Prospective study of nasal growth in bilateral cleft lip and palate patients after naso-alveolar moulding and primary columella lengthening compared to controls at 5, 10 and 20 years.

INTRODUCTION: A short columella, wide nostrils and a flat nasal tip are common features in patients with bilateral complete cleft lip and palate (BCLP). The objective of this study was to evaluate nasal morphology during growth in patients treated with naso-alveolar moulding (NAM) and primary surgical columella lengthening (PCL) compared with matched non-cleft individuals. STUDY DESIGN: Prospective longitudinal case-control study. PARTICIPANTS AND METHODS: Thirty-four consecutively treated BCLP patients at 5 and 10 years and at the end of growth (19.7 ± 2.0 years) were compared through normalized photogrammetry to a control of 34 age and sex-matched non-cleft individuals. Regression Models for Panel Data assessed how nasal measurements were influenced by surgery, age and gender. RESULTS: Nasal protrusion was equal to non-cleft controls at all ages. Length of the columella was also comparable to controls at 5 and 10 years, but significantly shorter at the end of growth. Inter-alar and nasal tip width and nasolabial angle were significantly wider than controls at all ages: More than 60% of the patients have asked for correction of the nasal width, but no early surgery for columella lengthening was needed. CONCLUSIONS: NAM and PCL have provided a nasal projection close to that of non-cleft individuals until adulthood, while length of the columella was physiological at 5 and 10, but shorter than controls at age 20. Width of the nasal tip and width of the alar bases were significantly wider than the controls and eventually required secondary nasal width correction in over two thirds of the sample.

Cross-sectional evaluation of periodontal inflammation and oral hygiene status between fixed appliances and Invisalign in patients affected by craniofacial anomalies.

OBJECTIVE: The objective of this cross-sectional study was to compare the difference in the oral health status and oral hygiene of orthodontic treatment with aligners (AL) and with fixed appliances (FA) in patients affected by craniofacial anomalies (CFA). MATERIALS AND METHODS: The sample consisted of 100 Caucasian patients affected by various CFA from two different hospitals. Fifty patients treated with AL were matched for sex, age and CFA with a control sample of 50 patients treated with FA. Patients' periodontal conditions were evaluated in both samples. O'Leary Plaque Control Record, bleeding on probing (BOP) and DMT/dmft Index were evaluated in both samples. RESULTS: The FA group presented an O'Leary Plaque Control Record of 60% ± 30, while AL presented an O'Leary Plaque Control Record of 40% ± 29.7 (p-value = 0.02), BOP was 22.1% ± 14 in FA and 12% ± 0.13 in AL (p-value = 0.03). The DMFT/dmft was not statistically different (p-value = 0.13). p-value was set at <0.039. CONCLUSION: The study shows that the sample with FA presented a higher O'Leary Plaque Control Record and BOP compared to the AL sample. AL might, therefore, be an interesting alternative to FA in patients with CFA, who generally have a lower level of oral hygiene.

Photometric Evaluation of Adult Patients With Bilateral Cleft Lip and Palate Treated With Nasoalveolar Molding and Primary Columella Lengthening.

OBJECTIVE: The aim of this study was to assess the nasal shape of young adults with BCLP treated with primary surgical columella lengthening and nasoalveolar molding (NAM). SETTING AND PATIENTS: A group of 28 young adult patients with BCLP (mean age: 19.1±1.4 years) was compared through normalized photogrammetry to a control of 28 age- and sex-matched noncleft young adults. RESULTS: Nasal protrusion and length of the columella were not different from noncleft young adults. On the other hand, nasolabial angle, columellar width, interalar, and nasal tip width were significantly wider than the noncleft controls. Thus, 27% of the patients have requested at this time secondary correction of the excessive nasal width. CONCLUSIONS: Both NAM and primary rhinoplasty in patients with BCLP resulted in a near normal length of the columella and nasal projection until young adulthood. Nevertheless, width of all nasal features was significantly wider than the noncleft population and required secondary nasal correction in one-third of the sample.

