Palatal Growth Research Articles

Prenatal growth patterns of the upper jaw complex with implications for laryngeal echolocation in bats.

Craniofacial morphology is extremely diversified within bat phylogeny, however growth and development of the palate in bats remains unstudied. The formation of both midline and bilateral orofacial clefts in laryngeally echolocating bats, morphologically similar to the syndromic and non-syndromic cleft palate in humans, are not well understood. Developmental series of prenatal samples (n = 128) and adults (n = 10) of eight bat species (two pteropodids, four rhinolophoids, and two yangochiropterans), and two non-bat mammals (Mus musculus and Erinaceus amurensis), were CT-scanned and cranial bones forming the upper jaw complex were three-dimensionally visualised to assess whether differences in palate development can be observed across bat phylogeny. Volumetric data of bones composing the upper jaw complex were measured to quantify palate growth. The premaxilla is relatively reduced in bats compared to other mammals and its shape is heterogeneous depending on the presence and type of orofacial cleft across bat phylogeny. The palatine process of premaxillary bones is lacking in pteropodids and yangochiropterans, whereas the premaxilla is a mobile structure which is only in contact caudally with the maxilla by a fibrous membrane or suture in rhinolophoids. In all bats, maxillary bones progressively extend caudally and palatine bones, in some cases split into three branches, extend caudally so that they are completely fused to another one medially prior to the birth. Ossification of the vomer and fusion of the maxillary and palatine bones occur earlier in rhinolophoids than in pteropodids and yangochiropterans. The vomer ossifies bilaterally from two different ossification centres in yangochiropterans, which is uncommon in other bats and non-bat mammals. Analysis of ontogenetic allometric trajectories of the upper jaw complex revealed faster development of maxillary, vomer, and palatine bones in yangochiropterans compared to other bats, especially rhinolophoids. Ancestral state reconstruction revealed that yangochiropterans have a higher magnitude of change in ossification rate compared to other bats and E. amurensis a lower magnitude compared to M. musculus and bats. This study provides new evidence of heterochronic shifts in craniofacial development and growth across bat phylogeny that can improve understanding of the developmental differences characterising nasal and oral emission strategies.

In utero nicotine exposure affects murine palate development.

Despite data linking smoking to increased risk of fetal morbidity and mortality, 11% of pregnant women continue to smoke or use alternative nicotine products. Studies confirm that nicotine exposure during pregnancy increases the incidence of birth defects; however, little research has focused on specific anatomic areas based on timing of exposure. We aim to determine critical in utero and postnatal periods of nicotine exposure that affect craniofacial development, specifically palate growth. Malformation of the palatal structures can result in numerous complications including facial growth disturbance, or impeding airway function. We hypothesized that both in utero and postnatal nicotine exposure will alter palate development. We administered pregnant C57BL6 mice water supplemented with 100 μg/mL nicotine during early pregnancy, throughout pregnancy, during pregnancy and lactation, or lactation only. Postnatal day 15 pups underwent micro-computed tomography (μCT) analyses specific to the palate. Resultant pups revealed significant differences in body weight from lactation-only nicotine exposure, and μCT investigation revealed several dimensions affected by lactation-only nicotine exposure, including palate width, palate and cranial base lengths, and mid-palatal suture width. These results demonstrate the direct effects of nicotine on the developing palate beyond simple tobacco use. Nicotine exposure through tobacco alternatives, cessation methods, and electronic nicotine delivery systems (ENDS) may disrupt normal growth and development of the palate during development and the postnatal periods of breastfeeding. Due to the recent dramatic increase in the use of ENDS, future research will focus specifically on this nicotine delivery method.

Mll4 regulates postnatal palate growth and midpalatal suture development.

