An Integrated Perspective on Managing Cleft Lip and Palate: Innovations and Prospective Developments

Anaesthesia for cleft lip and palate surgery

Congenital cleft lip and palate is a common birth defect that seriously affects the lives of the afflicted children and their families. Previously, no research has been done to investigate the pathogenic characteristics of cleft lip and palate among ethnic minorities, for example, Tibetans, a minority ethnic group with a large population in China. This study aims to investigate the relationship between the occurrence of cleft lip and palate in Tibetans and Han Chinese in western China and the distribution of ABO blood groups and Rh blood groups to provide a theoretical basis for the precise prevention and treatment of cleft lip and palate. In this study, statistics on Tibetan patients with cleft lip and palate, some Han patients with cleft lip and palate, and normal controls from western China were retrospectively collected. All participants were patients from West China Stomatology Hospital, Sichuan University. All patients with cleft lip and palate received treatment at the hospital between January 2016 and September 2023. The normal controls were outpatients or inpatients who did not have cleft lip and palate, and who received treatment at the hospital between January 2020 and October 2023. Information on the A, B, O, and AB blood groups and Rh positive and negative blood groups of the patients was collected and compared with that of the normal controls. The incidence of different phenotypes, including cleft lip alone, cleft palate alone, and cleft lip with cleft palate, in patients of blood groups A, B, O and AB were statistically analyzed by Chi-square test. A total of 1227 Tibetan patients with cleft lip and palate, 4064 Han patients with cleft lip and palate, and 5360 normal controls were included in the study. Among all the patients with cleft lip and palate, 1863 had cleft lip alone, 1425 had cleft palate alone, and 2003 had cleft lip with cleft palate. The ABO blood group distribution of Tibetan patients with cleft lip and palate was characterized as O>B>A>AB, with Rh positive blood group accounting for 100%, blood type O accounting for 41.15%, and blood type B accounting for 30.64%. The blood group distribution of the Han patients with cleft lip and palate was characterized as O>A>B>AB, with Rh positive blood group accounting for 99.58%, blood type O accounting for 35.78%, and type A accounting for 30.54%. There was a significant difference in ABO blood groups between Tibetan and Han patients with cleft lip and palate (P<0.005), but no significant difference in Rh blood groups. The ABO blood group distribution of the Tibetan patients with cleft lip and palate showed an obvious difference from that of the control group, while those of the Han patients with cleft lip and cleft palate and the control group did not show obvious differences. In the analysis of the subtypes, it was found that the blood group distribution in the subtypes of cleft lip alone, cleft palate alone, and cleft lip with cleft palate in the Tibetan population was O>B>A>AB, while that in the Han Chinese population was O>A>B>AB. There were differences in blood group distribution between Tibetans and Hans of the subtypes of cleft lip alone and cleft lip with cleft palate (P<0.001), but there was no difference in blood group distribution in the population of cleft palate-only subtype. The proportion of blood type O in Tibetan patients with cleft lip and palate was significantly higher than that in the Han patients with cleft lip and palate. The blood group distribution of Tibetan patients with cleft lip and palate in Sichuan Province, Xizang Autonomous Region, and Qinghai Province was always O>B>A>AB. Tibetan patients from Shiqu County and Baiyu County, Ganzi Tibetan Autonomous Prefecture and Chaya County, Qamdo City were predominantly of blood type B, and those from other regions were mainly of blood type O. There were significant differences in the phenotype composition and ABO blood group distribution between the Tibetan and Han populations with cleft lip and palate in western China. The distribution of blood group O in the population with cleft lip and palate was higher than that in the normal population, and the same trend was observed for different phenotypes. However, differences between Tibetan and Han populations in ABO blood group distribution were only found in the phenotypes of cleft lip only and cleft lip with palate. Tibetans with blood type O are more prone to cleft lip deformity than Han people, and the effect in the phenotype of cleft lip with palate is less pronounced than that in the phenotype of cleft lip only.

