Assessment of Two Years of Free Surgical Treatment of Cleft Lip, Palate and Alveolar (CLPA) in the Maxillofacial Surgery and Stomatology Department of the Hospital University of Treichville-Abidjan

Introduction: Cleft lip, palate and alveolar (CLPA) are congenital malformations of the face due to a defect in the fusion of embryonic buds during the first weeks of embryogenesis. These malformations affect the upper lip, the alveolar bone and the palate. The incidence in Africa ranges from 1/2000 to 1/500 births. Their multidisciplinary management is long and costly. Thus, the help provided by humanitarian organisations during free care campaigns is welcome. Materials and Methods: This is a retrospective descriptive study conducted from August 2014 to July 2016 in the Maxillofacial Surgery and Stomatology Department of the Treichville University Hospital in Abidjan, Côte d’Ivoire. The objective was to describe the epidemiological, clinical and therapeutic aspects of CLPA during a humanitarian campaign for free care. Results: 51 cases of CLPA were operated on. Males were involved in 54.9% of the cases, i.e. a sex ratio of 1.2. The average age of the patients at the time of the operation was 3.44 years with extremes of 3 months and 52 years. Patients with low socioeconomic status represented 84.3% of the cases. Cleft lips (31.4%) and cleft palates (33.33%) predominated. For cleft lips, unilateral forms were the most frequent (73.5%) and the left side was most often affected (59.2%). The most common surgical techniques used were MILLARD cheiloplasty for cleft lips (79.36%) and Dorrance pushback for cleft palates (78.05%). The postoperative course was simple in the majority of cases (80.47%). Patients and/or parents were satisfied with the postoperative results in over 90% of cases. Discussion: Cleft lip and palate are common. Their management by humanitarian missions through mass campaigns allows us to receive a large number of patients affected by this pathology who are treated with a high satisfaction rate. Conclusion: The characteristics of cleft lip and palate in this study are in many respects identical to those described in the literature, but with some differences specific to Africa, notably the absence of antenatal diagnosis and the advanced age at the time of treatment.

Rhinoplasty in Cleft Lip and Palate

Various surgical techniques and approaches have been described to repair cleft nose deformities. It is necessary to consider that since it is a congenital deformity, surgical management must consider the patient’s growth process, as well as the healing itself from the surgery. The present study aims to evaluate an alternative solution to secondary rhinology, aesthetic, and functional alterations to unilateral or bilateral cleft lift palate to minimize deformities and ensure good results. 11 patients were studied between 1995 to 2002, ten male and one female. In 8 cases, the patients had a history of cleft lip and palate on the left side, 2 patients with cleft lift palate on the right, and 1 patient with bilateral cleft lip and palate. 100% of the patients increased their naso-labial angle. This improved their appearance and structure, starting from a preoperative arithmetic mean of 39 degrees to a postoperative arithmetic mean of 96 degrees. Such intervention increased the naso-labial angle by 57 degrees. At the base of the nose, it was possible to improve the inclination of the alar line (line B) in 10 of the cases with a variation of 2 to 3 mm in relation to the perpendicular line A and only one case remained with the same inclination.

The Craniofacial Morphology in Adult Patients with Unoperated Isolated Cleft Palate

Objective： To address the effect of intrinsic factors on craniofacial growth by analyzing the craniofacial morphology of unoperated isolated cleft palate in Chinese adult. Materials and Methods： This study included 37 nonsyndromic isolated cleft palate and 39 age and gender matched non-clefts. Twenty-six cephalometric measurements were employed to evaluate the facial morphology. Independent samples T test and Mann- Whitney U were used for comparison. Significant difference was defined at 95% level. Results： Data from this study showed patients with unoperated isolated cleft palate have a reduced maxillary sagittal length （ANS-PMP, A-PMP, P〈0.05）, a smaller ANB angle （ANB, P〈0.05） and a retrusive ANS point （S-N-ANS, P〈0.05; Ba-N-ANS, P〈0.05）. Measurements descripted position of maxilla （S-Ptm, P〉0.05）, depth of bony pharynx （Ba-PMP, P〉0.05）, anterior and posterior maxillary height （N-ANS, P〉0.05; R-PMP, P〉0.05） and mandible morphology （including linear measurements and angle measurements） did not show any significant difference between case and control groups. Conclusions： Patients with isolated cleft palate were characterized by maxillary retrusion. Mandible morphology and cranial basal morphology in isolated cleft palate showed no significant difference with nonclefts. Patients with isolated cleft palate are more vulnerable to cross bite than nonclefts. Intrinsic deficiencies did detrimental effect on maxilla sagittal length, but did no detrimental effect on maxilla position, mandible size and position.

