A Geometric Morphometric Approach to the Analysis of Lip Shape during Speech: Development of a Clinical Outcome Measure

Objective assessments of lip movement can be beneficial in many disciplines including visual speech recognition, for surgical outcome assessment in patients with cleft lip and for the rehabilitation of patients with facial nerve impairments. The aim of this study was to develop an outcome measure for lip shape during speech using statistical shape analysis techniques. Lip movements during speech were captured from a sample of adult subjects considered as average using a three-dimensional motion capture system. Geometric Morphometrics was employed to extract three-dimensional coordinate data for lip shape during four spoken words decomposed into seven visemes (which included the resting lip shape). Canonical variate analysis was carried out in an attempt to statistically discriminate the seven visemes. The results showed that the second canonical variate discriminated the resting lip shape from articulation of the utterances and accounted for 17.2% of the total variance of the model. The first canonical variate was significant in discriminating between the utterances and accounted for 72.8% of the total variance of the model. The outcome measure was created using the 95% confidence intervals of the canonical variate scores for each subject plotted as ellipses for each viseme. The method and outcome model is proposed as reference to compare lip movement during speech in similar population groups.     

Birth prevalence of cleft lip and palate in British Columbia between 1952 and 1986: stability of rates.

We examined the birth prevalence of cleft lip with or without cleft palate and of isolated cleft palate in British Columbia between 1952 and 1986 using the data of the BC Health Surveillance Registry. The rates fluctuated over the study period, but linear trend analysis showed no increase or decrease for cleft lip with or without cleft palate; however, there was a significant increase for isolated cleft palate, attributed to improved ascertainment around 1963-66. Given the possible effects of newer agents used in both silviculture and agriculture, as well as the general concern over drugs and other environmental agents, such a long-term monitoring program is important. Furthermore, if significant clustering occurs, good background data are essential for comparison. The general public''s perception is that the rates of birth defects are increasing. Our findings should give some reassurance with respect to orofacial clefts.     

Growth status of children treated for unilateral cleft lip and palate

Cephalometric distances, angles, and proportions were evaluated for 32 children 5 to 8 years of age treated for unilateral cleft lip and palate. The children were age and sex matched with untreated controls with normal skeletal relationships. The unilateral cleft lip and palate sample was treated by the same surgeon and orthodontist using the same techniques and appliances. Measures of overall facial proportions, facial convexity, and prognathism were not significantly different between the two groups. The primary group differences pertain to the posterior aspect of the maxilla, which is vertically short in the unilateral cleft lip and palate sample. Horizontally, the maxilla of the unilateral cleft lip and palate children was significantly longer, producing a steeper palatal plane. In addition, the zygoma and orbits of unilateral cleft lip and palate children were somewhat retruded; the posterior cranial base and total mandibular length also were longer in the unilateral cleft lip and palate children.     

Craniofacial growth in subjects with unilateral complete cleft lip and palate, and unilateral incomplete cleft lip, from 2 to 22 months of age

This paper reports a longitudinal quantitative cephalometric analysis of the craniofacial growth in subjects with unilateral complete cleft lip and palate (UCCLP), and unilateral incomplete cleft lip (UICL), from 2 to 22 months of age. The purpose of the study was to determine the amount and direction of growth in UCCLP compared to UICL (control group) from 2 months of age (just prior to lip repair) to 22 months of age, 20 months later. The sample comprised of 49 subjects with UCCLP (37 males and 11 females) and 45 with UICL (29 males and 16 females). The cephalometric analysis of the craniofacial morphology included lateral, frontal, and axial projections. The data were presented as mean plots of the craniofacial region including the calvaria, cranial base, orbits, nasal bone, maxilla, mandible, cervical column, pharynx, and soft-tissue profile. A valid common coordinate system (registration according to the n-s line in the lateral projection, latero-orbitale line in the frontal projection, and meatus acusticus externus line in the axial projection for the landmark positions at examination 1 and 2) was ascertained. The growth at a specific anatomical location in a patient was defined as the displacement vector from the coordinate of the corresponding landmark in the X-ray at examination 1 to its coordinate at examination 2, corrected for X-ray magnification. The growth of an anatomical region in a patient was assessed by investigating the growth pattern formed by a collection of individual growth vectors in that region. The amount of growth in the UCCLP and UICL group was very similar. The general craniofacial growth pattern, in terms of the direction of growth, was also fairly similar in the UCCLP group and the control group. However, the maxilla and mandible showed a more vertical growth pattern than that observed in the control group. This study confirms that UCCLP is a localized deviation, and not a craniofacial anomaly, due to the fact that a normal growth potential has been observed in all craniofacial regions, except where the growth had been directly influenced by surgical intervention. Furthermore, the vertical growth pattern of the maxilla and mandible supports the hypothesis of a special facial type in cleft lip and palate individuals, and the facial type as a liability factor increasing the probability of cleft lip and palate.     

