Reducing delayed detection of isolated cleft palate-related deformity: a call for routine intraoral examination of newborns

Abstract Objective: To provide healthcare professional-friendly practical recommendations for early detection of cleft palate-related deformities in newborns and offer an overview of managing these high-prevalent congenital abnormalities. Source of data: PubMed, SciELO, Lilacs, Cochrane, ScienceDirect, and Scopus databases were reviewed for cleft- and diagnosis-related studies. Summary of the findings: Unfortunately, the global prevalence of delayed detection of cleft palate-related deformities remains unacceptably high, with over a quarter of cleft palates missed at birth. This delayed identification causes physical and psychological distress for patients and families, including feeding challenges and weight faltering. To improve cleft management, it is essential to adopt routine detailed, in-depth intraoral examination immediately after birth. It is recommended not only to finger-assisted palpate the intraoral structures but also to visually inspect the oral cavity from gingiva to uvula using a wooden tongue depressor and light-assisted examination. With timely diagnosis and referral to specialized care, pediatricians, nurses, speech therapists, and plastic surgeons provide life-changing treatments, including health care maintenance, anticipatory guidance, feeding support, primary surgical reconstruction, and age-and condition-specific protocols. Conclusions: Encouraging neonatologists and pediatricians, who are the first to examine new-borns, to actively investigate the intraoral region for cleft palate-related deformities is instrumental in optimizing therapeutic approaches and prioritizing age-phases in treatment. Their crucial role in early detection and referral can lead to transformative outcomes, impacting not only the future of the newborns by facilitating functional integration into society but also yielding positive effects on families and the health system.

Orofacial Clefts and Maternal Risk Factors: A Population-Based Case-Control Study.

BACKGROUND/OBJECTIVES: Orofacial clefts (OFCs) are some of the most common congenital anomalies worldwide. The aim of this case-control study was to evaluate the association of OFCs with selected maternal characteristics. METHODS: Data on isolated non-syndromic cases of OFCs were extracted from the population-based registry of congenital anomalies of Tuscany. A sample of live-born infants without any congenital anomaly was used as the control group. We investigated the association with sex and some maternal characteristics: age, body mass index, smoking, and education. Adjusted odds ratios (OR) were calculated using a logistic regression model. Analyses were performed for the total OFCs and separately for cleft lip (CL) and cleft palate (CP). RESULTS: Data on 219 cases and 37,988 controls were analyzed. A higher proportion of males (57.9%) was observed, particularly for CL. A decreasing trend among the maternal age classes was observed (OR:0.81 (95%CI 0.70-0.94)). Underweight mothers had a higher prevalence of OFCs, in particular for CL (OR:1.88 (95%CI 1.08-3.26)). CONCLUSIONS: We found an association of OFCs with lower maternal age. The association with maternal age remains controversial and further epidemiological evidence is needed through multicenter studies. We observed that CL was more common in underweight mothers, suggesting actions of primary prevention.

Three-Dimensional Anthropometric Analysis of the Effect of Lip Reconstructive Surgery on Children with Cleft Lip and Palate at Three Different Times.

OBJECTIVES: This investigation aimed to assess the optimal timing for lip repair in children with cleft lip and palate via 3D anthropometric analysis to evaluate their maxillofacial structures. METHODS: The sample comprised 252 digitized dental models, divided into groups according to the following timing of lip repair: G1 (n = 50): 3 months; G2 (n = 50): 5 and 6 months; G3 (n = 26): 8 and 10 months. Models were evaluated at two-time points: T1: before lip repair; T2: at 5 years of age. Linear measurements, area, and Atack index were analyzed. RESULTS: At T1, the intergroup analysis revealed that G1 had statistically significant lower means of I-C', I-C, C-C', and the sum of the segment areas compared to G2 (p = 0.0140, p = 0.0082, p = 0.0004, p < 0.0001, respectively). In addition, there was a statistically significant difference when comparing the cleft area between G2 and G3 (p = 0.0346). At T2, the intergroup analysis revealed that G1 presented a statistically significant mean I-C' compared to G3 (p = 0.0461). In the I-CC' length analysis, G1 and G3 showed higher means when compared to G2 (p = 0.0039). The I-T' measurement was statistically higher in G1 than in G2 (p = 0.0251). In the intergroup growth rate analysis, G1 and G2 showed statistically significant differences in the I-C' measurement compared to G3 (p = 0.0003). In the analysis of the Atack index, there was a statistically significant difference between G1 and the other sample sets (p < 0.0001). CONCLUSION: Children who underwent surgery later showed better results in terms of the growth and development of the dental arches.

