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.

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.

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.

Determination of safety margin of nasal septum osteotomy for sphenoid sinus in cleft lip and palate patients.

BACKGROUND: Nasal septum osteotomy is used for separating the nasal septum and maxilla during a Le Fort I osteotomy. If this osteotomy is applied too high or is tilted into the nasal cavity, the sphenoid sinus and various adjacent vital structures may be damaged, and serious bleeding, neurological complications, blindness or even death may occur. The aim of this study is to determine the safety margin of the nasal septum osteotomy for sphenoid sinus during the Le Fort I surgery in cleft lip and palate (CLP) patients. METHODS: Twenty cleft lip and palate (the CLP group) and 20 healthy individuals (the control group) were included in this study. Three values (two lines and an angle) were measured by cone beam computed tomography (CBCT). The first line is the line passing through the junction of the spina nasalis anterior point and the lower point of the perpendicular lamina of the palatine bone. The undersired line is the line passing through the junction of the spina nasalis anterior point and the lower anterior border of the base of the sphenoid sinus. The osteotomy angle is the angle between these two lines. RESULTS: In the control group; a surgical line of 44.11-61.14 mm (mean 51.91 ± 4.32), an undesired line of 52.48-69.58 mm (mean 59.14 ± 5.08) and an angle of 18.22-27.270 (mean 22.66 ± 2.55) were found, while in the CLP group, a surgical line of 34.53-51.16 mm (mean 43.38 ± 4.79), an undesired line of 46.86-61.35 mm (mean 55.02 ± 3.24) and an angle of 17.60-28.810 (mean 22.60 ± 2.81) were found. CONCLUSIONS: Although the angle to the sphenoid sinus was not significantly affected by CLP, careful planning and consideration of these anatomical differences are crucial to prevent complications and ensure the safety of Le Fort I surgery in CLP patients. Further research with larger sample sizes and subgroup analysis of unilateral and bilateral CLP cases is needed to improve our understanding of these anatomical variations and improve surgical approaches to individuals with CLP undergoing orthognathic procedures.

Prenatal incidence of cleft lip/palate and cocaine abuse in parents: a systematic review and meta-analysis.

BACKGROUND: The study aimed to investigate the association between maternal cocaine abuse during pregnancy and the prevalence of cleft lip/palate (CL/P) in offspring, synthesizing existing evidence through a systematic review and meta-analysis. CL/P is a congenital craniofacial anomaly with complex etiology, and prior research has suggested potential links between maternal cocaine use and CL/P. However, these associations remain inconclusive. METHODS: A comprehensive literature search was conducted to identify relevant studies published up to the study's cutoff date in September 2021. Several databases were systematically searched using predefined search terms. Inclusion criteria were set to encompass studies reporting on the prevalence of CL/P in infants born to mothers with a history of cocaine use during pregnancy, with a comparison group of non-cocaine-using mothers. Data were extracted, and a meta-analysis was performed using a random-effects model to calculate pooled odds ratios (OR) and relative risks (RR) with their respective 95% confidence intervals (CI). RESULTS: The review included data from 4 studies that met the inclusion criteria. The combined OR from two studies was 0.05 (95% CI: 0.00, 4.41), which does not suggest a statistically significant association between prenatal cocaine exposure and the incidence of CL/P due to the confidence interval crossing the null value. Additionally, the combined RR was 0.17 (95% CI: 0.04, 0.66), indicating a statistically significant decrease in the risk of CL/P associated with prenatal cocaine exposure. These results, with an OR that is not statistically significant and an RR suggesting decreased risk, should be interpreted with caution due to considerable heterogeneity and variability among the included studies' findings. Further research is needed to clarify these associations. CONCLUSION: The findings from this systematic review and meta-analysis suggest that maternal cocaine use during pregnancy is not a statistically significant independent risk factor for the development of CL/P in offspring. These results underscore the multifactorial nature of CL/P etiology and emphasize the importance of considering other genetic, environmental, and nutritional factors in understanding the condition's origins. While the study provides important insights, limitations such as data heterogeneity and potential confounders should be acknowledged. Future research should adopt rigorous study designs and explore a broader range of potential risk factors to comprehensively elucidate CL/P development.

