单侧唇裂修复术改善鼻部畸形

目的探讨单侧唇裂修复手术对鼻部畸形的治疗影响。方法我院2002年至2006年收治单侧唇裂186例,回顾分析其手术方式与鼻唇部修复情况。结果单侧唇裂修复术后,鼻畸形35例,其中Millard法修复术后鼻畸形12例（12/77,15.6%）;Tennison法修复16例（16/56,28.6%）,上旋转下三角瓣法修复7例（7/53,13.2%）。结论对于单侧唇裂,选择适宜的手术方式,可同期修复鼻部畸形,减少患者痛苦。     

Accessory nose associated with unilateral incomplete cleft lip

We describe a 6-month-old Turkish girl who was found to have a mass near her nose at birth and incomplete cleft lip. No other clinical and radiological abnormalities were demonstrable elsewhere in her body. Histological examination of the excised mass showed an organoid structure that was consistent with an accessory nose.     

Prolabial lengthening by Turkish tulip method in bilateral cleft lip repair

OBJECTIVE: In bilateral cleft lip, there is a characteristic deformity called cleft lip nose characterized by short columella and prolabium with a pressed nose. Although lots of surgical techniques were described for columella lengthening and correction of the nose deformity, no technical method was suggested for prolabium lengthening. STUDY DESIGN: In this paper we propose a simultaneous bilateral cleft lip repair and lengthening of the prolabium, and describe a new technique called "Turkish tulip" for this aim. PATIENTS AND METHOD: Eleven patients (6 males and 5 females) with bilateral cleft lip were treated using this method. Patients' ages ranged from 3 months to 17 years at the time of operation. Five patients had incomplete and six had complete bilateral cleft lips. The patients were evaluated in terms of functional and aesthetic results in postoperative period. RESULTS.: The average follow-up time was 8 months (ranged from 4 months to 15 months). There were no postoperative complications. The prolabium was lengthened adequately in all patients. No notch and whistle deformity was seen in our series. The patient or parent satisfaction was good or perfect in all cases. CONCLUSIONS: To avoid the disadvantage of the long time course required to correct the nose deformity and to lengthen the prolabium, we propose the "Turkish tulip" technique with the primary repair of bilateral cleft lips simultaneously. With this technique it is possible to lengthen the columello-prolabial complex with cleft lip repair in the same session without any intervention to any part of the nose including the columella. As a preliminary study, according to the early results, this new technique seems to have good cosmetic outcomes.     

Treatment outcome after neonatal cleft lip repair in 5-year-old children with unilateral cleft lip and palate

IntroductionThe aim of this study was to assess speech outcomes and dental arch relationship of 5-year-old Czech patients with unilateral cleft lip and palate (UCLP) who have undergone neonatal cleft lip repair and one-stage palatal closure.Methods and materialsTwenty-three patients with UCLP, born between 2009 and 2010, were included in the study. Three universal speech parameters (hypernasality, articulation and speech intelligibility) have been devised for speech recordings evaluation. Outcomes of dental arch relationship were evaluated by applying the GOSLON Yardstick and subsequently compared with the GOSLON outcome of other cleft centers.ResultsModerate hypernasality was present in most cases, the mean value for articulation and speech intelligibility was 2.07 and 1.93, respectively. The Kappa values for inter-examiner agreement for all the three speech outcomes ranged from 0.786 to 0.808. Sixty-three percent of patients were scored GOSLON 1 and 2, 26% GOSLON 3, and 10% GOSLON 4. GOSLON mean score was 2.35. Interrater agreement was very good, represented by kappa value of 0.867.ConclusionThe treatment protocol, involving neonatal cleft lip repair and one-stage palatal repair performed up to the first year of UCLP patient's life, has shown good speech outcomes and produced very good treatment results in regard to maxillary growth, comparable with other cleft centers.     

Blood transfusion requirements in cleft lip surgery

Objective

Cleft lip surgery is a common procedure performed by surgeons worldwide. The aim of the study was to determine blood transfusion requirements and factors influencing blood transfusion in cleft lip surgery.

