10 years, but significantly shorter at the end of growth. Inter-alar and nasal tip width and nasolabial angle were significantly wider than controls at all ages: More than 60% of the patients have asked for correction of the nasal width, but no early surgery for columella lengthening was needed. CONCLUSIONS: NAM and PCL have provided a nasal projection close to that of non-cleft individuals until adulthood, while length of the columella was physiological at 5 and 10, but shorter than controls at age 20. Width of the nasal tip and width of the alar bases were significantly wider than the controls and eventually required secondary nasal width correction in over two thirds of the sample.

Three-dimensional evaluation of secondary alveolar bone grafting in patients with unilateral cleft lip and palate: A 2-3 year post-operative follow-up.

OBJECTIVES: The present study aims to quantitatively assess secondary alveolar bone graft (SABG) resorption in unilateral cleft lip, alveolus and palate (UCLAP) patients in a 2-3 year longitudinal follow-up setting by using a validated 3D protocol. Furthermore, the potential relation of SABG resorption with maxillary canine position and a number of patient-related factors was investigated. METHODS: UCLAP patients who underwent SABG and had good quality CBCT images at the following timepoints were included in the study: pre-operative (T0), immediate (T1), 6 months (T2) and either 1-2 years (T3) or 2-3 years (T4) post-operative. The final bone grafted region was defined on the T1 scans and refined in the registered T0 scans. The bone graft after resorption was determined by applying threshold-based segmentation on the registered T2, T3 or T4 scans within the segmented bone graft volume. The position of the canines was determined at every timepoint at the cleft and non-cleft side. RESULTS: Forty-five UCLAP patients (mean age 9.0 ± 1.3 years) were included. In the first 6 months after SABG, 43.6% bone resorption was recorded. 2-3 years post-operative, 56% bone resorption was found if the maxillary canine was not yet erupted and 42.7% if it erupted through the graft. The vertical position of the canines was significantly higher on the cleft side at T3. CONCLUSIONS: The present study reports significant SABG resorption over time. However, no correlation was found between SABG resorption and canine position, nor between other patient-related factors.

Patient-reported outcomes in Irish adolescents who were born with cleft lip and palate.

BACKGROUND & PURPOSE: Cleft Lip and/or Palate, which affects approximately 1:650 live births in Ireland, is a complex congenital condition with lifelong implications. It can affect upper airway function, feeding, hearing, speech development, dental development as well as oral functioning, facial growth and physical appearance. Within cleft surgery, rigorous audit of speech, facial growth and nasolabial aesthetic outcomes is well-established. The importance of including patient-reported outcomes in our routine data-collection is now recognised. The purpose of the current study was to examine patient-reported outcomes (PROs) in a consecutive series of adolescents attending the Dublin Cleft Centre (DCC). METHODS: A validated patient-reported outcome measure (PROM), the CLEFT-Q, was prospectively administered to 156 patients attending the cleft clinic. Results were analysed according to cleft type and compared to those recorded in the CLEFT-Q validation study. RESULTS: Between (February 2020 and March 2022), the CLEFT-Q was administered to 156 patients with a mean age of 13.5 years (range 10-19 years). Males scored higher satisfaction across all subdomains irrespective of age. Satisfaction was higher in younger age groups compared to older patients in both appearance and quality of life outcomes. Patients with isolated cleft palate scored highest for satisfaction in school, social and psychological function. CONCLUSIONS: PRO data now informs consultations with patients and families at the DCC. This information is also useful in targeting service development to the specific needs of this patient group.

Predictors for long-term relapse of orthodontic treatment in patients with cleft lip and palate. A clinical follow-up study.