LncR NA H19 and Target Gene-mediated Cleft Palate Induced by TCDD

This study investigated the role of long non‐coding RNAs（lnc RNAs） in the development of the palatal tissues. Cleft palates in mice were induced by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin（TCDD）. Expression levels of long non‐coding RNA H19（lncR NA H19） and insulin‐like growth factor 2（IGF2） gene were measured by quantitative real‐time polymerase chain reaction（q RT‐PCR）. The rate of occurrence of cleft palate was found to be 100% by TCDD exposure, and TCDD could cause short upper limb, cerebral fissure, webbed neck, and short neck. The expression levels of lnc RNA H19 and IGF2 gene specifically showed embryo age‐related differences on E13, E14, and E15 in the palatal tissues. The expression levels of lnc RNA H19 and IGF2 gene showed an inverse relationship on E13, E14, and E15. These findings demonstrated that lnc RNA H19 and IGF2 can mediate the development of mouse cleft palate.

Accurate diagnosis of prenatal cleft lip/palate by understanding the embryology

Cleft lip with or without cleft palate(CP) is one of the most common congenital malformations. Ultrasonographers involved in the routine 20-wk ultrasound screening could encounter these malformations. The face and palate develop in a very characteristic way. For ultrasonographers involved in screening these patients it is crucial to have a thorough understanding of the embryology of the face. This could help them to make a more accurate diagnosis and save time during the ultrasound. Subsequently, the current postnatal classification will be discussed to facilitate the communication with the CP teams.

Genome-wide and Interaction Linkage Scan for Nonsyndromic Cleft Lip with or without Cleft Palate in Two Multiplex Families in Shenyang,China

Objectives To identify the loci involved in nonsyndromic cleft lip with or without cleft palate （NSCL/P） in Northern Chinese people in Shenyang by using genomewide and interaction linkage scan.Methods Two multiplex families in Shenyang from North China were ascertained through probands with NSCL/P.Blood of every member was drawn for DNA extraction and analysis.Genotypes were available for 382 autosomal short tandem repeat （STR） markers from the ABI Prism Linkage Mapping Set version 2.5.Linkage between markers and NSCL/P was assessed by 2-point parametric LOD scores,multipoint heterogeneity parametric LOD scores （HLODs）,and multipoint nonparametric linkage score （NPL）.Results The initial scan suggested linkage on Chromosomes 1,2,and 15.In subsequent fine mapping,1q32-q42 showed a maximum multipoint LOD score of 1.9（empirical P=0.013） and an NPL score of 2.35 （empirical P=0.053）.For 2p24-p25,the multipoint NPL increased to 2.94 （empirical P=0.007）.2-locus interaction analysis obtained a maximum NPL score of 3.73 （P=0.00078） and a maximum LOD score of 3 for Chromosome 1 （at 221 cM） and Chromosome 2 （at 29 cM）.Conclusion Both parametric and nonparametric linkage scores greatly increased over the initial linkage scores on 1q32-q42,suggesting a susceptibility locus in this region.Nonparametric linkage gave a strong evidence for a candidate region on chromosome 2p24-p25.The superiority of 2-locus linkage scores compared to single-locus scores gave additional evidence for linkage on 1q32-q42 and 2p24-p25,and suggested that certain genes in the two regions may contribute to NCSL/P risks with interaction.

BHMT Gene Polymorphisms as Risk Factors for Cleft Lip and Cleft Palate in a Chinese Population

Objective Convincing evidence suggests a link between increased risk of nonsyndromic cleft lip with or without cleft palate （NSCL/P） and low intake of folic acid by the mother during pregnancy. The present study was designed to explore if genetic variation in the betaine‐homocysteine methyltransferase （BHMT） gene contributes to NSCL/P. Methods DNA was obtained from 166 individuals with NSCL/P and 285 healthy subjects. Three known single nucleotide polymorphisms （SNPs） present in the BHMT gene （rs651852, rs3797546, and rs3733890） were investigated by real‐time PCR‐based TaqMan genotyping. Results Neither allelic nor genotypic association was found between NSCL/P and SNPs rs651852 and rs3733890. SNP rs3797546 did not show allelic association with NSCL/P; however, a higher proportion of NSCL/P patients carry the CC genotype compared with the TT＋CT genotype （P=0.020, OR=2.10, 95% CI=1.11‐3.95）. Conclusion Our study suggests that polymorphism rs3797546 in the BHMT gene may confer genetic risk of NSCL/P in a recessive manner.

