Rehabilitative treatment of cleft lip and palate: experience of the Hospital for Rehabilitation of Craniofacial Anomalies/USP (HRAC/USP) - Part 1: overall aspects

C left lip and palate is the most common among craniofacial malformations and causes several esthetic and functional implications that require rehabilitation. This paper aims to generally describe the several aspects related to this complex pathology and the treatment protocol used by the Hospital for Rehabilitation of Craniofacial Anomalies, University of So Paulo (HRAC-USP) along 40 years of experience in the treatment of individuals with cleft lip and palate.

Is missing maxillary lateral incisor in complete cleft lip and palate a product of genetics or local environment?

Objective: To test the null hypothesis: Subjects with isolated complete unilateral cleft lip and palate (UCLP) show no differences in overall frequency of tooth agenesis (hypodontia), comparing a subsample with cleft-side maxillary lateral incisor (MxI2) agenesis to a subsample without cleftside MxI2 agenesis. Findings could clarify the origins of cleft-side MxI2 agenesis. Materials and Methods: Tooth agenesis was identified from dental radiographs of 141 subjects with UCLP. The UCLP cohort was segregated into four categories according to the status and location of MxI2 in the region of the unilateral cleft: group M: subjects with one tooth, located on the mesial side of the alveolar cleft; group D: subjects with one tooth, located on the distal side of the alveolar cleft; group MD: subjects with two teeth present, one mesial and one distal to the cleft; and group ABS: subjects with lateral incisor absent (agenesis) in the cleft area. Results: The null hypothesis was rejected. Among UCLP subjects, there was a twofold increase (P < .0008) in overall frequency of tooth agenesis outside the cleft region in a subsample with cleftside MxI2 agenesis (ABS), compared to a subsample presenting with no agenesis of the cleft-side MxI2 (M+D+MD). Conclusions: Cleft-side MxI2 agenesis in CLP subjects appears to be largely a genetically controlled anomaly associated with cleft development, rather than a collateral environmental consequence of the adjacent cleft defect, since increased hypodontia involving multiple missing teeth observed remote from a cleft clearly has a significant genetic basis. (Angle Orthod. 2012;82:959-963.)

Alveolar Bone Morphology in Patients With Bilateral Complete Cleft Lip and Palate in the Mixed Dentition: Cone Beam Computed Tomography Evaluation

Objectives: To verify the thickness and level of alveolar bone around the teeth adjacent to the cleft by means of cone beam computed tomography (CBCT) in patients with complete bilateral cleft lip and palate prior to bone graft surgery and orthodontic intervention. Method: The sample comprised 10 patients with complete bilateral cleft lip and palate (five boys and five girls) in the mixed dentition. The mean age was 9.5 years, and all subjects showed a G3 interarch relationship according to the Bauru index. The thickness of alveolar bone surrounding the maxillary incisors and the maxillary canines was measured in CBCT axial section using the software iCAT Xoran System. The distance between the alveolar bone crest and the cement-enamel junction (CEJ) was measured in cross sections. Results: The tomography images showed a thin alveolar bone plate around teeth adjacent to clefts. No bone dehiscence was observed in teeth adjacent to clefts during the mixed dentition. A slight increase in the distance between the alveolar bone crest and the CEJ was observed in the mesial and lingual aspects of canines adjacent to cleft. Conclusion: In patients with BCLP in the mixed dentition, teeth adjacent to the alveolar cleft are covered by a thin alveolar bone plate. However, the level of alveolar bone crest around these teeth seems to be normal, and no bone dehiscence was identified at this age.

Relationship Between Occlusion and Lisping in Children With Cleft Lip and Palate

Introduction: The literature suggests that individuals with history of cleft lip and palate who present with midfacial growth deficiency are at higher risk of presenting lisping. The relationship between distortions during production of linguoalveolar fricative sounds and the severity of malocclusion, however, has not been established for the population with cleft. Objective: To study the association between lisping and dental arch relationship. Methodology: Speech samples and dental arch casts were obtained from 106 children with operated unilateral cleft lip and palate (UCLP) during the stage of mixed dentition and before orthodontic treatment. Videotaped productions of the phrase/u saci saiw sedu/were rated by speech-language pathologists for the identification of lisping during [s]. Dental arch casts were rated by orthodontists using the Goslon Yardstick and the Five-Year Index to establish dental arch relationship. Results: Multiple logistic regression showed no significant association between lisping and dento-occlusal index (p = .802) and age (p = .662). Substantial interjudge agreement during auditory-perceptual ratings was found (kappa = .63). Almost perfect agreement was found between orthodontists while establishing the dental arch relationship (kappa = .81). Discussion: This study failed to reveal an association between lisping and dental arch relationship in children with operated UCLP. Multiple variables may play a role in determining occurrence of lisping, warranting further investigation.

