The current understanding of cleft lip malformations

Cleft lip with or without cleft palate is one of the most common congenital malformations. Epidemiology differentiates between cleft malformations connected with syndromes and the more common nonsyndromic forms not associated with other deformities. Although many syndromes with cleft lip with or without cleft palate are known, the majority of orofacial clefts are of the nonsyndromic form. These are known to be of multifactorial origin, with both environmental and genetic factors in their etiology, most of which remain to be fully investigated. Recent literature reveals that wide ethnical and racial variations in the occurrence of cleft lip and/or palate exist. The purpose of this overview is to show the current standing of research in this field. Genetics, environmental factors, and morphogenesis of the primary and secondary palate in normal development and cleft malformations are especially emphasized.     

Embryology and epidemiology of cleft lip and palate

Craniofacial anomalies, in particular cleft lip and palate, are major human birth defects with a worldwide frequency of 1 in 700 and substantial clinical impact. This article reviews the embryology of the face, lip, and palate to enhance the understanding of the pathogenesis of these lesions, with particular attention to the period of susceptibility during gestation, complexity, and the factors that may influence their development. It includes an overview of the prevalence and environmental and genetic causes of cleft lip-with or without cleft palate- and cleft palate.     

Variability of expression of oral-facial-digital syndrome type I in 15 Saudi girls: Why is there a high rate of median cleft lip in the phenotype?

BACKGROUND:

It is well known that the incidence of nonsyndromal cleft lip and palate varies greatly according to ancestry: 0.3 to 0.4 per 1000 live births in blacks, one in 1000 in Caucasians, and two in 1000 in Asians and individuals from the central province of Saudi Arabia. Median cleft lip is a variable feature in oral-facial-digital syndrome type I (OFD-I).

OBJECTIVE:

To test the hypothesis that genetic factors may determine the lip phenotype in OFD-I patients.

METHODS:

A study involving 15 Saudi girls (from the central province of Saudi Arabia) with OFD-I showed a high rate (93.3%) of median cleft lip and palate. This rate in OFD-I patients is known to range from 33% to 56% in Caucasians and also known to be very low in blacks. The authors compared the rate of median cleft lip with or without cleft palate in the Arabian series (93.3%) with the rate in Caucasians and blacks.

RESULTS:

The difference in median cleft lip with or without cleft palate among the three groups was significant.

CONCLUSION:

This supports the hypothesis that ancestral genetic factors may determine the lip phenotype in OFD-I patients.     

Chief teratogenic factors in facial abnormalities

Congenital anomalies of the face mainly originate in chromosomal and teratogenic factors. Cleft lip and cleft palate are common anomalies of the face and palate. Cleft lip, with or without cleft palate, occurs about once in 1000 births. Cleft palate occurs about once in 2500 births. Most cases of cleft lip and palate are determined by multiple factors, genetic and nongenetic, each causing only a minor developmental disturbance. This is called multifactorial inheritance. The purpose of this study is a review on teratogenic factors with action on the newborn face.     

Normal and abnormal development of the lip and palate

Largely because fusion of the lip and the palate are developmental weak points, common facial clefts may arise in a great many ways, both experimentally and in man. However, we believe that the vast majority of human clefts have similar origins with minor variations. One must always question the appropriateness of animal models. Apparently appropriate animal models are giving us considerable insight into the manner in which genetic and environmental factors alter development and how they interact with one another in the developing embryo. These studies help us understand the nature of the multifactorial threshold concept as it applies to cleft lip and cleft palate, and they emphasize the potential importance of even "minor" environmental factors in determining on which side of the threshold for clefting an individual embryo may fall.     

The clinical observation of difficult laryngoscopy and difficult intubation in infants with cleft lip and palate

BACKGROUND: The aims of this study were to evaluate the incidence of difficult laryngoscopy in infants with cleft lip and palate and to observe its relationships with age, sites, and degrees of deformities. METHODS: A total of 985 infants aged 1 month to 3 years, undergoing repair of cleft lip and palate were included in this study. The infants suffering from unilateral cleft lip, simple cleft palate, and combined bilateral cleft lip and palate were 465, 421, and 79 respectively. They were divided into three groups according to age; 1-6 months group, 6-12 months group and 1-3 years group. RESULTS: The total incidence of difficult laryngoscopy was 4.77%. The incidence of difficult laryngoscopy was closely related to age, sites and degrees of deformities, and micrognathia. The incidence of difficult laryngoscopy was 7.06% in 1-6 months group, 2.90% in 6-12 months group, and 3.13% in 1-3 years group, and was greatest for infants with combined bilateral cleft lip and palate, less for those with left cleft lip and least for those with right cleft lip and simple cleft palate. The incidences of difficult laryngoscopy in infants with and without micrognathia were 50% and 3.83% respectively. The incidences of moderately difficult, difficult, and failed intubations were 1.02%, 0.91%, and 0.102% respectively. CONCLUSIONS: Infants with cleft lip and palate, left cleft lip and alveolus, combined bilateral cleft lip and palate, micrognathia, and age <6 months were the important risk factors for difficult laryngoscopy. Difficult intubation occurred mainly in infants with laryngoscopic views of grade III and IV.     