3D evaluation of the maxillary sinus volumes in patients with bilateral cleft lip and palate.

One of the most common congenital anomalies of the head and neck region is a cleft lip and palate. This retrospective case-control research aimed to compare the maxillary sinus volumes in individuals with bilateral cleft lip and palate (BCLP) to a non-cleft control group. The study comprised 72 participants, including 36 patients with BCLP and 36 gender and age-matched control subjects. All topographies were obtained utilizing Cone Beam Computed Tomography (CBCT) for diagnostic purposes, and 3D Dolphin software was utilized for sinus segmentation. Volumetric measurements were taken in cubic millimeters. No significant differences were found between the sex and age distributions of both groups. Additionally, there was no statistically significant difference observed between the BCLP group and the control group on the right and left sides (p > 0.05). However, the mean maxillary sinus volumes of BCLP patients (8014.26 ± 2841.03 mm3) were significantly lower than those of the healthy control group (11,085.21 ± 3146.12 mm3) (p < 0.05). The findings of this study suggest that clinicians should be aware of the lower maxillary sinus volumes in BCLP patients when planning surgical interventions. The utilization of CBCT and sinus segmentation allowed for precise measurement of maxillary sinus volumes, contributing to the existing literature on anatomical variations in BCLP patients.

The impact of passive alveolar molding vs. nasoalveolar molding on cleft width and other parameters of maxillary growth in unilateral cleft lip palate.

OBJECTIVE: Passive alveolar molding (PAM) and nasoalveolar molding (NAM) are established presurgical infant orthodontic (PSIO) therapies for cleft lip palate (CLP) patients. PAM guides maxillary growth with a modified Hotz appliance, while NAM also uses extraoral taping and includes nasal stents. The effects of these techniques on alveolar arch growth have rarely been compared. MATERIAL AND METHODS: We retrospectively compared 3D-scanned maxillary models obtained before and after PSIO from infants with unilateral, non-syndromic CLP treated with PAM (n = 16) versus NAM (n = 13). Nine anatomical points were set digitally by four raters and transversal/sagittal distances and rotations of the maxilla were measured. RESULTS: Both appliances reduced the anterior cleft, but NAM percentage wise more. NAM decreased the anterior and medial transversal width compared to PAM, which led to no change. With both appliances, the posterior width increased. The alveolar arch length of the great and small segments and the sagittal length of the maxilla increased with PAM but only partially with NAM. However, NAM induced a significant greater medial rotation of the larger and smaller segment compared to PAM with respect to the lateral angle. CONCLUSIONS: NAM and PAM presented some significant differences regarding maxillary growth. While NAM reduced the anterior cleft and effectively rotated the segments medially, PAM allowed more transversal and sagittal growth. CLINICAL RELEVANCE: The results of this study should be taken into consideration when to decide whether to use PAM or NAM, since they show a different outcome within the first few months. Further studies are necessary regarding long-term differences.

Design of a Novel Orthodontic Appliance to Prevent Pedicle Trauma in Patients Undergoing Double-Opposing Buccal Flaps for Palatal Lengthening.

OBJECTIVE: To describe a novel orthodontic appliance to prevent pedicle trauma in patients undergoing double-opposing buccal flap surgery for secondary palatal lengthening. DESIGN: Case series. SETTING: Cleft and craniofacial clinic, Johns Hopkins Children's Center. PATIENTS, PARTICIPANTS: Four patients undergoing double-opposing buccal flap surgery for repair of velopharyngeal insufficiency. INTERVENTIONS: Patients were fitted with the device, which consists of a lower lingual holding arch with acrylic bite blocks. MAIN OUTCOME MEASURE: Presence of pedicle trauma postsurgery and tolerability of the device. RESULTS: The appliance was well tolerated in all 4 patients and no biting trauma to the pedicles was observed. CONCLUSIONS: A reliable appliance has been developed to prevent biting trauma to the pedicles in patients undergoing double-opposing buccal flap surgery in the permanent dentition stage.