Methods

Transfusion rate in 100 consecutive patients who had cleft lip surgery was prospectively evaluated at the Lagos University Teaching Hospital, Nigeria. Data collected included age and sex of patients, type of cleft defects, type of surgery done, preoperative haematocrit, duration of surgery, amount of blood loss during surgery, the number of units of blood cross-matched and those used. Cardiovascular parameters at the point of transfusion were also recorded. Each patient was made to donate a unit of homologous blood prior to surgery.

Results

Mean estimated blood loss during surgery was 26.5 ± 47.1 ml. Most patients (92%) lost between 2 and 50 ml of blood. Mean estimated blood loss in unilateral cleft lip surgery was not significantly differently from that of bilateral cleft lip surgery (P = 0.46). Only five patients (5%) required blood transfusion. The mean blood transfused was 50.0 ± 16.9 ml. All the patients transfused had a preoperative haematocrit of <30% (23-27%). The cross-match-to-transfusion ratio for cleft surgery was 20. The transfusion index was 0.05 and overall blood-ordering quotient was 20.

Conclusion

Cleft lip surgery is a low volume blood loss surgery. Homologous blood donation prior to cleft lip surgery in patients with preoperative haematocrit of 30% or more is not necessary. For patients with preoperative haematocrit of less than 30%, type and screen of donated blood should be adequate.     

鼻翼软骨肌肉环在单侧重度唇裂鼻畸形矫正术中的作用

目的：探讨鼻翼软骨肌肉环在单侧重度唇裂术后鼻畸形整复中的作用。方法：经鼻小柱基底的“V—Y”型切口行患侧鼻翼软骨肌肉环修复,对裂侧上颌骨退缩明显者,在裂侧梨状孔边缘处充填自体肋软骨组织,整复76例唇裂鼻畸形患者,观察近、远期效果。结果：76例切口均一期愈合,随访12～38个月,对唇裂鼻畸形患者的鼻尖、鼻翼、鼻孔及鼻小柱畸形矫治术后外形满意。结论：唇裂患者因鼻翼软骨肌肉环发育不良,进而导致了鼻部肌力的失衡。 因此,唇裂鼻畸形矫正中修复鼻翼软骨环肌肉状结构具有重要意义。     

The nasopharynx in infants with cleft lip and palate

Objective

The purpose of this study was to use three-dimensional computed tomography data and computer imaging technology to assess the skeletal components of the naso-pharyngeal area in patients with cleft lip and palate and to quantify anatomical variations.

Methods

CT scans were obtained from 29 patients of Malay origin with cleft lip and palate aged between 0 and 12 months and 12 noncleft patients in the same age group, using a GE Lightspeed Plus Scanner housed in Hospital Universiti Sains Malaysia. Measurements were obtained using the ‘Persona’ three-dimensional software package, developed at Australian Craniofacial Unit, Adelaide.

Results

The results of the present study show that there is an increased nasopharyngeal space in cleft lip and palate that may lead to compression of the nasopharyngeal structures, including the Eustachian tube. Alterations of the medial pterygoid plate and the hamulus may lead to an alteration in the origin and orientation of the tensor veli palatini muscle leading to alteration in its function.

Conclusions

These anatomical variations may compromise the dilatory mechanism of the Eustachian tube, thus leading to recurrent middle ear infections in cleft children and subsequent loss of hearing.     

Growth in infants in the first two years of life after neonatal repair for unilateral cleft lip and palate

Objective

To evaluate the growth during the first two years of life in infants after unilateral cleft lip and palate neonatal repair.

Method

All mature infants with nonsyndromic unilateral cleft lip and palate (NSUCLP) born between 2004 and 2007 were included. Information concerning growth was collected. Weight and length at birth, 6, 12, 18 and 24 months of age measurements and data regarding feeding were obtained.

