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PubMed1999

Candidate genes for nonsyndromic cleft lip and palate and maternal cigarette smoking and alcohol consumption: evaluation of genotype-environment interactions from a population-based case-control study of orofacial clefts.

Previous studies suggest that the relationship between genes and nonsyndromic cleft lip +/- cleft palate (CLP) or cleft palate only (CP) may be modified by the environment. Using data from a population-based case-control study, we examined allelic variants for three genes, i.e., transforming growth factor alpha (TGFA), transforming growth factor beta 3 (TGFB3), and Msh (Drosophila) homeobox homolog 1 (MSX1), and their interactions with two exposures during pregnancy (maternal cigarette smoking and alcohol consumption) as risk factors for CLP and CP. For each cleft phenotype, risk estimates associated with most allelic variants tended to be near unity. Risk estimates for maternal smoking (> or = 10 cigarettes/day) were significantly elevated for CP and were most elevated among infants with allelic variants at the TGFB3 or MSX1 sites. By comparison, risk estimates for maternal alcohol consumption (> or = 4 drinks/month) were significantly elevated for CLP and were most elevated among infants with allelic variants at the MSX1 site. Our results suggest that development of CLP and CP may be influenced independently by maternal exposures but more significantly by interaction of such exposures and specific allelic variants.

Alcohol Drinking↗
PubMed1985

Thyroxine-induced differential mortality of cleft lip mouse embryos: dose- and time-response studies of the A/WySn strain.

Pregnant A/WySn mice, 20 to 30% of whose offspring have spontaneous cleft lip, were treated with thyroxine. Following treatment, cleft lip and normal embryos died, but cleft lip embryos died at a higher rate. The increased liability of cleft lip embryos to thyroxine-induced death was considered as a possible experimental route to identify the basic genetic defect that causes cleft lip. A time-response study indicated that cleft lip embryos responded more than normals following treatment on any of days 7 to 12 of gestation, that there is no sharply defined critical period, and that normal and cleft lip embryos do not differ in time of maximum sensitivity. A dose-response study showed linear responses of normal and cleft lip embryos on a probit-log dose scale, with a common slope and LD50's of 1.9 and 1.3 mg respectively. These dose-response properties indicate that normal and cleft lip embryos are probably killed by the same mechanism, but differ in dosage tolerance. That is, they differ quantitatively, not qualitatively. Thyroxine did not significantly change the cleft lip frequency, and the difference between normal and cleft lip embryos that leads to cleft lip itself is therefore not in the same pathway as that which leads to thyroxine-induced death. A hypothetical example of the defect basic to both pathways is presented.

Animals↗
PubMed1996

Dental findings in parents of children with cleft lip and palate.

The incidence of dental abnormalities in the cleft lip and palate population has been reported to be much higher than in the normal population. The role of genes in the production of a cleft lip and palate, and dental anomalies is thought to be complex, with autosomal dominant, recessive, and x-linked genes all playing a role. Noncleft parents can carry some of the cleft lip and palate genes, which produce clinically subtle manifestations in their facial skeleton. The purpose of this study was to look for evidence of increased dental anomalies in the non-cleft parents of cleft lip and palate children. The dentitions of the parents of 60 children with different types of cleft lip and palate were examined prospectively to see whether or not they exhibited features found more readily in the cleft lip and palate rather than did the normal population. Their dentitions were studied to record the following dental features: congenitally missing teeth, supernumerary teeth, or morphologic changes of the crowns of the permanent teeth. The number and position of any frenal attachments were also recorded. The results of this study did not show any differences in incidence of dental anomalies from the noncleft population. There was no evidence to support the hypothesis that congenital absence of lateral incisors is a microform of cleft lip and palate. Further, these results also failed to reveal any consistent pattern in the number and position of frenal attachments.

Adolescent↗
PubMed1991

Sucking efficiency of early orthopaedic plate and teats in infants with cleft lip and palate.

