Transcriptomics unravels molecular players shaping dorsal lip hypertrophy in the vacuum cleaner cichlid, Gnathochromis permaxillaris.

BACKGROUND: Teleosts display a spectacular diversity of craniofacial adaptations that often mediates ecological specializations. A considerable amount of research has revealed molecular players underlying skeletal craniofacial morphologies, but less is known about soft craniofacial phenotypes. Here we focus on an example of lip hypertrophy in the benthivorous Lake Tangnayika cichlid, Gnathochromis permaxillaris, considered to be a morphological adaptation to extract invertebrates out of the uppermost layer of mud bottom. We investigate the molecular and regulatory basis of lip hypertrophy in G. permaxillaris using a comparative transcriptomic approach. RESULTS: We identified a gene regulatory network involved in tissue overgrowth and cellular hypertrophy, potentially associated with the formation of a locally restricted hypertrophic lip in a teleost fish species. Of particular interest were the increased expression level of apoda and fhl2, as well as reduced expression of cyp1a, gimap8, lama5 and rasal3, in the hypertrophic lip region which have been implicated in lip formation in other vertebrates. Among the predicted upstream transcription factors, we found reduced expression of foxp1 in the hypertrophic lip region, which is known to act as repressor of cell growth and proliferation, and its function has been associated with hypertrophy of upper lip in human. CONCLUSION: Our results provide a genetic foundation for future studies of molecular players shaping soft and exaggerated, but locally restricted, craniofacial morphological changes in fish and perhaps across vertebrates. In the future, we advocate integrating gene regulatory networks of various craniofacial phenotypes to understand how they collectively govern trophic and behavioural adaptations.

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.

How to eliminate bilateral cleft lip stigmata 30 year experience.

PURPOSE: To report a surgical algorithm for the treatment of bilateral cleft lip stigmata. METHODS: The investigators designs a retrospective study composed of patients with bilateral cleft lip stigmata. The surgical approach is on the basis of the severity of the deformity and of course the age of the patient. It consists in Simple scar revision with orbicularis muscle synthesis; Two dermal flaps tunneled in the central vermilion; Abbe flap. The investigators analyzes early and late complications, and performs the evaluation of the cosmetic appearance by a parent or patient himself/herself, a surgeon and a blinded third party observer. RESULTS: The sample was composed of 351 patients. At short-term follow-up, viability of the flaps, function and morphology are good. At long-term follow-up, we observed significant improvement of the characteristics and profile of the patient's face and a normal function of the lips. We recorded a good scarring and a high satisfaction rate by evaluation of patients/ surgeon/ blinded third party observer. CONCLUSION: The results of this study suggest that a surgical algorithm on the basis of the severity of the deformity and of course the age of the patient can represent an option of choice for most patients with bilateral cleft lip stigmata. KEY WORDS: Abbe flap, Bilateral cleft lip stigmata, Cleft lip, Dermal flaps, Orbicularis muscles.

Nasolabial Growth in Individuals With Unilateral Cleft Lip and Palate: A Preliminary Study of Longitudinal Observation Using Three-Dimensional Stereophotogrammetry.

There are limited numbers of studies comparing the preoperative and postoperative facial features of infants with unilateral cleft lip and palate (UCLP) using three-dimensional (3D) stereophotogrammetry. The authors attempted an anthropometric analysis of nasolabial asymmetry 1 year after primary lip repair using a handheld 3D imaging system. Five different nasolabial dimensions in 24 infants with UCLP were measured using 3D images captured during primary lip repair and again, 1 year after the repair. The nasal and upper-lip elements of the cleft side were significantly changed after primary lip repair, and nasolabial asymmetry was anthropometrically improved. This is a preliminary longitudinal observation of nasolabial growth in individuals with UCLP using 3D stereophotogrammetric technique. The authors would like to follow these children until adulthood, capturing 3D images at every intervention.

The Changing Nasolabial Dimensions following Repair of Unilateral Cleft Lip: An Anthropometric Study in Late Childhood.

