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.

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.

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.

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.

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.

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.

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.

Growth maturation aging: how the dental team enhances facial and dental esthetics for a lifetime.

As the body of research regarding facial esthetics increases, dentists are gaining a deeper understanding of their broadening roles in defining facial characteristics. Dentists are required to advance their repertoire of diagnostic skills in order to meet patients' esthetic needs and demands. The focus has been shifting from treatment plans being based entirely on the occlusal relationships to the balance of the teeth and smile presentation as well as soft-tissue support and facial appearance. This article presents two cases illustrating these principles.

Long-term results in the bilateral cleft lip repair by Mulliken's method.

PURPOSE: To evaluate long-term results in the bilateral cleft lip repair by Mulliken's method, using anthropometric measurements, we assessed the growth of the nose and upper lip after the operation by comparing with those from 30 children without bilateral cleft lip. MATERIALS AND METHODS: Forty-four patients had their bilateral cleft lip and nasal deformity repaired simultaneously by Mulliken's method during the period from July 1997 to December 2007. Of these patients, 15 patients had bilateral complete cleft lip, 17 patients had bilateral incomplete cleft lip, and 12 patients had a mixed type of complete and incomplete bilateral cleft lip.To follow up on the growth of the lips and nose after the operation, the following 6 anthropometric measurements were analyzed: nasal tip protrusion, nasal width, columellar length, upper lip height, cutaneous lip height, and vermilion mucosa height. RESULTS: In most patients, nasal length, nasal tip projection, columellar length, and upper lip shape were appropriate. Nasal tip protrusion, nasal width, upper lip height, and vermilion-mucosal height were within normal limit. However, columellar length and cutaneous lip height were relatively shorter than the average values of children without bilateral cleft lip. CONCLUSIONS: By performing Mulliken's method, we can achieve natural lip and nasal shape, harmonious Cupid's bow, appropriate nasal projection, and natural philtrum.

Superimposition of 3-dimensional cone-beam computed tomography models of growing patients.

INTRODUCTION: The objective of this study was to evaluate a new method for superimposition of 3-dimensional (3D) models of growing subjects. METHODS: Cone-beam computed tomography scans were taken before and after Class III malocclusion orthopedic treatment with miniplates. Three observers independently constructed 18 3D virtual surface models from cone-beam computed tomography scans of 3 patients. Separate 3D models were constructed for soft-tissue, cranial base, maxillary, and mandibular surfaces. The anterior cranial fossa was used to register the 3D models of before and after treatment (about 1 year of follow-up). RESULTS: Three-dimensional overlays of superimposed models and 3D color-coded displacement maps allowed visual and quantitative assessment of growth and treatment changes. The range of interobserver errors for each anatomic region was 0.4 mm for the zygomatic process of maxilla, chin, condyles, posterior border of the rami, and lower border of the mandible, and 0.5 mm for the anterior maxilla soft-tissue upper lip. CONCLUSIONS: Our results suggest that this method is a valid and reproducible assessment of treatment outcomes for growing subjects. This technique can be used to identify maxillary and mandibular positional changes and bone remodeling relative to the anterior cranial fossa.

Changes in lip 1 year after modified Millard repair.

The aim of this study was to observe changes in the lip 1 year after performing a modified Millard cleft lip repair, by comparing the preoperative and 1-year follow-up appearance of the lip. Twenty-three patients with a unilateral complete cleft were photographed by a standardized method before repair, 7 days after surgery and 12 months after surgery. Lips on the cleft side were measured and compared with the opposite side. Possible results were: equal, longer and shorter. There was no linear correlation between the preoperative and 1-year postoperative appearance of the lip, but there was a linear correlation in lip height between the 7-day and 12-month postoperative results. No matter how severe the initial deformity, primary repair of the cleft lip is crucial in maintaining labial symmetry 1 year after operation.

Long-term changes of the upper lip position relative to the incisal edge.

INTRODUCTION: One result of postadolescent facial growth is elongation of the upper lip and subsequent decrease of incisal display on smiling. The aim of this study was to evaluate the long-term change of upper lip position relative to the incisal edge. METHODS: Fifty-four subjects with cephalometric x-rays taken at the end (T2) of orthodontic treatment, at least 10 years postretention (T3), and at least 20 years postretention (T4) were selected from the postretention records of the University of Washington, Seattle. On each cephalogram, length of the upper lip, anterior and posterior facial height, and positions of the maxillary and mandibular incisors were registered. RESULTS: From T2 to T3, both upper lip elongation and growth of the facial skeleton were more pronounced in males than in females. The stomion-incision superius distance diminished by 1.3 mm in males, whereas in females this distance increased by 0.3 mm. From T3 to T4, the facial skeleton showed relative stability in both sexes, whereas the upper lip elongated by approximately 2 mm. The stomion-incision superius distance decreased by about 1.2 mm. CONCLUSIONS: Elongation of the upper lip continues throughout life. In the second and third decades of life, facial growth balances lip elongation. When late facial growth is minimal, the stomion-incision superius distance steadily decreases.