AN ANALYSIS OF ACOUSTIC CHARACTERISTICS OFCLEFT PALATE SPEECH WITH COMPUTERIZED SPEECH SIGNAL PROCESSING SYSTEM

The acoustic characteristics or the chinese vowels of 24 children with cleft palate and 10 normal control children were analyzed by computerized speech signal processing system (CSSPS),and the speech articulation was judged with Glossary of clert palate speech(GCPS).The listening judgement showed that the speech articulation was significantly different between the two groups(P<0.01).The objective quantitative measurement suggested that the formant pattern(FP)of vowels in children with cleft palate was different from that of normal control children except vowel[a](P< 0.05).The acoustic vowelgraph or the Chinese vowels which demonstrated directly the relationship of vocal space and speech perception was stated with the first formant frequence(F1)and the second formant frequence(F2).The authors conclude that the values or F1 and F2 point out the upward and backward tongue movement to close the clert, which reflects the vocal characteristics of trausmission of clert palate speech.

Comparison of Congenital Tooth Deficiencies Seen in Permanent Teeth in Individuals with Unilateral Cleft Lip and Palate to Those without Cleft Lip and Palate

Objective: To compare the congenital tooth deficiencies seen in permanent dentition in individuals with unilateral cleft lip and palate (UCLP) to non-cleft individuals with Angle Class I malocclusion. Method: The study was performed on orthopantomograph films of 50 individuals with UCLP aged between 12 - 16 years and 50 individuals with Angle Class I malocclusion individuals aged between 13 - 15 years. Individuals with UCLP;32 clefts were on the left side and 18 clefts were on the right side. Permanent third molar teeth deficiency was excluded from the study. Results: In 50 individuals with UCLP;35 (70%) upper lateral incisors were congenitally deficient in the cleft area, while 15 (30%) missing lateral teeth were found in the non-cleft side. In control group, 12 (24%) of 50 patients had congenital lateral incisor deficiency. Congenital deficiency of upper lateral incisor in UCLP;the cleft area was higher than the non-cleft side (p < 0.01). The difference was statistically important when compared with the control group (p < 0.001). In 50 individuals with UCLP;while 27 (54%) of second premolar teeth were congenitally deficient in cleft side, 23 (46%) were missing in non-cleft side. In control group, 18 (36%) congenital second premolar deficiency was detected. However, second premolar congenital deficiency was higher in UCLP group when compared to control group (p < 0.01). Conclusion: The deficiency of the lateral incisors in the cleft side is more often congenitally deficient than upper second premolar teeth and this should be considered in the treatment planning from an early age.

A Case-control Study of Environmental Risk Factors for Nonsyndromic Cleft of the Lip and/or Palate in Xuzhou,China

In this study, we sought to determine the association between environmental factors and nonsyndromic cleft of the lip and/or palate （NSCLP） to understand the etiology of the disease. A total of 200 NSCLP cases and 327 controls were recruited at the Maternal and Child Health Hospital of Xuzhou City. We conducted face-to-face interviews with the mothers of both cases and controls. The factors increasing the risk of NSCLP were a positive family history [odds ratio （OR）=56.74], pesticide exposure （OR=8.90）, and indoor decoration pollution （OR= 4.32）. On the other hand, the factors decreasing the risk of NSCLP were a high education level （OR=0.22） and supplementation of folic acid （OR=0.23） and multivitamins （OR=0.16）. Positive family history, pesticide exposure, and indoor decoration pollution are associated with the risk of NSCLP. In contrast, high education level and folic acid and multivitamin supplementation are protective factors against NSCLP.

