Proteomic analysis illustrates the potential involvement of motor proteins in cleft palate development.

Cleft palate (CP) is a congenital condition characterized by a complex etiology and limited diagnostic and therapeutic options. In this study, we delved into the molecular mechanisms associated with retinoic acid (RA)-induced CP in Kun Ming mice. Proteomic analysis of control and RA-induced CP samples at embryonic day 15.5 revealed 25 upregulated and 19 downregulated proteins. Further analysis identified these differentially expressed proteins (DEPs) as being involved in extracellular matrix organization, actin cytoskeleton, and myosin complex. Moreover, these DEPs were found to be enriched in pathways related to motor protein activity and extracellular matrix-receptor interaction. Protein-protein interaction network analysis identified 10 hub proteins, including motor proteins and ECM-related proteins, which exhibited higher expression levels in CP compared to control tissues. These findings provide insights into the molecular mechanisms underlying CP and highlight potential targets for diagnostic and therapeutic purposes.

Peripheral giant cell granuloma in a child with ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome: a case report.

BACKGROUND: Ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome mainly affects ectodermal and mesodermal tissues. It is usually manifested as split hands and feet, ectodermal dysplasia, and orofacial clefting, along with other signs and symptoms. A multidisciplinary approach to treatment is required, in which dentists play an important role in identifying and treating various oral conditions that may be genetically linked to or may be the result of EEC syndrome. CASE PRESENTATION: The present case describes the oral condition of a young child suffering from EEC syndrome and presenting with peripheral giant cell granuloma (PGCG) in the mandibular anterior region. After obtaining a thorough medical and family history and a clinical examination, the lesion was surgically excised under local anesthesia. The patient was followed up at periodic intervals for the next twenty four months, during which no recurrence of the lesion was observed. CONCLUSION: This report highlights the role of a dentist in the management of the oral conditions of patients suffering from EEC syndrome.

Three-dimensional analysis of palatal morphology and PAS in patients with cleft lip and palate prior to orthodontic treatment.

BACKGROUND: Since many different conclusions of craniofacial anomalies and their relation to the posterior airway space coexist, this comparative clinical study investigated the palatal morphology concerning volumetric size, posterior airway space dimension and the adenoids of patients with and without a cleft before orthodontic treatment. METHODS: Three-dimensional intraoral scans and cephalometric radiographs of n = 38 patients were used for data acquisition. The patients were divided into three groups: unilateral cleft lip and palate (n = 15, 4 female, 11 male; mean age 8.57 ± 1.79 years), bilateral cleft lip and palate (n = 8, 0 female, 8 male; mean age 8.46 ± 1.37 years) and non-cleft control (n = 15, 7 female, 8 male; mean age 9.03 ± 1.02 years). The evaluation included established procedures for measurements of the palatal morphology and posterior airway space. Statistics included Shapiro-Wilk-Test and simple ANOVA (Bonferroni) for the three-dimensional intraoral scans and cephalometric radiographs. The level of significance was set at p < 0.05. RESULTS: The palatal volume and cephalometric analysis showed differences between the three groups. The palatal volume, the superior posterior face height and the depth of the bony nasopharynx of patients with cleft lip and palate were significantly smaller than for non-cleft control patients. The superior posterior face height of bilateral cleft lip and palate patients was significantly smaller than in unilateral cleft lip and palate patients (BCLP: 35.50 ± 2.08 mm; UCLP: 36.04 ± 2.95 mm; p < 0.001). The percentage of the adenoids in relation to the entire nasopharynx and the angle NL/SN were significantly bigger in patients with cleft lip and palate than in the non-cleft control. In particular, the palatal volume was 32.43% smaller in patients with unilateral cleft lip and palate and 48.69% smaller in patients with bilateral cleft lip and palate compared to the non-cleft control. CONCLUSIONS: Skeletal anomalies relate to the dimension of the posterior airway space. There were differences among the subjects with cleft lip and palate and these without a cleft. This study showed that the morphology of the palate and especially transverse deficiency of the maxilla resulting in smaller palatal volume relates to the posterior airway space. Even the adenoids seem to be affected, especially for cleft lip and palate patients.