Auditory complaints and audiologic assessment in children with surgically repaired cleft lip and palate

Introduction: At the initial consultation, the speech-language pathologist and audiologist may consider possible diagnostic hypotheses based on the child's history and the parents' complaint. Aim: To investigate the association of hearing complaints with the findings obtained in the conventional audiologic assessment in children with cleft lip and palate. Retrospective study. Methods: We analyzed medical charts of 1000 patients with cleft lip and palate who underwent surgical repair between 1988 and 1995 at a mean age of 6 years 8 months. We excluded charts with records of inconsistent audiological responses and charts with missing data for any of the audiologic evaluations considered. Thus, the sample consisted of 393 records. Results: Two hundred thirty-nine patients presented hearing loss in one or both ears, but only 3.8% reported hearing complaints. The most frequent were otorrhea followed by otalgia. There was no statistical significance between the complaint and gender (p = 0.26) nor between the complaint and hearing loss (p = 0.83). Conclusion: This study showed no association between the hearing complaint and the conventional audiologic assessment

Rehabilitative treatment of cleft lip and palate: experience of the Hospital for Rehabilitation of Craniofacial Anomalies/USP (HRAC/USP) – part 4

Treatment of patients with cleft lip and palate is completed with fixed prostheses, removable, total, implants and aims to restore aesthetics, phonetics and function and should be guided by the basic principles of oral rehabilitation, such as physiology, stability, aesthetics, hygiene and the expectations of the patient. In order to obtain longevity of a prosthetic rehabilitation, the periodontal and dental tissue as well as the biomechanics of the prosthesis are to be respected. The purpose of this article is to describe the types of prosthetics treatment, which are performed at HRAC/USP for the rehabilitation of cleft area in adult patients.

Prevalence of enamel defects in permanent teeth of patients with complete cleft lip and palate

Objective: To evaluate the prevalence, types, location, and characteristics of enamel defects in anterior permanent teeth of patients with complete unilateral and bilateral cleft lip and palate, as well as the relation with the cleft. Setting: Hospital for Rehabilitation of Craniofacial Anomalies, Bauru, São Paulo, Brazil. Participants: Eighty patients of both genders, 12 years and older, with unilateral or bilateral cleft lip and palate. Methods: A single examiner carried out clinical examination under artificial light with a dental probe and mirror after drying teeth according to the modified DDE index. Results: Seventy-four of 80 patients presented with at least one tooth affected by enamel defects: 165 of 325 evaluated teeth (50.8%) presented enamel defects, with hypoplasia being the most prevalent (50.7%), followed by diffuse opacity (23.1%) and demarcated opacity (18.4%). The most affected tooth was 21 (36.5%), followed by 11 (34%), located at the middle (40%) and incisal (33%) thirds. Most defects occur at the buccal surface (47.7%), followed by the distal (22.7%), the mesial (19%), and the palatal (10.6%) surfaces. A significant relationship was found between the cleft side and enamel defects. Conclusion: Upper anterior teeth of patients with complete cleft lip and palate present a high prevalence of enamel defects; the highest percentage on the cleft side suggests that the cleft does influence the occurrence of enamel defects in permanent teeth.

Comparison of two scoring systems for evaluation of treatment outcome in patients with complete bilateral cleft lip and palate

Objective : To compare two scoring systems: the Huddart/Bodenham system (HB system) and the Bauru-BCLP yardstick (BCLP yardstick), which classify treatment outcome in terms of dental arch relationships in patients with complete bilateral cleft lip and palate (CBCLP). The predictive value of these scoring systems for treatment outcome was also evaluated. Design : Retrospective longitudinal study. Patients : Dental arch relationships of 43 CBCLP patients were evaluated at 6, 9, and 12 years. Setting : Treatment outcome in BCLP patients using two scoring systems. Main Outcome Measures : For each age group, the HB scores were correlated with the BCLP yardstick scores using Spearman's correlation coefficient. The predictive value of the two scoring systems was evaluated by backward regression analysis. Results : Intraobserver Kappa values for the BCLP yardstick scoring for the two observers were .506 and .627, respectively, and the interobserver reliability ranged from .427 and .581. The intraobserver reliability for the HB system ranged from .92 to .97 and the interobserver reliability from .88 to .96. The BCLP yardstick scores of 6 and 9 years together were predictors for the outcome at 12 years (explained variance 41.3%). Adding the incisor and lateral HB scores in the regression model increased the explained variance to 67%. Conclusions : The BCLP yardstick and the HB system are reliable scoring systems for evaluation of dental arch relationships of CBCLP patients. The HB system categorizes treatment outcome into similar categories as the BCLP yardstick. In case a more sensitive measure of treatment outcome is needed, selectively both scoring systems should be used.