Malonylcarnitine in Newborns with Non-syndromic Cleft Lip with or without Cleft Palate

Aim Malonyl-CoA is regarded as a key signaling molecule in mammalian ceils. It is converted to acetyl-CoA, and to a lesser extent, to malonyl acid and malonylcamitine （C3DC）. Availability of carnitine has been reported to be essential for the developing fetus. The objectives of the present study were to analyze associations of malonylcarnitine, acetylcarnitine （C2）, and free carnitine （CO） in subjects with orofacial clefts. Methodology We performed a retrospective analysis of carnitine concentration obtained from a newborn screening program carried out in our institution. Concentrations of whole blood malonylcarnitine, acetylcarnitine, and free carnitine were measured using tandem mass spectrometry. The study group consisted of 51 children with nonsyndromic cleft lip with or without cleft palate. In total, 106 healthy children without congenital anomalies served as controls. Cut-off points were established using likeli-hood ratio values. Results The mean concentration of malonylcarnitine in the cleft group was lower than that of the control group, 0.048 μmol.L^1 vs. 0.058 μmol.L^-1, respectively （P=-0.009）. In patients with orofacial cleft, low malonylcarnitine levels （〈0.047 μmol.L-1） were 1.7 times more predominant than in healthy individuals （P=-0.03）. The mean concentration of acetylcarnitine was also lower in affected newborns in comparison to controls, 33.8 μol.L^-1 vs. 37.8 μmol·L^-1, respectively （P=-0.026）. After analysis of acetylearnitine and free carnitine concentrations, the likelihood ratio test did not indicate valuable cut-offpoints. Conclusion The study provides initial data indicating a potential association between decreased malonylcarnitine and abnormal palatogenesis.

Value of acoustic perceptual method for analysis of compensatory articulation errors in postoperative patients with cleft palate

Objective To establish an acoustic perceptual method analyzing the compensatory articulation errors in children with operated cleft palate via the formants of Chinese pure vowels. Methods The first three formants which represent vocal transmission character in Chinese pure vowels of 84 subjects with operated cleft palate, were measured by Computerized Speech Signal Processing System (CSSPS). The Chinese vowel graph of postoperative patients with cleft palate was stated by the first formant frequencies (F1) and the second formant frequencies (F2) of the Chinese pure vowels between the two groups. Results Values of F1 and F2 of vowels except [a] in the poor articulation group (Group A) were significantly different from those in the good articulation group (Group B) (P<0.05 or P<0.01). As compared with that in Group B, the vowel graph demonstrated the decreased perceptual distances in Group A. These findings indicated that there might still be the backward movements of tongue, perverted mandibular movements and disharmonious lip movements in addition to the velopharyngeal insufficiency (VPI) in Group A. Conclusion The speech articulation of children with repaired cleft palate should be gained by correcting the aberrant compensatory articulation errors in the condition of velopharyngeal competence. Computerized Speech Signal Processing System (CSSPS), which is regarded as the content of objective quantitative measurement, is a precise, simple, reliable and atroumatic technique for children with cleft palate to analyze pathological compensatory articulation errors.

TYMS gene 5'-and 3'-untranslated region polymorphisms and risk of non-syndromic cleft lip and palate in an Indian population

Dear Editor： Increased homocysteine levels due to vitamin B6 or B12 deficiency or genetic defects in folate pathway genes are associated with an increased incidence of non-syndromic cleft lip with or without cleft palate （NSCLP）tlj. Thymidylate synthase （TS） is a folate-dependent enzyme that catalyzes methylation of 2＇-deoxyuridine-5＇-monophosphate （dUMP） to 2＇-deox- ythymidine-5＇-monophosphate （dTMP）, a rate-limiting step in DNA synthesis,

Association of Single Nucleotide Polymorphisms in IRF6 and TGFA Genes With Nonsyndromic Cleft Lip With Or Without Cleft Palate in Chinese Patients

Objective： Nonsyndromic cleft lip with or without cleft palate（NSCL/P） is a common birth defect with unclear etiology. Both genetic and environmental factors may contribute to NSCL/P. Many genes have been identified as candidate genes associated with this disease. Interferon regulatory factor 6（IRF6） gene and transforming growth factor-a（TGFA） gene seem to be crucial in the predisposition of NSCL/ P. Here we evaluated some single nucleotide polymorphisms（SNPs） loci of TGFA and IRF6 genes in Chinese nuclear families consisting of fathers, mothers and affected offspring with NSCL/P. Methods：Fifty patients of NSCL/P were confirmed by the plastic surgeons. They and their parents were included in the study, all with the informed consents. SNPs loci of TGFA and IRF6 genes were analyzed by microarray technology. Some PCR products were randomly chosen and sequenced to check microarray results. The distribution of gene type and allele frequency between patient group and parents group were compared. Then a Haplotype Relative Risk（HRR） and Transmission Disequilibrium Test（TDT） were performed. Results：The sequences of randomly selected PCR products were all consistent with the microarray results. All loci were in Hardy-Weinberg equilibrium. There were no significant differences in the distribution of genotypes and alleles between patients and their parents. Using HRR and TDT analyses the V274I of IRF6 was associated with NSCL/P, while another SNP locus oflRF6 was not. Strong evidence of linkage disequilibrium was found between the 2 SNP loci of TGFA and disease with the HRR analysis, but not with the TDT analysis. Conclusion：Our study confirms the contribution of IRF6 in the etiology of NSCL/P in populations of Asian ancestry. The association of TGFA with NSCL/P requires further research.