Craniofacial morphological variability in orthodontic patients with non-syndromic orofacial clefts: an approach using geometric morphometrics.

OBJECTIVES: Orofacial clefts are complex congenital anomalies that call for comprehensive treatment based on a thorough assessment of the anatomy. This study aims to examine the effect of cleft type on craniofacial morphology using geometric morphometrics. MATERIALS AND METHODS: We evaluated lateral cephalograms of 75 patients with bilateral cleft lip and palate, 63 patients with unilateral cleft lip and palate, and 76 patients with isolated cleft palate. Generalized Procrustes analysis was performed on 16 hard tissue landmark coordinates. Shape variability was studied with principal component analysis. In a risk model approach, the first nine principal components (PC) were used to examine the effect of cleft type. RESULTS: We found statistically significant differences in the mean shape between cleft types. The difference is greatest between bilateral cleft lip and palate and isolated cleft palate (distance of means 0.026, P = 0.0011). Differences between cleft types are most pronounced for PC4 and PC5 (P = 0.0001), which together account for 10% of the total shape variation. PC4 and PC5 show shape differences in the ratio of the upper to the lower face, the posterior mandibular height, and the mandibular angle. CONCLUSIONS: Cleft type has a statistically significant but weak effect on craniofacial morphological variability in patients with non-syndromic orofacial clefts, mainly in the vertical dimension. CLINICAL RELEVANCE: Understanding the effects of clefts on craniofacial morphology is essential to providing patients with treatment tailored to their specific needs. This study contributes to the literature particularly due to our risk model approach in lieu of a prediction model.

Comparison of temporomandibular joint osseous components in unilateral and bilateral cleft lip and palate patients and normal controls: A CBCT study.

OBJECTIVE: The objective of this study was to conduct a comparative analysis of the components of the temporomandibular joint in individuals with unilateral, bilateral cleft lip and palate (CLP), and in healthy individuals, utilizing cone beam computed tomography (CBCT) images. METHOD AND MATERIAL: The present study employed a cross-sectional design and recruited participants aged 18 to 30 years. The participants were categorized into three groups: a control group consisting of 36 individuals without any cleft, a group of 35 patients with unilateral cleft lip and palate (UCLP), and a group of 15 patients with bilateral cleft lip and palate (BCLP). The analysis of CBCT images encompassed the examination of condylar height and angulation, glenoid fossa height and width, articular eminence inclination, as well as joint spaces across all three groups. The Kruskal-Wallis and Mann-Whitney tests were employed to ascertain the significant differences among the three groups. RESULTS: The UCLP and BCLP groups demonstrated a statistically significant reduction in condylar height and articular eminence inclination in comparison to the control group. Furthermore, a significant difference in the width of the glenoid fossa was seen between the group with clefts and the control group. CONCLUSION: The CBCT images showed significant differences in several aspects of the temporomandibular joint, including condylar height, articular eminence inclination, and glenoid fossa width, in individuals with cleft palate. These abnormalities can contribute to the development of temporomandibular joint diseases. Therefore, recognizing these distinctions can help prevent further deterioration and progression of temporomandibular disorders (TMD) in CLP patients.

Mexican patient with Ellis-van Creveld syndrome and cleft palate: Importance of functional hemizygosity and phenotype expansion.

BACKGROUND: Ellis-van Creveld syndrome (EvCS) is a chondroectodermal dysplasia caused by germline pathogenic variants in ciliary complex subunit 1 and 2 genes (EVC, EVC2) on chromosome 4p16.2. This disease has a broad phenotype, and there are few described phenotype-genotype correlations. METHODS: Ethical Compliance: Written informed consent was obtained from the parents. Here, we report a genetically confirmed Mexican patient with EvCS having two inherited pathogenic variants in trans in EVC2: c.[1195C>T];[2161delC]. RESULTS: This patient allowed a genotypic-phenotypic comparison with another Mexican subject who presented a more attenuated phenotype; furthermore, our patient also presented cleft palate, a rarely reported feature. CONCLUSION: Our case shows the importance of comparing functional hemizygosity between patient's phenotypes when they share a variant, and our case also supports the association of alterations in the palate as part of the EvCS phenotype.