Signaling through Tgf-beta type I receptor Alk5 is required for upper lip fusion

Cleft lip with or without cleft palate is one of the most common congenital malformations in newborns. While numerous studies on secondary palatogenesis exist, data regarding normal upper lip formation and cleft lip is limited. We previously showed that conditional inactivation of Tgf-beta type I receptor Alk5 in the ectomesenchyme resulted in total facial clefting. While the role of Tgf-beta signaling in palatal fusion is relatively well understood, its role in upper lip fusion remains unknown. In order to investigate a role for Tgf-beta signaling in upper lip formation, we used the Nes-Cre transgenic mouse line to delete the Alk5 gene in developing facial prominences. We show that Alk5/Nes-Cre mutants display incompletely penetrant unilateral or bilateral cleft lip. Increased cell death seen in the medial nasal process and the maxillary process may explain the hypoplastic maxillary process observed in mutants. The resultant reduced contact is insufficient for normal lip fusion leading to cleft lip. These mice also display retarded development of palatal shelves and die at E15. Our findings support a role for Alk5 in normal upper lip formation not previously reported.     

Analysis of the lengthening effect of the muscle repair in functional cleft lip repair

In 14 patients undergoing functional cleft lip repair, changes in the lengths of the key lip segments were measured preoperatively, after the muscle layer was repaired, and after the skin was repaired using pieces of wire bent to follow the curves of the lip in three dimensions. The cleft side of the lip was shorter than the normal side in the vertical and horizontal dimensions. Freeing the muscle from its dermal insertions, splitting it, and advancing it into the medial side of the cleft lengthened the cleft side of the lip vertically and horizontally. The Z-plasty skin repair further lengthened the cleft side of the lip in the vertical dimension. The lengthening effect of the muscle repair appears to be the result of the loose skin redraping over the dissected muscle and further explains elimination of the orbicularis bulge and superior scar formation in the functional cleft lip repair.     

Three-dimensional nasolabial displacement during movement in repaired cleft lip and palate patients

The objective of this study was two-fold: (1) to explore the suitability of a novel modified Procrustes fit method to adjust data for head motion during instructed facial movements, and (2) to compare the adjusted data among repaired unilateral (n = 4) and bilateral (n = 5) cleft lip and palate patients and noncleft control subjects (n = 50). Using a video-based tracking system, three-dimensional displacement of 14 well-defined nasolabial landmarks was measured during four set facial animations without controlling for head motion. The modified Procrustes fit method eliminated the contributions of head motion by matching the most stable landmarks of each video-recorded frame of the face during function to frames at rest. Its effectiveness was found to approximate that of a previous method (i.e., use of a maxillary occlusal splint to which stable dentition-based markers were attached). Data from both the unilateral and bilateral cleft lip and palate patients fell outside the normal range of maximum displacements and of asymmetry, and individual patients demonstrated greater right-versus-left asymmetry in maximum displacement than did individual noncleft subjects. It is concluded that the modified Procrustes fit method is fast, is easy to apply, and allows subjects to move the head naturally without the inconvenience of a splint while facial movement data are being collected. Results obtained using this method support the view that facial movements in cleft patients may be severely hampered and that assessment of facial animation should be strongly considered when contemplating surgical lip revisions.     

Detecting Genetic Association of Common Human Facial Morphological Variation Using High Density 3D Image Registration

Human facial morphology is a combination of many complex traits. Little is known about the genetic basis of common facial morphological variation. Existing association studies have largely used simple landmark-distances as surrogates for the complex morphological phenotypes of the face. However, this can result in decreased statistical power and unclear inference of shape changes. In this study, we applied a new image registration approach that automatically identified the salient landmarks and aligned the sample faces using high density pixel points. Based on this high density registration, three different phenotype data schemes were used to test the association between the common facial morphological variation and 10 candidate SNPs, and their performances were compared. The first scheme used traditional landmark-distances; the second relied on the geometric analysis of 15 landmarks and the third used geometric analysis of a dense registration of ∼30,000 3D points. We found that the two geometric approaches were highly consistent in their detection of morphological changes. The geometric method using dense registration further demonstrated superiority in the fine inference of shape changes and 3D face modeling. Several candidate SNPs showed potential associations with different facial features. In particular, one SNP, a known risk factor of non-syndromic cleft lips/palates, rs642961 in the IRF6 gene, was validated to strongly predict normal lip shape variation in female Han Chinese. This study further demonstrated that dense face registration may substantially improve the detection and characterization of genetic association in common facial variation.     