22q11 Deletion in children with cleft lip and palate--is routine screening justified?

OBJECTIVE: To ascertain the prevalence of 22q11 deletion in children with a diagnosis of cleft lip and/or palate that had been referred to the Cleft Lip & Palate Service, Newcastle-upon-Tyne. DESIGN: Retrospective analysis of results of 22q11 FISH testing performed in all such referrals. PARTICIPANTS: 191 children, of whom 13 had a bilateral cleft lip and palate, two had a median cleft, 77 had a cleft palate only, 44 had a unilateral cleft lip, 47 had a unilateral cleft lip and palate and eight had a submucous cleft palate. RESULTS: nine patients had a positive 22q11 FISH test. CONCLUSION: This represents a higher percentage than has been previously reported. All children with cleft lip and/or palate should routinely have a 22q11 FISH test in view of the implications of a diagnosis of velocardiofacial syndrome.     

Failure to thrive in babies with cleft lip and palate.

We established the frequency of failure to thrive (FTT) in children undergoing primary cleft procedures by using growth charts and standard-deviation scores. Initially, 147 babies with cleft lip and/or palate undergoing 186 primary lip-and-palate repairs were studied between 1993 and 1996. Rates of FTT were categorised according to cleft type. There was an increasing rate of FTT from 32% for unilateral cleft lip and palate to 38% for bilateral cleft lip and palate to 49% for cleft palate. There was a high incidence of FTT in palatal clefts, especially if these were associated with a syndrome or anomaly (P= 0.001). The incidence of FTT with the Pierre Robin sequence was 100%. In view of the high rates of FTT, two changes were instituted: a feeding-support nurse was appointed to supervise and monitor patients at risk and all patients with the Pierre Robin sequence had supervised airway management. Thereafter, the incidence of FTT was prospectively studied in 68 babies undergoing 84 primary procedures between 1997 and 1999. There was a decrease in the incidence of FTT in comparison with the earlier cohort (9% for unilateral cleft lip and palate, 20% for bilateral cleft lip and palate, 26% for cleft palate). There was a significant decrease in the incidence of FTT in the group with the Pierre Robin sequence, from 100% to 40%. As a result of the provision of a feeding-support nurse and airway management of patients with the Pierre Robin sequence, the incidence of FTT was reduced and the audit loop closed.     

Clinical and epidemiologic studies of nonsyndromic cleft lip and palate in china: analysis of 4268 cases

The aim of our study was to review clinical and epidemiologic characteristic of the nonsyndromic cleft lip and cleft palate over a period of 10 years at West China Stomatological Hospital, Sichuan University. Four thousand two hundred sixty-eight nonsyndromic cleft lip and cleft palate cases were retrospectively analyzed according to the following variables: general information, cleft type, maternal age, familial history, as well as associated malformations, et al. In these cases, 1075 of which were cleft lip, 1985 were cleft lip with cleft palate; 1208 were isolated cleft palate. There were more men than women in the cleft lip and cleft lip with cleft palate group, while there were more women than men in the isolated cleft palate group. There were significantly more unilateral cleft lip cases than cleft lip on both sides; the cases of cleft lip on the left side were more than that of cleft lip on the right side. The cases with inherited history accounted for 6.68% of all the cases. Most infection cases occurred among the deleterious factors and the complications experienced during the first 3 months after the pregnancy. In all of the 14 twin cases, only 1 of the babies was affected. There were totally 152 cases with other associated malformations. Patients with cleft lip born in November to January were less than those born in the other three quarters of the year. Patients of A blood group composed a higher proportion than the control group. Our data may provide references for appropriate resource use, cleft lip and cleft palate prevention programs, and counseling programs with China-specific data.     