Retinoic Acid Upregulates METTL14 Expression and the m6A Modification Level to Inhibit the Proliferation of Embryonic Palate Mesenchymal Cells in Cleft Palate Mice.

Cleft palate only (CPO) is one of the most common craniofacial birth defects. Environmental factors can induce cleft palate by affecting epigenetic modifications such as DNA methylation, histone acetylation, and non-coding RNA. However, there are few reports focusing on the RNA modifications. In this study, all-trans retinoic acid (atRA) was used to simulate environmental factors to induce a C57BL/6J fetal mouse cleft palate model. Techniques such as dot blotting and immunofluorescence were used to find the changes in m6A modification when cleft palate occurs. RNA-seq and KEGG analysis were used to screen for significantly differentially expressed pathways downstream. Primary mouse embryonic palate mesenchymal (MEPM) cells were successfully isolated and used for in vitro experimental verification. We found that an increased m6A methylation level was correlated with suppressed cell proliferation in the palatine process mesenchyme of cleft palate mice. This change is due to the abnormally high expression of m6A methyltransferase METTL14. When using siRNAs and the m6A methyltransferase complex inhibitor SAH to interfere with the expression or function of METTL14, the teratogenic effect of atRA on primary cells was partially alleviated. In conclusion, METTL14 regulates palatal mesenchymal cell proliferation and cycle-related protein expression relies on m6A methylation modification, affecting the occurrence of cleft palate.

Qualitative and quantitative analysis of MED12 c.887G>A causing both missense and splicing variants in X-linked Ohdo syndrome.

The phenotypes associated with MED12 pathogenic variants are diverse. Male patients usually have missense variants, but the effects of base substitutions on mRNA splicing have not been investigated. Here, we report a Japanese brother with intellectual disability, characteristic facial appearance with blepharophimosis, cleft palate, Fallot tetralogy, vesicoureteral reflux, and deafness. A known missense pathogenic variant was detected in MED12, NM_005120.3:c.887G>A p.(Arg296Gln), and X-linked Ohdo syndrome was diagnosed in combination with their phenotype. mRNA splicing of MED12 was evaluated qualitatively and quantitatively using long-range PCR-based targeted RNA sequencing (reverse transcribed long amplicon sequencing), and it was shown that this missense variant simultaneously causes aberrant splicing of the 42-bp in-frame deletion in exon 7, r.847_888del, which accounts for approximately 30% of the mRNAs in both siblings. The X chromosome inactivation study showed that the X chromosome carrying the mutant allele was 100% inactivated in the carrier mothers. mRNA level analysis is essential for the accurate interpretation of the effects of variants. In this case, the MED12 protein function may be reduced by more than just an amino acid substitution, resulting in the patients with the most severe phenotype of MED12-related syndrome in males.

Correlating Jaw Bone Growth and Nasal Morphology Among Adult Patients With Cleft Lip and Palate: A Retrospective Cephalometric Study.

This retrospective cross-sectional study reviewed adult patients with operated cleft lip and/or palate (CL/P) and normal control, and performed comprehensive craniofacial and nasal morphological analyses based on lateral cephalometric radiographs. Pearson or Spearman correlation coefficient assessed intraclass correlation. Seven hundred fifty-seven operated patients with CL/P, and 165 noncleft normal controls were enrolled. Among the normal and CL/P groups, S-N-A angle registered positive correlations with nasal base prominence (S-N'-Sn, degrees). Upper facial height (N-ANS, mm) had positive correlations with nasal dorsum length (N'-Prn, mm) and nasal bone length (N-Na, mm). Although in patients with bilateral cleft lip and palate, there were moderate negative correlations ( r =-0.541, P <0.05) with soft tissue facial profile angle (FH-N'Pog', degree) and nasolabial angle (Cm-Sn-ULA, degree). Correlation exists between the morphology of jaw bones and external nose among patients with CL/P. Maxillary sagittal insufficiency is associated with concave nasal profile, and maxilla height is associated with nasal length.

Early embryogenesis in CHDFIDD mouse model reveals facial clefts and altered cranial neurogenesis.