Intraoral negative pressure during bottle feeding with two kinds of teats (a regular Nuk and a cleft Nuk) was measured in 7 infants with cleft lip and palate, 8 infants with cleft palate, 2 infants with cleft lip, 4 infants with operated cleft lip and palate and 7 normal infants. Infants with cleft lip and palate or cleft palate were unable to generate negative pressure before cleft lip and palate closure. The presence or absence of an early orthopaedic plate did not make any difference. In infants with unoperated cleft lip and with operated cleft lip and palate, peak negative pressure during feeding differed little from that of normal infants.

Bottle Feeding↗
PubMed1994

The occurrence of hypodontia in patients with cleft lip and/or palate.

The frequency of hypodontia (but for the third molar) was studied in a series of 600 patients with cleft lip and/or palate. The series was subdivided into three groups according to the type of facial cleft. As compared to the general normal population the occurrence of hypodontia was markedly increased in patients with clefts. The highest percentage of hypodontia was recorded in patients with cleft lip and palate, the lowest frequency was present in cleft lip only. In cleft lip and in cleft lip and palate girls were affected significantly more frequently than boys. The occurrence of hypodontia in the lower and in the upper jaw differed according to the type of cleft. The upper jaw was affected more often in cleft lip and in cleft lip and palate, the mandible was involved more frequently in isolated cleft palate. The dental bud of the upper lateral incisor was affected most commonly in cleft lip and in cleft lip and palate, while the second lower premolar was most frequently absent in isolated cleft palate.

Adolescent↗
PubMed2006

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.

Child, Preschool↗
PubMed2003

Audiologic and tympanometric findings in children with cleft lip and palate.

OBJECTIVE: To evaluate the otologic and audiologic status of 50 children with repaired cleft lip, cleft palate, or both in Hacettepe University, Ankara, Turkey. DESIGN: Audiometric and tympanometric evaluation of 100 ears in 50 children were performed. Hearing levels < or = 15 dB and middle ear pressures between -50 to +50 decaPascals were considered to be normal. Results were examined according to cleft type and laterality. The least and most affected frequencies were calculated. A simple evaluation of speech characteristics including nasal resonance, nasal air escape, and errors of articulation was also performed. RESULTS: Sixty-three of the 100 ears had normal hearing status, whereas 40 had normal middle ear pressures. No evidence was found to suggest that individual cleft type and laterality of the ear had any effect on hearing loss or middle ear disease. Two-thirds of the patients had normal or acceptable degree of language skills. CONCLUSION: The final hearing status of patients with cleft palate is a result of a combination of surgical correction, developmental factors, and treatment of middle ear disease. Early and aggressive ventilation tube placement is the standard of cleft care in many countries. Our long-term hearing outcome is relatively good in a population not treated with routine insertion of ventilation tubes. The majority of patients also have satisfactory speech. Patients with cleft palate should have close follow-up for middle ear disease, but further research is warranted to determine the aggressive usage of ventilation tubes.

Acoustic Impedance Tests↗
PubMed2001

Management of the cleft lip deformity.

Repair of the unilateral cleft lip deformity is a challenging and rewarding procedure. Historically, many techniques have been described to reconstruct the unilateral cleft lip. These have included straight-line repairs and various geometric flap closures. The rotation-advancement flap technique of Millard is a reliable and versatile method for repair of the unilateral cleft lip deformity. This technique allows lip repair and tip rhinoplasty while camouflaging the scars in the newly formed philtral border. If properly applied, the rotation-advancement repair produces excellent functional and aesthetic results (Figs. 18A and 18B).

Cleft Lip↗
PubMed2006

Three-dimensional computer graphics for surgical procedure learning: Web three-dimensional application for cleft lip repair.