唇腭裂1386例发病特点回顾性分析

目的：通过对唇腭裂患者临床资料进行回顾性统计分析,研究该病的发病特点,为唇腭裂的预防及治疗提供临床参考。方法：统计分析2007年1月～2010年1月手术治疗的1386例唇腭裂患者,分别从患者诊断、性别、年龄、出生地,唇腭裂裂型分布情况等方面进行回顾性调查。结果：本组病例中,单纯唇裂356例（25．69％）,唇裂合并腭裂580例（41．84％）,单纯腭裂450例（32．47％）;男809例,女577例,男：女=1．40：1;单侧唇裂伴或不伴腭裂明显多于双侧者,两者之比为5．67：1,其中左侧多于右侧（1．82：1）。结论：唇腭裂发病以唇裂合并腭裂居多,男性发病多于女性,在腭裂患者中女性发病高于男性;单侧发病多于双侧,左侧多于右侧。     

Correlation of cleft type with incidence of perioperative respiratory complications in infants with cleft lip and palate

BACKGROUND: A retrospective survey of 339 infants who had undergone primary plastic surgery for cleft lip and palate was performed to evaluate the concomitant preoperative assessment based on severity grading of the common cold and the correlation of cleft type with the incidence of perioperative respiratory complications. METHODS: We assessed the severity of common cold symptoms in the preoperative period using the Common Cold Score, which comprises 10 symptoms and findings. We then determined the association of the incidence of perioperative respiratory complications with the increasing severity of common cold symptoms and also compared the complication incidence in the three cleft types in healthy infants without a common cold. RESULTS: The incidence of perioperative respiratory complications was greater in the group with a suspected presence of a common cold. Infants with severer cleft, who had bilateral cleft lip and palate, even without common cold symptoms, had a significantly higher incidence of perioperative respiratory complications (8.9%) than infants with simple cleft lip (1.7%, P < 0.05). CONCLUSIONS: Clinicians should consider postponing primary plastic surgery for cleft lip and palate in infants with a suspected presence of a common cold. Our results also suggest that the presence of a wide cleft is a risk factor for causing perioperative respiratory complications in infants with cleft lip and palate. We believe that a careful preoperative assessment of common cold symptoms in these infants can decrease the incidence of perioperative respiratory complications.     

Significant differences in the incidence of orofacial clefts in fifty-two Czech districts between 1983 and 1997

Between 1983 and 1997 a total of 2029 children with CL/P (cleft lip, cleft lip and palate or cleft palate), who were born in the Bohemian districts of the Czech Republic and who underwent surgery and treatment at the Clinic of Plastic Surgery in Prague, were analysed. One possibility for decreasing the risk of delivery of a child with CL/P is to decrease or eliminate its prenatal exposure to embryotoxic factors. Detection of the embryotoxic factors acting at the individual level (e.g. elevated temperature, drug consumption, x-ray examination or infection) is easier than the detection of embryotoxic factors operating at the population level (e.g. water contamination, air pollution). When searching for the latter factors, we first have to reveal regional differences in CL/P incidence. The aim of the present paper was to determine significant differences in the mean incidence of newborns with CL/P in Bohemian districts during a 15 year period. The correlation between the incidence of CL/P and the birth rate in the different districts was also examined. The mean incidence of CL/P in all Bohemian districts was 1.86 per 1000 newborns (1.86/1000). Districts were divided into three groups, according to significant differences in the incidence of CL/P using a confidence interval. The lowest mean incidence of CL/P was detected in the Svitavy district (0.72/1000) and Louny (1.05/1000). The highest mean incidence was found in the Beroun district (2.86/1000). Besides Beroun, a high mean incidence of CL/P (more than 1.96/1000) was also found in Klatovy, M?lník, Tábor, Kolín, Semily, Ceská Lípa, Pardubice, Teplice, Cesky Krumlov, Sokolov, Chomutov, Praha-západ, Jicín, Rakovník, Kladno, Prachatice, Rokycany, Tachov, Liberec, Pelhrimov. Paradoxically, the districts with a higher or lower birth rate exhibited a lower (1.62/1000) or higher (1.92/1000) incidence of CL/P, respectively. Future studies should elucidate whether the significant regional differences in the incidence of CL/P can be related to differing exposure of pregnant women to harmful environmental embryotoxic factors.     