Three-dimensional analysis of facial morphology surface changes in untreated children from 12 to 14 years of age.

INTRODUCTION: The developing face is of interest to orthodontists, especially if orthodontic treatment can influence the outcome of facial growth. New 3-dimensional (3D) modalities have enabled clinicians to better understand the facial changes in a developing child. METHODS: Fifty-nine children with normal body mass indexes were evaluated with a previously validated 3D laser imaging device over a 2-year period. Surface changes were evaluated on normal and average faces. These changes were seen as mean surface changes and color maps. RESULTS: The results suggest that the surface areas of change in average faces were generally downward and forward with respect to the nose and soft-tissue nasion. The lips also translated in a downward direction as the nose grew, and there was a general increase in the vertical dimension. Some subjects were in the "great changes" category, boys significantly more so than girls. CONCLUSIONS: The following conclusions can be made from this 3D study of changes of facial morphology in children: (1) surface changes are greater in boys than in girls; (2) differences in the timing of surface changes in boys and girls are clinically significant, with boys exhibiting more changes later; (3) positive surface changes occur in the nose, brows, lips, and vertical dimensions of the face; (4) the eyes deepen, and the cheeks become flatter; and (5) 3D imaging is a useful tool in analyzing changes to the face over time.

Cross-sectional growth changes in skeletal and soft tissue cephalometric landmarks of children.

In order to provide standard values for craniofacial growth of normal children, we evaluated the growth changes of skeletal and soft tissue cephalometric landmarks from lateral cephalograms of 180 Japanese children. They were divided into three groups: primary dentition, mixed dentition, and permanent dentition. Specific skeletal angles and distances showed significant gender differences with increasing age. The only significant soft tissue gender difference was nose height in the oldest group. Upper pharynx dimension and nose height differed significantly among the groups in both genders. Positions of both the upper and lower lip changed significantly between the intermediate and oldest groups of both genders. Nasolabial angle did not change significantly with growth. The results of this study should be useful for predicting craniofacial growth and development or determining the effect of orthodontic treatment.

Soft-tissue changes during facial growth in skeletal Class II individuals.

INTRODUCTION: In orthodontic treatment, a harmonious soft-tissue profile can be difficult to achieve; the thickness of the soft tissues can vary greatly, and changes with growth and treatment can be difficult to predict. The purpose of this study was to investigate changes in the thickness and the length of the soft tissues of the nose, upper and lower lips, and chin due to growth from 6 to 16 years of age. METHODS: Cephalograms of 36 subjects (22 boys, 15 girls) with skeletal Class II malocclusions were analyzed. They participated in the Burlington Growth Study, and longitudinal records had been collected at ages 6, 9, 12, 14, and 16 years. The cephalograms were digitized and analyzed with Dentofacial Planner Plus (version 2.0; Dentofacial Software, Toronto, Ontario, Canada) software. Statistical analysis was performed with the nonparametric Friedman test, and comparisons among means were made with 1-way ANOVA software. RESULTS: All structures showed some growth at all stages. The nose showed the greatest increases in thickness and length in both sexes. There was sexual dimorphism at 16 years, with higher values for boys. Upper lips tended to reduce in the girls. Upper lip length showed slight increases, and base of the upper lip showed small increases for both sexes. The lower lip had moderate increases in all measurements, and its thickness showed sexual dimorphism at almost all ages. The soft tissues of the chin increased in both thickness and length, with no sexual dimorphism.

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.

Craniofacial development in children with unilateral cleft lip and palate.

Unilateral cleft lip and palate is the most common cleft in humans. We investigated the craniofacial morphology of Turkish children with unilateral complete cleft lip and palate who had operations to close the cleft lip when they were 3 months old and to close the palate at 12 months. They were not given orthopaedic or orthodontic treatment. We compared 42 patients with unilateral complete cleft lip and palate (UCCLP) with 45 control children without UCCLP at mean ages of 13 and 15 years. The children with UCCLP had considerable morphological deviations compared with the matched children without clefts. They had significantly shorter and more posteriorly positioned maxillas (p<0.01). There was also an increase in cranial base angle (p<0.05), mandibular plane and gonial angle (p<0.01). There was a reduction in the posterior facial height (p<0.05) and an increase in the anterior facial height (p<0.01). The profile of the soft tissue was more convex (p<0.001) and the upper lip was thinner than in the children in the control group (p<0.01), and their noses were relatively further backwards and downwards (p<0.01).