Orthodontic Pre Grafting Closure of Large Alveolar Bony and Soft Tissue Gaps: A Novel Nonsurgical Protraction of the Lesser Segments in Growing Patients With Cleft Lip and Palate.

BACKGROUND: Closure of wide alveolar clefts with large soft tissue gaps and reconstruction of the dentoalveolar defect are challenging for the surgeon. Some authors successfully used interdental segmental distraction, which requires an additional surgical procedure. OBJECTIVE: This study evaluates the effectiveness of tooth borne devices utilized to orthopedically advance the lesser segments, with a complete approximation of the soft tissue of the alveolar stumps, allowing traditional simultaneous soft tissue closure and bone grafting, and avoiding the need for supplementary surgery. METHODS: Eight growing patients, 2 with unilateral complete cleft lip and palate (UCLP) and 6 with bilateral complete cleft lip and palate (BCLP), with large soft tissue and bony alveolar defects prior to bone grafting were prospectively selected. A banded rapid palatal expander (RPE) in BCLP and a modified RPE in UCLP combined with protraction face mask in younger patients or a modified Alt-Ramec in patients older than 12 years were applied. Radiographic and photographic records were available at T0, at the end of protraction (T1) and at least 1 year after bone grafting (T2). RESULTS: Patients with large gaps showed a significant reduction in the bony cleft area and approximation of the soft tissues at T1. All patients received bone grafting with good healing and ossification at T2. CONCLUSION: In growing patients with UCLP and BCLP with large gaps, presurgical orthodontic protraction seems to be an efficient method to reduce the cleft defect, minimizing the risk of post grafting fistulas, reducing the need for supplementary surgical procedures.

Costochondral graft in growing patients with hemifacial microsomia case series: Long-term results compared with non-treated patients.

OBJECTIVE(S): The aim of this study was to evaluate the long-term effectiveness of costochondral graft in hemifacial microsomia (HFM) type III patients. SETTINGS AND SAMPLE POPULATION: A sample of 10 patients affected by HFM type III treated during growth in the same Centre with costochondral graft (CCG patients group) is compared with a control group (CG) sample of 10 non-treated patients affected by the same malformation in order to understand whether surgery during growth provides advantages in terms of bony and facial symmetry after an 8-year follow-up. MATERIALS AND METHODS: The growth of the CCG was assessed on panoramic X-rays. To assess facial symmetry, a photometric evaluation on the frontal view was carried out. RESULTS: In CCG patients group the graft grown in mean less than the healthy ramus, a good facial symmetry was achieved after surgery, but was lost in the majority of the cases at the most recent control. In CG, occlusal canting slightly increased and facial asymmetry was relatively stable during the years. CONCLUSION: In patients with a congenital deformity, restoring the height of the ramus leads to an immediate restitution of facial symmetry, but in the long term, there is a return to the asymmetrical pattern. In CG, the asymmetry is stable during years with no increase of the facial deformity.

Comparison of Pain Perception in Patients Affected by Cleft and Cranio Facial Anomalies Treated With Traditional Fixed Appliances or Invisalign.

INTRODUCTION: The objective of this prospective study was to compare the difference in pain perception between treatment with aligners (AL) and fixed appliances (FA) in patients affected by cleft and craniofacial anomalies (CFA). METHODS: The sample consisted of 100 syndromic caucasian patients affected by various CFA from 2 different hospitals. Fifty patients treated with AL were matched for sex, age, and CFA with a control sample of 50 patients treated with FA. A modification of the Mc Gill Pain Questionnaire was adapted to our needs. RESULTS: Statistical differences were found. Aligners induced more tightness and tension than FA, while FA induced more pain descriptors and patients reported a higher intake of painkillers. CONCLUSIONS: The results of this study documented a higher pain perception with FA than with AL in patients affected by CFA. The higher sensitivity to pain in cleft and craniofacial patients with fixed treatment could be related to their higher prior sensitization, given the past surgeries and orthodontic treatments. Thus, this study might suggest that Invisalign treatment might be a further interesting treatment option for patients with cleft in order to reduce their burden of orthodontic pain.