Malnutrition in cleft lip and palate children in Uganda

The objective of this study is to investigate the nutritional status of patients with cleft lip and/or palate when compared to non-cleft lip or palate patients. A retrospective analysis was carried out of all patients aged less than 1 year who were operated on in the Comprehensive Rehabilitation Services in Uganda hospital since opening in April 2009 to November 2010. The data was divided into three groups: cleft lip patients; cleft lip and palate patients and non-cleft patients. The WHO anthropometric calculator was used to calculate weight-for-age Z scores on each patient for the initial outpatient appointment and the operation. The demographic data and Z scores were compared using independent T tests. Three hundred and twenty-one patients were identified, 131 patients had cleft lip alone, 112 patients had cleft lip and palate and 78 patients had no cleft. The cleft lip and palate group had significantly lower Z scores for both the outpatient appointment and operation (i.e. were more malnourished) than either the cleft lip group or the non-cleft group. Malnutrition is a well-documented problem associated with cleft lip and palate. Our research confirms this malnutrition but also highlights the severity of the malnutrition. The patients with cleft lip and palate are unable to feed adequately and therefore need intervention. We operate on these patients once they reach a target weight of 3 kg and repair both lip and palate in one operation to enable patients to feed and improve their nutritional status.     

Oral clefts in the Sultanate of Oman

This is a retrospective study of the epidemiology of congenital clefts of the lip and palate in babies of Omani nationals born in the Sultanate of Oman between 1989 and 1995. Babies of non-Omani immigrants were excluded from the study. The data were collected from two sources. The first was the Centralized Plastic Surgery Service of Khoula Hospital at Muscat, the capital city of Oman between 1989 and 1995, which registers all oral cleft cases in the country. These data revealed the overall incidence of oral clefts (OC) to be 1.5 per 1000 live births, with incidences of 0.62 per 1000 for combined lip and palate (CLP) cleft, 0.34 per 1000 for cleft lip (CL), and 0.54 per 1000 for isolated cleft palate (CP). The second data source was national delivery records from maternity sections of all hospitals in the country from 1989 to 1995, which include oral clefts as congenital anomalies identified at birth. These statistics were similar to those from the first source for CL/CLP but underestimated the number of isolated cleft palates (CP). The histories of patients attending the Plastic Surgery Clinic of Khoula Hospital during the last year of the study period could be examined in detail. A study of the 177 OC cases registered in 1995 alone revealed associated congenital anomalies in 38.4%. A higher inbreeding coefficient of 0.0294 was noted among oral cleft cases than in the general population, which was calculated at 0.0198. Familial clefts accounted for 23% of all cases. Greater parental age and birth order were found to be associated with increased risk of oral cleft. High temperatures during the tropical desert summers in Oman (when temperatures reach 48°C) do not seem related to the incidence of oral clefts.     

Otitis media and feeding with breast milk of children with cleft palate.

The purpose of the present study was to analyse the incidence of acute and secretory otitis media (OM), and feeding with breast milk, and the use of a grommet in children with a cleft palate (CP/CLP) or cleft lip (CL), compared with controls. A total of 84 children between 6 and 10 years of age were studied. The CP/CLP group consisted of 48 children with an isolated cleft palate (n = 28), or a cleft lip and palate (n = 20). The CL group consisted of 15 children with an isolated cleft lip. The controls were 21 children without clefts. Children with CP/CLP had acute OM significantly more often than children without clefts (43/48 compared with 10/21), and secretory OM (40/48 compared with 4/21), despite the use of grommets. CP/CLP children were breast fed for a mean of 2.8 months (range 0-13), compared with 3.6 months (0-12) for CL, and 7.5 (0-24) months for controls. There was a significant correlation during the first 18 months of life between longer duration of feeding with breast milk and a lower incidence of acute and secretory OM in the three study groups combined. The incidence of otitis media was not affected by care in a day centre, having a sibling attending a day care centre, or by the family's medical history. Despite cleft repair and early treatment with grommets, both secretory and acute OM are common among children with cleft palate, presumably as a result of their eustachian tube dysfunction. The present study suggests that premature cessation of feeding with breast milk may contribute to an increased incidence of acute and secretory OM.     