MLL4, also known as KMT2D, is a histone methyltransferase that acts as an important epigenetic regulator during various organogenesis programs. Mutations in the MLL4 gene are the major cause for Kabuki syndrome, a human developmental disorder that involves craniofacial birth defects, including anomalies in the palate. The purpose of this study was to investigate the role of Mll4 and the underlying mechanisms in the development and growth of the palate. We generated a novel conditional knockout (cKO) mouse model with tissue-specific deletion of Mll4 in the palatal mesenchyme. By using micro-computed tomography (CT), histology, cell mechanism assays, and gene expression analysis approaches, we examined the development and growth of the palate in the Mll4 -cKO mice. Gross intra-oral examination at adult stages showed that Mll4 -cKO mice had defects along the midline of the palate, which included disrupted rugae pattern and widened midpalatal suture. Micro-CT-based skeletal analysis in the adult mice revealed that the overall palate width was decreased in the Mll4 -cKO mice. By using whole-mount and histological staining approaches at perinatal stages, we identified that the midline defects started to appear as early as 1 day prior to birth, manifesting initially as a widened midpalatal suture, accompanied by increased cell apoptosis in the suture mesenchyme cells. Genome-wide analysis of mRNA expression in the midpalatal suture tissue showed that Mll4 is essential for timely expression of major genes for cartilage development, such as Col2a1 and Acan , at birth. These results were validated through immunofluorescence staining, confirming that the expression of chondrogenic markers Sox9 and Col2a1 were markedly decreased, whereas that of the osteogenic marker Runx2 remained unchanged, in the midpalatal suture of the Mll4 -cKO mice. Indeed, time-course histological analysis during postnatal palate growth revealed retardation in the development of the suture cartilage in the Mll4 -cKO mice. In parallel, time-course micro-CT analysis during postnatal palatogenesis confirmed a transverse growth deficit in the palate of the Mll4 -cKO mice. Taken together, our results show that Mll4 is essential for timely occurrence of key cellular and molecular events that lead to proper midpalatal suture development and palate growth.

Palatal segment contributions to midfacial anterior-posterior growth.

Anterior-posterior (A-P) elongation of the palate is a critical aspect of integrated midfacial morphogenesis. Reciprocal epithelial-mesenchymal interactions drive secondary palate elongation that is coupled to the periodic formation of signaling centers within the rugae growth zone (RGZ). However, the relationship between RGZ driven morphogenetic processes, the differentiative dynamics of underlying palatal bone mesenchymal precursors, and the segmental organization of the upper jaw has remained enigmatic. A detailed ontogenetic study of these relationships is important, because palatal segment growth is a critical aspect of normal midfacial growth, can be modified to produce dysmorphology, and is a likely basis for evolutionary differences in upper jaw morphology. Variation in palatal-segment specific growth may also underlie known differences in palatal segment proportions between inbred mouse strains. We completed a combined whole mount gene expression and morphometric analysis of normal murine palatal growth dynamics and their association with palatal segment elongation and resulting upper jaw morphology. Our results demonstrated that the first formed palatal ruga (ruga 1), found just posterior to the RGZ, maintained an association with important nasal, neurovascular and palatal structures throughout early midfacial development; suggesting that these features are positioned at a proximal source of embryonic midfacial directional growth. Our detailed characterization of midfacial morphogenesis revealed a one-to-one relationship between palatal segments and upper jaw bones during the earliest stages of palatal elongation. Growth of the maxillary anlage within the anterior secondary palate is uniquely coupled to RGZ-driven morphogenesis that more than doubles the length of this palatal segment prior to palatal shelf fusion. Our results also demonstrate that the future maxillary-palatine suture, approximated by the position ruga 1 and consistently associated with the palatine anlage, forms predominantly via the posterior differentiation of the maxilla within the expanding anterior secondary palate. Our complementary ontogenetic comparison of three inbred mouse strains identified small but significant strain-specific differences in early embryonic palatal segment contributions to the upper jaw. Although early palatal segment specific growth is not primarily responsible for adult differences in upper jaw morphology between these strains, our ontogenetic series of measurements provide a useful foundation for understanding the impact of background genetic effects on facial shape and elongation. In combination, our results provide a novel and particularly detailed picture of the earliest spatiotemporal dynamics of intramembranous midfacial skeletal specification and differentiation within the context of the surrounding palatal segment A-P elongation and associated rugae formation.

Across-surface distances after one- and two-stage palatoplasty in children with oral cleft.