Ultrastructural analysis of collagen fibril diameter distribution in cleft lip.

OBJECTIVE: A preliminary study to determine collagen fibril diameter (CF-ED) distribution on medial and lateral sides of cleft lip (CL). MATERIAL AND METHODS: Tissue samples from medial and lateral sides of CL were fixed in 2.5% glutaraldehyde and 1% osmium tetroxide and embedded in Araldite CY212 resin for transmission electron microscopy. The analysis of CF-ED was performed using the ImageJ program. To characterize the packaging of collagen fibrils (CFs) in the two tissues, we estimated the collagen number density (CF-ND) and fibril-area-fraction (FAF). Differences in measurements across the two sides were calculated using Wilcoxon signed-rank test. RESULTS: The CF-ED was statistically significantly (p < 0.001) smaller on the medial side (45.69 ± 7.89 nm) than on the lateral side (54.18 ± 7.62 nm). The medial side had a higher CF-ND and a higher percentage of FAF than the lateral side. CONCLUSION: Our finding of a smaller CF-ED and higher CF-ND and FAF for the medial side suggests possible differences in size and distribution of CFs between medial and lateral sides of CL. This finding provides knowledge toward underlying tissue biomechanics that may help reconstruction of perioral tissue scaffolds, ultimately resulting in better treatment of patients with oral clefts.

LINE-1 methylation in cleft lip tissues: Influence of infant MTHFR c.677C>T genotype.

OBJECTIVE: To investigate the influence of MTHFR c.677C>T genotype on LINE-1 methylation in lateral and medial tissues from cleft lip (CL). METHODS: Forty-five consecutive non-syndromic cleft lip with or without cleft palate (nsCL/P) cases were included in the study. Genomic DNA was extracted from tissues at both sides of cleft lip, and LINE-1 methylation was detected by bisulfite conversion and pyrosequencing. MTHFR c.677C>T genotyping was carried out using the TaqMan genotyping assay. RESULTS: LINE-1 methylation level was significantly higher on medial side of cleft lip compared with lateral side (p = 0.001). This difference was not significantly influenced by the case's sex or cleft type. However, MTHFR c.677C>T genotyping revealed that the difference in LINE-1 methylation across cleft lip was restricted to carriers of C allele of MTHFR c.677C>T and was not apparent in TT homozygous cases (p = 0.027). CONCLUSION: This integrated analysis supports the previous finding of differences in DNA methylation across the two sides of cleft lip and further suggests a possible role of MTHFR c.677C>T genotype in establishing this difference.

Short- and Long-Term Effects of Late Maxillary Advancement With the Liou-Alt-RAMEC Protocol in Unilateral Cleft Lip and Palate.

OBJECTIVE: The objective of this retrospective longitudinal study was to evaluate short- and long-term results of the application of the Liou Alt-RAMEC (alternate rapid maxillary expansion and constriction) technique, a late orthopedic maxillary protraction technique, with intraoral anchorage, in patients with cleft. MATERIALS AND METHODS: Twenty-six patients with unilateral cleft lip and palate (UCLP) were consecutively treated with the Alt-RAMEC technique. The average age of the patients was 11.7 years (10.3-13.2 years) before protraction and 18.3 years (17.4-21.1 years) at long-term follow-up. A sample of nontreated patients with UCLP was used as a control group. It was matched for sex, skeletal class III, and age (11.3 years). The control sample had records at the end of growth (18.7 years). RESULTS: The sagittal advancement of A-point, after the application of the technique, was 5.7 (2.17) mm. Some mandibular dentoalveolar and positional adaptation was noted. The position of the maxilla was stable in the long term. On the other hand, the UCLP control group showed hardly any growth at the maxillary level during the long-term follow-up period. CONCLUSION: Our results showed that the Alt-RAMEC technique, performed at the correct time, with a double-hinged expander, followed by class III spring or elastic traction, 24 hours per day, allows for satisfactory maxillary protraction, with, at this stage, apparently stable long-term results. Nevertheless, as only 50% of the patients had long-term follow-up data, we are still unable to predict the percentage of patients which will not eventually need orthognathic surgery.