Pathophysiology of cleft lip muscle

Although attention has been focused for decades on the correction of cleft lip deformities, our knowledge about the etiology of such deformities has remained presumptive. Sixty-six muscle biopsy specimens from cleft lip infants were obtained at the time of primary closure. Histochemical stains, histographic analysis, and electron microscopy were performed. A nonneurogenic muscle atrophy was seen that varied in severity, with muscle fibers near the cleft being the most atrophic and disorganized. Muscle fibers stained with the modified Gomori trichrome technique also demonstrated "ragged red" fibers typical of a mitochondrial myopathy. Electron microscopy confirmed large accumulations of mitochondria distorting the fibrils. These mitochondria also were increased in size and densely packed with cristae. This study thus demonstrates that the muscles in cleft lip deformities are not normal. Instead, they reflect either myopathy in the facial mesenchymal mitochondrion or at least a delay in maturation. We hypothesize that some of the morphologic deformities associated with cleft lip may cause a failure of mesenchymal reinforcement of the facial processes at a critical time in development.     

Upper lip measurements at the time of surgery and follow-up after modified rotation-advancement flap repair in unilateral cleft lip patients

The purpose of this prospective study was to determine whether unilateral cleft lip repaired by the rotation-advancement flap will grow short on the repaired side. This study involved 56 patients with nonsyndromic unilateral cleft lip (31 with complete and 25 with incomplete cleft lip) who underwent a rotation-advancement flap repair by a single surgeon between 1989 and 1997. Eleven patients were lost to follow-up. Forty-five patients have been followed for a varying period of between 8 and 84 months (mean = 37 months). The upper lip was measured immediately after the lip repair and follow-up using calipers. The growth ratios of vertical, horizontal, and nostril sill dimensions were compared between the cleft side and the noncleft side of the same face. Statistical analysis was performed to compare the growths between the cleft and noncleft sides. There was not a significant difference in the growth ratios of vertical (Wilcoxon signed rank test, p = 0.85) and horizontal dimensions (Student's t test, p = 0.18) between the cleft and noncleft sides. There was, however, a statistically significant difference in the growth ratios of nostril sill width between the cleft and noncleft sides (Student's t test, p = 0.02). Our findings indicated that a repaired unilateral cleft retained the vertical and horizontal dimensions determined at the time of the initial repair.     

Distinct functions for Bmp signaling in lip and palate fusion in mice

Previous work suggested that cleft lip with or without cleft palate (CL/P) is genetically distinct from isolated cleft secondary palate (CP). Mutations in the Bmp target gene Msx1 in families with both forms of orofacial clefting has implicated Bmp signaling in both pathways. To dissect the function of Bmp signaling in orofacial clefting, we conditionally inactivated the type 1 Bmp receptor Bmpr1a in the facial primordia, using the Nestin cre transgenic line. Nestin cre; Bmpr1a mutants had completely penetrant, bilateral CL/P with arrested tooth formation. The cleft secondary palate of Nestin cre; Bmpr1a mutant embryos was associated with diminished cell proliferation in maxillary process mesenchyme and defective anterior posterior patterning. By contrast, we observed elevated apoptosis in the fusing region of the Nestin cre; Bmpr1a mutant medial nasal process. Moreover, conditional inactivation of the Bmp4 gene using the Nestin cre transgenic line resulted in isolated cleft lip. Our data uncover a Bmp4-Bmpr1a genetic pathway that functions in lip fusion, and reveal that Bmp signaling has distinct roles in lip and palate fusion.     

A comparison of the craniofacial morphology in 2-month-old unoperated infants with unilateral complete cleft lip and palate, and unilateral incomplete cleft lip.