CDK13-related disorder, also known as congenital heart defects, dysmorphic facial features and intellectual developmental disorder (CHDFIDD) is associated with mutations in the CDK13 gene encoding transcription-regulating cyclin-dependent kinase 13 (CDK13). Here, we focused on the development of craniofacial structures and analyzed early embryonic stages in CHDFIDD mouse models, with one model comprising a hypomorphic mutation in Cdk13 and exhibiting cleft lip/palate, and another model comprising knockout of Cdk13, featuring a stronger phenotype including midfacial cleft. Cdk13 was found to be physiologically expressed at high levels in the mouse embryonic craniofacial structures, namely in the forebrain, nasal epithelium and maxillary mesenchyme. We also uncovered that Cdk13 deficiency leads to development of hypoplastic branches of the trigeminal nerve including the maxillary branch. Additionally, we detected significant changes in the expression levels of genes involved in neurogenesis (Ache, Dcx, Mef2c, Neurog1, Ntn1, Pou4f1) within the developing palatal shelves. These results, together with changes in the expression pattern of other key face-specific genes (Fgf8, Foxd1, Msx1, Meis2 and Shh) at early stages in Cdk13 mutant embryos, demonstrate a key role of CDK13 in the regulation of craniofacial morphogenesis.

DISP1 deficiency: Monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations.

PURPOSE: DISP1 encodes a transmembrane protein that regulates the secretion of the morphogen, Sonic hedgehog, a deficiency of which is a major cause of holoprosencephaly (HPE). This disorder covers a spectrum of brain and midline craniofacial malformations. The objective of the present study was to better delineate the clinical phenotypes associated with division transporter dispatched-1 (DISP1) variants. METHODS: This study was based on the identification of at least 1 pathogenic variant of the DISP1 gene in individuals for whom detailed clinical data were available. RESULTS: A total of 23 DISP1 variants were identified in heterozygous, compound heterozygous or homozygous states in 25 individuals with midline craniofacial defects. Most cases were minor forms of HPE, with craniofacial features such as orofacial cleft, solitary median maxillary central incisor, and congenital nasal pyriform aperture stenosis. These individuals had either monoallelic loss-of-function variants or biallelic missense variants in DISP1. In individuals with severe HPE, the DISP1 variants were commonly found associated with a variant in another HPE-linked gene (ie, oligogenic inheritance). CONCLUSION: The genetic findings we have acquired demonstrate a significant involvement of DISP1 variants in the phenotypic spectrum of midline defects. This underlines its importance as a crucial element in the efficient secretion of Sonic hedgehog. We also demonstrated that the very rare solitary median maxillary central incisor and congenital nasal pyriform aperture stenosis combination is part of the DISP1-related phenotype. The present study highlights the clinical risks to be flagged up during genetic counseling after the discovery of a pathogenic DISP1 variant.

Nasolabial morphological changes in patients with unilateral cleft lip and palate using a Korat-modified nasoalveolar moulding appliance with primary correction.

OBJECTIVE: The objective of this study is to measure the morphological changes of the nose and lip in patients with unilateral cleft lip and palate before and after cheiloplasty with primary rhinoplasty (primary correction) in conjunction with Korat-NAM usage. DESIGN: Longitudinal cohort study. SETTING: Cleft Center Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima, Thailand. SUBJECTS: Twenty-six patients with unilateral cleft lip and palate. INTERVENTIONS: Control group: only active obturator before primary correction. Experimental group: an active obturator and Korat-NAM I before primary correction. A customized endotracheal tube was retained in the nostril for 3 weeks before switching to Korat-NAM II for 1 year. MAIN OUTCOME MEASURES: Six measurements comprising nostril rim length, nostril height, nostril sill width, columella angle, vertical lip height, and horizontal lip length were measured from the patients' photographs. All measurements, except the columella angle, were reported as the cleft side/non-cleft side value ratio. Measurements were taken at the initial appointment, immediately before, 3 weeks after, and 1 year after primary correction. RESULTS: Nostril rim length ratio, nostril height ratio, nostril sill width ratio, columella angle on the cleft side, and vertical lip height ratio were improved using Korat-NAM before and 3 weeks after primary correction. Nostril rim length and height ratios were significantly better than the control group. CONCLUSIONS: Korat-NAM improved nose and lip morphology before primary correction. An overcorrection improved the nose and lip morphology on the cleft side. The nostril rim length and vertical lip height on the cleft side also improved with Korat-NAM II 1 year after primary correction.