Results

Weight and length at birth, 6, 12, 18 and 24 months of age were identical with reference curve values. Children with NSUCLP showed a normal growth at two years. The weight curves lie between 5th and the 50th percentile for girls and between 10th and higher than the 97th percentile for boys. The height curves lie between −1 Standard Deviation and +1 Standard Deviation for girls and 0 and +2 Standard Deviation for boys.

Conclusion

Feeding difficulties are reported in infants with cleft lip and/or palate CLP/CP. However, the growth in children with NSUCLP and after neonatal cleft lip repair is identical with reference curve values.     

MSX1 gene polymorphisms in Mexican patients with non-syndromic cleft lip/palate

ObjectiveNon-syndromic cleft lip/palate malformation (CL/P) is one of the most common birth defects in humans and has a complex etiology involving genetic and environmental factors. Mutations in the MSX1 gene are critical during craniofacial development. The purpose of this study was to investigate the contribution of MSX1 gene polymorphisms to the risk of developing CL/P in a sample of Mexican patients.MethodsThe sample consisted of 282 subjects (69 cases and 213 relatives). Four single-nucleotide polymorphisms (SNP1, P147Q, SNP5 and P278S) were tested for association with CL/P in triad and case-pseudo-control analyses. Polymorphism typing was performed by restriction fragment length polymorphism and dot-blot techniques. Allele and genotype frequencies were calculated between patients and pseudo-controls and compared using the Chi square test with Yates correction. Odds ratios and 95% confidence intervals were obtained using SPSS software (v19). Triad analysis was also performed using the program HAPLIN (v5.3).ResultsIn the cases and pseudo-controls, an association was found between CL/P and the SNP1-G allele (P = 0.031) and the SNP1-G/G genotype (P = 0.032), a polymorphism located near MSX1. Triad analysis showed a tendency toward CL/P susceptibility for the genotype SNP1-G/G (P = 0.075) and an association between CL/P and the haplotype GCTC (P = 0.037). No associated haplotype was found in the cases and pseudo-controls. Two partial haplotypes, GT (SNP1-SNP5) (P = 0.032) and GC (SNP1-P278S) (P = 0.033), were associated with susceptibility in the heterozygous and homozygous types, respectively. In contrast, haplotype AT (SNP1-SNP5) was associated with protection (P = 0.012) in the homozygous type.ConclusionsThe results of this study suggest an association between CL/P susceptibility and SNP1, located near the MSX1 gene, in the Mexican population.     

Human genetic factors in nonsyndromic cleft lip and palate: an update

Nonsyndromic cleft lip and/or palate (or orofacial cleft, OFC) is a malformation characterized by an incomplete separation between nasal and oral cavities without any associated anomalies. The last point defines the distinction between syndromic and nonsyndromic OFC. Nonsyndromic OFC is one of the most common malformations among live births and is composed of two separate entities: cleft lip with or without cleft palate (CL+/-P) and cleft palate isolated (CPI). Because of the complex etiology of nonsyndromic OFC, which is due to the differences between CL+/-P and CPI, and the heterogeneity of each group, caused by the number of genes involved, the type of inheritance, and the interaction with environmental factors, we reviewed those genes and available loci in the literature whose involvement in the onset of nonsyndromic OFC has more sound scientific evidence. Genetic studies on human populations have demonstrated that CL+/-P and CPI have distinct genetic backgrounds and, therefore, environmental factors probably disclose only these malformations. In CL+/-P several loci, OFC from 1 to 10 have been identified. The first locus, OFC1, has been mapped to chromosome 6p24. Other CL+/-P loci have been mapped to 2p13 (OFC2), 19q13.2 (OFC3) and 4q (OFC4). OFC5-8 are identified by mutations in the MSX1, IRF6, PVRL1, and TP73L gene, respectively. OFC9 maps to 13q33.1-q34, whereas OFC10 is associated with haploinsufficiency of the SUMO1 gene. In addition, MTHFR, TGF-beta3, and RARalpha play a role in cleft onset. In CPI one gene has been identified (TBX22) at present, but others are probably involved. Greater efforts are necessary in order to have a complete picture of the main factors involved in lip and palate formation. These elements will permit us to better understand and better treat patients affected by OFC.     