A new yardstick for rating dental arch relationship in patients with complete bilateral cleft lip and palate

Objective: To develop yardsticks for assessment of dental arch relationship in young individuals with repaired complete bilateral cleft lip and palate appropriate to different stages of dental development. Participants: Eleven cleft team orthodontists from five countries worked on the projects for 4 days. A total of 776 sets of standardized plaster models from 411 patients with operated complete bilateral cleft lip and palate were available for the exercise. Statistics: The interexaminer reliability was calculated using weighted kappa statistics. Results: The interrater weighted kappa scores were between .74 and .92, which is in the "good" to "very good" categories. Conclusions: Three bilateral cleft lip and palate yardsticks for different developmental stages of the dentition were made: one for the deciduous dentition (6-year-olds' yardstick), one for early mixed dentition (9-year-olds' yardstick), and one for early permanent dentition (12-year-olds' yardstick).

A longitudinal three-center study of dental arch relationship in patients with bilateral cleft lip and palate

OBJECTIVE: To compare and evaluate longitudinally the dental arch relationships from 4.5 to 13.5 years of age with the Bauru-BCLP Yardstick in a large sample of patients with bilateral cleft lip and palate (BCLP). DESIGN: Retrospective longitudinal intercenter outcome study. PATIENTS: Dental casts of 204 consecutive patients with complete BCLP were evaluated at 6, 9, and 12 years of age. All models were identified only by random identification numbers. SETTING: Three cleft palate centers with different treatment protocols. MAIN OUTCOME MEASURES: Dental arch relationships were categorized with the Bauru-BCLP yardstick. Increments for each interval (from 6 to 9 years, 6 to 12 years, and 9 to 12 years) were analyzed by logistic and linear regression models. RESULTS: There were no significant differences in outcome measures between the centers at age 12 or at age 9. At age 6, center B showed significantly better results (p=.027), but this difference diminished as the yardstick score for this group increased over time (linear regression analysis), the difference with the reference category (center C, boys) for the intervals 6 to 12 and 9 to 12 years being 10.4% (p=.041) and 12.9% (p=.009), respectively. CONCLUSIONS: Despite different treatment protocols, dental arch relationships in the three centers were comparable in final scores at age 9 and 12 years. Delaying hard palate closure and employing infant orthopedics did not appear to be advantageous in the long run. Premaxillary osteotomy employed in center B appeared to be associated with less favorable development of the dental arch relationship between 9 and 12 years.

Mutation analysis of the PVRL1 gene in caucasians with nonsyndromic cleft lip/palate.

Nonsyndromic cleft lip with or without cleft palate (nsCL/P, MIM 119530) is perhaps the most common major birth defect. Homozygous PVRL1 loss-of-function mutations result in an autosomal recessive CL/P syndrome, CLPED1, and a PVRL1 nonsense mutation is associated with sporadic nsCL/P in Northern Venezuela. To address the more general role of PVRL1 variation in risk of nsCL/P, we carried out mutation analysis of PVRL1 in North American and Australian nsCL/P cases and population-matched controls. We identified a total of 15 variants, 5 of which were seen in both populations and 1 of which, an in-frame insertion at Glu442, was more frequent in patients than in controls in both populations, though the difference was not statistically significant. Another variant, which is specific to the PVRL1 beta (HIgR) isoform, S447L, was marginally associated with nsCL/P in North American Caucasian patients, but not in Australian patients, and overall variants that affect the beta-isoform were significantly more frequent among North American patients. One Australian patient had a splice junction mutation of PVRL1. Our results suggest that PVRL1 may play a minor role in susceptibility to the occurrence of nsCL/P in some Caucasian populations, and that variation involving the beta (HIgR) isoform might have particular importance for risk of orofacial clefts. Nevertheless, these results underscore the need for studies that involve very large numbers when assessing the possible role of rare variants in risk of complex traits such as nsCL/P.

Genomic screening identifies novel linkages and provides further evidence for a role of MYH9 in nonsyndromic cleft lip and palate.