Evaluation of Results of the Furlow’s Modified Technique in the Management of Cleft Palate in the Teaching Hospital of Conakry

Introduction: Cleft palate (CP) is a congenital dysmorphosis that results from a failure of the palatal processes of the maxillary buds and nasal septum to merge. The objectives of this study were to determine the frequency of complications of the modified Furlow technique and to evaluate its anatomical and functional outcomes. Materials and Method: This was a retrospective study that took place over a period of 4 years (from January 1st, 2015 to December 31th, 2018) in the Department of Odontostomatology and Maxillofacial Surgery at the National Hospital of Donka (Conakry, Guinea). Data retrieval consisted of records from patients operated on for cleft palate according to Furlow’s modified technique only. The operative technique consisted of marginal incisions of the cleft according to the technique of the double Z-plasty of Furlow. Subsequently, the defect created between the 2 flaps and the anterior edge of the cleft was filled by two fat masses of Bichat sutured to each other with Vicryl 3-0. Four years after surgery, the patients were recalled for an evaluation of the anatomical and functional results. Results: 13 patients underwent surgical loading according to the modified Furlow technique. The average age of the patients was 6.9 years with an age range of 7 months and 17 years. Females were the most affected, with 61.54% of cases and a sex ratio of 0.62. The primary repair rate was 84.61% of cases. Immediate operative follow-up was simple with epithelialization of the flaps in all patients. Four (4) years after the surgeries, 12 patients were reevaluated (92.30%), among them one case (8.33%) of fistula complication was noted. The mobility of the veil and the phonation were good in 85.71% and 60% respectively. Articular disorders with nasonation were found in 2 patients (16.67%). Swallowing was normal in 85.72% of cases. Conclusion: The modified Furlow technique is an important contribution to cleft palate surgery significantly reducing the occurrence of postoperative complications. However, the delay of the surgical operation remains a real obstacle for obtaining a normal phonation.

Upper Airway Changes after Maxillary Distraction Osteogenesis in Cleft Lip and Palate Patients

Purpose: To measure the upper airway changes associated with maxillary distraction osteogenesis in cleft lip and palate patients in the immediate post operative period and 12 months later. Materials and Methods: Seven patients with repaired cleft lip and palate (CLP) presented with severe maxillary hypoplasia. They were examined initially at T1 predistraction phase. Records taken included radiographs (orthopantograms OPG, lateral cephalometric, posteroanterior). Cephalometric analysis was done to evaluate the upper airway. Mean age is 17 years and the reverse overjet > 6 mm. They underwent maxillary Le Fort I distraction using external rigid distracters (RED). Cephalometric analysis to evaluate the upper airway was repeated at the end of the consolidation phase T2 and twelve months after distractor removal T3. Results: The range of maxillary advancement was between 8 - 15 mm (mean 9 mm). The anteroposterior distance of the superior velopharynx (PPS) and middle velopharynx (SPPS) increased at T2. A small amount of reduction in these values was recorded at T3. The inferior velopharynx (MPS) and the oropharynx (IPS, EPS) showed minimum increase in anteroposterior distance in only two patients at T2 and no change at T3. Conclusion: All seven patients showed clinical improvement in the upper airway and an increase in the upper airway values on lateral cephalometric radiographs.