A Systematic Review: Early Simultaneous Vomer Flap with Primary Cleft Lip Repair, Does it Bring More Benefits?

INTRODUCTION: Vomer flap is a technique to close cleft lip and palate. This technique is a simple procedure that has many benefits. However, the vomer flap's application together with primary lip closure is still questionable. OBJECTIVE: To find out whether the vomer flap's application in primary cleft lip repair can provide significant benefits. DESIGN: A systematic review was conducted using the PRISMA methodology has been licensed in PROSPERO databases (CRD42023399487). SETTING: A comprehensive search was set out, utilizing eight data sources up to March 2023. PARTICIPANTS: Both cohort studies and randomized control trials regarding the use of vomer flaps performed concurrently with cleft lip repair in children up to six months old. RESULTS: This article involved 8 studies involving 542 patients who met the inclusion criteria, consisting of 6 retrospective cohort studies, 1 RCT study, and 1 prospective cohort study. Vomer flaps provide a reduction in palatal cleft distance of 3-5 mm, a relatively small number of fistulas (0-4%), improvement of velopharyngeal function (nasal tone and nasal emission), maximal development of the maxilla although it is still controversial. CONCLUSION: The vomer flap's application in primary cleft lip repair provides many advantages, such as reduced palatal and alveolar clefts, decreased risk of oronasal fistula, increased velopharyngeal function, and increased maxillary growth. It is reliable for the management of cleft lip and palate.

"Challenges and concerns faced by parents of a group of Egyptian children with cleft lip/palate: a qualitative study".

BACKGROUND: Cleft lip and palate are the most common developmental anomalies that affect the mouth and related structures. They can both affect children physiologically, socially, and functionally and lead to psychological distress in their parents. The present study aims to understand the challenges parents of cleft lip and palate patients face in Egypt, elucidate how they cope with these challenges, and assess their concerns for the future. METHODS: For the present phenomenological qualitative exploration, the parents of cleft lip and palate patients attending the cleft care clinic were invited to participate in the study through face-to-face recruitment at the clinic. An interview guide about the research question was developed to include standardized open-ended questions providing a framework for structured discussions. The interviews were audio-recorded after obtaining written informed consent from participants then collected data were transcribed for data analysis. RESULTS: Of the 12 participants, there were nine mothers and three fathers. Their children's ages ranged from 1.5 years to 19 years and had different presentations of cleft lip and palate from unilateral cleft lip to complete bilateral cleft lip and palate. Feeding difficulty was one of the main challenges encountered by the parents. At the same time, fear of being subjected to bullying was the main concern for the future of their children. Six themes were noted that were continually reported: Health & Wellbeing; Parental emotions; Parental attitudes & behaviors; Financial aspects; Relationship aspects; and Career/Education. CONCLUSIONS: There were 4 factors that directly impacted the themes, namely: the type of cleft, gender of the child, gender role of the parent, and the age of the child impacted the parental concerns and the challenges faced under the influence of sociocultural beliefs and existing support systems.

Effects of Alt-RAMEC protocol with facemask therapy in cleft lip palate patients in a sample of Pakistani population.

OBJECTIVE: The objective of the study is to evaluate the skeletal, dentoalveolar and soft tissue changes before and after treatment with Alt-RAMEC protocol and protraction headgear in comparison to the controls. MATERIAL AND METHODS: A quasi experimental study was conducted in the orthodontic department on 60 patients of cleft lip and palate. These patients were divided into two groups. Group I was the Alt-RAMEC group that underwent Alt-RAMEC protocol followed by facemask therapy while group II was the control group that underwent RME and facemask therapy. Total treatment time in both the groups was approximately 6 to 7 months. Mean and standard deviation was calculated for all the quantitative variables. Pre and post treatment changes between treatment and control groups were made using paired t-test. Intergroup comparison between treatment and control group was analyzed using independent t-test. Significance for all tests was predetermined at a P-value of ≤ 0.05. RESULTS: The Alt-RAMEC group showed significant forward movement of maxilla and improvement in the maxillary base. A remarkable improvement in SNA was seen. The overall outcome was better maxillo-mandibular relationship as shown by positive ANB values and angle of convexity. More effect on maxilla and least effect on mandible was notified with Alt-RAMEC protocol and facemask therapy. Improvement in transverse relationship was also evident in the Alt-RAMEC group. CONCLUSION: Alt-RAMEC protocol in combination with protraction headgear is a better alternative to treat cleft lip and palate patients in comparison to the conventional protocol.