OBJECTIVE: In surgical procedures for cleft lip, surgeons attempt to use various skin incisions and small flaps to achieve a better and more natural shape postoperatively. They must understand the three-dimensional (3D) structure of the lips. However, they may have difficulty learning the surgical procedures precisely from normal textbooks with two-dimensional illustrations. Recent developments in 3D computed tomography (3D-CT) and laser stereolithography have enabled surgeons to visualize the structures of cleft lips from desired viewpoints. However, this method cannot reflect the advantages offered by specific surgical procedures. To solve this problem, we used the benefits offered by 3D computer graphics (3D-CG) and 3D animation. DESIGN AND RESULTS: By using scanning 3D-CT image data of patients with cleft lips, 3D-CG models of the cleft lips were created. Several animations for surgical procedures such as incision designs, rotation of small skin flaps, and sutures were made. This system can recognize the details of an operation procedure clearly from any viewpoint, which cannot be acquired from the usual textbook illustrations. This animation system can be used for developing new skin-flap design, understanding the operational procedure, and using tools in case presentations. The 3D animations can also be uploaded to the World Wide Web for use in teleconferencing.

Cleft Lip↗
PubMed1998

The effects of soft-tissue expansion on lip repair and midfacial growth in a rabbit cleft lip model.

Midfacial hypoplasia following primary cleft lip repair is a common clinical correlate. Recent experimental work has suggested that increased lip pressure following an undermined lip repair may contribute to midfacial growth inhibition. Soft-tissue expansion has been used to generate additional soft tissue for reconstruction in the cranial region. The use of this technique in the labial region may allow lip repair to be performed with less tension (pressure) and thus facilitate midfacial growth. To test this hypothesis, 40 4-week-old rabbits were randomly divided into four groups. Two groups had surgically created lip and alveolar defects. Ipsilateral labial tissue expanders were placed in all four groups. One cleft and one normal group underwent expansion. The other two groups served as a control. The expanders were removed at 4 weeks, and an undermined lip repair was performed in both cleft groups. Findings revealed that soft-tissue expansion increased labial surface area significantly by approximately 96% (p < 0.001). Labial soft-tissue expansion alone had no effect on midfacial growth during the observation period. In contrast, cleft animals undergoing tissue expansion exhibited significantly reduced (p < 0.05) postoperative lip pressure and increased midfacial growth compared with cleft animals without expansion through 36 weeks of age. Results suggest that preoperative tissue expansion reduced postoperative lip pressure and improved midfacial growth in a rabbit cleft lip model.

Animals↗
PubMed2006

Genetic evidence for the role of loci at 19q13 in cleft lip and palate.

BACKGROUND: Clefts of the lip and palate are common birth defects, affecting approximately 1 in 700 births worldwide. The aetiology of clefting is complex, with multiple genetic and environmental influences. METHODS: Genotype based linkage disequilibrium analysis was conducted using the family based association test (FBAT) and the likelihood ratio test (LRT). We also carried out direct sequencing of the PVR and PVRL2 candidate genes based on their homology to PVRL1, a gene shown previously to cause Margarita Island clefting. Participants included 434 patients with cleft lip with or without cleft palate or cleft palate only and their mothers from eight countries in South America, 205 nuclear triads (father-mother-affected child) from Iowa, 541 nuclear triads from Denmark, and 100 patients with cleft lip and palate from the Philippines. RESULTS: An allelic variant in the PVR gene showed statistically significant association with both South American and Iowa populations (p = 0.0007 and p = 0.0009, respectively). Direct sequencing of PVR and PVRL2 yielded 26 variants, including two rare amino acid changes, one in each gene, which were not seen in controls. CONCLUSIONS: We found an association between a common variant in a gene at 19q and isolated clefting in two heterogeneous populations. However, it is unclear from our data if rare variants in PVR and PVRL2 are sufficient to cause clefting in isolation.

Alleles↗
PubMed1995

Cumulative operative procedures in patients aged 14 years and older with unilateral or bilateral cleft lip and palate.