Cleft deformities in Zimbabwe, Africa: socioeconomic factors, epidemiology, and surgical reconstruction

In the African country of Zimbabwe, a variety of socioeconomic factors have contributed to a lack of specialty care and resources for the indigent population. Although cleft lip and palate has a lower incidence in Africa (0.67 per 1000 births) than in Latin America or Asia, access to reconstructive surgery is often difficult to obtain. A surgical team worked with Zimbabweans at the Harare Central Hospital, Harare, to perform cleft surgery for 39 patients. We review the epidemiology of cleft deformities in Africa, our experience with 39 patients with cleft lip and palate, and the techniques used to address 2 patients with midfacial clefts. To our knowledge, this retrospective case review and epidemiologic literature review is the first review of cleft care in Zimbabwe. Poverty in Zimbabwe, caused in part by the highest inflation rate in the world, has contributed to the emigration of a large number of specialists to other countries. In addition, the health care system is overwhelmed by a high prevalence rate of human immunodeficiency virus (25%), leading to a drastically reduced parental life expectancy (mean life expectancy, 36 years). Primary and secondary cleft lip and palate repairs were completed without complications. Children requiring care beyond the scope of this mission were referred to the Republic of South Africa. The cooperation among the Zimbabwean administration, physicians, and nurses was integral to the organization and successful execution of this reconstructive surgical mission. Ultimately, until the socioeconomic conditions improve in Zimbabwe, training and continuing education of local physicians are imperative to advance the care of children with cleft lip and palate.     

Palatal Fistulae Following Cleft Palate Surgery

The occurrence and treatment of palatal fistulae have been studied in 1108 CLP patients who had their primary operations performed during the years 1954–69. No fistulae were recorded in 263 patients with incomplete cleft of the primary palate only. These patients were excluded, leaving 845 patients for analysis. The Le Mesurier or Millard technique had been used for the primary lip operation, and the von Langenbeck procedure for closure of the palate; in complete clefts, the anterior part of the palate had been closed using Veau's vomer flap operation simultaneously with lip closure. The observation period ranged from 7 to 22 years, during which time each patient was examined at least once and the majority on several occasions by members of the cleft palate team. The overall incidence of fistulae was 18%. Fistulae were recorded in 11.3% of all complete clefts of the primary palate, and in 36.1% of all complete total clefts. In cases of cleft palate only, fistulae were found in 3.5% of the incomplete clefts, and in 20% of the complete clefts. In patients with bilateral complete clefts, closure of both sides of the lip and anterior palate in one operation seemed to have greatly increased the risk of fistula formation. There was a much higher incidence of fistulae in patients operated on during the years 1954–61 than in those treated in the period 1962–69. Fistula symptoms requiring surgical intervention were recorded in 113 patients. Closure of the fistula was achieved in 84.1%. Of 18 patients with a residual fistula. 17 were asymptomatic or had symptoms so slight that they were considered insignificant and not justifying operation.     

Left or right hand dominance in children with cleft lip and palate.

The relationship between unilateral cleft lip, bilateral cleft lip, palatal clefting and left-right hand dominance was studied in 337 patients with cleft lip and/or palate aged between 3 and 14 years. There was no statistically significant difference in the laterality of handedness between different types of cleft nor between unilateral left and right sided cleft lip with or without cleft palate.     

Velopharyngeal insufficiency in hemifacial microsomia: analysis of correlated factors.

OBJECTIVE: To investigate the incidence of unilateral hypodynamic palate (UHP) and velopharyngeal insufficiency (VPI) in hemifacial microsomia (HFM), and to determine the dysmorphic manifestations having significant associations with UHP/VPI in HFM. STUDY DESIGN: This was a nonrandomized study of 48 patients with unilateral HFM without cleft palate. The correlation between each anomaly and UHP/VPI was analyzed statistically. In addition, we observed 4 HFM patients with cleft palate to examine the influence on cleft palate speech. RESULTS: The incidence of UHP in HFM was 50.0% and that of VPI was 14.6%. All the VPI patients had UHP. Severe micrognathia and soft tissue deficiency, macrostomia, and mental retardation were significant risk factors for developing VPI in HFM. Moreover, UHP exacerbated speech in HFM with cleft lip and palate. CONCLUSIONS: Significant correlations were detected between VPI and HFM. This finding should be helpful in the overall management of HFM.     

5459例唇腭裂患者临床资料分析

目的：对20年来唇腭裂的治疗及唇腭裂患者的构成情况进行回顾。方法：对5459例唇腭裂患者病历资料分类整理，进行统计学分析。结果：唇腭裂各类型性别比例差异有显著性意义，唇腭裂患者的首次手术年龄差异有显著性意义，其主要修复方式随年代的变化而不同。结论：唇腭裂患者中男性明显多于女性。自1980年以来，唇腭裂患者的首次手术年龄呈逐渐下降趋势，主要手术方法也有很大的变化。