Facial Clefts Research Articles

Distribution of Immunomodulation, Protection and Regeneration Factors in Cleft-Affected Bone and Cartilage.

Craniofacial clefts can form a significant defect within bone and cartilage, which can negatively affect tissue homeostasis and the remodeling process. Multiple proteins can affect supportive tissue growth, while also regulating local immune response and tissue protection. Some of these factors, like galectin-10 (Gal-10), nuclear factor kappa-light-chain-enhancer of activated B cells protein 65 (NF-κB p65), heat shock protein 60 (HSP60) and 70 (HSP70) and cathelicidin (LL-37), have not been well studied in cleft-affected supportive tissue, while more known tissue regeneration regulators like type I collagen (Col-I) and bone morphogenetic proteins 2 and 4 (BMP-2/4) have not been assessed jointly with immunomodulation and protective proteins. Information about the presence and interaction of these proteins in cleft-affected supportive tissue could be helpful in developing biomaterials and improving cleft treatment. Two control groups and two cleft patient groups for bone tissue and cartilage, respectively, were organized with five patients in each group. Immunohistochemistry with the semiquantitative counting method was implemented to determine Gal-10-, NF-κB p65-, HSP60-, HSP70-, LL-37-, Col-I- and BMP-2/4-positive cells within the tissue. Factor-positive cells were identified in each study group. Multiple statistically significant correlations were identified. A significant increase in HSP70-positive chondrocytes in cleft patients could indicate that HSP70 might be reacting to stressors caused by the local tissue defect. A significant increase in Col-I-positive osteocytes in cleft patients might indicate increased bone remodeling and osteocyte activity due to the presence of a cleft. Correlations between factors indicate notable differences in molecular interactions within each group.

PDGFRα signaling regulates Srsf3 transcript binding to affect PI3K signaling and endosomal trafficking.

Signaling through the platelet-derived growth factor receptor alpha (PDGFRα) plays a critical role in craniofacial development, as mutations in PDGFRA are associated with cleft lip/palate in humans and Pdgfra mutant mouse models display varying degrees of facial clefting. Phosphatidylinositol 3-kinase (PI3K)/Akt is the primary effector of PDGFRα signaling during skeletal development in the mouse. We previously demonstrated that Akt phosphorylates the RNA-binding protein serine/arginine-rich splicing factor 3 (Srsf3) downstream of PI3K-mediated PDGFRα signaling in mouse embryonic palatal mesenchyme (MEPM) cells, leading to its nuclear translocation. We further showed that ablation of Srsf3 in the murine neural crest lineage results in severe midline facial clefting, due to defects in proliferation and survival of cranial neural crest cells, and widespread alternative RNA splicing (AS) changes. Here, we sought to determine the molecular mechanisms by which Srsf3 activity is regulated downstream of PDGFRα signaling to control AS of transcripts necessary for craniofacial development. We demonstrated via enhanced UV-crosslinking and immunoprecipitation (eCLIP) of MEPM cells that PDGF-AA stimulation leads to preferential binding of Srsf3 to exons and loss of binding to canonical Srsf3 CA-rich motifs. Through the analysis of complementary RNA-seq data, we showed that Srsf3 activity results in the preferential inclusion of exons with increased GC content and lower intron to exon length ratio. Moreover, we found that the subset of transcripts that are bound by Srsf3 and undergo AS upon PDGFRα signaling commonly encode regulators of PI3K signaling and early endosomal trafficking. Functional validation studies further confirmed that Srsf3 activity downstream of PDGFRα signaling leads to retention of the receptor in early endosomes and increases in downstream PI3K-mediated Akt signaling. Taken together, our findings reveal that growth factor-mediated phosphorylation of an RNA-binding protein underlies gene expression regulation necessary for mammalian craniofacial development.