The goal of this study was to digitally evaluate the development of maxillary dental arches of children with unilateral cleft lip and palate treated with one- and two-stage palatal closure. One hundred and sixty-eight digitized dental models of cheiloplasty and one-stage palatoplasty (G1) and cheiloplasty and two-stage palatoplasty (G2) were evaluated at preoperative time 1 (T1), preoperative time 2 (T2), and postoperative (T3). The following surface distances were evaluated: across surface distance; cleft widths anterior (P-P') and posterior (U-U') cleft widths, intercanine width (C-C'), and intertuberosity width (T-T'); smallest (P'-T') and largest (P-T) segment lengths; and smallest (C'-D') and largest (C-D) segment cleft depths. In G1, P-P', U-U', and C-C' reduced at T2, unlike P'-T' (P<0.05). P-T and C'-D' distances increased at T3 (P<0.05), while C-D increased at all stages (P<0.001). In G2, U-U' and C-C' reduced at T2 (P<0.05), while P'-T', P-T, C'-D', and C-D' increased at T3 (P<0.001). In an intergroup analysis of growth rate, G2 showed higher growth percentages compared to G1, in which C'-D' was significant (P=0.038). Furthermore, C'-D' presented a coefficient of determination of 0.076 (P=0.039). In conclusion, dental arch development is influenced by the rehabilitation protocol. However, in the sample evaluated, the comparison suggested that individuals whose palate was operated on in two stages had the most favorable palatal growth.

Respiratory Fluid Mechanics of the Effect of Mouth Breathing on High-Arched Palate: Computational Fluid Dynamics Analyses.

Computational fluid dynamics (CFD) was introduced into the study of palate growth and development to explain the mechanisms by which mouth breathing affects palate descent from an aerodynamic perspective. Cone beam computed tomography (CBCT) data were used to reconstruct a 3-dimensional model during natural mouth breathing of a volunteer. The model was imported into CFX 19.0 for numerical simulation of nasal breathing, mouth-nasal breathing, and mouth breathing. The pressure in the oronasal cavity was analyzed, and the pressure difference between the oral and nasal surfaces of hard palate under different breathing patterns was calculated. CFD can be used to simulate the stress on the oral and nasal surfaces of the palate under different breathing patterns. The pressure differences and resultant force between the oral and nasal surfaces of the hard palate during nasal inspiration, nasal expiration, mouth-nasal inspiration, mouth-nasal expiration, mouth inspiration, and mouth expiration were 0Pa, 4Pa (upward), 9Pa (upward), 3Pa (downward), 474Pa (upward), 263Pa (downward), respectively, and 87.99N (upward), 88.03N (upward), 88.01N (upward), 88.01N (upward), 88.05N (upward), 87.94N (upward), respectively. Therefore, CFD can be used to investigate the growth and development of the palate. When the volunteer opened his mouth, the pressure difference between the oral and nasal surfaces of the hard palate was about 88N upward regardless of whether there was airflow in the mouth. The reversal of the direction of the force on the hard palate may be one of the factors affecting its descent of it.

Palatal surface development from 6 years of age to early adulthood: data modelling using 3D geometric morphometrics.

The study followed the modelling of postnatal growth of a healthy palate of the Central European (Czech) population sample based on transverse data on sex and age from 6 to 19 years. Digitised 3D models of 212 healthy palatal surfaces were evaluated using 3D geometric morphometrics and superimpositions. The individuals were grouped based on age (preschool, younger and older school age, younger and older adolescents, young adults) and sex (♂ n = 101, ♀ n = 111). Female palatal development was non-linear and was interrupted between the 10-12 years and then proceeded intensively until the age of 15 when it ceased. In contrast, male-modelled growth was consistent throughout the follow-up and continued linearly until at least 19 years of age. The palate did not widen further with increasing age, and primarily palatal vaulting and heightening were found. The characteristics and distribution of areas with extensive modelled growth changes were comparable in females and males, as confirmed by the location of principal components (PC1 and PC2) within modal space and growth trajectories. The extent of sexual dimorphism increased from 15 years of age due to pubertal spurt combined with earlier completion of palatal development in females. The study showed modelled healthy palatal development from 6 years of age to early adulthood, which might be utilised as reference standards for the Central European population sample. The comparison of normal reference subjects with patients with cranio-maxillo-facial dysmorphologies represents the first step in diagnosing and establishing effective therapy.