"Long term speech outcomes after using the Sommerlad technique for primary palatoplasty: a retrospective study in the Wilhelmina Children's Hospital, Utrecht."

OBJECTIVES: After cleft lip and/or palate (CL/P) repair, children may develop velopharyngeal insufficiency (VPI) leading to speech imperfections, necessitating additional speech correcting surgery. This study examines the incidence of VPI and speech correcting surgery after Sommerlad's palatoplasty for CL/P, and its association with various clinical features. MATERIALS AND METHODS: A retrospective cohort study was performed in the Wilhelmina Children's Hospital in Utrecht and child records from 380 individuals with CL/P registered from 2008 to 2017 were retrospectively reviewed. Inclusion criteria comprised the diagnosis of CL/P, primary palatoplasty according to Sommerlad's technique, and speech assessment at five years or older. Association between cleft type and width, presence of additional genetic disorders and postoperative complications (palatal dehiscence, fistula) were assessed using odds ratios and chi squared tests. RESULTS: A total of 239 patients were included. The VPI rate was 52.7% (n = 126) and in 119 patients (49.8%) a speech correcting surgery was performed. Severe cleft type, as indicated by a higher Veau classification, was associated with a significant higher rate of speech correcting surgeries (p = 0.033). Significantly more speech correcting surgeries were performed in patients with a cleft width >10 mm, compared to patients with a cleft width ≤10 mm (p < 0.001). Patients with oronasal fistula underwent significantly more speech correcting surgeries than those without fistula (p = 0.004). No statistically significant difference was found in the incidence of speech correcting surgery between patients with and without genetic disorders (p = 0.890). CONCLUSIONS/CLINICAL RELEVANCE: Variations in cleft morphology, cleft width and complications like oronasal fistula are associated with different speech outcomes. Future research should focus on creating a multivariable prediction model for speech correcting surgery in CL/P patients.

Risk Factors for Replacement of Tympanostomy Tubes After Surgical Removal for Pediatric Patients.

OBJECTIVES: Ear tube removal and patch myringoplasty are frequently performed. The indication and timing for surgery varies among otolaryngologists. This study identifies risk factors associated with the need for the replacement of tympanostomy tubes after tube removal and myringoplasty. STUDY DESIGN: Case series with chart review. SETTING: Single institution academic otolaryngology practice. METHODS: Patients younger than 12 years of age who underwent tympanostomy tube removal and myringoplasty at the University of Rochester Medical Center from March 2011 to September 2019. Patients with tympanostomy tube removal due to chronic otorrhea were excluded. RESULTS: One hundred sixty-one patients (230 ears) met inclusion criteria and had sufficient follow-up. Myringoplasty success after tube removal was 94.8%. Successful myringoplasty was associated with shorter tube duration (32 months) versus unsuccessful myringoplasty (40 months) (P = .02). Replacement tympanostomy tubes after myringoplasty occurred in 9.6% of ears. There was no difference in average patient age (P = .96) or duration of tubes (P = .74) in patients who required replacement of tympanostomy tubes versus patients who did not require tube replacement. Patients with a cleft abnormality were more likely to require tympanostomy tube replacement (P < .001). CONCLUSIONS: Most children do not need tubes replaced after removal. This study identified cleft abnormality as a factor that increased the need for replacement tubes. Longer tube durations of over 3 years negatively impacted myringoplasty success. Tympanostomy tube removal should be considered 2 to 3 years after placement in most patients with longer tube durations considered in children with a repaired cleft palate.

Ectodermal dysplasia and cholesteatoma: A cross-sectional analysis of otologic issues.