BACKGROUND: Repair of unilateral cleft lip and nasal deformity in three dimensions requires anticipation of changes in the fourth dimension that can be determined by periodic and objective assessment. METHODS: Fifty patients with unilateral cleft lip with or without cleft palate underwent primary repair from 1999 to 2004 and were followed through 2014. Anthropometry was performed immediately postoperatively and at a first and second follow-up interval, occurring at an average age of 6.6 and 11.5 years, respectively. Measured differences between cleft and noncleft sides included heminasal width (subnasale-alare), cutaneous labial height (subnasale-crista philtri inferior, subalare-crista philtri inferior), and transverse labial width at the cutaneous-vermilion border (crista philtri inferior-chelion). Contrasts for the rates of growth were assessed with t tests for correlated measures. Using the same method, the difference between growth on cleft and noncleft sides in the second period was compared to that in the first period. RESULTS: Heminasal width remained narrower on the cleft side, but this difference decreased over time. Subnasale-crista philtri inferior remained longer on the cleft side; there was no difference between the rate of growth on the cleft and noncleft sides in the second period. Subalare-crista philtri inferior remained shorter on the cleft side by a consistent difference at both times of follow-up measurements. Transverse labial width at the cutaneous-vermilion border remained shorter on the cleft side, but this difference decreased in the second period. CONCLUSION: Understanding how nasolabial features change with growth is critical to crafting the initial repair of unilateral cleft lip and nasal deformity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Assessment of Labionasal Structures in Patients With Unilateral Cleft Lip.

INTRODUCTION: Unilateral cleft lip (UCL) patients have lip and nose deformities that must be addressed during lip repair. Currently, devices to achieve lip and nose improvements have been developed. The most researched presurgical molding device is the nasoalveolar molding (NAM), which has shown favorable results. However, clinical observation shows that unilateral cleft patients, even without molding devices, achieve spontaneous improvements. The aim of this study is to compare morphological and symmetry changes in nose and lip, between patients less than 30-day old and those submitted to cheiloplasty, at 6 months of age. MATERIALS AND METHODS: A total of 27 UCL patients with 2 photographs were selected. The pictures were taken from frontal view and nasal base view at 2 distinct moments: before 30 days of life (t1) and at 6 months of age, during cheiloplasty surgery (T2). Images were analyzed with indirect measurement to assess lip and nose dimensions and nasal symmetry. ImageJ software was used to perform the analyses. RESULTS: A total of 20 patients (P < 0.05) had an average cleft width reduction of 15% [standard deviation (SD) ± 11%]. A 55% average increase (SD ± 29%) was observed in nostril height of cleft side in 16 of patients (P < 0.05). There was an reduction in facial asymmetry of nostril width (P < 0.05), from 95% (SD ± 90%) (t1) to 59% (SD ± 50) (T2). Also, nasal base width asymmetry (P < 0.05) was decreased from 64% (SD ± 66%) (t1) to 40% (SD ± 29%) (T2). CONCLUSION: Facial growth causes a natural improvement on cleft morphological changes and nasal symmetry.

Interactions of hard tissues, soft tissues, and growth over time, and their impact on orthodontic diagnosis and treatment planning.

The approach to orthodontic diagnosis has changed gradually but steadily over the past 2 decades. The shift away from diagnosis based entirely on hard tissue evaluations has been a result of a broadened recognition of the importance of facial and smile appearance to our patients, and how they change over time. The purpose of this article is to describe and illustrate the integration of the new soft tissue paradigm into long-term treatment planning, with a focus on the esthetic goals of treatment.

Longitudinal study of cephalometric soft tissue profile traits between the ages of 6 and 18 years.

OBJECTIVE: To study the longitudinal changes in 19 soft tissue cephalometric traits (according to the Bergman cephalometric soft tissue facial analysis). MATERIALS AND METHODS: Cephalograms and photographs of 40 subjects (20 male, 20 female, from the Burlington Growth Centre) that were obtained at ages 6, 9, 12, 14, 16, and 18 years were used. Subjects were orthodontically untreated whites and had Class I dentoskeletal relationships (ideal overjet and overbite). Images were obtained with the lips in a relaxed position or lightly touching. RESULTS: Three groups of soft tissue traits were identified: (1) traits that increased in size with growth (nasal projection, lower face height, chin projection, chin-throat length, upper and lower lip thickness, upper lip length, and lower lip-chin length); (2) traits that decreased in size with growth (interlabial gap and mandibular sulcus contour [only in females]); and (3) traits that remained relatively constant during growth (facial profile angle, nasolabial angle, lower face percentage, chin-throat/lower face height percentage, lower face-throat angle, upper incisor exposure, maxillary sulcus contour, and upper and lower lip protrusion). CONCLUSION: Current findings identify areas of growth and change in individuals with Class I skeletal and dental relationships with ideal overjet and overbite and should be considered during treatment planning of orthodontic and orthognathic patients.

Soft-tissue profile changes following early Le Fort III distraction in growing children with syndromic craniosynostosis.