OBJECTIVES: To identify predictors for long-term relapse of orthodontic therapy in patients with cleft lip and palate (CLP). MATERIALS AND METHODS: Patients with uni- and bilateral non-syndromal CLP were followed up at least two years after completion of their orthodontic therapy. Plaster casts of the start of treatment (T1), after completion of treatment (T2), and at follow-up (T3) were measured using the modified Huddart Bodenham Index. Characteristics of multidisciplinary therapy were taken from the patient files. Potentially influencing factors of relapse were investigated using logistic regression analyses and Spearman correlations. RESULTS: In total 58.07% of the included 31 patients showed a stable treatment outcome at follow-up after an average of 6.9 years. Even if relapse occurred, 61.54% of these patients still showed improvement regarding their occlusion compared to baseline. Predictors for the occurrence of relapse were the severity of dysgnathia at baseline (p = 0.039) and the extent of therapeutic change (p = 0.041). The extent of therapeutic change was additionally a predictor for the extent of post-therapeutic relapse (ρ = 0.425; p = 0.019). CONCLUSIONS: Patients with CLP benefit from their orthodontic therapy in the long term despite an increased tendency to relapse. CLINICAL RELEVANCE: Results of this long-term study could be used to adapt the treatment concept for patients with CLP and reinforce the significance of a patient-centered orthodontic treatment concept for affected patients.

Craniofacial morphological variability in orthodontic patients with non-syndromic orofacial clefts: an approach using geometric morphometrics.

OBJECTIVES: Orofacial clefts are complex congenital anomalies that call for comprehensive treatment based on a thorough assessment of the anatomy. This study aims to examine the effect of cleft type on craniofacial morphology using geometric morphometrics. MATERIALS AND METHODS: We evaluated lateral cephalograms of 75 patients with bilateral cleft lip and palate, 63 patients with unilateral cleft lip and palate, and 76 patients with isolated cleft palate. Generalized Procrustes analysis was performed on 16 hard tissue landmark coordinates. Shape variability was studied with principal component analysis. In a risk model approach, the first nine principal components (PC) were used to examine the effect of cleft type. RESULTS: We found statistically significant differences in the mean shape between cleft types. The difference is greatest between bilateral cleft lip and palate and isolated cleft palate (distance of means 0.026, P = 0.0011). Differences between cleft types are most pronounced for PC4 and PC5 (P = 0.0001), which together account for 10% of the total shape variation. PC4 and PC5 show shape differences in the ratio of the upper to the lower face, the posterior mandibular height, and the mandibular angle. CONCLUSIONS: Cleft type has a statistically significant but weak effect on craniofacial morphological variability in patients with non-syndromic orofacial clefts, mainly in the vertical dimension. CLINICAL RELEVANCE: Understanding the effects of clefts on craniofacial morphology is essential to providing patients with treatment tailored to their specific needs. This study contributes to the literature particularly due to our risk model approach in lieu of a prediction model.

Comparison of craniomaxillofacial morphology in children with unilateral cleft lip and palate treated with/without presurgical nasoalveolar molding - a retrospective study with a mean age of 5 years.

OBJECTIVES: To three-dimensionally assess differences in craniomaxillofacial skeletal development in patients with operated unilateral cleft lip and palate (UCLP) treated with/without presurgical nasoalveolar molding (PNAM) with a mean age of 5 years. MATERIALS AND METHODS: Cone-beam CT radiographs of 30 patients with UCLP who had undergone PNAM and 34 patients with UCLP who did not receive PNAM were analyzed. The data were stored in DICOM file format and were imported into the Dolphin Imaging program for 3D image reconstruction and landmark identification. 33 landmarks, 17 linear and three angular variables representing craniofacial morphology were analyzed and compared by using the Mann-Whitney U tests. RESULTS: The vast majority of linear variables and 3D coordinates of landmark points reflecting craniofacial skeletal symmetry were not significantly different between the two groups. In terms of craniofacial skeletal development, the PNAM group had a significantly smaller anterior nasal spine offset in the midsagittal plane and a greater maxillary length compared to the non-PNAM group. CONCLUSIONS: Evaluations performed in early childhood showed that treatment with/without PNAM in the neonatal period was not a major factor influencing craniomaxillofacial hard tissue development in patients with UCLP; moreover, PNAM treatment showed significant correction of skeletal deviation at the base of the nose. CLINICAL RELEVANCE: Follow-up in early childhood has shown that PNAM treatment administered during the neonatal stage does not impede maxillary development and has benefits in correcting nasal floor deviation. It is a viable option for improving nasal deformity in children with unilateral cleft lip and palate.