OBJECTIVES: Previous studies have also associated cleft palate with increased cholesteatoma risk. Despite this close relation, the incidence of cholesteatoma and associated otologic issues in patients with ectodermal dysplasia types highly associated with cleft palate (EDT-ACPs) has not been formally analyzed. This study provides insight to guide clinicians caring for patients with ED types associated with cleft palate. METHODS: Individuals with TP63 disorders and Goltz syndrome/Focal Dermal Hypoplasia in the National Foundation for Ectodermal Dysplasia database were contacted for participation in an online REDCap survey from Sept-Dec '22. Descriptive statistics were generated using SAS JMP Pro 17 statistical software. RESULTS: 65 individuals participated in the survey (response rate approx. 18 %). The median [IQR] age was 22 [14, 43], 41 (63 %) were female, and Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate Syndrome (EEC) was most common (n = 26, 40 %). We found that, among our respondents with a history of cleft palate, the incidence of cholesteatoma was 39 %. Among respondents without a history of cleft palate, the incidence of cholesteatoma was 13 % CONCLUSIONS: Otologic issues, such as cholesteatoma, can have permanent implications including hearing loss that can be minimized by early identification and treatment. The estimated incidence of cholesteatoma among our participants is far above the estimated incidence of cholesteatoma in the general population with and without a history of cleft palate, suggesting an independent contribution of EDT-ACPs to the risk of cholesteatoma.

Speech Outcomes after Delayed Hard Palate Closure and Synchronous Secondary Alveolar Bone Grafting in Patients with Cleft Lip, Alveolus and Palate.

Background The best timing of closure of the hard palate in individuals with cleft lip, alveolus, and palate (CLAP) to reach the optimal speech outcomes and maxillary growth is still a subject of debate. This study evaluates changes in compensatory articulatory patterns and resonance in patients with unilateral and bilateral CLAP who underwent simultaneous closure of the hard palate and secondary alveolar bone grafting (ABG). Methods A retrospective study of patients with nonsyndromic unilateral and bilateral CLAP who underwent delayed hard palate closure (DHPC) simultaneously with ABG at 9 to 12 years of age from 2013 to 2018. The articulatory patterns, nasality, degree of hypernasality, facial grimacing, and speech intelligibility were assessed pre- and postoperatively. Results Forty-eight patients were included. DHPC and ABG were performed at the mean age of 10.5 years. Postoperatively hypernasal speech was still present in 54% of patients; however, the degree of hypernasality decreased in 67% ( p < 0.001). Grimacing decreased in 27% ( p = 0.015). Articulation disorders remained present in 85% ( p = 0.375). Intelligible speech (grade 1 or 2) was observed in 71 compared with 35% of patients preoperatively ( p < 0.001). Conclusion This study showed an improved resonance and intelligibility following DHPC at the mean age of 10.5 years, however compensatory articulation errors persisted. Sequential treatments such as speech therapy play a key role in improvement of speech and may reduce remaining compensatory mechanisms following DHPC.

Review of Current Techniques of Cleft Palate Repair Concerning Palatal Innervation: A Preliminary Assumption.

OBJECTIVE: To highlight the possible surgical steps that could affect the neural supply of soft palate and velopharyngeal sphincter during Furlow palatoplasty and posteriorly-based myo-mucosal buccal flaps in patients with persistent velopharyngeal insufficiency after primary cleft palate repair. DESIGN: Institution-based retrospective study. SETTING: Academic Medical Center. PATIENTS: Non-syndromic patients with persistent hypernasality (after primary cleft palate repair) who had Furlow palatoplasty or posteriorly-based buccal myo-mucosal flaps and were followed up for at least 60 months after the secondary surgery. INTERVENTIONS: All patients were examined using a fiberoptic endoscopy, the movement of components of the velopharyngeal sphincter: soft palate, and lateral pharyngeal walls were traced on the monitor and given a score from 0-4. The pattern of VPS closure was reported whether coronal, circular, or sagittal for each case. MAIN OUTCOME MEASURES: Patients' characteristics, auditory perceptual assessment, the severity of hypernasality, intraoperative lengthening of the palate, and operative complications were recorded. RESULTS: At postoperative (at least 60 months) evaluation of the patients statistically non-significant differences were reported when comparing the pre-versus post-operative auditory perceptual assessment following both procedures (P value ≥0.05). A greater tendency towards improvement was noticed with BF but was non-significant. CONCLUSION: The nerve supply of the palate could be jeopardized by many techniques of primary or secondary repair of the cleft palate leaving behind a deceiving intact but weak poor-functioning palate. All efforts should be made to provide more neural-preservation techniques in primary/secondary repair of the cleft palate. Further wide-scale research is essential to have final clear conclusions.