Growth of the hard palate between the ages of 6 and 10 years: A longitudinal study

Several studies have found that the shape of the palate can affect articulation of speech sounds, but not much information is available characterizing the three-dimensional shape of the palate. This is especially important in children, since their speech is maturing at the same time that the palate is still growing. This study examines the longitudinal growth of the palate from 8 children between the ages of 6 and 10 years, based on high-resolution three-dimensional digitized palate impressions. Measures of palate width, height, depth, and symmetry were derived from three anatomically defined points: the marginal gingiva between the front teeth, and between the second premolar and the first molar on both sides. While palate height was most difficult to measure accurately, it was also most highly correlated with age (R2 = .42, p&amp;lt;.001), while palate depth, width, and symmetry were poorly correlated with age (R2&amp;lt;.07, p&amp;gt;.17). Age and standing height were strongly correlated (R2 = .77, p&amp;lt;.001). At the individual level, palate height appeared to grow linearly with age, while the growth of palate width and depth was nonlinear and even non-monotonic, indicating a complex interaction between growth and the ongoing structural rearrangement of dentition in this age group. [Work supported, in part, by the NSF.]

A Novel Homozygous Missense Variant in the LRRC32 Gene Is Associated With a New Syndrome of Cleft Palate, Progressive Vitreoretinopathy, Growth Retardation, and Developmental Delay.

Cleft lip and/or cleft palate are a common group of birth defects that further classify into syndromic and non-syndromic forms. The syndromic forms are usually accompanied by additional physical or cognitive abnormalities. Isolated cleft palate syndromes are less common; however, they are associated with a variety of congenital malformations and generally have an underlying genetic etiology. A single report in 2019 described a novel syndrome in three individuals, characterized by cleft palate, developmental delay and proliferative retinopathy due to a homozygous non-sense mutation in the LRRC32 gene encoding glycoprotein A repetitions predominant (GARP), a cell surface polypeptide crucial for the processing and maturation of transforming growth factor β (TGF-β). We describe a patient who presented with cleft palate, prenatal and postnatal severe growth retardation, global developmental delay, dysmorphic facial features and progressive vitreoretinopathy. Whole exome sequencing (WES) revealed a very rare homozygous missense variant in the LRRC32 gene, which resulted in substitution of a highly conserved isoleucine to threonine. Protein modeling suggested this variant may negatively affect GARP function on latent TGF-β activation. In summary, our report further expands the clinical features of cleft palate, proliferative retinopathy and developmental delay syndrome and emphasizes the association of LRRC32 pathogenic variants with this new syndrome.

Interrelationship Between Microstructure &amp; Macrostructure in the Growing Hard Palate

Bone strength is the result of microstructure (material properties) and macrostructure (size and shape), and deficiencies in either can produce skeletal fragilities with increased likelihood of injury. The micro‐ and macro‐architecture work together during re/modeling, ensuring that bone is resistant to repetitive loading and fracture. Bone is particularly responsive to loading during the rapid growth occurring in early life. Within the craniofacial complex, the hard palate is a unique structure that undergoes continuous loading due to resting/active tongue pressure and bite force. Because of this, palatal growth is theorized to drive midfacial growth. The aim of this study is to investigate longitudinal changes in palatal micro‐ and macro‐structure in the context of a perturbation to type I collagen (Col1). Col1 is the structural protein that forms osteoid (the precursor to bone), forms a scaffold for bone mineralization, and determines bone toughness. Here we use the OIM mouse (B6C3FE a/a‐Col1a2OIM/J), a strain with a Col1 mutation. We hypothesize that OIM and unaffected wild‐type (WT) mice will be most similar in bone micro‐ and macro‐structure in regions of the palate that experience high loading and therefore necessitate high rates of bone modeling or remodeling to form a structure which can withstand the stress.Mice were micro‐CT scanned at two timepoints: week 4 (juvenile) and week 16 (adult). BMD was collected at 3 regions (anterior, mid, and posterior palate). Mann‐Whitney U tests were used to compare BMD between genotypes. 28 fixed and 10 sliding landmarks were placed across the palate. Geometric morphologic analyses were conducted to determine variation between genotypes in overall shape and curvature throughout growth.Average BMD decreased along an anteroposterior gradient for all mice. While juvenile OIM mice had lower palate BMD than WT mice at all regions, adult OIM mice had significantly lower BMD at only the anterior and posterior regions but not the midpalate. Procrustes ANOVA revealed significant differences in palatal shape between the genotypes at both the juvenile (p=0.001) and adult (p=0.0015) stage. Principal component analyses revealed that juvenile OIM mice had a shorter anterior palate and broader palate compared to WT mice, while adult OIM mice had a shorter posterior palate than WT mice. OI mice had flatter palatal arches in the coronal plane as juveniles, and in the midsagittal plane as juveniles and adults.Results show significant differences in palatal BMD and morphology between genotypes throughout growth, with fewer significant differences at the adult stage. Increased loading of the anterior palate during incisive gnawing may result in the convergence of bone macrostructure among adult mice, while increased strain at the midpalatal suture may necessitate increased BMD even in the presence of a biomineralization defect. Further research is needed to understand the functional significance of the anteroposterior palatal gradient and its relation to soft tissue attachments, particularly given the transition in oral behaviors between juveniles and adults.