Characterization of the oral microbiota and the relationship of the oral microbiota with the dental and periodontal status in children and adolescents with nonsyndromic cleft lip and palate. Systematic literature review and meta-analysis.

OBJECTIVE: To identify the characteristics of the oral microbiota and the relationship of the dental caries and periodontal status in patients aged 0 to 18 years with non-syndromic cleft lip and palate (CLP). MATERIALS AND METHODS: A systematic review of the literature was carried out. Five databases were consulted, including publications in English, Spanish and Portuguese. The evaluations of the quality of the observational studies and the experimental studies were carried out with the Newcastle-Ottawa scale and CONSORT guidelines, respectively. The risk of bias of the studies was determined using Rev Manager 5.4, and 5 publications were meta-analyzed. RESULTS: The cariogenic microbiota of children and adolescents with cleft lip and palate was similar to that of children without clefts, although with higher counts of Streptococcus mutans and Lactobacillus spp. The periodontopathogenic microbiota was related to the presence of Campylobacter spp, Fusobacterium spp, Fusobacterium nucleatum, Prevotella intermedia/nigrescens, Parvimonas micra and Porphyromonas gingivalis, considered microorganisms with high pathogenic capacity. Heterogeneity was shown in relation to the microbiota and the type of fissure, presenting numerous microorganisms associated with the pre- and post-surgical condition (cheilorrhaphy and palatorrhaphy) such as Staphylococcus aureus, Streptococcus beta hemolyticus, Klebsiella pneumoniae and Klebsiella oxytoca, Moraxella catarrhalis, Candida spp, Candida albicans, Candida krusei and Candida tropicalis. The meta-analysis revealed that patients with cleft lip and palate were 2.03 times more likely to have caries than the control group (p<0.005). CONCLUSION: In the microbiota, there was a great diversity of microorganisms that can vary according to the type of fissure and surgical interventions predisposing patients to a greater probability of dental caries, it is important to take into account the technique used to describe the oral microbiota in order to be able to compare the different studies. CLINICAL RELEVANCE: Studying the microbiota and the relationship of dental caries and periodontal status in children and adolescents with cleft lip and palate can facilitate the comprehensive care of patients with these conditions.

Comparison of different maxillary advancement protocols in patients with unilateral cleft lip and palate: a finite element analysis.

OBJECTIVES: The aim of this study was to evaluate the stress distributions and possible amount of movement in the maxillofacial region resulting from different maxillary advancement protocols in patients with unilateral cleft lip and palate. MATERIALS AND METHODS: A unilateral cleft lip and palate model (CLP model) with Goslon score 4 was created for finite element analysis. Three different protocols were compared: Group 1: usage of a face mask with elastics placed at a 30? angle to the occlusal plane over a conventional acrylic plate; Group 2: usage of a face mask with elastics placed at a 30? angle to the occlusal plane over miniplates placed in the infrazygomatic crest region; Group 3: usage of elastic from the menton plate placed in the mandible to the infrazygomatic plates in the maxilla. RESULTS: Dental effects were greater in the maxillary protraction protocol with a face mask over a conventional acrylic plate (Von Misses Stress Values; Group 1?=?cleft side:0.076, non-cleft side:0.077; Group 2?=?cleft side:0.004, non-cleft side: 0.003; Group 3?=?cleft side:0.0025; non-cleft side:0.0015), whereas skeletal effects were greater in maxillary protraction protocols with face mask using skeletal anchorage (Von Misses Stress Values; Group 1:0.008; Group 2:0.02; Group 3:0.0025). The maximum amount of counterclockwise rotation of the maxilla as a result of protraction was observed in traditional acrylic plate face mask protocol, and the minimum amount was observed by using elastics between infrazygomatic plates and menton plate. CONCLUSIONS: In individuals with unilateral cleft lip and palate with Goslon score 4, it was observed that the skeletally anchored face mask caused more skeletal impact and displacement than both the traditional acrylic plate face mask model and the pure skeletally supported maxillary protraction model. CLINICAL RELEVANCE: When planning maxillary protraction treatment in patients with cleft lip and palate, it should be considered that more movement in the sagittal plane might be expected on the cleft side than the non-cleft side, and miniplate and screws on the cleft side are exposed to more stress when using infrazygomatic plates as skeletal anchorage.