Impact of Orofacial Clefts on Oral Health Quality of Life: A Cross-sectional Survey Study in Saudi Arabia.

AIM: To evaluate the effect of facial clefts on the dental health quality of life of affected individuals, and to determine whether age and gender affect the oral health quality of life differently. MATERIALS AND METHODS: The cross-sectional survey included 50 participants (32 females and 18 males) from the northern region of Saudi Arabia, using a reliable and validated questionnaire, the Child Oral Health Impact Profile (COHIP), which measured self-reported oral health-related quality of life (OHRQoL) in children and adults using a five-point Likert scale. Statistical analysis was performed, and results were considered significant if the p-value was less than 0.05. RESULTS: The highest scores in the oral health domain were related to bad breath and reluctance in speaking or reading aloud in class within the school environment domain, with mean scores of 3.44 ± 1.3 and 3.52 ± 1.2, respectively. Most patients showed apprehension regarding necessary dental treatments (mean = 1.44 ± 0.07). The study found a non-statistically significant difference in tooth discomfort between age groups (p = 0.092), with individuals aged from 20 to 29 experiencing higher levels of discomfort than other age groups surveyed. CONCLUSION: The two topics with the highest mean scores in the oral health domain and the school environment domain were bad breath and not wanting to speak or read aloud in class. Females reported more discomfort, and there was a substantial association between gender and tooth pain/sensitivity. CLINICAL SIGNIFICANCE: Understanding the difficulties cleft patients face is crucial, as doing so will enable dentists to encourage and handle these issues more effectively.

Cultural Beliefs on the Causes of Cleft Lip and/or Palate in Malaysia: A Multicenter Study.

OBJECTIVE: To identify the cultural beliefs about the causes of cleft among parents of patients with nonsyndromic cleft lip and/or palate in a multiethnic society in Malaysia and the difficulties encountered in receiving cleft treatment. DESIGN: A descriptive cross-sectional multicenter study based on a study questionnaire was conducted of parents of patients with cleft lip and/or palate. SETTING: Three centers providing cleft care from different regions in Malaysia: the national capital of Kuala Lumpur, east coast of peninsular Malaysia, and East Malaysia on the island of Borneo. PARTICIPANTS: Parents/primary caregivers of patients with cleft lip and/or palate. RESULTS: There were 295 respondents from different ethnic groups: Malays (58.3%), indigenous Sabah (30.5%), Chinese (7.1%), Indian (2.4%), and indigenous Peninsular Malaysia and Sarawak (1.7%). Malay participants reported that attributing causes of cleft to God's will, superstitious beliefs that the child's father went fishing when the mother was pregnant or inheritance. Sabahans parents reported that clefts are caused by maternal antenatal trauma, fruit picking, or carpentry. The Chinese attribute clefts to cleaning house drains, sewing, or using scissors. Cultural background was reported by 98.3% of participants to pose no barrier in cleft treatment. Those from lower socioeconomic and educational backgrounds were more likely to encounter difficulties while receiving treatment, which included financial constraints and transportation barriers. CONCLUSION: There is a wide range of cultural beliefs in the multiethnic society of Malaysia. These beliefs do not prevent treatment for children with cleft. However, they face challenges while receiving cleft treatment, particularly financial constraints and transportation barriers. Such barriers are more likely experienced by parents from lower income and lower education backgrounds.

Continuous Multidisciplinary Care for Patients With Orofacial Clefts-Should the Follow-up Interval Depend on the Cleft Entity?