Dental Arch Changes with Two Different Trans-Palatal Arch

Background: Rapid maxillary expansion (RME) is a dentofacial orthopedic treatment often used to treat patients with narrow palate and transverse maxillary growth deficiency. Introduction: This treatment leads to correction of posterior dental crossbites, coordination of the upper and lower arches and gaining arch perimeter in patients with tooth size/arch size discrepancies. To stabilize the results obtained with RME and to limit or avoid the relapse, the use of Transpalatal Arch (TPA) would be recommended. Objectives: The aim of this study is to evaluate short-term maxillary changes in patients treated with RME followed by TPA with and without palatal arms. Materials and Methods: 30 patients, 16 females and 14 males (mean age of 9.7 yrs ranging between 9 and 12), were treated by expansion with palatal Hyrax-type expander. After this period, it was removed and one of the two different types of TPA was used. The two different TPA were a 0.036-inch stainless steel wire with a loop directed mesially in the middle, one maintained the original design (TPA), the second one presented arms extended to canines (TPAa). Dental casts were collected for each patient for each treatment step; before (T0), after expansion (T1) and after TPA or TPAa (T2). To assess differences in dental arches after the two treatment phases, three-dimensional (3D) dental casts were used to make more predictable measurements compared with caliper measurements that presented intra-examiner and inter-examiner measurements errors. Results: In TPAa group, differences between the value at the end of the retention period and at the end of expansion showed no statistical significance. Instead in TPA group, the same measurements suggested a reduction of value in almost all dental transverse diameters. Statistically significant differences in dental measurements were found between TPAa and TPA. Conclusion: Results confirm the hypothesis that TPAa can allow to better maintain dental transverse dimensions.

The involvement of hormone-sensitive lipase in all-trans retinoic acid induced cleft palate.

Abnormally high concentrations of all-trans retinoic acid (atRA) induce cleft palate, which is accompanied by abnormal migration and proliferation of mouse embryonic palatal mesenchyme (MEPM) cells. Hormone-sensitive lipase (HSL) is involved in many embryonic development processes. The current study was designed to elucidate the mechanism of HSL in cleft palate induced by atRA. To establish a cleft palate model in Kunming mice, pregnant mice were administered atRA (70 mg/kg) by gavage at embryonic Day 10.5 (E10.5). Embryonic palates were obtained through the dissection of pregnant mice at E15.5. Hematoxylin and eosin (H&E) staining was used to evaluate growth changes in the palatal shelves. The levels of HSL in MEPM cells were detected by immunohistochemistry, quantitative real-time reverse transcription-polymerase chain reaction (qRT‒PCR) and western blotting. RNAi was applied to construct vectors expressing HSL small interference RNAs (siRNAs). The vectors were transfected into MEPM cells. Cell proliferation and migration were evaluated by the cell counting kit-8 (CCK-8) assay and wound healing assay, respectively. The palatal shelves in the atRA group had separated at E15.5 without fusing. In MEPM cells, the expression of HSL was reversed after atRA treatment, which caused cleft palate in vivo. In the atRA group, the proliferation of HSL siRNA-transfected cells was remarkably promoted, and the migration rate significantly increased in the HSL siRNA-transfected MEPM cells. These results suggested that HSL may be involved in cleft palate induced by atRA and that atRA enhances HSL levels to inhibit embryonic palate growth.

Digital Volumetric Monitoring of Palate Growth in Children With Cleft Lip and Palate.