Potential teratogenic effect of prenatal dexamethasone administration on palate development: Experimental study in rats

BackgroundThe interaction of cell populations and synchronization of cell signaling pathways during craniofacial development can cause malformations such as facial clefts when interrupted by teratogenic agents including synthetic corticosteroids. Therefore, this study aimed to determine the potentially disturbing dexamethasone (Dex) effect on palatal shelf development in rat embryos and the possible reasons for this teratogenic potential in relation to fibroblast growth factor 10 (FGF10) as well as FGF10 receptor2 (FGFR2) signaling. MethodsThirty pregnant rats were used, which were then randomly categorized into three groups of ten animals each: the control group, where pregnant rats received no treatment, Sham group in which pregnant rats were injected subcutaneously with saline (0.4 mg/kg body weight) during the mid-pregnancy period at gestational day 9–14, and Dex-treated group, where pregnant rats received 0.4 mg/kg of Dex at mid-gestational period. Pregnant animals from all groups were sacrificed on day 20 of gestation before birth and the fetuses were removed for examination of the palatal shelves using a light microscope (LM). In addition, a real-time polymerase chain reaction and a reverse transcription-polymerase chain reaction (RT-PCR) were done to evaluate FGF10 and its receptor FGFR2 gene expression. ResultsThe cleft palate incidence rates in the groups of embryos were determined. Only the offspring in the Dex group showed a cleft palate. Moreover, the cleft palate incidence rate in the Dex group was significantly different compared to controls. Moreover, a significant decrease in FGF10 and FGFR2 expression levels was reported in the Dex group than in the controls. ConclusionsDex treatment in mid-gestation may increase the incidence of cleft palate development, which may be due to modulation of FGF signaling. This calls for caution when using this medication in the first half of pregnancy unless absolutely necessary and under close medical supervision.

"A Retrospective Evaluation of the Impact of Prenatal Diagnosis of Facial Clefts. Does Prenatal Diagnosis Matter?"

With the advent of improved prenatal detection, some patients with facial clefting are diagnosed prenatally while others are diagnosed postnatally. There is limited data regarding the utility of prenatal diagnosis and how this affects care of patients with facial clefts. A retrospective chart review was performed. Children with incomplete demographic data and those with syndromic conditions were excluded. The data were analyzed via Fisher's exact tests and Kruskal-Wallis tests (p < 0.05). 106 patients met inclusion criteria. Facial clefting was diagnosed prenatally at different frequencies depending on type of facial cleft- patients with cleft palate alone were less likely to be identified prenatally (p < 0.0001). Patients diagnosed prenatally were seen by craniofacial specialists at an earlier age compared to those diagnosed after birth (0.27 months vs 0.7 months, p < 0.001). Similarly, those with prenatal diagnosis underwent surgery at a younger age compared to those who were diagnosed postnatally (median: 3.6 months vs 10.67 months, p < 0.001) and experienced shorter lag time (median: 3.4 months vs 8.4 months, p = 0.027) from consultation to surgery. Importantly, prenatal diagnosis resulted in pre-surgical therapy more often than in children diagnosed postnatally (86% vs 22.2%, p < 0.001). Our data suggests that patients with prenatal diagnosis of facial clefts were more likely to undergo pre-surgical therapy, presented to a craniofacial specialist at an earlier age, underwent surgery at an earlier age, and experienced less lag time between initial visit and surgery. More study is warranted to improve protocols for prenatal diagnoses to improve surgical outcomes.