Evaluation of a Sample of Patients With Unilateral Cleft Lip and Palate Treated With a Two-Stage Protocol.

The aim of this paper was to assess growth, speech, and aesthetic results at the completion of growth in patients with unilateral cleft lip and palate treated with the 2 stages Milan surgical protocol.Craniofacial growth was evaluated with cephalometric analysis and a theoretical need for orthognathic surgery.Nasolabial appearance was qualitatively assessed using the Asher McDade Aesthetic Index.Speech was assessed using the Gos.Sp.Ass '98 modified for Italian language scoring system.Burden of care was recorded in terms of number of secondary surgical procedures. All of the patients were treated and evaluated at San Paolo Hospital, Smile House, Milan.Fifty-two consecutive patients treated by the same surgeon were recalled, 12 patients did not come for assessment.The first surgical step (average age of 6 months) was cheilorhinoplasty (Millard modified Delaire technique) and soft palate rapair (Pigott). The second step (average age of 35 months) was hard palate and alveolar repair performed simultaneously with an early secondary gengivo alveolo plasty. Fifty-six percent of the patients did not need further surgery after the 2-stage surgery protocol.The 2-stage surgical protocol of Milano, Smile House, seems to be effective for treatment of unilateral cleft lip and palate, with good results in terms of speech, labial appearance, and alveolar cleft management. Nevertheless, maxillary growth was moderately impaired by the protocol.

Photometric Evaluation in Adolescence of Patients With Bilateral Cleft Lip and Palate Treated With Nasoalveolar Molding and Primary Columella Lengthening.

OBJECTIVE: Nasal stigma in patients with bilateral cleft lip and palate (BCLP) are a short columella and a flattened nasal tip. DESIGN: The aim of this study was to evaluate the aesthetics of adolescents with BCLP, operated with a modified Cutting primary columella lengthening technique, associated to a modified Grayson orthopedic nasoalveolar molding (NAM). SETTING AND PATIENTS: 72 BCLP patients were operated with this approach. Standardized photographic records were taken every 2 years. A group of 23 patients between 12 and 13 years of age was compared through normalized photogrammetry to a matched control of 23 noncleft adolescents. RESULTS: Nasal protrusion and length of the columella were very close to normal. On the other hand, nasolabial angle and interalar width were still excessively wide compared to the noncleft sample. CONCLUSIONS: NAM and primary columella lengthening in BCLP has allowed to avoid traditional secondary columella lengthening at 5 to 6 years of age and given the patients a more pleasing, near-normal nasolabial appearance until adolescence. Some of the patients will require correction of the nasal width at a later stage.

Use of Buccinator Myomucosal Flap in Tongue Reconstruction.

The myomucosal buccinator flap, first described by Bozola in 1989, has become an important tool for intraoral defects reconstruction. In the literature, there is a variety of proposed myomucosal cheek flaps, both pedicled and island, based on the buccal or the facial arteries. From January 2007 to December 2011, the authors used a pedicled buccinator flap based posteriorly on the buccal artery to reconstruct partial lingual defects following tumor resection in 27 patients. The buccal fat pad was translated to cover the donor site defect. After 3 to 4 weeks from the original surgery, a second procedure under local anesthesia was performed to detach the pedicle and remodel the flap. The morphological and functional outcomes of the procedures were evaluated by the surgeons and a speech and language therapist. All patients presented satisfactory results. The authors consider the use of the described technique as the gold standard in the reconstruction of partial tongue defects after tumor resection.