Estimated Time of Arrival: Impact of Healthcare Disparities on Access to and Outcomes of Multidisciplinary Cleft Lip and Palate Care.

OBJECTIVE: To determine the impact of sociodemographic and clinical factors on patient presentation into the cleft care pathway and determine how delayed interventions may affect post-surgical outcomes. DESIGN: Retrospective study. SETTING: Multidisciplinary craniofacial clinics of two university hospitals. PATIENTS, PARTICIPANT: 135 patients with cleft lip and/or palate. INTERVENTIONS: Primary cheiloplasty, primary palatoplasty. MAIN OUTCOME MEASURES: Age at initial presentation, age at first surgery, lag time, delayed surgery, rate of return to the emergency department (ED), readmission rate, reoperations, and oronasal fistula development. RESULTS: Patients referred by OBGYN who underwent cheiloplasty had an earlier age at initial presentation (p < 0.01), earlier age at first surgery (p = 0.01), and a shorter lag time (p < 0.01) compared to children from other referral pathways. African American children had an older age at first surgery (p = 0.01) and a longer lag time (p = 0.02) when compared to non-African American children. Children with syndromes had an older age at first surgery (p < 0.01) and a longer lag time (p < 0.01) than children without syndromes. Patient race, cleft type, and syndromic status increased the odds of receiving delayed surgery. Patients who received delayed palatoplasty returned to the ED at a higher rate than patients who received non-delayed palatoplasty (p = 0.02). CONCLUSIONS: Our data suggest that referral source, race, and syndromic status influence the timeliness of cleft care. Surgeons should develop strong referral networks with local OBGYNs and hospitals to allow for an early entry into the cleft care pathway.

Protective effect of Sasa veitchii extract against all-trans-retinoic acid-induced inhibition of proliferation of cultured human palate cells.

Cleft palate is the most common facial birth defect worldwide. It is caused by environmental factors or genetic mutations. Environmental factors such as pharmaceutical exposure in women are known to induce cleft palate. The aim of the present study was to investigate the protective effect of Sasa veitchii extract against medicine-induced inhibition of proliferation of human embryonic palatal mesenchymal cells. We demonstrated that all-trans-retinoic acid inhibited human embryonic palatal mesenchymal cell proliferation in a dose-dependent manner, whereas dexamethasone treatment had no effect on cell proliferation. Cotreatment with Sasa veitchii extract repressed all-trans-retinoic acid-induced toxicity in human embryonic palatal mesenchymal cells. We found that cotreatment with Sasa veitchii extract protected all-trans-retinoic acid-induced cyclin D1 downregulation in human embryonic palatal mesenchymal cells. Furthermore, Sasa veitchii extract suppressed all-trans-retinoic acid-induced miR-4680-3p expression. Additionally, the expression levels of the genes that function downstream of the target genes ( ERBB2 and JADE1 ) of miR-4680-3p in signaling pathways were enhanced by cotreatment with Sasa veitchii extract and all-trans-retinoic acid compared to all-trans-retinoic acid treatment. These results suggest that Sasa veitchii extract suppresses all-trans-retinoic acid-induced inhibition of cell proliferation via modulation of miR-4680-3p expression.

Nonsurgical improvement of severe upper airway obstruction in infants with Robin sequence and cleft palate using Stanford Orthodontic Airway Plate treatment.