OBJECTIVE: The multidisciplinary follow-up of patients with cleft lip with or without palate (CL/P) is organized differently in specialized centers worldwide. The aim of this study was to evaluate the different treatment needs of patients with different manifestations of CL/P and to potentially adapt the frequency and timing of checkup examinations accordingly. DESIGN: We retrospectively analyzed the data of all patients attending the CL/P consultation hour at a tertiary care center between June 2005 and August 2020 (n = 1126). We defined 3 groups of cleft entities: (1) isolated clefts of lip or lip and alveolus (CL/A), (2) isolated clefts of the hard and/or soft palate, and (3) complete clefts of lip, alveolus and palate (CLP). Timing and type of therapy recommendations given by the specialists of different disciplines were analyzed for statistical differences. RESULTS: Patients with CLP made up the largest group (n = 537), followed by patients with cleft of the soft palate (n = 371) and CL ± A (n = 218). There were significant differences between the groups with regard to type and frequency of treatment recommendations. A therapy was recommended in a high proportion of examinations in all groups at all ages. CONCLUSION: Although there are differences between cleft entities, the treatment need of patients with orofacial clefts is generally high during the growth period. Patients with CL/A showed a similarly high treatment demand and should be monitored closely. A close follow-up for patients with diagnosis of CL/P is crucial and measures should be taken to increase participation in follow-up appointments.

Predictors of Complication Following Cleft Lip and Palate Surgery in a Low-Resource Setting: A Prospective Outcomes Study in Nicaragua.

BACKGROUND: Higher rates of postoperative complication following cleft lip or palate repair have been documented in low resource settings, but their causes remain unclear. This study sought to delineate patient, surgeon, and care environment factors in cleft complications in a low-income country. DESIGN: Prospective outcomes study. SETTING: Comprehensive Cleft Care Center. PATIENTS: Candidate patients presenting for cleft lip or palate repair or revision. INTERVENTIONS: Patient anthropometric, nutritional, environmental and peri- and post-operative care factors were collected. Post-operative evaluation occurred at standard 1-week and 2-month postoperative intervals. MAIN OUTCOME MEASURES: Complication was defined as fistula, dehiscence and/or infection. RESULTS: Among 408 patients enrolled, 380 (93%) underwent surgery, of which 208 (55%) underwent lip repair (124) or revision (84), and 178 (47%) underwent palate repair (96) or revision (82). 322 (85%) were evaluated 1 week and 166 (44%) 2 months postoperatively. 50(16%) complications were identified, including: 25(8%) fistulas, 24(7%) dehiscences, 17(5%) infections. Mid-upper arm circumference (MUAC) ≤12.5 cm was associated with dehiscence after primary lip repair (OR = 28, p = 0.02). Leukocytosis ≥11,500 on pre-operative evaluation was associated with dehiscence (OR = 2.51, p = 0.04) or palate revision fistula (OR = 64, p < 0.001). Surgeons who performed fewer previous-year palate repairs had higher likelihood of palate complications, (OR = 3.03, p = 0.01) although there was no difference in complication rate with years of surgeon experience or duration of surgery. CONCLUSIONS: Multiple patient, surgeon, and perioperative factors are associated with higher rates of complication in a low-resource setting, and are potentially modifiable to reduce complications following cleft surgery.

The Impact of Maxillary Osteotomy on Fricatives in Cleft Lip and Palate: A Perceptual Speech and Acoustic Study.