This paper reports a cephalometric analysis of the craniofacial morphology in infants with unoperated unilateral complete cleft lip and palate (UCCLP) and unoperated unilateral incomplete cleft lip (UICL). The purpose of the study was to determine the nature and extent of the craniofacial deviations in UCCLP as compared to the morphology in UICL, which has previously been shown to be close to normal. The samples comprised 82 infants with UCCLP (58 males and 24 females) and 75 with UICL (48 males and 27 females). The mean age was about 2 months in both groups. The cephalometric analysis of craniofacial morphology included the lateral, frontal, and axial projections. The data were presented as mean plots of the craniofacial region including the calvaria, cranial base, orbits, nasal bone, maxilla, mandible, cervical column, pharynx, and soft-tissue profile. The most pronounced deviations in the UCCLP group were observed in the maxillary complex and the mandible. The most striking findings were: markedly increased width of the maxilla, a short mandible, and bimaxillary retrognathia except for the premaxillary area, which was relatively protruding and asymmetric. The study did not support the hypothesis previously suggested in the literature that cleft lip and palate is a craniofacial anomaly as size and shape of the calvaria and cranial base were found to be normal. The etiology of cleft lip and palate is still incompletely understood. Based on the present study, we suggest that facial type may be a liability factor that could represent a developmental threshold increasing the probability of cleft lip and palate.     

A comparative study of development during primary palate formation in A/WySn, C57BL/6, and their F1 crosses

Preliminary to a study comparing the morphological differences in facial growth of A/WySn (25% cleft lip) and C57BL/6 (0% cleft lip) mice, the growth and development of these strains and their reciprocal F1 hybrids was examined. Litters of these four populations were observed at D 10/8, D 10/20, D 11/8, and D 11/20 and scored for crown-rump length (CRL), somite number, and stage of facial development. Analysis of the data showed that, at any given gestational age, a hierarchy exists in which A/WySn is the smallest (based on CRL), has the fewest somites, and has the least-developed face. It is followed by the A/WySn-C57BL/6 (AC) cross, C57BL/6, and the C57BL/6-A/WySn (CA) cross, in order of increasing growth and development. The significant differences occurring between AC and CA indicate that maternal effects exist in A/WySn that retard the growth and development of its progeny. When the four populations were compared at similar facial stages, there was no significant difference between A/WySn and C57BL/6 in CRL or somite number. However, the hybrid populations tended to have significantly fewer somites and to be significantly larger than the parental populations at comparable stages of facial development. This suggests that, although somatic growth and development are coordinated with facial development in both cleft lip-susceptible and resistant strains, the association can be influenced by hybrid vigor. Thus, maternal effects do not appear to produce cleft lip through selective retardation of facial development in the purebred A/WySn. Nonetheless, these effects may still potentiate the expression of cleft lip.     

唇腭裂矫形修复中的美学研究

本文介绍用双重牙列修复唇腭裂患者面中1/3缺陷,其特点是方法简便、效果明显和患者乐意接受。并提出评判唇腭裂患者的面容面貌改善不能单纯以正常美貌人群中面部指数为标准,而应在介于正常人与唇腭裂患者之间寻找一个能协调、柔和、均衡、匀称的面部指娄作为评判标准。     

A model for fetal cleft lip repair in lambs.

Fetal wounds heal without inflammation and scar formation. This phenomenon may, in the future, be applicable to human cleft lip and palate repair. However, extensive experimental work must first be done to document the benefits of in utero repair. We developed a large animal model for creation and repair of a complete cleft lip and alveolus using fetal lambs. The cleft lip and alveolus deformity was created in eight 75-day-gestation fetuses (term = 145 days) and either repaired in three layers or left unrepaired. There were four sham-operated fetuses, and all animals were alive at harvest. Repaired, unrepaired, and control fetuses were harvested at 7, 14, 21, and 70 days following surgery. The unrepaired fetuses demonstrated a complete cleft lip and alveolus with an oronasal fistula. The maxilla was asymmetrical, with the greater segment deviated toward the cleft and with decreased anterior maxillary width. In contrast, repaired cleft lip and alveolus animals showed no scar, normal thickness of the lip, and a symmetrical maxilla. Histologic analysis of the repaired wounds showed evidence of tissue regeneration without scar formation. The results of this preliminary study indicate that the fetal lamb cleft lip and alveolus model is technically feasible with an excellent survival rate. Healing occurs without scar formation. In the repaired animals, the maxilla was symmetrical. This model will be used to document facial growth following in utero repair of a cleft lip and alveolus.     