The risk of nonsyndromic cleft lip with or without cleft palate and Vax1 rs7078160 polymorphisms in southern Han Chinese

IntroductionNon-syndromic cleft lip with or without cleft palate is a common worldwide birth defect due to a combination of environmental and genetic factors. Genome-wide association studies reported the rs7078160 of Vax1 is closely related to non-syndromic cleft lip with or without cleft palate in European populations. The following studies showed the same results in Mongolian, Japanese, Filipino, Vietnamese populations etc. However, conflicting research had been reported in Chinese population,ObjectiveThe aim of this study was to investigate the association between the rs7078160 polymorphism and non-syndromic cleft lip with or without cleft palate in Southern Chinese patients.MethodsIn this study, we investigated the polymorphism distribution of rs7078160 in 100 complete patient trios (39 patients with non-syndromic cleft lip and palate; 36 patients with non-syndromic cleft lip only; 25 had non-syndromic cleft palate only; and their parents) from Southern ethnic Han Chinese. 60 healthy trios were selected as control. Polymerase chain reaction and Sanger sequencing were used to genotype rs7078160 in Vax1; both case–control and family-based associations were analyzed.ResultsThe case–control analyses revealed the rs7078160 polymorphism was significant, associated with non-syndromic cleft lip with or without cleft palate (p = 0.04) and non-syndromic cleft lip and palate (p = 0.01), but not associated with non-syndromic cleft lip only and non-syndromic cleft palate only patients. The genotype composition of rs7078160 comprises mutated homozygous AA, heterozygous AG and wild homozygous GG. Cases with AG + AA genotypes compared with GG homozygotes showed an increased risk of non-syndromic cleft lip with or without cleft palate (p = 0.04, OR = 2.05, 95% CI: 1.01–4.16) and non-syndromic cleft lip and palate (p = 0.01, OR = 3.94, 95% CI: 1.34–11.54). In addition, we did not detect any transmission-disequilibrium in rs7078160 (p = 0.68).ConclusionThis study suggests that rs7078160 polymorphism is a risk factor of non-syndromic cleft lip with or without cleft palate, and Vax1 is strongly associated with non-syndromic cleft lip with or without cleft palate in Southern Chinese Han populations.     

Role of angiogenesis-related genes in cleft lip/palate: Review of the literature

Objectives

Cleft lip and cleft palate (CLP) are the most common congenital craniofacial anomalies. They have a multifactorial etiology and result from an incomplete fusion of the facial buds. Two main mechanisms, acting alone or interacting with each other, were evidenced in this fusion defect responsible for CLP: defective tissue development and/or defective apoptosis in normal or defective tissues. The objective of this work was to study the implication and role of angiogenesis-related genes in the etiology of CL/P.

Methods

Our methodological approach included a systematic and thorough analysis of the genes involved in CL/P (syndromic and non-syndromic forms) including previously identified genes but also genes that could potentially be angiogenesis-related (OMIM, Pub Med).We studied the interactions of these different genes and their relationships with potential environmental factors.

Results

TGFβ, FGA, PDGFc, PDGFRa, FGF, FGFR1, FGFR2 growth factors as well as MMP and TIMP2 proteolytic enzymes are involved in the genesis of CLP (P>L). Furthermore, 18 genes involved in CLP also interact with angiogenesis-related genes.

Discussion

Even if the main angiogenesis-related genes involved in CLP formation are genes participating in several biological activities and their implication might not be always related to angiogenesis defects, they nevertheless remain an undeniably important research pathway. Furthermore, their interactions with environmental factors make them good candidates in the field of CLP prevention.     

SUMO1 as a candidate gene for non-syndromic cleft lip with or without cleft palate: no evidence for the involvement of common or rare variants in Central European patients

Objective

Studies in mice and humans have suggested that SUMO1, which codes for the small ubiquitin-related modifier 1 (SUMO1), is a promising candidate gene for non-syndromic cleft lip with or without cleft palate (NSCL/P). To investigate the possible involvement of this gene in NSCL/P patients from Central Europe, we performed: (i) a case control association study, and (ii) a resequencing study.