Sagittal Growth Restriction of the Midface Following Isolated Cleft Lip Repair: A Systematic Review and Meta-Analysis.

Midface hypoplasia (MFH) is a long-term sequela of cleft lip and palate repair, and is poorly understood. No study has examined the aggregate data on sagittal growth restriction of the midface following repair of the lip, but not palate, in these patients.A systematic review of 3780 articles was performed. Twenty-four studies met inclusion criteria and 11 reported cephalometric measurements amenable to meta-analysis. Patients with Veau class I-III palatal clefts were included so long as they had undergone only lip repair. Groups were compared against both noncleft and unrepaired controls.Cephalometrics were reported for 326 patients (31.3% female). Noncleft controls had an average SNA angle of 81.25° ± 3.12°. The only patients demonstrating hypoplastic SNA angles were those with unilateral CLP with isolated lip repair (77.4° ± 4.22°). Patients with repaired CL had SNA angles similar to noncleft controls (81.4° ± 4.02°). Patients with unrepaired CLP and CL tended toward more protruding maxillae, with SNA angles of 83.3° ± 4.04° and 87.9° ± 3.11°, respectively. Notably, when comparing SNA angles between groups, patients with CLP with isolated lip repair had significantly more hypoplastic angles compared to those with repaired CL (P < .0001). Patients with CLP with isolated lip repair were also more hypoplastic than noncleft controls (P < .0001). In contrast, there was no significant difference between the SNA of patients with repaired CL and controls (P = .648).We found that cleft lip repair only appeared to contribute to MFH in the setting of concurrent cleft palate pathology, suggesting that scarring from lip repair itself is unlikely to be the predominant driver of MFH development. However, studies generally suffered from inadequate reporting of timing, technique, follow-up time, and cleft severity.

Symmetrical parapagus diprosopus: A comparative, computed tomographic, and pathoanatomical study of a new case in domestic pig.

BACKGROUND: Parapagus diprosopus are conjoined twins characterized by craniofacial duplication and only one body, representing one of the rarest types of these twins. Their occurrence has been recorded in different species of vertebrates, including humans, but few cases have been studied in domestic pigs. CASE: A pair of conjoined twin pigs was studied using x-rays, computed tomography, and necropsy. The abnormalities found were compared with those of the rare swine cases presented in the literature as well as with other species, and the different etiopathogenetic possibilities were addressed. The degree of duplication of the head bones decreased caudally, as did that of the structures of the central nervous system. In the two oral cavities, there was a complete cleft palate. All the cervical vertebrae and thoracic vertebrae up to T3 were partially duplicated. The heart and great vessels were normal, as were the other thoracic and abdominal organs. CONCLUSIONS: The conjoined twin pigs of this study are a case of parapagus diprosopus tetraophthalmus triotus, presenting the same pattern of abnormalities of human diprosopus and that of other species. The scarcity of detailed studies on craniofacial duplication in pigs and the lack of a definitive explanation on the etiology and pathogenesis of conjoined twins shows the need for further research and the publication of more cases.

Molecular Modeling Analysis Provides Genotype-Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the TP63 gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and differentiation. We present here a typical AEC case of a four-year-old girl with extensive skin erosions and erythroderma of the scalp and the trunk, and to a lesser extent of the limbs, nail dystrophy on the fingers and toes, xerophthalmia, a high-arched palate, oligodontia, and hypohidrosis. Mutation analysis of the TP63 gene detected a de novo missense mutation in exon 14 (c.1799G>T; p.Gly600Val). We discuss the phenotype-genotype correlation by presenting the clinical features of AEC in the patient, and the effect of the detected mutation in p63 structure and function using protein structural modeling, in view of similar cases in the literature. We performed a molecular modeling study in order to link the effect on the protein structure level of the missense mutation G600V. We noted that the introduction of the bulkier Valine residue in place of the slim Glycine residue caused a significantly altered 3D conformational arrangement of that protein region, pushing away the adjacent antiparallel α helix. We propose that the introduced locally altered structure of the G600V mutant p63 has a significant functional effect on specific protein-protein interactions, thus affecting the clinical phenotype.