Rare facial clefts: treatment during charity missions in developing countries

During 10 charity missions in developing countries, 14 patients of a total of 374 children with cleft lip and palate deformities were treated for rare facial clefts. There were three midline clefts (Tessier no. 0 cleft, n = 1; Tessier no. 14 cleft, n = 2), four oblique facial clefts (Tessier no. 3 cleft, n = 2; Tessier no. 5 cleft, n = 2), and seven lateral facial clefts (Tessier no. 7 cleft). Surgical treatment focused on cleft repair by soft-tissue reconstruction apart from two Tessier no. 14 clefts, in which the bony gap was also closed using bone grafts from the iliac crest. The postoperative course was uneventful except for one local wound infection that was treated successfully using oral antibiotics. This article summarizes the authors' experience with the surgical management of these malformations and considers the limitations under conditions of charity missions in developing countries. Furthermore, some rare forms of cleft formation are added to the existing literature.     

Facial clefts in Saudi Arabia: an epidemiologic analysis in 179 patients

One hundred and seventy-nine consecutive cases of facial clefts that were treated at the King Khalid University Hospital, in Riyadh, Saudi Arabia, were analyzed for an epidemiologic study. Isolated cleft lip was present in 38 percent, cleft of lip and palate in 37.4 percent, and cleft of the posterior palate in only 22.4 percent. There was a male preponderance in all types. In cases of cleft lip with or without cleft palate, the more commonly affected side was the left, followed by bilateral cases. Associated malformations were present in 13.4 percent. A positive family history was found in 26.8 percent of cases. A significant number of patients (7.8 percent) were first seen at more than 10 years of age. The incidence of facial clefts at this hospital was 0.3 per 1000 live births, computed over a period of 6 years. This incidence is significantly lower than that reported from European and Far Eastern countries.     

Pai syndrome: first patient with agenesis of the corpus callosum and literature review

BACKGROUND: Pai syndrome (PS) is a rare regional developmental defect of the face, mainly characterized by the variable association of midline cleft of the upper lip (MCL), duplicated maxillary median frenulum, and midline facial cutaneous and midanterior alveolar process polyps. Its entire clinical spectrum is still poorly delineated and the etiology remains unknown. CASE: We describe a 1-month-old boy presenting with MCL, left nostril hamartomatous mass, midline pedunculated polyp originating from the columella base, midline alveolar cleft, duplication of the upper median frenulum, unilateral persistent papillary membrane, lipoma of the corpus callosum, and additional minor facial dysmorphism. This patient also presents with agenesis of the corpus callosum, which has never been reported in PS. Literature review was carried out comparing clinical data of the 20 previously published patients with those observed in the present case. CONCLUSIONS: The minimum diagnostic criteria for PS has been fixed in one or more hamartomatous nasal polyps plus MCL (with or without cleft alveolus) and/or midanterior alveolar process congenital polyp. Additional common ancillary findings include duplicated median maxillary frenulum, hypertelorism, nasal cleft, midfrontal skin tags, and ocular and CNS structural abnormalities. However, mental retardation is only an occasional feature and seems to be related to coexisting conditions (such as chromosome imbalance). Literature review shows that PS is etiologically heterogeneous, as it may result from chromosome abnormalities and environmental/stochastic events, as well as de novo mutations.     

Left cleft lip predominance and genetic similarities of L line and CL/Fr strain mice

Newborn litters of the L line and CL/Fr and A/JFr strains were examined, and sex, frequency and type of cleft lip (left, right or bilateral) were recorded. Embryos and fetuses from crosses between these strains and line were collected on days 13 to 16 of gestation, and frequency and type of cleft lip recorded. Overall cleft frequencies in L X CL/Fr, CL/Fr X L, and CL/Fr X A/JFr crosses (female stated first) were similar, while in A/JFr X L (10.3%) they were significantly lower than in L X A/JFr (23.3%). The data suggested that the same maternal effect genes were present in CL/Fr and the related L line and absent from A/JFr. In the L, CL/Fr, and A/JFr newborns, there was a tendency for males to have higher frequencies of cleft lip and bilateral cleft lip and the latter was significant for L. Left cleft lip frequency was significantly higher than right for L and CL/Fr newborns and in embryos of the CL/Fr X L and L X CL/Fr cross. No significant differences in laterality were found in the A/JFr strain, A/JFr X L, L X A/JFr, and CL/Fr X A/JFr crosses. It was concluded that (1) the embryonic and maternal effect genes for cleft lip are similar or identical in CL/Fr and L; and (2) using data from the literature, there are additional genetic factor(s) increasing left cleft lip occurrence acting in the embryo, which are present in CL/Fr, L, A/HeJ, A/He, and A/St and absent from A/JKt, A/J, A/JFr, and A/WySn.