This study aimed to evaluate longitudinally the volume of the dental arches in children with unilateral cleft lip and palate before and after the rehabilitative plastic surgeries. This is a longitudinal retrospective study was composed by 102 digitized dental casts of children with unilateral complete cleft lip (G1) and cleft lip and palate (G2). The palate volume was evaluated at 3 periods: preoperative (T1), postoperative 1 (T2), and postoperative 2 (T3). The intra- and inter-examiner reliability was analyzed by Wilcoxon test/Dahlberg formula and interclass correlation coefficient, respectively. The intragroup comparison was analyzed by Wilcoxon test and Friedman test followed by post-hoc Dunn test. Mann-Whitney test was applied for the intergroup comparison (α = 5%). G1 had a significant growth at T2 (P = 0.031). G2 demonstrated a positive development at T2, but decreased at T3 (P = 0.003). The intergroup analysis revealed that G2 showed a greater volume at T1 and T2 (P < 0.0001 and P = 0.0024, respectively). T2-T1 exhibited no statistically significant difference (P = 0.262). In conclusion, there was a volumetric increase in the dental arches after cheiloplasty followed by a reduction after palatoplasty. Further investigations are necessary to validate the preliminary results of the present study.

A Non-Compliant Slow expansion devise in orthodontics: A case report on NiTi palatal expansion appliance.

Normal palatal growth is nearly complete by age 6 and increasing inter-digitation of the suture makes separation difficult to achieve after puberty. Palatal expansion can be done with either slow/ rapid maxillary expansion. In this case report, maxillary expansion was done with NiTi palatal expander by making use of its unique properties like temperature transition and shape memory to produce an expansion of the maxilla. Keywords: NiTi palatal expansder, shape memory, temperature transition

Influence of Bone-Borne Trans-Sutural Distraction Osteogenesis Therapy on the Hard Palate of Growing Children With Cleft Lip and Palate.

The efficacy of trans-sutural distraction osteogenesis therapy (TSDO) in treating midfacial hypoplasia in children with cleft lip and palate has been confirmed. However, few studies have reported that changes occur in the palate after TSDO treatment. To study the effect of TSDO on palatal morphology and its relative position in the craniofacial region, we retrospectively collected and measured the computed tomography images of 29 growing children with cleft lip and palate and midfacial hypoplasia, before and after TSDO. The results showed that the length and height of the palate did not change significantly, but the width and arch length increased, and the anterior area was more pronounced than the posterior area, with the median palatine suture still centered without obvious deviation. This suggests lateral palate growth after distraction, most likely around the median palatine suture. The distance from the palate to the cranial base also increased after distraction, and the anterior nasal spine moved forward, whereas the palate rotated by an average of 10.04° downward from the center of the anterior nasal spine. The increasing distance between the palate and cranial base may result from the growth of the nasal bone or the skull base. The oropharyngeal airway volume was also increased by an average of 2256.36 mm3, which may be beneficial to children's ventilatory function. In conclusion, TSDO therapy has influence on patients' palatal morphology and position, which should be considered before surgery.

Essential role of Msx1 in regulating anterior-posterior patterning of the secondary palate in mice

Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis; however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription repressor required for palate development. Here, we investigate the role of Msx1 in regional patterning of the secondary palate. The Wnt1-Cre-mediated expression of Msx1 (RosaMsx1Wnt1-Cre) throughout the palatal mesenchyme leads to cleft palate in mice, associated with aberrant cell proliferation and cell death. Osteogenic patterning of the hard palate in RosaMsx1Wnt1-Cre mice is severely impaired, as revealed by a marked reduction in palatine bone formation and decreased expression of the osteogenic regulator Sp7. Overexpression and knockout of Msx1 in mice show that the transcription repressor promotes the expression of the anterior palate-specific Alx1 but represses the expression of the medial-posterior palate genes Barx1, Meox2, and Tbx22. Furthermore, Tbx22 constitutes a direct Msx1 target gene in the secondary palate, suggesting that Msx1 can directly repress the expression of medial-posterior specific genes. Finally, we determine that Sp7 is downstream of Tbx22 in palatal mesenchymal cells, suggesting that a Msx1/Tbx22/Sp7 axis participates in the regulation of palate development. Our findings unveil a novel role for Msx1 in regulating the anterior-posterior growth and patterning of the secondary palate.