Long-Term Follow-Up of UCLP Patients: Surgical and Orthodontic Burden of Care During Growth and Final Orthognathic Surgery Need.

OBJECTIVE: The goal of this study was to evaluate the craniofacial morphology at 5 and 10 years of age and at the completion of growth, the need for final orthognathic surgery, and the orthodontic burden in a sample of patients with unilateral cleft lip and palate consecutively treated by the same surgeon with the same two-step protocol. DESIGN: A sample of 62 adult patients with unilateral cleft lip and palate was retrospectively collected (mean age, 17.5 years). Lateral cephalograms at three time points were traced. The need for orthognathic surgery was assessed, subdividing the sample into an orthognathic surgery group and nonorthognathic surgery group. Time and modality of orthodontic treatment were recorded. RESULTS: Cephalometric values related to maxillary growth (SNA, SNAns) and maxillomandibular relation (ANB, NAPg) were significantly different between the two groups already at 5 and 10 years of age. All patients presenting an ANB smaller than 2° at 5 years needed a Le Fort I osteotomy. Mandibular protrusion (SNB, SNPg) was not different at 5 and 10 years, but was different at the completion of growth. Patients with the same initial maxillomandibular relation did not show better growth when subjected to earlier or longer orthodontic treatment. CONCLUSION: Patients needing final jaw surgery had a more severe skeletal discrepancy during early childhood. The ANB angle at 5 years allowed doctors to identify 45% of the need for orthognathic surgery. The final craniofacial pattern does not seem to change significantly with early or prolonged orthodontic treatment.

Comprehensive surgical management of cocaine-induced midline destructive lesions.

PURPOSE: This article presents a review of the literature and proposes a protocol for managing acute and chronic midfacial cocaine-induced injuries. MATERIALS AND METHODS: This report describes a series of 4 patients affected by cocaine-induced midline destructive lesions. Three patients came to the authors' attention after 18 months of drug withdrawal and underwent surgical treatments to restore nasal and palatal morphology and function, and the fourth patient was referred because of acute cocaine-induced destructive lesions and was treated by aggressive debridement. An 18-month drug-free period is planned before beginning any reconstructive procedures in this latter patient. RESULTS: Long-term follow-up showed stable results without relapse of palatal fistulas and good esthetic nasal appearance in all 3 patients undergoing reconstruction. The fourth patient did not show any disease progression and will be monitored for drug withdrawal. CONCLUSION: Chronic cocaine consumption may cause multiple types of damage to the soft and hard tissues of the midface. Acute lesions must be addressed with aggressive debridement. As a result of chronic injury, the palate and nose are deformed in a very complex way and the vascularity of the remaining local tissues may be compromised or inadequate for flap harvesting. Palatal and nasal reconstructions are very delicate operations and should be addressed separately to maximize the predictability of the result.

The Use of Clear Aligners in Multi-Segmental Maxillary Surgery: A Case-Control Study in Cleft Lip and Palate and Skeletal Class III Patients.

Background: Maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery after growth completion. For most stable results, some cases may require segmental Le Fort I osteotomies. Unfortunately, Invisalign's software (6.0 version) still has some inherent limitations in predicting outcomes for complex surgeries. This study explores the potential of aligners, particularly in multiple-piece maxillary osteotomies in both cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with Invisalign were retrospectively matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth with a simple superimposition technique. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phases were needed in the Invisalign group to reach an acceptable pre-surgical occlusion, while the amount of pre-surgical impressions needed to reach adequate coordination with fixed appliance treatment was slightly higher (p > 0.05). Conclusions: it appears that clear aligner could serve as an effective treatment for individuals necessitating segmental Le Fort I osteotomies when aided by the suggested simple superimposition approach.

The role of pericranium grafts in the reduction of postoperative dehiscences and bone resorption after reconstruction of severely deficient edentulous ridges with autogenous onlay bone grafts.