Methods

Genotyping and the subsequent single marker and haplotype association analyses were performed for 413 NSCL/P patients and 412 controls. A total of 17 tagging single-nucleotide polymorphisms (SNPs) were used. In the resequencing study, the complete coding region and splice sites were sequenced in 65 index patients from multiply affected families.

Results

One of the 17 tested SNPs (rs16838917) had a borderline significant P-value of 0.0416 in the single-marker association analysis. However, this result did not withstand correction for multiple testing (P_corr = 0.707). No association was observed for any haplotypic marker combination. Sequencing failed to identify any novel rare sequence variants.

Conclusions

The results of the present study do not support the hypothesis that common or rare variants in SUMO1 play a significant role in the development of NSCL/P in Central-European patients. However, smaller effects of common variants or the presence of rare high penetrance mutations in other non-investigated familial cases cannot be excluded. Further analysis of SUMO1 in independent samples from Central European and other populations is therefore warranted.     

The financial impact of unrepaired cleft lip and palate in the Philippines

Objectives

There are over 96 million people in the Philippines. Close to 77 thousand persons in this country have orofacial clefting. We estimate nearly 64 thousand are unrepaired. Unemployment and underemployment because of the communication disorders associated with unrepaired clefts will affect family income and hence tax revenues. The purpose of this study is to understand the financial impact of unrepaired cleft lip and/or palate on families and identify how that would translate to the Philippine government in tax revenues.

Methods

The incidence of orofacial cleft in the Philippines was estimated to be at least 1 in 750 people, with only 16% anticipated to be repaired under current conditions. Assuming a 21% unemployment rate in subjects with untreated clefts, and a tax rate of 6–12.4%, projected lost personal income and federal tax revenue was calculated.

Results

In 2012 alone the financial impact on the families may be as much as $US 73–88 million in lost revenue from unemployment and underemployment. This would cost the government between $8.0 and $9.8 million dollars in lost tax revenue. Over a 20 year period at least $US 1.7 billion dollars in family income would be affected costing the government at least $US 194 million in taxes.

Conclusion

By appropriately caring for the cleft population tax revenues should increase substantially. The development of the infrastructure for surgical care of this problem would be costly but could be more than offset by revenues. Inattention to surgically correctable causes of communication disorders is not affordable.     

腭裂婴幼儿术前早期语言发育的初步研究

目的初步观察8～15个月龄腭裂婴幼儿术前的早期语言发育。方法对北京大学口腔医学院2006年9月～2007年1月就诊的符合条件的40名腭裂术前唇腭裂／腭裂患儿的养护人进行问卷调查。用两样本成组t检验与正常儿童进行比较。结果唇腭裂患儿语言理解和语言得分均值都低于正常儿童，差异没有统计学意义，且高于正常儿童均值的负两个标准差；在语言表达方面，14和15个月龄患儿明显低于正常儿童，两组之间差异有统计学意义，并低于正常儿童均值的负两个标准差。结论8～15个月龄唇腭裂婴幼儿腭裂术前语言理解和语言能力的发育不足，14和15个月龄患儿的语言表达迟缓，主要是能说的词汇量少，提示应该早期进行腭裂手术，为唇腭裂提供更好的发音条件，间接促进语言的发育。     

An analysis of the frame-content theory in babble of 9-month-old babies with cleft lip and palate

The aim of this study was to examine the consonant–vowel co-occurrence patterns predicted by the Frame-Content theory in 16 nine-month-old babies with unrepaired cleft palate (±cleft lip) and 16 age-matched non-cleft babies. Babble from these babies was phonetically transcribed and grouped according to the intrasyllabic predictions of the theory (labial–central, alveolar–front, and velar–back). Both groups demonstrated the three consonant–vowel co-occurrence patterns predicted by the Frame-Content theory. Other patterns not predicted by the Frame-Content theory emerged as strong patterns as well.Learning outcomes: The reader will be able to: • Describe consonant–vowel co-occurrence patterns produced by babies with and without cleft palate. • Describe vowel inventories of babies with cleft palate. • Identify possible therapy targets for babies with cleft palate.     