Three-dimensional Assessment of Longitudinal Surgical Outcome in Patients with Unilateral Cleft Lip and Palate: A Modified Rotation Advancement Technique.

BACKGROUND: Optimization of a modified rotation advancement technique is hampered by lack of objective measures to quantify the longitudinal surgical outcome. METHODS: We collected and assessed facial 3D images of 115 consecutive patients who underwent primary repair between 2017 and 2019. Photogrammetry was performed preoperatively, immediately postoperatively and at a first and second follow-up interval, occurring at an average year of 0.6 and 5.3 years, respectively. 10 additional age-matched noncleft control subjects were also included. RESULTS: Growth lag in cleft side lateral lip and gradual elongation of medial lip height on the cleft side caused continuous deviation of philtrum towards the cleft side. The columellar length on the cleft side continued to grow slower, accompanied by a persistent widening of alar base width on the cleft side, leading to in the gradual deviation of columella towards the cleft side. The pre-operative and post-operative nasolabial asymmetry would increase with greater degree of postoperative deficiencies. Right clefts presented with greater degrees of deficiencies in lateral lip height in preoperative measurement, but this discrepancy of the laterality of clefts was not observed in the two follow-up periods. CONCLUSION: The surgical outcome of this modified rotational advancement technique in unilateral cleft lip primary repair is promising. Growth lag in lateral lip and lateral displacement of alar base cause continuous deviation of philtrum towards the cleft side. Pre-operative severity does predict post-operative outcomes. Laterality of oral clefts does not significantly affect the long-term outcomes of surgery. PRACTICAL IMPLICATION: This surgical technique meets the current trend of cleft lip and palate primary repair and is worth promoting.

Stability between single and segmental maxillary osteotomies in bimaxillary surgery for cleft-associated class III deformity: a CBCT study.

OBJECTIVE: Segmental Le Fort I osteotomy through the cleft is a common strategy to narrow the alveolar cleft in adults. This study compared skeletal stability between single and segmental Le Fort I osteotomies in patients with unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: This retrospective analysis examined 45 adults with complete UCLP-associated class III deformities who underwent bimaxillary surgery with either single (n = 30) or segmental (n = 15) Le Fort I advancement. Cone beam computed tomography (CBCT) scans of the facial skeleton were acquired before surgery, 1-week postsurgery, and at follow-up. Measures of landmarks from the CBCT images for the two treatment groups were compared for translation (left/right, posterior/anterior, superior/inferior) and rotation (yaw, roll, pitch). RESULTS: Postsurgery, the downward movement of the maxilla was larger in the segmental group than the single group. At follow-up, the maxilla moved backward in both groups, and upward in the segmental group. The mandible moved forward and upward and rotated upward in both groups. The amount of upward movement and rotation was larger in the segmental group than the single group. CONCLUSIONS: Two years after bimaxillary surgery in patients with UCLP-associated class III deformity, greater relapse was found after segmental Le Fort I osteotomies in vertical translation of the maxilla and mandible, and pitch rotation of the mandible compared with single Le Fort I osteotomies. CLINICAL RELEVANCE: The vertical relapse of the maxilla was larger after segmental Le Fort I advancement compared with single Le Fort I advancement in clefts.

Congenital diaphragmatic hernia and cleft lip and palate: looking for a common genetic etiology.