BACKGROUND: The purpose of this study was to characterize soft-tissue profile changes following Le Fort III (midface) distraction in growing patients with syndromic craniosynostosis. METHODS: The cohort consisted of 20 syndromic patients who underwent Le Fort III osteotomy with midface advancement using a rigid external distraction device. The mean age at surgery was 5.7 years (range, 3 to 12.5 years). Lateral cephalograms were obtained preoperatively (time 1), after distraction device removal (time 2), and 1 year after distraction (time 3). Ten skeletal hard-tissue and 11 soft-tissue profile landmarks were identified and digitized at time points 1, 2, and 3. The x and y displacement of each landmark was studied to determine the ratios for soft- to hard-tissue change. RESULTS: The horizontal ratio of soft- to hard-tissue change for nasal dorsum to orbitale was 0.73:1 and the soft-tissue tip of nose to the anterior nasal spine was 0.86:1. The horizontal ratio of soft-tissue A point to hard-tissue A point was 0.88:1. The horizontal ratio of the upper lip position to the labial surface of maxillary incisor was 0.88:1. The ratio for nasal tip elevation to the anterior nasal spine advancement was 0.27:1. CONCLUSIONS: The result of this study supported the hypothesis that there exists a linear relationship between soft- and hard-tissue changes in the horizontal direction for the midface landmarks following Le Fort III distraction. However, there was a nonlinear relationship between soft- and hard-tissue changes in the vertical direction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A critical role for PDGFRα signaling in medial nasal process development.

The primitive face is composed of neural crest cell (NCC) derived prominences. The medial nasal processes (MNP) give rise to the upper lip and vomeronasal organ, and are essential for normal craniofacial development, but the mechanism of MNP development remains largely unknown. PDGFRα signaling is known to be critical for NCC development and craniofacial morphogenesis. In this study, we show that PDGFRα is required for MNP development by maintaining the migration of progenitor neural crest cells (NCCs) and the proliferation of MNP cells. Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRα function during MNP development. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels.

Repair of bilateral incomplete cleft lip: techniques and outcomes.

BACKGROUND: Primary repair of bilateral incomplete cleft lip appears to be uncomplicated but requires attention to technical details in the third dimension in anticipation of changes in the fourth dimension. METHODS: Direct anthropometry was used to document nasolabial dimensions before and immediately after repair in 51 infants with bilateral incomplete cleft lip. Technical details were analyzed in 48 patients; serial anthropometry was plotted in 22 male patients aged 2 to 20 years and compared to Farkas's normal growth lines. Revisions were also documented (n = 46). RESULTS: Nasal width was made narrow and widened to normal by adolescence. Nasal tip protrusion was elongated and grew parallel to normal. Columellar length was constructed above normal, lengthened slowly in childhood, and was slightly short by adulthood. The Cupid's bow was designed narrow, widened slightly, and maintained normal dimension in adulthood. The upper philtrum was tapered and remained less wide than the lower philtrum. Although maximum available cutaneous prolabium was used in repair, it was short postoperatively and philtral height failed to exhibit catchup growth. The median tubercle was constructed overly full, but growth frequently fell behind in adolescence; 39 percent of patients required secondary augmentation. Total upper labial height closely followed the normal growth curve. CONCLUSIONS: Serial anthropometry documented postoperative changes in nasolabial dimensions compared with normal growth lines. Repair of bilateral incomplete cleft lip requires primary correction of nasal and labial features based on their differential growth. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Evaluation of some facial anthropometric parameters in an Iranian population: infancy through adolescence.

OBJECTIVES: By finding the mean value of anthropometric parameters in normal samples of a population, it is possible to create a template for facial analysis. The aim of our study was to measure the anthropometric parameters in 0- to 12-year-old girls of Fars ethnic origin in the Northeast of Iran. STUDY DESIGN: Six hundred sixty-two newborn to 12-year-old girls of Fars ethnic origin participated in the study. A digital camera was used to take frontal full-face photographs of each child. Thirteen measurements were taken with the Smile Analyzer software: al-al, ch-ch, en-en, ex-ex, ft'-ft', go'-go', t-t, zy'-zy', n'-gn', n'-sn, t-g', t-gn', t-sn. Data were analyzed using the SPSS software at the significance level of 0.05. RESULTS: In almost all parameters, we found significant growth acceleration between 2 and 4 years as well as 5 and 6 years of age. Another growth spurt was seen between 9 and 11 years, although it was less noticeable. Comparing the linear regression equations suggests that different craniofacial dimensions do not grow similarly. CONCLUSIONS: By age, craniofacial dimensions change at different rates. Different craniofacial dimensions do not grow at consistent rates. Some parts grow slower compared with others. The intercanthal width has the slowest growth. Facial height shows the fastest growth.

Divergent regulation of Wnt-mediated development of the dorsomedial and ventrolateral dermomyotomal lips.