Orofacial clefts: treatment based on a multidisciplinary approach

Objective To evaluate the clinical value of color Doppler signal at the nasal lip in the diagnosis of fetal cleft palate. Methods Twenty fetuses diagnosed with fetal cleft lip and cleft palate by targeted ultrasonography and magnetic resonance imaging were enrolled in this study. Color Doppler was used during each ultrasound scan. All prenatal diagnoses were confirmed either by postnatal follow-up or autopsy. The location and degree of cleft lip and palate was also recorded. During inspiration or swallowing color signal acrossed the defects at the fetal palate was indicated cleft palate, and no color signal acrossed the defects at the fetal palate was indicated without cleft palate. Two dimensional ultrasound combined with color Doppler was used to diagnose cleft lip and palate in midsagittal plane or paratsagittal plane, then compared with the results of post-natal evaluation or abortion, and the value of color signal at the nasal lip in the diagnosis of fetal cleft palate was analyzed. Results Twenty cases of postpartum fetus (including post-natal evaluation or abortion ) confirmed 15 cases of cleft lip and palate, 5 cases of cleft lip (2 cases with upper alveolar cleft). For prenatal diagnosis, 5 cases of cleft lip and 15 cases of cleft lip and palate were diagnosed by two-dimensional ultrasound, of which 3 cases of cleft lip and palate were misdiagnosed as cleft lip, whereas 3 cases of cleft lip were misdiagnosed as cleft lip and palate with 2 cases combined with upper alveolar cleft. Two-dimensional ultrasound in the diagnosis of cleft lip and palate is consistent with postnatal results by additional evaluation of the color signal in nasolabial area in median sagittal section. In the cleft lip and cleft lip with the alveolar cleft fetuses, the color signal in nasolabial area was undetectable during fetal respiratory-like movement or swallowing by ultrasound.However, it was detectable in cleft lip and palate fetuses. A total of 3 cases of simple cleft lip and 17 cases of cleft lip and palate were detected by magnetic resonance imaging(MRI). In 2 cases of cleft lip and palate diagnosed by MRI, no blood flow signal was detected at the nasolabial area. Conclusions The connected color signal in nasolabial area assessed by color Doppler ultrasound during fetal respiratory-like movement or swallowing showed an promising value for prenatal diagnosis of cleft palate. Cleft palate could be ruled out if the connected color signal was undetectable in nasolabial area. Key words: Ultrasonography, prenatal; Cleft palate; Color Doppler signal

Early Intervention in Children with Cleft Palate

This study compares hospital-based care and associated charges among children with cleft lip, cleft palate, or both, and identifies subgroups generating the greatest cumulative hospital charges. The authors conducted a retrospective cohort study of cleft lip, cleft palate, or cleft lip and palate who underwent initial surgery from 2006 to 2008 in four U.S. states. Primary outcome was hospital-based care-emergency, outpatient, inpatient-within 4 years of surgery. Regression models compared outcomes and classification tree analysis identified patients at risk for being in the highest quartile of cumulative hospital charges. The authors identified 4571 children with cleft lip (18.2 percent), cleft palate (39.2 percent), or cleft lip and palate (42.6 percent). Medical comorbidity was frequent across all groups, with feeding difficulty (cleft lip, 2.4 percent; cleft palate, 13.4 percent; cleft lip and palate, 6.0 percent; p < 0.001) and developmental delay (cleft lip, 1.8 percent; cleft palate, 9.4 percent; cleft lip and palate, 3.6 percent; p < 0.001) being most common. Within 30 days of surgery, those with cleft palate were most likely to return to the hospital (p < 0.001). Hospital-based care per 100 children within 4 years was lowest among the cleft lip group, yet comparable among those with cleft palate and cleft lip and palate (p < 0.001). Cumulative 4-year charges, however, were highest among the cleft palate cohort (cleft lip, $56,966; cleft palate, $106,090; cleft lip and palate, $91,263; p < 0.001). Comorbidity, diagnosis (cleft lip versus cleft palate with or without cleft lip), and age at initial surgery were the most important factors associated with the highest quartile of cumulative hospital charges. Cleft lip and palate children experience a high rate of hospital-based care early in life, with degree of medical comorbidity being a significant burden. Understanding this relationship and associated needs may help deliver more efficient, patient-centered care.

Diminished maxillary growth is a consequence of labiopalatal repair, and many patients with cleft lip and palate require Le Fort I advancement. The goal of this study was to determine the frequency of maxillary hypoplasia as measured by need for Le Fort I. Retrospective cohort study of males born before 1987 and females before 1989. Records of 173 patients with cleft lip and palate and 34 with cleft palate were reviewed. Documented age, gender, cleft type, and need for Le Fort I. Pearson chi-square and Fischer's exact analyses were performed to evaluate the frequency of Le Fort I. Of 217 patients with cleft lip and palate or cleft palate, 40 were syndromic; of the remaining 177 patients, 69 had cleft lip, 78 had cleft lip and palate, and 30 had cleft palate. Thirty-seven of 177 patients (20.9%) required Le Fort I, subcategorized by cleft type: 0/69 for cleft lip, 37/78 for cleft lip and palate, and 0/35 for cleft palate (p<.0001). Of the 37/78 (47.4%) cleft lip and palate patients, the frequency of Le Fort I correlated with severity: 5/22 unilateral incomplete cleft lip and palate; 16/33 unilateral complete cleft lip and palate; 1/2 bilateral incomplete cleft lip and palate; 2/4 bilateral asymmetric complete/incomplete cleft lip and palate; 13/17 bilateral complete cleft lip and palate (p<.05). Overall frequency of Le Fort I was 20.9% in patients with cleft lip and palate and cleft palate. Of those with cleft lip and palate, 47.7% required maxillary advancement, but none with isolated cleft lip or cleft palate required correction. Frequency of Le Fort I osteotomy correlated with the spectrum of severity of labiopalatal clefting.