PURPOSE: Congenital diaphragmatic hernia (CDH) and cleft lip and/or palate (CL/P) are inborn closure defects. Genetic factors in and outcomes for patients with both anomalies (CDH+CL/P) remain unclear. We aimed to investigate associated genetic aberrations, prevalence of, and outcomes for, CDH+CL/P. METHODS: Data from Congenital Diaphragmatic Hernia Study Group (CDHSG) registry were collected. CL/P prevalence in CDH patients was determined. Genetic abnormalities and additional malformations in CDH+CL/P were explored. Patient characteristics and outcomes were compared between CDH+CL/P and isolated CDH (CDH-) using Fisher's Exact Test for categorical, and t-test or Mann-Whitney U-test for continuous, data. p < 0.05 was considered statistically significant. RESULTS: Genetic anomalies in CDH+CL/P included trisomy 13, 8p23.1 deletion, and Wolf-Hirschhorn syndrome (4p16.3 deletion). CL/P prevalence in CDH was 0.7%. CDH+CL/P had lower survival rates than CDH-, a nearly fourfold risk of death within 7 days, were less supported with extracorporeal life support (ECLS), had higher non-repair rates, and survivors had longer length of hospital stay. CONCLUSION: Genetic anomalies, e.g. trisomy 13, 8p23.1 deletion, and Wolf-Hirschhorn syndrome, are seen in patients with the combination of CDH and orofacial clefts. CL/P in CDH patients is rare and associated with poorer outcomes compared to CDH-, influenced by goals of care decision-making.

Three-dimensional nasal asymmetry analysis between adolescence and adulthood in postoperative patients with unilateral cleft lip and palate using computed tomography.

AIM: To investigate the differences of the nasal soft and hard tissue asymmetry in postoperative patients with unilateral cleft lip and palate (UCLP) between adolescence and adulthood, and to explore the correlation of nasal soft and hard tissue asymmetry. METHODS: CT data from 47 repaired UCLP patients were included and divided into two groups:1. adolescent group: 23 patients (15 males, 8 females; age: 10-12 years old). 2. adult group: 24 patients (16 males, 8 females; age:18-32 years old). The three-dimensional asymmetry in nasal soft and hard tissues was analyzed. Additionally, the correlation between nasal soft and hard tissue asymmetry was also analyzed. RESULTS: Both the adolescent group and adult group showed asymmetries in nasal soft and hard tissues. Compared to the adolescent group, the adult group had a significantly increased horizontal asymmetry of nasal soft tissues Sbal (P < 0.05). Furthermore, the sagittal asymmetry of soft tissue Glat (P < 0.05), Sbal (P < 0.001), Sni (P < 0.001) and hard tissue LPA (P < 0.05) also increased significantly. In the adult group, there were more landmarks with a correlation between the asymmetry of nasal hard tissue and soft tissue compared to the adolescent group. There were moderate to strong correlations between nasal hard and soft tissue symmetries in the horizontal and sagittal directions (0.444 < r < 764), but no correlation in the vertical direction in the adult group (P > 0.05). CONCLUSIONS: The asymmetry of nasal soft and hard tissues in patients with repaired UCLP becomes more apparent in the horizontal and sagittal dimensions from adolescence to adulthood. The correlation between the asymmetry of nasal hard tissue and soft tissue becomes stronger in the horizontal and sagittal dimensions. These factors should be taken into account when performing treatment for repaired UCLP patients in adolescence and adulthood.

Being Normal yet Different: A Qualitative Study on the Dualistic Experience of Living With Unilateral Cleft Lip and Palate.

The aim of the present study was to describe the experiences of young adults living with cleft lip and palate (CLP) and to explore potential gender differences.A descriptive qualitative study was designed involving semi-structured interviews. The interviews were analyzed using qualitative content analysis, as described by Graneheim and Lundman.A total of 9 women and 8 men, aged 22 to 26 years with UCLP.The main theme identified was: the duality of living with a cleft-being normal yet different, and 2 subcategories: "My cleft and me" and "My cleft and the World." The participants described themselves as normal yet different, both in relation to themselves and in relation to others. They also stated that gender norms regarding appearance affected their lives and how they saw the cleft.This study adds to the growing body of qualitative research on CLP. It highlights the dualistic experiences of feeling normal and different at the same time. The interviews indicated that this dualism was based on context and gender, showing the psychological complexity of an individual. The clinical implications of this study emphasizes the need of a person-centered care approach in the cleft care setting where the clinicians are aware of the potential dualistic experience that also may differ over time that individuals with cleft can experience. This can also help clinicians better understand and help patients reduce distress and strengthen positive coping mechanisms.