The mechanisms governing mouse embryonic palate mesenchymal cells' proliferation associated with atRA-induced cleft palate in mice: insights from integrated transcriptomic and metabolomic analyses.

While exposure to high levels of all-trans retinoic acid (atRA) during pregnancy is known to suppress murine embryonic palate mesenchymal (MEPM) cells proliferation and to result in cleft palate (CP) development, the underlying mechanisms are poorly understood. Accordingly, this study was designed with the goal of clarifying the etiological basis for atRA-induced CP. A murine model of CP was established via the oral administration of atRA to pregnant mice on gestational day (GD) 10.5, after which transcriptomic and metabolomic analyses were performed with the goal of clarifying the critical genes and metabolites associated with CP development through an integrated multi-omics approach. MEPM cells proliferation was altered by atRA exposure as expected, contributing to CP incidence. In total, 110 genes were differentially expressed in the atRA treatment groups, suggesting that atRA may influence key biological processes including stimulus, adhesion, and signaling-related activities. In addition, 133 differentially abundant metabolites were identified including molecules associated with ABC transporters, protein digestion and absorption, mTOR signaling pathway, and the TCA cycle, suggesting a link between these mechanisms and CP. Overall, combined analyses of these transcriptomic and metabolomic results suggested that the MAPK, calcium, PI3K-Akt, Wnt, and mTOR signaling pathways are particularly important pathways enriched in the palatal cleft under conditions of atRA exposure. Together, these integrated transcriptomic and metabolomic approaches provided new evidence with respect to the mechanisms underlying altered MEPM cells proliferation and signal transduction associated with atRA-induced CP, revealing a possible link between oxidative stress and these pathological changes.

Characterizing the microbiota of cleft lip and palate patients: a comprehensive review.

Orofacial cleft disorders, including cleft lip and/or palate (CL/P), are one of the most frequently-occurring congenital disorders worldwide. The health issues of patients with CL/P encompass far more than just their anatomic anomaly, as patients with CL/P are prone to having a high incidence of infectious diseases. While it has been previously established that the oral microbiome of patients with CL/P differs from that of unaffected patients, the exact nature of this variance, including the relevant bacterial species, has not been fully elucidated; likewise, examination of anatomic locations besides the cleft site has been neglected. Here, we intended to provide a comprehensive review to highlight the significant microbiota differences between CL/P patients and healthy subjects in various anatomic locations, including the teeth inside and adjacent to the cleft, oral cavity, nasal cavity, pharynx, and ear, as well as bodily fluids, secretions, and excretions. A number of bacterial and fungal species that have been proven to be pathogenic were found to be prevalently and/or specifically detected in CL/P patients, which can benefit the development of CL/P-specific microbiota management strategies.

Analysis of exome data in a UK cohort of 603 patients with syndromic orofacial clefting identifies causal molecular pathways.

Orofacial cleft (OC) is a common congenital anomaly in humans, which has lifelong implications for affected individuals. This disorder can be classified as syndromic or non-syndromic depending on the presence or absence of additional physical or neurodevelopmental abnormalities, respectively. Non-syndromic cleft is often non-familial in nature and has a complex aetiology, whereas syndromic forms tend to be monogenic. Although individual OC-related syndromes have been frequently described in the medical literature, there has not been a comprehensive review across syndromes, thereby leaving a gap in our knowledge, which this paper aims to address. Six hundred and three patients with cleft-related human phenotype ontology terms were identified within the Deciphering Developmental Disorders study. Genes carrying pathogenic/likely pathogenic variants were identified and reviewed enabling a diagnostic yield of 36.5%. In total, 124 candidate genes for syndromic OC were identified, including 34 new genes that should be considered for inclusion in clinical clefting panels. Functional enrichment and gene expression analyses identified three key processes that were significantly overrepresented in syndromic OC gene lists: embryonic morphogenesis, protein stability and chromatin organization. Comparison with non-syndromic OC gene networks led us to propose that chromatin remodelling specifically contributes to the aetiology of syndromic OC. Disease-driven gene discovery is a valid approach to gene identification and curation of gene panels. Through this approach, we have started to unravel common molecular pathways contributing to syndromic orofacial clefting.