PURPOSE: To compare: (i) the incidence of soft tissue dehiscences; (ii) bone resorption before and after implant placement; and (iii) the survival and success rates of implants placed in two groups of patients with severe bone defects of the jaws reconstructed with autogenous onlay bone grafts alone (control group) or in association with autogenous pericranium coverage (study group). MATERIAL AND METHODS: Forty-four patients affected by severe atrophy of the alveolar ridges underwent bone reconstruction with vertical/tridimensional autogenous onlay grafts harvested from the calvarium or the mandibular ramus. In 23 patients (study group), grafts were covered with autogenous pericranium before suturing, while in 21 patients (control group) no coverage of the grafts before suturing was performed. After a 4-7 month waiting period, 199 implants were placed (105 in the study group, 94 in the control group) and 3-4 months afterward prosthetic rehabilitation was carried out. The mean follow-up after the start of prosthetic loading was 23.9 months (range: 12-48 months). RESULTS: The incidence of soft tissue dehiscences was 5,7% in the study group and 16% in the control group. The mean graft resorption before implant placement was 0.12 mm (SD ± 0.32) in the study group and 0.98 mm (SD ± 2.79) in the control group. The mean peri-implant bone resorption at the end of the follow-up period was 0.21 mm (SD ± 0.48) in the study group and 0.43 mm (SD ± 0.83) in the control group. The survival rate of implants was 99.1% in the study group and 100% in the control group, while success rate was 96.2% in the study group and 93.6% in the control group. CONCLUSIONS: The use of pericranium as an autogenous membrane for the coverage of onlay bone grafts seems to reduce the risk of soft tissue dehiscences after the reconstruction of atrophic edentulous ridges to reduce peri-implant bone resorption over time, while it seems to have no significant effect in reducing bone resorption in the reconstructed areas before implant placement.

Recovery of emotional smiling function in free-flap facial reanimation.

PURPOSE: Long-standing unilateral facial palsy is treated primarily with free-flap surgery using the masseteric or contralateral facial nerve as a motor source. The use of a gracilis muscle flap innervated by the masseteric nerve restores the smiling function, without obtaining spontaneity. Because emotional smiling is an important factor in facial reanimation, the facial nerve must serve as the motor source to achieve this fundamental target. MATERIALS AND METHODS: From October 1998 to October 2009, 50 patients affected by long-standing unilateral facial paralysis underwent single-stage free-flap reanimation procedures to recover smiling function. A latissimus dorsi flap innervated by the contralateral facial nerve was transplanted in 40 patients, and a gracilis muscle flap innervated by the masseteric nerve in 10 patients. All patients underwent a clinical examination that analyzed voluntary and spontaneous smiling. RESULTS: All patients who received a latissimus dorsi flap innervated by the contralateral facial nerve and recovered muscle function (92.5%) showed voluntary and spontaneous smiling abilities. All patients who received a gracilis free flap innervated by the masseteric nerve recovered function, but only 1 (10%) showed occasional spontaneous flap activation. During those rare activations, much less movement was visible on the operated side than when the patient was asked to smile voluntarily. CONCLUSIONS: The masseteric nerve is a powerful motor source that guarantees free voluntary gracilis muscle activation; however, it does not guarantee any spontaneous smiling. Single-stage procedures that use a latissimus dorsi flap innervated by the contralateral facial nerve have a lower success rate and obtain less movement; however, spontaneous smiling is always observed.

Comparison of the psychosocial impact on patients affected by cranio facial anomalies between traditional orthodontic brackets and aligners.