Expectations of Caregivers of Patients with Cleft Lip and Palate Attending the Cleft Clinic of KATH for the First Time

Background: Cleft lip and palate (CLP) is one of the most prevalent congenital malformations affecting the face worldwide, with high prevalence in Asians, Americans, and Caucasians and low in Africans. Orofacial Clefts (OFCs) are among the causes of perinatal death in Ghana. The children often experience difficulties in swallowing, feeding, and speaking. These children often face problems in cognition, education, and communication. Caregivers’ ignorance of treatment, poverty, and noncompliance with follow-up schedules are obstacles to optimal cleft care. Most studies focus on the incidence of cleft, but not much is known about caregivers’ expectations. Methodology: An exploratory qualitative study design was used for this research between October and November 2020. The study site was the Komfo Anokye Teaching Hospital, (KATH), Kumasi, Ghana. The respondents were recruited from the oral health clinic. Included in the study were all CLP caregivers attending the cleft clinic for the first time. Purposive sampling was used to select fifteen caregivers who met the inclusion criteria. Face-to-face interviews with a semi-structured interview guide were used to collect data. The data were analyzed using NVivo software. Three major themes and six sub-themes emerged from the data analysis using thematic analysis. Ethical clearance was obtained for data collection. Results: Most caregivers were expecting their babies to be operated on, and they were certain that the cleft would be repaired at the end of the treatment, but they were unfamiliar with the process and cost of treatment. Less than half of the caregivers reported that they were oblivious to what to expect the first time visiting but had hopes that the healthcare professionals would be able to close the cleft for their babies. Conclusion: The majority of the caregivers expressed fear and disappointment at the diagnosis of their child. Some caregivers were very scared to the level where they had to hide the babies from the public. Others reported being already in financial difficulties, so their children’s conditions would compound them.

A Novel Method for the Prenatal Diagnosis of Cleft Palate Based on Amniotic Fluid Metabolites

Background and purpose The prenatal diagnosis of cleft palate is an important component of sequential therapy,but the relevant diagnostic methods are still limited.We aimed here,to explore the possibility of an early prenatal diagnosis of cleft palate by assessing metabolites in pregnant mice.Methods Twenty-four inseminated females were randomly divided into retinoic acid(RA)-treated(treated with retinoic acid at 10.5 gestation days)and control groups.The metabolites of the embryonic palatal tissue,maternal amniotic fluid,and serum were characterized using 9.4T magnetic resonance spectroscopy in vitro.Then,a predictive model was established through the principal component analysis(PCA),and the correlations between the metabolites of amniotic fluid and palatal tissue were explored using orthogonal-2 partial least squares(O2-PLS).Results The incidences of cleft palate were 100%and 0%in the RA-treated and control groups,respectively.A predictive PCA model with a high specificity and sensitivity was established for the early prenatal diagnosis of isolated cleft palate using amniotic fluid metabolic data.Between RA-treated and control mice,we found that two metabolites in the amniotic fluid and palatal tissue were correlated.Creatinine showed the same trend in the palatal tissue and amniotic fluid,while choline showed opposite trends in the two tissues.However,the data for serum metabolites could not be used to establish a prediction model.Conclusion This study indicates that assessing the metabolites of amniotic fluid is a potential approach for the prenatal diagnosis of isolated cleft palate.

Three-dimensional finite element analysls for external midface distraction after different osteotomy in patients with cleft lip and palate

Objective To study three - dimensional finite element analysis for external midface distraction after different osteotomy in patients with cleft lip and palate ( Clp) . Methods Three - dimensional Fem models of Le Fort Ⅰ,Ⅱand Ⅲ,osteotomy in Clp patients were estabolished. External midface distraction were simulated. An anteriorly and inferiorly directed 900 g force was

Identification of shared and unique gene families associated with oral clefts

Oral clefts, the most frequent congenital birth defects in humans, are multifactorial disorders caused by genetic and environmental factors. Epidemiological studies point to different etiologies underlying the oral cleft phenotypes, cleft lip(CL),CL and/or palate(CL/P) and cleft palate(CP). More than 350 genes have syndromic and/or nonsyndromic oral cleft associations in humans. Although genes related to genetic disorders associated with oral cleft phenotypes are known, a gap between detecting these associations and interpretation of their biological importance has remained. Here, using a gene ontology analysis approach, we grouped these candidate genes on the basis of different functional categories to gain insight into the genetic etiology of oral clefts. We identified different genetic profiles and found correlations between the functions of gene products and oral cleft phenotypes. Our results indicate inherent differences in the genetic etiologies that underlie oral cleft phenotypes and support epidemiological evidence that genes associated with CL/P are both developmentally and genetically different from CP only, incomplete CP, and submucous CP. The epidemiological differences among cleft phenotypes may reflect differences in the underlying genetic causes. Understanding the different causative etiologies of oral clefts is important as it may lead to improvements in diagnosis, counseling, and prevention.