A de novo 10q11.23q22.1 deletion detected by whole genome mate-pair sequencing: a case report

BackgroundInterstitial deletions of chromosome band 10q11-q22 was a genomic disorder distinguished by developmental delay, congenital cleft palate and muscular hypotonia. The phenotypes involved were heterogeneous, hinge on the variable breakpoints and size.Case presentationHere, we presented a patient with soft palate cleft, growth and development delay. The patient was a 2 years and 5 months girl who was not able to walk unless using a children’s crutches to support herself. Whole-exome sequencing (WES) and whole-genome mate-pair sequencing (WGMS) were both performed by next generation sequencing (NGS). A 20.76 Mb deletion at 10q11.23q22.1 (seq[GRCh37/hg19]del(10)(50,319,387-71,083,899) × 1) was revealed by the WGMS, which was verified as de novo by quantitative polymerase chain reaction (QPCR).ConclusionChildren with 10q11-q22 deletions greater than 20 MB have never been reported before, and we are the first to report and provide a detailed clinical phenotype, which brings further knowledge of 10q11-q22 deletions.

The Fibroblast Growth Factor 9 (Fgf9) Participates in Palatogenesis by Promoting Palatal Growth and Elevation.

Cleft palate, a common global congenital malformation, occurs due to disturbances in palatal growth, elevation, contact, and fusion during palatogenesis. The Fibroblast growth factor 9 (FGF9) mutation has been discovered in humans with cleft lip and palate. Fgf9 is expressed in both the epithelium and mesenchyme, with temporospatial diversity during palatogenesis. However, the specific role of Fgf9 in palatogenesis has not been extensively discussed. Herein, we used Ddx4-Cre mice to generate an Fgf9–/– mouse model (with an Fgf9 exon 2 deletion) that exhibited a craniofacial syndrome involving a cleft palate and deficient mandibular size with 100% penetrance. A smaller palatal shelf size, delayed palatal elevation, and contact failure were investigated to be the intrinsic causes for cleft palate. Hyaluronic acid accumulation in the extracellular matrix (ECM) sharply decreased, while the cell density correspondingly increased in Fgf9–/– mice. Additionally, significant decreases in cell proliferation were discovered in not only the palatal epithelium and mesenchyme but also among cells in Meckel’s cartilage and around the mandibular bone in Fgf9–/– mice. Serial sections of embryonic heads dissected at embryonic day 14.5 (E14.5) were subjected to craniofacial morphometric measurement. This highlighted the reduced oral volume owing to abnormal tongue size and descent, and insufficient mandibular size, which disturbed palatal elevation in Fgf9–/– mice. These results indicate that Fgf9 facilitates palatal growth and timely elevation by regulating cell proliferation and hyaluronic acid accumulation. Moreover, Fgf9 ensures that the palatal elevation process has adequate space by influencing tongue descent, tongue morphology, and mandibular growth.

Palatal growth changes in newborns with unilateral and bilateral cleft lip and palate from birth until 12 months after early neonatal cheiloplasty using morphometric assessment.

To compare palatal growth changes in infants with complete unilateral (UCLP) or bilateral (BCLP) cleft lip and palate during the first year of life. Upper dental arches of 68 neonates with UCLP and BCLP were evaluated using 2D and 3D morphometry based on dental casts obtained in two age categories (T0 before early neonatal cheiloplasty-UCLP 4 ± 3days, BCLP 6 ± 5days; T1 before palatoplasty-UCLP 10 ± 2months, BCLP 12 ± 3months). Intensive palatal growth was manifested in both directions of the palate. Palatal growth in the anterior direction was not restricted, despite the intercanine (CC´) and anterior (LL´) widths being significantly narrowed in the BCLP group (CC´ p = 0.019, LL´ p = 0.009). The posterior dental arches were significantly enlarged (UCLP p ≤ 0.001; BCLP p ≤ 0.001). The negative effect of cleft severity on palatal length was not confirmed (p = 0.802). Variability of the palate was immense mainly in BCLP infants (T0); however, it decreased in both cleft types, confirming the formative effect of palatal growth leading to alveolar cleft closure (UCLP p ≤ 0.001; BCLP p = 0.006 on the right, 0.005 on the left). Both analyzed cleft groups (UCLP, BCLP) grew favorably during the first year of life, and the palatal growth was not limited in any direction. Geometric morphometry allowed a comprehensive analysis of the palate, which can contribute to the improvement of surgical methods.

Orofacial clefts: treatment based on a multidisciplinary approach

Orofacial clefts: treatment based on a multidisciplinary approach