The dermomyotome is the dorsal compartment of the somite which gives rise to multiple cell fates including skeletal muscle, connective tissue, and endothelia. It consists of a pseudostratified, roughly rectangular epithelial sheet, the margins of which are called the dermomyotomal lips. The dermomyotomal lips are blastema-like epithelial growth zones, which continuously give rise to resident dermomyotomal cells and emigrating muscle precursor cells, which populate the subjacent myotomal compartment. Wnt signaling has been shown to regulate both dermomyotome formation and maintenance of the dermomyotomal lips. Whereas the epithelialization of the dermomyotome is regulated via canonical, ß-catenin-dependent Wnt signaling, the downstream signaling mechanisms suppressing epithelial-mesenchymal transition (EMT) in the mature dermomyotomal lips have been unknown. Here, we present evidence that dermomyotomal lip sustainment is differentially regulated. Whereas the dorsomedial dermomyotomal lip is maintained by canonical Wnt signaling, development of the ventrolateral dermomyotomal lip is regulated by non-canonical, PCP-like Wnt signaling. We discuss our results in the light of the different developmental prerequisites in the dorsomedial and ventrolateral lips, respectively, thus providing a new perspective on the regulation of dermomyotomal EMT.

The morphological features and developmental changes of the philtral dimple: a guide to surgical intervention in cases of cleft lip.

OBJECTIVE: This study was undertaken to analyse in detail the morphological features of the philtral dimple and the developmental changes of philtral morphology, including a comparison with patients with a cleft lip. PATIENTS AND PARTICIPANTS: Fifty-five normal Japanese adults, seventy-five children and fifteen patients with complete unilateral cleft lip were referred for analysis. DESIGN: 3D facial data were acquired with a non-contacting laser scanner. We calculated the desired linear and angular components, defining the features of the philtrum with analysing software. RESULTS: The philtral dimple was morphologically expressed by the two different deepest points in the horizontal and sagittal sectional view, respectively. These decreased with age and did not show any correlation. In contrast, philtral measurements on the X-Y coordinates increased during the course of development. Most of the linear and angular variables in the patients with the cleft lip had exhibited greater values than the normal subjects, reflecting the deformed philtral morphology. CONCLUSIONS: To obtain an optimally natural philtral construction accompanied by a symmetrical lip in cleft surgery, it is critical to take into consideration both the geometric features of the philtral depth and age-appropriate morphological features of the philtrum as objective criteria.

Developmental changes in the variability of tongue and lip movements during speech from childhood to adulthood: an EMA study.

This study investigated the developmental variability of lip and tongue movement in 48 children and adults. Motion of the tongue-tip, tongue-body and lower lip was recorded using electromagnetic articulography during productions of sentences containing /t/, /s/, /l/, /k/ and /p/. Four groups of speakers participated in the study: (1) aged 6-7 years; (2) 8-11 years; (3) 12-17 years; and (4) adults. The variation in distance, duration, speed, acceleration and deceleration of the articulators during single open-close speech movements was analysed, and the stability of multiple movement sequences was examined using the spatiotemporal index. The experimental findings revealed a gradual developmental progression from 6 years to adulthood. At adolescence, speakers continued to exhibit significantly more variable speech motor output compared to adult speakers. The observed developmental pattern suggests that attenuated, but important, changes in the speech motor system occurs from mid-childhood, through adolescence, to adulthood.

Effects of age and gender on upper airway, lower airway and upper lip growth.

The aim of the present retrospective study was to evaluate the influence of age and gender on upper and lower airway width and upper lip length. In this study, 390 lateral cephalograms were divided into 13 age groups (ranging from 6 to 18 years) and were analyzed. The intergroup differences were analyzed using a MANOVA (Multivariate Analysis of the Variance), and the intragroup differences were analyzed using an ANOVA (Analysis of the Variance) and Tukey's test. The results of the present study indicated that although the airway width and the upper lip length increased with age, the lower airway width exhibited variable growth between the ages of six and eighteen years. The airway width was significantly greater in females than males, whereas the upper airway width was similar between these two genders. The lip length was significantly shorter in females than males. The lower airway width and upper lip length were significantly different between males and females, whereas the upper airway width was similar for the genders. The upper airway width and upper lip exhibited incremental growth between the ages of six and eighteen years. The upper lip closely followed the growth pattern of the upper airway width; the growth plateaued between the ages of 6 and 9 years, increased from 9 to 16 years and plateaued from 16 to 18 years.