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth anomaly that requires prolonged multidisciplinary rehabilitation. Although variation in several genes has been identified as contributing to NSCLP, most of the genetic susceptibility loci have yet to be defined. To identify additional contributory genes, a high-throughput genomic scan was performed using the Illumina Linkage IVb Panel platform. We genotyped 6008 SNPs in nine non-Hispanic white NSCLP multiplex families and a single large African-American NSCLP multiplex family. Fourteen chromosomal regions were identified with LOD>1.5, including six regions not previously reported. Analysis of the data from the African-American and non-Hispanic white families revealed two likely chromosomal regions: 8q21.3-24.12 and 22q12.2-12.3 with LOD scores of 2.98 and 2.66, respectively. On the basis of biological function, syndecan 2 (SDC2) and growth differentiation factor 6 (GDF6) in 8q21.3-24.12 and myosin heavy-chain 9, non-muscle (MYH9) in 22q12.2-12.3 were selected as candidate genes. Association analyses from these genes yielded marginally significant P-values for SNPs in SDC2 and GDF6 (0.01

Self-esteem, coping styles, and quality of life in polish adolescents and young adults with unilateral cleft lip and palate.

Objectives : To evaluate self-esteem, coping styles, and health-related quality of life and their relationships in Polish adolescents and young adults with unilateral complete cleft lip and palate and related sex differences. Design and Participants : Self-report questionnaires measuring self-esteem (Multidimensional Self-Esteem Inventory), coping styles (Coping Inventory for Stressful Situations), and health-related quality of life (WHOQOL-BREF) were completed by 48 participants with cleft lip and palate (age, 16 to 23 years; 31 males, 17 females) and 48 controls without cleft lip and palate (age, 16 to 23 years; 28 males, 20 females) matched for age, place of residence, and socioeconomic status. Results : Regarding self-esteem, individuals with cleft lip and palate scored higher on body functioning (P < .01) and defensive self-enhancement (P < .05). Self-control showed an interaction effect: Females with cleft lip and palate scored higher than controls, but males did not differ between groups (P < .05). Males with cleft lip and palate scored lower than controls in personal power but higher in body functioning (P < .05); females showed no differences between groups. The groups did not differ with regard to coping styles or quality of life, but several correlations were found between self-esteem and coping styles, and quality of life (P < .01). Conclusions : Late adolescents and young adults with and without cleft lip and palate differed little in terms of psychological adjustment measures. The higher scores in defensive self-enhancement of individuals with cleft lip and palate suggest the need for instruments measuring social approval in psychosocial adjustment research involving this group.

Familial component of epilepsy in cleft lip and palate

It is well recognized that offspring of women with epilepsy who are taking anticonvulsant medications have an increased incidence of clefting abnormalities. This increase has been attributed to the teratogenic effects of anticonvulsant medications but an alternative explanation involving a genetic association of epilepsy and clefting has also been proposed. Five family studies attempting to resolve this controversy have been inconclusive either because of study design or analytic limitations. This family study was designed to determine whether epilepsy aggregates in families ascertained by an individual with a clefting disorder. The Mayo Clinic medical linkage registry was used to identify individuals with cleft lip with or without cleft palate and cleft palate in southeast Minnesota from 1935-1986. Only those cases who were 15 years or younger during this period were included in the study. The proband's parents and descendants of their parents, including the proband's sibs, children, grandchildren, niece/nephews, grandnieces/nephews, halfsibs and spouses were also identified and all of their medical records were reviewed for seizure disorders. The standardized morbidity ratios for epilepsy of 0.9 (95% CI 0.2-2.6) observed for first degree relatives (excluding parents) and 0.0 for second degree relatives were not increased. The SMRs ranged from 0.7-2.2 for the individual relative types (parents 1.5, sibs 0.7, children 2.2, probands 1.1, spouses 2.0) and were also not increased. These results do not support the suggestions of some that clefting and epilepsy aggregate together in families. ^

FZD6, MATN2 AND SLC25A32, POSSIBLE CANDIDATE GENES IN NONSYNDROMIC CLEFT LIP AND PALATE

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with a multifactorial etiology. Despite decades of research, the genetic underpinnings of NSCLP still remain largely unexplained. A genome wide association study (GWAS) of a large NSCLP African American family with seven affected individuals across three generations found evidence for linkage at 8q21.3-24.12 (LOD = 2.98). This region contained three biologically relevant candidate genes: Frizzled-6 (FZD6) (LOD = 2.8), Matrilin-2 (MATN2) (LOD = 2.3), and Solute Carrier Family 25, Member 32 (SLC26A32) (LOD = 1.6). Sequencing of the coding regions and the 5’ and 3’ UTRs of these genes in two affected family members identified a rare intronic variant, rs138557689 (c.-153+432A>C), in FZD6. The rs138557689/C allele segregated with the NSCLP phenotype; in silico analysis predicted and EMSA analysis showed that the 138557689/C allele creates new DNA binding sites. FZD6 is part of the WNT pathway, which is involved in craniofacial development, including midface development and upper lip fusion. Our novel findings suggest that an alteration in FZD6 gene regulation may perturb this tightly controlled biological pathway and in turn contribute to the development of NSCLP in this family. Studies are underway to further define how the rs138557689/C variant affects expression of FZD6.