STUDY OBJECTIVES: Severe respiratory distress of neonates with Robin sequence (RS) is traditionally managed by surgery. Stanford Orthodontic Airway Plate treatment (SOAP) is a nonsurgical option. The study aimed to determine if SOAP can improve polysomnography (PSG) parameters of neonates with RS. METHODS: PSG of neonates with RS treated with SOAP at a single hospital were retrospectively analyzed. Patients without PSG at all 4 time points (pre-, start of-, mid-, and post-treatment) were excluded. Data were analyzed using a linear mixed effects model. RESULTS: Sixteen patients were included. All patients had cleft palate (CP). The median age (min, max) at the start of treatment was 1.1 months (0.5, 2.3) with the treatment duration of 4.5 months (3.5, 6.0). The mean obstructive apnea-hypopnea index (95% confidence interval) decreased from 39.3 events/hour (32.9, 45.7) to 12.2 events/hour (6.7, 17.7) (P < 0.001), obstructive apnea index decreased from 14.1 (11.2, 17.0) events/hour to 1.0 (-1.5, 3.5) events/hour (P < 0.001), and oxygen nadir increased from 79.9% (77.4, 82.5) to 88.2% (85.5, 90.8) (P < 0.001) between pre- and start of treatment. Respiratory improvements were sustained during and after the treatment. All patients avoided mandibular distraction osteogenesis or tracheostomy following SOAP. CONCLUSIONS: As being a rare diagnosis, the number of participants was, as expected, low. However, the current study demonstrates that SOAP can improve PSG parameters, demonstrating its potential utility before surgical interventions for neonates with RS and CP experiencing severe respiratory distress.

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.

Single vs. Double-Opposing Z-Plasty: Evaluating Their Impact on Palatoplasty Postoperative Outcomes.

BACKGROUND: The double-opposing Z-plasty is a fundamental approach for cleft palate repair. Recently, some surgeons have begun implementing a single Z-Plasty, igniting discussions on the most effective technique for enhancing postoperative outcomes. Consequently, this study sought to evaluate the outcomes of employing single and double Z-plasties within the modified Sommerlad-Furlow technique. METHODS: 116 cleft palate patients undergoing primary surgical repair were divided into two groups: those treated with the Sommerlad-Furlow method using a double-opposing Z-plasty (S.F.2.Z.P. group, n = 58) and those receiving a single nasal Z-plasty (S.F.1.Z.P. group, n = 58). Data on cleft type and width, soft palate length, palatal fistula, and velopharyngeal function were collected. Mann-Whitney test compared the mean values between groups. RESULTS: The S.F.2ZP group demonstrated a statistically significant increase in soft palate length compared to those in the S.F.1ZP group (p = 0.008). However, the S.F.1ZP group demonstrated adequate soft palate length (7.9 ± 2.8 mm) compared to the S.F.2ZP group (9.3 ± 2.8 mm). The velopharyngeal function was good in both groups, with no significant differences (P = 0.52). While the proper velopharyngeal closure was 81% in the S.F.1ZP group and 87.9% in the S.F.2ZP group, velopharyngeal insufficiency was 10.3% and 5.2%, respectively. The rates of persistent palatal fistula were 5.2% in the S.F.1ZP group and 3.4% in the S.F.2ZP group, with no significant differences found between both groups (P = 0.64). CONCLUSIONS: There were no significant differences in crucial outcomes such as velopharyngeal function and the incidence of persistent palatal fistulas, indicating the effectiveness of both techniques. While the double-opposing Z-plasty demonstrated a statistically significant increase in soft palate length, the a nasal Z-plasty demonstrated adequate soft palate length which sufficiently enables effective velopharyngeal closure. These outcomes suggest that a single Z-plasty is both effective and easy to perform, making it a valuable surgical approach for achieving the desired outcomes.. CLINICAL RELEVANCE: The current study suggests that although the soft palate may not be as elongated with nasal Z-plasty alone compared to the double Z-plasty, it sufficiently enables effective velopharyngeal closure.

Dexmedetomidine as a total intravenous anesthetic in pediatric patients undergoing cleft lip and palate surgery: a case series.