INTRODUCTION: Abnormal facial growth is a recognized outcome in cleft lip and palate (CLP), resulting in a concave profile and a class III occlusal status. Maxillary osteotomy (MO) is undertaken to correct this facial deformity, and the surgery can impact speech articulation, although the evidence remains limited and ill-defined for the CLP population. AIMS: The aim of the study was to investigate the impact of MO on the production of the fricatives /f/ and /s/, using perceptual and acoustic analyses, and to explore the nature of speech changes. METHODS: Twenty participants with CLP were seen 0-3 months pre-operatively (T1) and 3 months (T2) and 12 months (T3) after MO. A normal group (N = 20) was similarly recruited. Perceptual speech data was collected according to a validated framework and ratings made on audio and audio-video recordings (VIDRat). Spectral moments were centre of gravity (CG), standard deviation (SD), skewness (SK) and kurtosis (KU). Reliability studies were carried out for all speech analyses. RESULTS: For the CLP group, VIDRat identified dentalization/interdentalization as the main type of pre-operative error for /s/ with a statistically significant improvement over time, χ2(2) = 6.889, p = 0.032. Effect sizes were medium between T1 and T3 (d = 0.631) and small between T2 and T3 (d = 0.194). For the acoustic data, effect sizes were similarly medium between T1 and T2 (e.g., SK, /f/ d = 0.579, /s/ d = 0.642) and small between T1 and T3 across all acoustic parameters. Independent t tests showed mainly statistically significant differences between both groups at all time points with large effect sizes (e.g., T2 CG, t = -4.571, p < 0.001, d =1.581), indicating that /s/ was not normalized post-operatively. For /f/, differences tended to be at T1 with large effect sizes (e.g., CG, t = -2.307, p = 0.028, d = 0.797), reflecting normalization. CONCLUSIONS AND IMPLICATIONS: This is the first speech acoustic study on /f/ for individuals with CLP undergoing MO. The surgery has a positive impact on /f/ and /s/, which appear to stabilize 3 months post-operatively. Speech changes are an automatic and a direct consequence of the physical changes brought about by MO, effecting articulatory re-organization. The results of the study have direct clinical implications for the clinical care pathway for patients with CLP undergoing MO.

Comparing the Temporal Aspects of Velopharyngeal Closure in Children with and without Cleft Palate.

INTRODUCTION: Children with cleft palate exhibit differences in the 4 temporal components of nasalization (nasal onset and offset intervals, nasal consonant duration, and total speech duration), with various patterns having been noted based on different languages. Thus, the current study aimed to examine the temporal aspects of velopharyngeal closure in children with and without cleft palate; this is the first study to do so in the Turkish language. METHODS: This study evaluated and compared the 4 temporal characteristics of velopharyngeal closure in children (aged 6-10 years) with (n = 28) and without (n = 28) cleft palate using nonword consonant and vowel speech samples, including the bilabial nasal-to-stop combination /mp/ and the velar nasal-to-stop combination /ηk/. Acoustic data were recorded using a nasometer, after which acoustic waveforms were examined to determine the 4 temporal components of nasalization. Flexible nasoendoscopy was then used to evaluate velopharyngeal closure patterns. RESULTS: With regard to the 4 closure patterns, significant differences in the nasal offset interval (F4-25 = 10.213, p = 0.04; p < 0.05) and the nasal consonant duration ratio (F4-25 = 12.987, p = 0.02; p < 0.05) were observed for only /ampa/. The coronal closure pattern showed the longest closure duration (0.74 s). Children with cleft palate showed prolonged temporal parameters in all 4 characteristics, reflecting oral-nasal resonance imbalances. In particular, the low vowel sound /a/ was significantly more prolonged than the high vowel sounds /i/ and /u/. CONCLUSIONS: The examined temporal parameters offer more accurate characterizations of velopharygeal closure, thereby allowing more accurate clinical assessments and more appropriate treatment procedures. Children with cleft palate showed longer nasalization durations compared to those without the same. Thus, the degree of hypernasality in children with cleft palate may affect the temporal aspects of nasalization.

Dental anomalies and their therapeutic implications: retrospective assessment of a frequent finding in patients with cleft lip and palate.