Sixty-seven consecutive patients over the age of 14 with either unilateral (n = 38) cleft lip and palate or bilateral (n = 29) cleft lip and palate seen over a 15-month period at the University of Michigan Craniofacial Program were reviewed to determine the total number of surgical procedures performed over the course of treatment. The demographics of the two groups differed: There were 25 males and 13 females who were a mean age of 17 years and 9 months with unilateral cleft lip and palate and 23 males and 6 females who were a mean age of 18 years and 5 months with bilateral cleft lip and palate. Lip and palate repairs were carried out on all patients. Lip adhesions were performed in 29 and 62 percent; pharyngoplasties (either pharyngeal flap or modified Ortichochea) in 39 and 38 percent; alveolar bone grafts in 82 and 79 percent; Abbé flaps in 0 and 10 percent; and orthognathic surgery was done in 10.5 and 13.8 percent and recommended and/or done in 26 and 24 percent of patients with unilateral cleft lip and palate and bilateral cleft lip and palate, respectively. Lip revisions averaged 1.13 and 2.17 per patient and secondary nasal surgeries averaged 1.13 and 1.18 per patient in the unilateral cleft lip and palate and bilateral cleft lip and palate, respectively. All totaled, the average number of operations was 6.12 per patient (range 3 to 12) in the unilateral cleft lip and palate and 8.04 per patient (range 5 to 15) in the bilateral cleft lip and palate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2005

Mulliken method of bilateral cleft lip repair: anthropometric evaluation.

BACKGROUND: Simultaneous surgical correction of bilateral cleft lip and nasal deformity is becoming more common. This is a major change from the conventional strategy of secondary nasal correction. METHODS: Thirty patients with bilateral cleft lip and nasal deformity were repaired using the Mulliken method between July of 1997 and December of 2002. This series was composed of 10 infants with bilateral complete cleft lip, 12 with bilateral incomplete cleft lip, and eight with bilateral asymmetric cleft lip, defined as complete on one side and incomplete on the other. A preoperative orthopedic appliance was employed in five infants who had severe collapse of the lateral maxillary segments. Mean age at the time of repair was 3.8 months. RESULT: Postoperative results were evaluated anthropometrically. The mean follow-up period was 3.8 years (range, 1.2 to 5.5 years). Nasal tip protrusion was low; interalar dimension was wide; columellar length was slightly short; upper cutaneous labial height was short; and vermilion-mucosal height was near normal. All anthropometric values approached controls by 5 years. CONCLUSION: Our modified Mulliken method is effective in correction of all forms of bilateral cleft lip and nasal deformity. Further evaluation is needed for possible differences in outcome based on race and age at the time of operation.

Anthropometry↗
PubMedDate not supplied

Caries experience and oral health behavior in Chinese children with cleft lip and/or palate.

PURPOSE: The aims of this study were to investigate whether there were different caries levels in 3- to 6-year-old Chinese children who had a cleft lip compared to those with a cleft lip/palate. The goal also was to evaluate parental attitudes toward the feeding habits and oral health care for their children. METHODS: A cross-sectional study was carried out through a dental examination of a sample of children and a questionnaire to their parents. A sample of 104 3- to 6-year-old children (66 boys and 38 girls) with cleft lip, cleft palate or both were selected from those receiving pre-surgical treatment. Each child was examined and a short questionnaire was given to parents of the children. The form included questions about infant feeding practices, frequency consumption of specific drinks and, children's toothbrushing frequency. RESULTS: One hundred and four children were examined. Seventy-five percent had some caries experience and rampant caries was present in 26%. Children with cleft palate had a higher prevalence of rampant caries (30%) compared to those with cleft lip (12%). A multivariate analysis yielded feeding practices and mother's education as the variables significantly associated with caries and rampant caries. CONCLUSIONS: The results of this study show that: 1. Children with a cleft lip/palate have higher levels of dental caries compared to those with a cleft lip alone; 2. The two most important factors for dental caries were: a. whether the child had been bottle-fed and; b. the educational attainment level of the mother.