Investigación en fisuras faciales: quo vadis España? / Investigation in facial fissures: quo vadis Spain?

Las fisuras orofaciales representan un grupo heterogéneo de malformaciones congénitas que afectan a distintas estructuras de la cavidad oral y de la cara. Globalmente, los bebés con estos trastornos presentan una mayor morbilidad y mortalidad a lo largo de su vida en comparación con individuos no afectados. Por ello, los avances en la investigación biomédica resultan ineludibles. Así, el objetivo general de este trabajo fue llevar a cabo una revisión bibliográfica para analizar narrativamente los 10 principales estudios primarios sobre fisuras orofaciales llevados a cabo en España, publicados del 2018 hasta la actualidad. Según esto, a nivel institucional, destaca la Universidad Complutense de Madrid (UCM) con cuatro artículos publicados por el grupo de investigación UCM 920202. También sobresale la Universidad Rey Juan Carlos de Madrid, con tres artículos relacionados con diferentes aspectos de la personalidad y la calidad de vida de los pacientes fisurados, así como otras muchas variables cognitivo-emocionales. En relación con la Universidad de Valencia, encontramos dos artículos llevados a cabo en amplias muestras de pacientes con fisuras. Por último, en Barcelona resulta destacable un estudio observacional sobre problemas otorrinolaringológicos en pacientes operados de fisura palatina. En conclusión, si bien en los últimos años se han publicado varios artículos sobre distintos aspectos relacionados con las fisuras, aún queda mucho trabajo por hacer. España debería seguir potenciando proyectos con líneas de trabajo centradas en estas alteraciones del desarrollo craneofacial. Se necesitan estudios amplios, multicéntricos y colaborativos, para ahondar en los mecanismos etiológicos y, en última instancia, en las posibles herramientas para su prevención. Del mismo modo, se necesitan ayudas para dilucidar mejor las cuestiones relacionadas con los tratamientos en todas las dimensiones de la salud, preferentemente a partir de ensayos clínicos controlados aleatorizados, que faciliten la traslación de conocimientos y su accesibilidad universal dentro del sistema sanitario público español.

SUMMARY: Orofacial clefts represent a heterogeneous group of congenital malformations affecting different structures of the oral cavity and face. Overall, infants with these disorders have a higher lifetime morbidity and mortality compared to unaffected individuals. Therefore, advances in biomedical research are unavoidable. Thus, the overall objective of this work was to conduct a literature review to narratively analyse the 10 main primary studies on orofacial clefts carried out in Spain, published from 2018 to date. According to this review, at an institutional level, the Complutense University of Madrid (UCM) is notable with 4 articles published by the UCM 920202 research group. The Rey Juan Carlos University of Madrid also stands out, with three papers related to different aspects of the personality and quality of life of cleft patients, as well as many other cognitive-emotional variables. In relation to the University of Valencia, we found two studies carried out on large samples of cleft patients. Finally, in Barcelona, an observational study on otorhinolaryngological problems in cleft palate patients is noteworthy. In conclusion, although several studies have been published in recent years on different aspects related to clefts, there is still much work to be done. Spain should craniofacial development. Large, multicenter and collaborative studies are needed to delve deeper into the aetiological mechanisms and, ultimately, into the possible tools for their prevention. Similarly, support is needed to better elucidate questions related to treatments in all dimensions of health, preferably randomised controlled clinical trials, which facilitate the transfer of knowledge and its universal accessibility within the Spanish public health system.

Pleomorphic Adenoma of the Palate: A Rare Case in an Adolescent With Cleft lip and Palate.

Benign salivary gland tumors are rarely found in children and adolescents compared with adults. Pleomorphic adenomas (PAs), the most common benign salivary gland tumor, account for only 1% of all head and neck lesions and fewer than 5% of all salivary gland tumors in individuals under the age of 16 years. The data on palatal PA in the first 2 decades of life is confined to published case reports and case series. To date, there has never been a report of palatal PA in a patient with cleft lip and palate. Here we describe an adolescent female with bilateral cleft lip and palate with PA of the hard and soft palate who underwent wide local excision and reconstruction with a buccal fat pad and buccal myo-mucosal flap.