BACKGROUND: Orofacial clefts are characterized by a frequent occurrence of dental anomalies. Numerous studies demonstrate the high prevalence of dental aplasia, supernumerary teeth, and hypoplastic teeth in patients with cleft lip with/without cleft palate (CL/P), yet the therapeutic consequences are rarely discussed. This study explores prevalence, localization, and association between primary and secondary dentition in a large European collective and begins to evaluate the significance of dental anomalies in the therapeutic course of patients with CL/P. METHODS: The medical reports of 1070 patients with different entities of CL/P who presented to our clinic within a 15-year investigation period were evaluated retrospectively. Dental anomalies were classified into three different diagnostic groups: dental aplasia, supernumerary teeth and hypoplastic teeth. The statistical analyses included studies of the frequency and localization of dental anomalies in different cleft entities as well as of the association between primary and secondary dentition and the therapeutic consequences. RESULTS: Uni- or bilateral cleft lip and palate (CLP) (47.5%) occurred most frequently, followed by cleft palate only (CPO) (32.9%) and cleft lip with or without alveolus (CL ± A) (19.6%). Dental anomalies were found significantly more often on the side of the cleft. Aplastic permanent teeth were mostly found in patients with CLP (54.8%), while supernumerary permanent teeth occurred primarily in patients with CL ± A (21.7%). Patients with CPO presented dental aplasia but no patient with CPO showed supernumerary teeth. The occurrence of dental aplasia in the primary dentition significantly increases the probability of aplastic teeth in the permanent dentition. Dental anomalies, in particular dental aplasia, significantly increase patients' need for subsequent orthodontic therapy and orthognathic surgery. CONCLUSION: Dental aplasia and hypoplasia are common in patients with CL/P not only in the cleft area but in the whole dentition. In the event of dental aplasia in the primary dentition, the frequency of aplastic teeth in the permanent dentition is significantly higher. Additionally, the need for therapeutic interventions, especially concerning orthognathic surgery, seems to be significantly higher in patients with CL/P who are affected by dental anomalies. Clinicians should take this into account when creating long-term treatment plans.

Association of social and psychological aspects of quality of life and educational level of patients with different orofacial cleft.

OBJECTIVE: To determine the social and psychological domains of quality of life of children with orofacial clefts in the context of different types of clefts and educational levels. METHODS: The cross-sectional study was conducted at Clapp Hospital and Mayo Hospital, Lahore, Pakistan from September 1, 2020, to January 31, 2021, and comprised subjects of either gender aged 6-18 years having orofacial clefts. Data was collected using the CLEFT-Questionnaire along with a basic demographic sheet. Data was analysed using SPSS 23. RESULTS: Of the 80 subjects, 40(50%) each were males and females. The overall mean age was 12.41±3.39 years. A significant association of types of orofacial clefts with social function (p<0.05) and psychological function (p<0.05) was observed. The highest mean score of 27.89±3.41 and 26.11±1.76 was noted for unilateral left side cleft lip, and primary palate, respectively. No significant association of level of education with social function (p>0.05) and psychological function (p>0.05) was noted. CONCLUSIONS: Different types of orofacial clefts affected the psychological and social aspects of quality of life of patients differently, but the difference was not significantly correlated with the education level.

Mutations in the Epithelial Cadherin-p120-Catenin Complex Cause Mendelian Non-Syndromic Cleft Lip with or without Cleft Palate.

Non-syndromic cleft lip with or without cleft palate (NS-CL/P) is one of the most common human birth defects and is generally considered a complex trait. Despite numerous loci identified by genome-wide association studies, the effect sizes of common variants are relatively small, with much of the presumed genetic contribution remaining elusive. We report exome-sequencing results in 209 people from 72 multi-affected families with pedigree structures consistent with autosomal-dominant inheritance and variable penetrance. Herein, pathogenic variants are described in four genes encoding components of the p120-catenin complex (CTNND1, PLEKHA7, PLEKHA5) and an epithelial splicing regulator (ESRP2), in addition to the known CL/P-associated gene, CDH1, which encodes E-cadherin. The findings were also validated in a second cohort of 497 people with NS-CL/P, comprising small families and singletons with pathogenic variants in these genes identified in 14% of multi-affected families and 2% of the replication cohort of smaller families. Enriched expression of each gene/protein in human and mouse embryonic oro-palatal epithelia, demonstration of functional impact of CTNND1 and ESRP2 variants, and recapitulation of the CL/P spectrum in Ctnnd1 knockout mice support a causative role in CL/P pathogenesis. These data show that primary defects in regulators of epithelial cell adhesion are the most significant contributors to NS-CL/P identified to date and that inherited and de novo single gene variants explain a substantial proportion of NS-CL/P.