Bottle Feeding↗
PubMed1979

Simplified method of feeding infants born with cleft palate with or without cleft lip.

Most infants born with a cleft palate with or without cleft lip are undergrown and have histories of difficult feeding. For the past two years, all of the infants born with isolated cleft palate with or without cleft lip, referred to the Boston Floating Cleft Palate Clinic, were fed using a simplified method. A standard nipple that was cross cut and a standard glass baby bottle were used. The infants were fed in the sitting position and burped frequently. Data indicating that nutrition in these infants is adequate as judged by weight gain was provided.

Bottle Feeding↗
PubMed1983

Radical muscle mobilisation in surgery for a unilateral cleft lip.

The embryological basis of a unilateral cleft lip is briefly outlined. The abnormal configuration of the orbicularis oris in a unilateral cleft lip is viewed on a model. The effect of freeing this muscle from its abnormal attachments and radically mobilising it, is theoretically discussed. The actual effects of such a mobilisation in clinical practice are shown. Post operative results of 16 unilateral cleft lips treated by radical muscle mobilisation are presented and discussed. The need for a longer follow up is recognised.

Adult↗
PubMed1999

A long-term, controlled-outcome analysis of in utero versus neonatal cleft lip repair using an ovine model.

Successful open repair of a cleft lip in utero has the advantage of scarless wound healing in the fetus. Unfortunately, no long-term outcome studies have been performed to evaluate the efficacy of these repairs. Moreover, no study to date has compared the long-term results of an in utero cleft lip repair to a similar, control-matched, newborn cleft repair. This study was performed to evaluate the 9-month outcome of in utero cleft lip surgery compared with an identical cleft lip repair performed on infant lambs. In utero epithelialized cleft lips were created through an open hysterotomy in sixteen 65-day-old fetal lambs (term = 140 days) using methods described by Longaker et al. Eight of 16 animals underwent subsequent in utero repair of these clefts at 90 days gestational age. The repair of the remaining eight animals was delayed until 1 week postpartum. At 9 months, the animals were analyzed for changes in lip contour and for the degree of scarring by hematoxylin and eosin and Masson's trichrome collagen staining. Two animals in each group died from preterm labor. Of the animals that survived to term, all repaired lips had some degree of abnormality postoperatively. One of six lips repaired in utero dehisced before delivery. Three of six neonatal repairs dehisced in the first postoperative month. In the remaining animals with intact lip repairs, the vertical lip height on the repaired side was an average of 9 to 12 mm shorter than the normal lip in both the in utero and neonatally repaired animals. Phenotypically, the postnatally repaired animals had more lip distortion and visible notching. Histologically, the in utero repair was scarless and the neonatal repairs had scar throughout the entire vertical height of the lip with an associated loss of hair in this region. Maxillary growth was also evaluated. There was no inhibition of maxillary growth in the animals that underwent in utero cleft lip repair. However, in the neonatal repair group, significant maxillary retrusion was evident. Compared with the cleft side of the maxilla, horizontal growth was decreased by 11 percent (p = 0.01). Compared with the intrauterine repair group, there was a 17-percent decrease in horizontal maxillary width (p = 0.01). Straight-line in utero repair of a cleft lip produces a better long-term result in terms of maxillary growth than a similar repair performed postnatally in the ovine model. There was no diminution in maxillary growth in the animals treated in utero. Histologically, in utero repair of clefts was indeed scarless. However, both lip repairs produced lips that were significantly shorter than their contralateral noncleft sides. This degree of lip shortening would require a secondary lip revision, thereby defeating the purpose of performing an intrauterine repair. Comparisons now need to be made between in utero and neonatal repairs using a Millard-type rotation advancement technique before intrauterine treatment can be considered to be more beneficial than our current treatment modalities.

Animals↗