Effects of maxillary expansion on hearing and voice function in non-cleft lip palate and cleft lip palate patients with transverse maxillary deficiency: a multicentric randomized controlled trial

IntroductionThe association between the treatment of transverse maxillary de?ciency and the recovery of hearing and voice functions has gained attention in recent years.ObjectiveThis prospective controlled trial aimed to evaluate the effects of rapid maxillary expansion on hearing and voice function in children with non-cleft lip palate and bilateral cleft lip palate with transverse maxillary deficiencyMethods53 patients (26 non-cleft and 27 bilateral cleft lip palate; mean age, 11.1 ± 1.8 years) requiring rapid maxillary expansion for correction of narrow maxillary arches were recruited for this trial. Eight sub-groups were established based on the degree of hearing loss. Pure-tone audiometric and tympanometric records were taken for each subject at four different time periods. The first records were taken before rapid maxillary expansion (T0), the second after expansion (T1) (mean, 0.8 months), the third after three months (T2) (mean, 3 months) and the fourth at the end of retention period (T3) (mean, 6 months). ANOVA and Tukey HSD post-hoc tests were used for data analysis. Additionally, voice analysis was done using an updated PRAAT software program in a computerized speech lab at T0 and T2. A paired-samplet-test was used for comparisons of mean values of T0 and T2 voice parameters within both groups.ResultsRapid maxillary expansion treatment produced a significant increase in the hearing levels and middle ear volumes of all non-cleft and bilateral cleft lip palate patients with normal hearing levels and with mild conductive hearing loss, during the T0–T1, T1–T2, T0–T2, and T0–T3 observation periods (p < 0.05). The significant increase was observed in right middle ear volumes during the T0–T1, T0–T2 and T0–T3 periods in non-cleft patients with moderate hearing loss. For voice analysis, significant differences were observed only between the T0 and T2 mean fundamental frequency (F0) and jitter percentage (p < 0.05) in the non-cleft group. In the cleft group, no significant differences were observed for any voice parameter between the T0 and T2 periods.ConclusionCorrection of the palatal anatomy by rapid maxillary expansion therapy has a beneficial effect on both improvements in hearing and normal function of the middle ear in both non-cleft and bilateral cleft lip palate patients. Similarly, rapid maxillary expansion significantly influences voice quality in non-cleft patients, with no significant effect in BCLP patients.     

Prospective evaluation of the effect of early nasal layer closure on definitive repair in cleft palate patients

IntroductionThe cleft palate is one of the most common congenital anomalies treated by plastic surgeons. The cleft width increases the tension of repair and necessitates excessive dissection that might affect maxillary growth. Decreasing the width of cleft minimize tension, dissection and may limit the impact on maxillary growth.ObjectivesThe purpose of the study was to evaluate the effect of nasal layer closure of the hard palate at the time of cleft lip repair in patients with complete cleft lip and palate, to demonstrate the efficacy of narrowing the gap and to reduce the incidence of fistulae or other complications.MethodsThirty patients less than 1 year of age were included in this prospective observational study. A superiorly based vomer flap was used to repair the nasal layer of the cleft hard palate at the time of primary cleft lip repair. 12–14 weeks after the vomer flap, the cleft soft and hard palate was definitively repaired. Alveolar and palatal gaps were recorded during the 1st and 2nd operations to demonstrate the reduction of the gap defect.ResultsThe mean reduction of the alveolar cleft width in patients who had a vomer flap in the first stage was 4.067 mm and the mean reduction of the palatal gap was 4.517 mm. Only 3 patients developed small fistula on the repaired nasal layer that was discovered and corrected during definitive palatoplasty.ConclusionNasal layer closure is a simple surgical technique that can be used to close the hard palate at the time of cleft lip repair. It is a valuable addition to cleft lip and palate repair that may prevent some cleft palate surgical complications.