BACKGROUND: Surgery for pediatric cleft lip and palate repair often utilizes high-dose opioids and inhaled anesthesia, thereby causing postoperative complications such as desaturation and/or severe agitation after anesthesia. These complications are detrimental to the child and medical personnel and cause tremendous psychologic stress to parents. Our aim is to decrease these complications through dexmedetomidine, an alpha-2 receptor agonist with anxiolytic, sympatholytic, and analgetic properties. Devoid of respiratory depressant effect, it allows patients to maintain effective ventilation and reduce agitation, postoperatively. Its unique anesthetic property may shed light on providing safe anesthesia and gentle emergence to this young, vulnerable population. CASE PRESENTATION: A total of 21 patients of Sundanese ethnicity, aged 3 months to 8 years (9 males and 12 females), underwent cleft lip or cleft palate surgery using total intravenous dexmedetomidine. Anesthesia was induced using sevoflurane, fentanyl, and propofol, and airway was secured. Intravenous dexmedetomidine 1.5 µg/kg was administered within 10 minutes, and a maintenance dose of 1.5 µg/kg/hour was continued as the sole anesthetic maintenance agent thereafter. Hemodynamics and anesthetic depth using Patient State Index (SEDLine™ monitor, Masimo Corporation, Irvine, CA, USA) were monitored carefully throughout the surgical procedure. Dexmedetomidine did not cause any hemodynamic derangements or postoperative complications in any of our patients. We found agitation in 9.5% (2/21) of patients. CONCLUSION: Dexmedetomidine can be used as a total intravenous anesthetic agent to maintain anesthesia and provide gentle emergence to infants and young children undergoing cleft lip and palate repair.

A retrospective analysis of factors affecting speech production in school-aged children with cleft palate (+- cleft lip).

OBJECTIVE: The present investigation examined how factors such as cleft type, age of primary palatal surgery, diagnosed syndromes, hearing problems, and malocclusions could predict persistent speech difficulties and the need for speech services in school-aged children with cleft palate. METHODS: Participants included 100 school-aged children with cleft palate. Americleft speech protocol was used to assess the perceptual aspects of speech production. The logistic regression was performed to evaluate the impact of independent variables (IV) on the dependent variables (DV): intelligibility, posterior oral CSCs, audible nasal emission, hypernasality, anterior oral CSCs, and speech therapy required. RESULTS: Sixty-five percent of the children were enrolled in (or had received) speech therapy. The logistic regression model shows a good fit to the data for the need for speech therapy (Hosmer and Lemeshow's χ2(8)=9.647,p=.291). No IVs were found to have a significant impact on the need for speech therapy. A diagnosed syndrome was associated with poorer intelligibility (Pulkstenis-Robinson's χ2(11)=7.120,p=.789). Children with diagnosed syndromes have about six times the odds of a higher hypernasality rating (Odds Ratio = 5.703) than others. The cleft type was significantly associated with audible nasal emission (Fisher'sexactp=.006). At the same time, malocclusion had a significant association with anterior oral CSCs (Fisher'sexactp=.005). CONCLUSIONS: According to the latest data in the Cleft Registry and Audit Network Annual Report for the UK, the majority of children with cleft palate attain typical speech by age five. However, it is crucial to delve into the factors that may influence the continuation of speech disorders beyond this age. This understanding is vital for formulating intervention strategies aimed at mitigating the long-term effects of speech disorders as individuals grow older.

Knockout mice with pituitary malformations help identify human cases of hypopituitarism.

BACKGROUND: Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) and holoprosencephaly (HPE), are midline defects that cause significant morbidity for affected people. Variants in 67 genes are associated with CH, but a vast majority of CH cases lack a genetic diagnosis. Whole exome and whole genome sequencing of CH patients identifies sequence variants in genes known to cause CH, and in new candidate genes, but many of these are variants of uncertain significance (VUS). METHODS: The International Mouse Phenotyping Consortium (IMPC) is an effort to establish gene function by knocking-out all genes in the mouse genome and generating corresponding phenotype data. We used mouse embryonic imaging data generated by the Deciphering Mechanisms of Developmental Disorders (DMDD) project to screen 209 embryonic lethal and sub-viable knockout mouse lines for pituitary malformations. RESULTS: Of the 209 knockout mouse lines, we identified 51 that have embryonic pituitary malformations. These genes not only represent new candidates for CH, but also reveal new molecular pathways not previously associated with pituitary organogenesis. We used this list of candidate genes to mine whole exome sequencing data of a cohort of patients with CH, and we identified variants in two unrelated cases for two genes, MORC2 and SETD5, with CH and other syndromic features. CONCLUSIONS: The screening and analysis of IMPC phenotyping data provide proof-of-principle that recessive lethal mouse mutants generated by the knockout mouse project are an excellent source of candidate genes for congenital hypopituitarism in children.