Cleft-orthognathic surgery

Global prevalence of cleft palate, cleft lip and cleft palate and lip: A comprehensive systematic review and meta-analysis

Objective To investigate the characteristics of patients with non-syndromic cleft lip with or without cleft palate (NSCL/P), and to provide the basis for the treatment. Methods 1435 cases of NSCL/P were collected from January 2012 to December 2014. Characteristics of the gender, type and side, blood type, associated malformation, genetic history of the patients were analyzed retrospectively. Results In the 1435 cases, 397 cases (27.67%) presented with cleft lip, 655 cases (45.64%) with cleft palate, and 383 cases (26.68%) with cleft lip and palate. 801 (55.82%) were male, and 634 (44.18%) were female. In cleft lip, male 60.20% (n=239) were more than female 39.80% (n=158); left side was 57.43% (n=228) more than right 27.96% (n=111) and the right were more than bilateral 14.61% (n=58). In cleft lip and palate, male 78.33% (n=300) were more than female 21.67% (n=83), left 41.51% (n=159) were more than right 28.20% (n=108) and bilateral 30.29% (n=116). In cleft palate, female 60.00% (n=393) were more than male 40.00% (n=262). Blood type AB with cleft lip (28/369) were higher than ones with cleft palate (28/627). All of the differences were statistically significant (P<0.05). 5.09% (n=73) patients with malformation were found out of 1435 cases. The patients with congenital heart disease (n=36, 2.51%) was the largest number of total deformity. Conclusions In patients with cleft lip, male is more than female; left side is more than right; unilateral clefts are higher that bilateral ones. In cleft lipand palate, male were more than female, left side were higher. In cleft palate, female were more than male. Blood type AB with cleft lip is higher than that of cleft palate. Key words: Cleft lip; Cleft palate; Cleft lip and palate; Statistical analysis

Some Underlooked Properties of the Multifactorial/Threshold Model

Long term health of the stomatognathic system as well as esthetic aspects is the therapeutic goals in patients with oro facial clefts. The aim of this study was to assess and compare the periodontal status of patients with cleft lip (CL), cleft palate (CP) and cleft lip, alveolus and palate (CLAP) reporting to a hospital in Chennai, India. The study group consisted of 80 cleft patients. Subjects were divided into three groups. Group 1: patients with cleft lip (CL), Group 2: subjects with cleft palate (CP) and Group 3: subjects with cleft lip alveolus and palate (CLAP). Community Periodontal Index for Treatment needs CPITN Index was recorded. Among the 80 study subjects, 51 (63.8%) were males and 29 (36.2%) were females. Among the 26 study subjects with cleft lip, 10 (38.5%) had healthy periodontium, 4 (15.4%) had bleeding on probing and 12 (46.1%) had calculus. Mean number of sextants coded for healthy and bleeding was maximum among the subjects with cleft palate. Mean number of sextants coded for calculus was maximum among the subjects with cleft lip alveolus and palate. Prevalence of periodontal disease is high among patients with cleft lip, alveolus and palate (35%) than in Cleft lip (32.5%) and Cleft Palate (32.5%). Gingivitis and Calculus is predominantly high in patients with Cleft Palate and Cleft Lip respectively.