OBJECTIVES: Malocclusion affects the psychological wellness and social interaction, impacting negatively on adolescents' quality of life and self-esteem. Facial attractiveness is mostly based on the esthetics of the smile and patients seek orthodontic treatment mainly to improve aesthetics. The aim of this prospective clinical study is to compare the psychosocial impact of aligners (AL) and fixed appliances (FA) as orthodontic treatments in patients affected by craniofacial anomalies (CFA). METHODS: 100 syndromic Caucasian patients with CFA followed in two different hospitals were divided in two groups: 50 patients treated with AL and 50 patients treated with FA. The two groups were matched for gender, age and CFA and filled out a modified psychosocial impact of dental aesthetics questionnaire (mPIDAQ). RESULTS: Patients affected by CFA treated with AL reported a better psychosocial impact than patients treated with FA, showing higher esthetic self-perception and self-esteem, lower social interaction impairments, and lower physical/practical disturbances. CONCLUSIONS: The results of this study suggest that AL could be a valid alternative, especially in complex patients with CFA. Since AL application requires more cooperative patients the orthodontist should dedicate more time to motivate the patient to adhere to the treatment schedule.

MTHFR promoter methylation might mitigate the effect of smoking at the level of LINE-1 in cleft lip tissues: A preliminary study.

BACKGROUND: The medial and maxillary aspects of the upper lip originate at separate embryonic stages and therefore may experience different maternal exposure patterns which may affect methylation. Based on this hypothesis, we investigated the level of methylation of the methylene tetrahydrofolate reductase promoter gene (mMTHFR) in tissues from cleft lip, and mMTHFR levels by MTHFR c.677C > T genotype. We further investigated whether mMTHFR mitigates the effect of smoking on long interspersed nuclear element (LINE-1) methylation in these tissues. METHODS: DNA extracted from medial and lateral tissues of 26 infants with nonsyndromic cleft lip with or without cleft palate (nsCL/P) was bisulfite converted and mMTHFR was measured on a pyrosequenser. LINE-1 methylation and MTHFR c.677C > T genotype data were obtained in our previous study. RESULTS: There was no substantial difference in mMTHFR (p = .733) and LINE-1 (p = .148) between the two tissues. mMTHFR was not influenced by MTHFR c.677C > T genotype, but there was suggestive evidence that the difference was larger among infants exposed to maternal smoking compared to nonexposed. LINE-1 methylation differences were significant (p = .025) in infants born to nonsmoking mothers, but this was not apparent (p = .872) in infants born to mothers who smoked. Our Pearson's correlation analysis suggested a weak inverse association between mMTHFR and LINE-1 (r = -.179, p = .381). CONCLUSION: Our preliminary observation of differences in patterns of mMTHFR levels in lip tissue suggests the interplay of gene and environment in the establishment of methylation in tissues at both sides of cleft lip. This requires investigation in a larger cohort, integrated with metabolic assessment.

Long-term longitudinal evalutation of mandibular growth in patients with Beckwith-Wiedemann Syndrome treated and not treated with glossectomy.

AIM: This study compares long-term mandibular growth between a group of Beckwith-Wiedemann Syndrome (BWS) patients who underwent glossectomy at an early age and a group of patients not operated. METHODS: Cephalometric measurements were performed in BWS patients comparing the data obtained between a group of patients operated at an early age and a group of non-operated patients who declined surgery. Statistics included independent sample T-test. RESULTS: Twenty-four out of 78 BWS patients followed since birth completed longitudinal cephalometric x-rays at age 5, 10 and 15. Eighteen patients needed early surgery. Eleven families accepted glossectomy at 2.3 ± 1.3 years of age; seven declined surgery. No differences in mandibular growth were found between the two groups. Inclination of maxillary incisors results were statistically greater in the non-operated group (operated compared to the non-operated group: 103.58 ± 11.30 Vs 108.98 ± 12.47; p-value 0.0168 at 5; 107.06 ± 7.98 Vs 115.14 ± 7.05; p-value 0.0206 at 10; 109.80 ± 4.68 Vs 116.75 ± 5.28; p-value 0.0233 at 15). CONCLUSION: Macroglossia has no role in the post-natal mandibular overgrowth in BWS and mandibular overgrowth is part of the syndrome. Therefore, early glossectomy does not change mandibular growth and does not prevent the development of class III skeletal malocclusion in these patients.