Effects of age and gender on upper airway, lower airway and upper lip growth

The aim of the present retrospective study was to evaluate the influence of age and gender on upper and lower airway width and upper lip length. In this study, 390 lateral cephalograms were divided into 13 age groups (ranging from 6 to 18 years) and were analyzed. The intergroup differences were analyzed using a MANOVA (Multivariate Analysis of the Variance), and the intragroup differences were analyzed using an ANOVA (Analysis of the Variance) and Tukey's test. The results of the present study indicated that although the airway width and the upper lip length increased with age, the lower airway width exhibited variable growth between the ages of six and eighteen years. The airway width was significantly greater in females than males, whereas the upper airway width was similar between these two genders. The lip length was significantly shorter in females than males. The lower airway width and upper lip length were significantly different between males and females, whereas the upper airway width was similar for the genders. The upper airway width and upper lip exhibited incremental growth between the ages of six and eighteen years. The upper lip closely followed the growth pattern of the upper airway width; the growth plateaued between the ages of 6 and 9 years, increased from 9 to 16 years and plateaued from 16 to 18 years.

New method for analysis of facial growth in a pediatric reconstructed mandible.

INTRODUCTION: The aim of this article was to present a new method of analysis for the assessment of facial growth and morphology after surgical resection of the mandible in a growing patient. METHODS: This was a 2-year longitudinal study of facial growth in a child who had undergone segmental resection of the mandible with immediate reconstruction as a treatment for juvenile aggressive fibromatosis. Three-dimensional digital stereo-photogrammteric cameras were used for image acquisition at several follow-up intervals: immediate, 6 months, and 2 years postresection. After processing and superimposition, shell-to-shell deviation maps were used for the analysis of the facial growth pattern and its deviation from normal growth. The changes were seen as mean surface changes and color maps. An average constructed female face from a previous study was used as a reference for a normal growth pattern. RESULTS: The patient showed significant growth during this period. Positive changes took place around the nose, lateral brow area, and lower lip and chin, whereas negative changes were evident at the lower lips and cheeks area. An increase in the vertical dimension of the face at the chin region was also seen prominently. CONCLUSIONS: Three-dimensional digital stereo-photogrammetry can be used as an objective, noninvasive method for quantifying and monitoring facial growth and its abnormalities.

Can commonly used profile planes be used to evaluate changes in lower lip position?

OBJECTIVES: To determine the validity of five profile planes commonly used to describe the horizontal changes of the lower lip during orthodontic treatment. MATERIALS AND METHODS: Pretreatment and posttreatment cephalograms of 79 patients (12.4 ± 2.8 years of age) were evaluated. Lower lip (labrale inferiorus) changes over time were measured relative to the Rickett's E-line, Steiner's S1-line, Burstone's B-line, Sushner's S2-line, and Holdaway's H-line. As an independent measure of actual horizontal lip changes, the labrale inferiorus was measured relative to a stable reference plane registered on the sella and oriented on the SN-7°. RESULTS: The lower lip actually moved anteriorly 2.35 ± 3.35 mm during orthodontic treatment; the five profile planes indicated that the lower lip moved to a more retrusive, posterior position. The five profile planes also showed no statistically significant sex differences in terms of the treatment changes that occurred, while the actual lip changes showed that males exhibited significantly greater changes than females. Actual treatment changes showed that the lower lip moved to a more protrusive position with nonextraction than with extraction treatments, changes that were not evident based on the five profile lines. While lip changes based on the five profile planes demonstrated moderately high to high intercorrelations ranging from 0.81 to 0.97, they showed only weak correlations (r < .35) with the actual horizontal changes of the labrale inferiorus. CONCLUSIONS: While all five planes measured similar aspects of positional change, none of them closely reflected the actual lower lip changes that occurred. These planes should not be used to measure changes in lip position that occur during treatment.

Three-dimensional analysis of facial morphology: growth, development and aging of the orolabial region.

Soft tissue analysis plays an increasing, strategic role in the recognition of facial alterations, but there are scanty three-dimensional reference data during normal growth, development and aging. In the current study, 532 male and 386 female healthy subjects aged 4 to 73 years were analyzed using a non-invasive, computerized electromagnetic digitizer, and normal dimensions of mouth and lips were obtained in the three-dimensional space. Labial thickness and curvature were also assessed in a selected group of 40 men and women, equally divided into young (age 21-30 yr, mean 25 yr) and old persons (age 45-65 yr, mean 55 yr). Lip vermilion area to volume, and vermilion height to cutaneous lip height ratios decreased with age in both sexes. On average, the lips were thicker in men and in young persons than in women and in old persons. Mean labial curvature was larger in young men than in the other groups, and it was more variable in young than in old persons. Data collected in the present investigation can be used as a data base for the quantitative description of human lip morphology during normal growth, development and aging.