Impact of anatomical abnormalities on velopharyngeal insufficiency in patients with submucous cleft palate.

BACKGROUND: Submucous cleft palate (SMCP) is a congenital anomaly characterized by the presence of Calnan's triad. However, in clinical practice, it is common for individuals to exhibit one or two anatomical abnormalities within the triad. Furthermore, the definition of SMCP has been diverse and ambiguous in literature. Therefore, this study aimed to analyze the correlation between anatomical abnormalities and development of velopharyngeal insufficiency (VPI). METHODS: We conducted a retrospective analysis of 99 patients referred to our clinic for speech issues or anatomical abnormalities identified during routine oral examinations from January 2012 to June 2023. A single surgeon performed all physical examinations. We evaluated the presence of bony notch, zona pellucida, and bifid uvula, assigned a score to each abnormality, and analyzed their correlation with VPI. The correlation of each of the abnormalities with VPI development was examined, along with the relationship between the number of abnormalities and VPI. RESULTS: Among the 99 patients, 27 were diagnosed with VPI. Only the bony notch had a significant correlation with VPI development. The incidence of VPI tended to increase with the presence of more anatomical abnormalities. VPI occurred in approximately 40% of patients exhibiting all three anatomical abnormalities. CONCLUSION: The study findings highlight the importance of meticulous intraoral examinations in patients with SMCP and careful monitoring of patients with a bony notch or two or more anatomical abnormalities.

A Geospatial Analysis of Barriers to Cleft Lip and Palate Care in the United States.

OBJECTIVE: This study evaluates the geospatial distribution of cleft lip and/or cleft palate (CL/P) care in the United States, assesses disparities between families with and without one-hour proximity to CL/P care, and recommends interventions for improving access. DESIGN: We identified American Cleft Palate Craniofacial Association-approved CL/P teams and calculated a one-hour driving radius around each clinic. We then used census data to compare risk factors for developing cleft (i.e., incidence risk factors) and obstacles to care (i.e., access risk factors) between counties with and without one-hour proximity. RESULTS: We identified 187 CL/P teams in 45 states. Most were in the South (n = 60, 32.0%), though children in the Middle Atlantic had the greatest access to care. Alabama, Mississippi, Tennessee, and Kentucky had the least access. Children without access were 39% more likely to have gestational tobacco exposure, 8% more likely to have gestational obesity exposure, and 28% less likely to have health insurance (p < 0.01). Children without access in the South were 29% more likely to have a low birth weight and 46% more likely to be living below the poverty line (p < 0.01). Children with access were twice as likely to live in immigrant families and 7-times more likely to speak English as a second language. CONCLUSIONS: Pronounced disparities affect patients with and without one-hour access to CL/P care. Interventions should address care costs for patients living furthest without access and language barriers for patients with access that speak English as a second language.

Laser therapy for treating cleft lip or/and palate scarring-a systematic review and meta-analysis.

This review aims to assess the efficacy and safety of laser therapy in managing scars resulting from cleft lip and/or palate (CL/P) repair surgeries, as well as to determine the optimal timing for intervention. A systematic search was conducted across four databases using a predefined search strategy. Studies included were randomized controlled trials, non-randomized studies, and case series focusing on laser therapy for CL/P scars. Data extraction and analysis were performed using Revman Software. A total of two randomized controlled trials, four non-randomized studies, and three case series were included in the analysis. The fractional CO2 laser was the most commonly utilized type of laser. Following laser therapy, there was a significant decrease in Vancouver Scar Scale (VSS) scores by 4.05 (95% CI, 2.10-5.99). Meta-analysis revealed that laser treatment groups exhibited a significantly lower mean VSS score (1.3; 95% CI, 0.02-2.67) compared to control groups. Moreover, initiating laser therapy intervention at one month postoperatively resulted in a significantly lower VSS score compared to initiation at three months postoperatively (difference of 1.70; 95% CI, 1.33-2.08). No severe complications were reported. Laser therapy demonstrates effectiveness and safety in improving CL/P scars, with earlier intervention yielding greater benefits.