The RYK, EPHB2, and EPHB3 genes are attractive candidates for cleft lip and/or palate and cleft palate only pathogenesis. Both the Ryk-deficient mouse and Ephb2/Ephb3 (genes for interaction molecules with RYK) double-mutant mouse show cleft palate. Mutation searches for RYK, EPHB2, and EPHB3 were carried out in a large number of Japanese and Vietnamese patients with cleft lip and/or palate and cleft palate only. Case-control study and transmission disequilibrium tests were performed also, using three single nucleotide polymorphisms within a linkage disequilibrium block in RYK. Seven haplotypes were constructed from the single nucleotide polymorphisms. A missense mutation, 1355G>A (Y452C), in RYK was identified in one Vietnamese patient with cleft lip and/or palate. This mutation was not found among 1646 Vietnamese, Japanese, and Caucasians, including 354 cleft lip and/ or palate and cleft palate only patients. Colony formation assay using NIH3T3 cells transfected with mutant cDNA revealed that mutant RYK had significantly reduced protein activity, compared with those with wild-type RYK, implying that the transformation ability of RYK is depleted by this mutation. Although a case-control study and transmission disequilibrium tests on three individual single nucleotide polymorphisms provided no evidence for association with oral clefts, a case-control study on one rare haplotype suggested a positive association in Japanese patients with cleft lip and/or palate and cleft palate only. No mutations in EPHB2 and EPHB3 were found in any patients examined. The findings suggested that a missense mutation, 1355G>A, and one rare single nucleotide polymorphisms haplotype may play a role in the development of cleft lip and/or palate in the Vietnamese, and cleft lip and/ or palate and cleft palate only in the Japanese.

Cleft lip and palate (CLP) is one of the most prevalent malformations occurring in the head and neck region. Cleft lip and palate is the second most birth defect in the US after club foot. The incidence of Cleft lip and cleft palate is also very common in Indian Population with the rate of 1 in 700 births approximately. In India, the main reason for the formation of Cleft Lip and cleft palate is consanguineous marriage due to less awareness among people. Cleft lip can be unilateral or bilateral and may involve or palate. Again it can be further classified as Complete or Incomplete cleft lip and /or Cleft palate. Most of the patients were deprived of treatment, mainly due to their unawareness and their lower status. Cleft patients need comprehensive, cleft care management. So the aim of this study is to find the incidence of bilateral cleft lip or palate in patients who reported toSaveetha Dental College and Hospital, Chennai. This study is done with 76 patients40 males, 36 females)who visited a Saveetha Dental College during one year between June 2019-April 2020. All available data were extracted from patients case sheets and results were obtained through SPSS analysis. In this study, we observed that 90.5 % of patients reported with unilateral cleft lip and palate, where only 9.1% of patients reported with bilateral cases. Males were having high prevalence with 52.6 % and females 47.4%. conclusion, male patients had higher cleft lip and palate compared to females. The incidence of bilateral cases seen among cleft lip and palate is fewer in males.

To examine the characteristics of the prevalence of congenital cleft lip with/without cleft palate in the ethnic Tibetan population and to provide support for the precise prevention and treatment of cleft lip with/without cleft palate in the Tibetan population. The clinical data of Tibetan patients with cleft lip with/without cleft palate were collected and the clinical characteristics of the patients were analyzed. The patients' age ranged from 2 months to 51 years old. All the subjects were admitted to West China Stomatology Hospital, Sichuan University for the treatment of cleft lip with/without cleft palate between January 2016 and August 2023. Most of the subjects came from Sichuan Province and the Tibet Autonomous Region. A total of 1051 patients were enrolled and children aged under 12 months (460 cases) accounted for the largest proportion. Among the subjects, 383 had cleft lip only (36.44%), 140 had cleft palate only (13.32%), and 528 had cleft lip with cleft palate (50.24%). The male-to-female ratios of patients with cleft lip only (0.99∶1), cleft palate only (0.54∶1), and cleft lip with cleft palate (1.67∶1) exhibited significant differences (P<0.001). However, there was no significant difference in the male-to-female ratio in patients with cleft lip only or those with cleft lip with cleft palate when the subjects were divided into two groups according to whether they had unilateral or bilateral cleft lip with/without cleft palate. Most of the patients with bilateral cleft lip were female, while most of the patients with unilateral cleft lip and unilateral or bilateral cleft lip with cleft palate were male. The unilateral cleft lip with/without cleft palate was located predominantly on the left side. Syndromic cleft lip with/without cleft palate accounted for 3.43% of all the cases and the most common concomitant deformity was congenital heart disease. 3.81% (40 cases) of the patients had a family history. In the patients with cleft lip only and those with cleft palate only, the proportion of patients having parents with corresponding phenotypes was higher than those of other phenotypes of cleft lip with/without cleft palate. Regarding the birth time distribution of the children with cleft lip with/without cleft palate, Spring saw the highest number of births of these children (311 cases, 29.59%), while Winter saw the lowest number of births (231 cases, 21.98%). The cases of cleft lip with/without cleft palate in the ethnic Tibetan population are predominantly cleft lip and palate. Unilateral cleft lip only or cleft lip with palate is predominantly located on the left side. Lip disease phenotypes may be more heritable.