Rare craniofacial clefts: Surgical management protocols

BackgroundStandardization of surgical protocols is an evolving issue owing to the low incidence of rare craniofacial clefts. In this article, we aimed to share our surgical management of rare craniofacial clefts and evaluate the postoperative results. MethodsThis study was conducted from 2013 to 2022, including patients who presented with craniofacial clefts. The results were assessed based on parents’ satisfaction and objective evaluations by two independent observers. ResultsWe received a total of 3679 patients with cleft anomalies; of these, 61 patients with 89 rare craniofacial clefts were observed with a prevalence of 2.42/100. The male to female ratio was 1:1.35. Craniofacial cleft “4” and “5” were the most common, with 17 (19.1%) and 16 (17.98%), respectively. Multiple craniofacial clefts were observed in 37.7% of patients. Associated craniofacial anomalies were found in 39.34% patients. In 71.6% of patients, the parents were very satisfied with the results. Based on two independent observer scores, 70.27% of the patients scored good. ConclusionThe rare nature of craniofacial clefts and involvement of various structures make the standardization of surgical procedures very challenging. Our experience with these clefts will help new surgeons both in didactics and in technical aspects of patient management. Key Points1. We aim to share our experience with rare craniofacial clefts.2. Each cleft presents with its own unique reconstructive challenges. Literature describes many techniques for each cleft with dozen permutations. We present a simplified techniques that has worked for us over the years for all tessier clefts in this article.

A Case of Treacher Collins Syndrome with simultaneous surgery for unilateral Tessier No. 3 and No. 5 facial clefts

A Case of Treacher Collins Syndrome with simultaneous surgery for unilateral Tessier No. 3 and No. 5 facial clefts

Perinatal management for fetal oral epignathus with duplication of the pituitary gland (DPG)-plus syndrome: A case report and literature review.

The prenatal diagnosis of epignathus presents a unique challenge for physicians. Differential diagnosis is usually based on the anatomic location of the tumor. Typical prenatal ultrasound characteristics of epignathus include a mixed solid and cystic lesion with vascularity in the solid component, originating from the hard or soft palate, and it is often associated with other anomalies such as craniofacial clefts or trans-sphenoidal intracranial extension. Herein, we present a case of prenatal diagnosis of epignathus with rare ultrasonographic findings, prenatal management requiring collaborative efforts of a multidisciplinary team, and a well-planned innovative ex utero intrapartum treatment procedure. In addition, this report highlights the evolving postnatal diagnosis of the rare developmental anomaly, duplication of the pituitary gland-plus syndrome, which includes various midline craniofacial, central nervous system, spinal, and endocrine abnormalities.

Detection of non-cardiac fetal abnormalities on ultrasound at 11-14 weeks: systematic review and meta-analysis.

To assess the diagnostic accuracy of two-dimensional ultrasound at 11-14 weeks' gestation as a screening test for individual fetal anomalies and to identify factors impacting on screening performance. This was a systematic review and meta-analysis that was developed and registered with PROSPERO (CRD42018111781). MEDLINE, EMBASE, Web of Science Core Collection and the Cochrane Library were searched for studies evaluating the diagnostic accuracy of screening for 16 predefined, non-cardiac, congenital anomalies considered to be of interest to the early anomaly scan. We included prospective and retrospective studies from any healthcare setting conducted in low-risk, mixed-risk and unselected populations. The reference standard was the detection of an anomaly on postnatal or postmortem examination. Data were extracted to populate 2 × 2 tables and a random-effects model was used to determine the diagnostic accuracy of screening for the predefined anomalies (individually and as a composite). Secondary analyses were performed to determine the impact on detection rates of imaging protocol, type of ultrasound modality, publication year and index of sonographer suspicion at the time of scanning. Post-hoc secondary analysis was conducted to assess performance among studies published during or after 2010. Risk of bias assessment and quality assessment were undertaken for included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. From 5684 citations, 202 papers underwent full-text review, resulting in the inclusion of 52 studies comprising 527 837 fetuses, of which 2399 were affected by one or more of the 16 predefined anomalies. Individual anomalies were not equally amenable to detection on first-trimester ultrasound: a high (> 80%) detection rate was reported for severe conditions, including acrania (98%), gastroschisis (96%), exomphalos (95%) and holoprosencephaly (88%); the detection rate was lower for open spina bifida (69%), lower urinary tract obstruction (66%), lethal skeletal dysplasias (57%) and limb-reduction defects (50%); and the detection rate was below 50% for facial clefts (43%), polydactyly (40%) and congenital diaphragmatic hernia (38%). Conditions with a low (< 30%) detection rate included bilateral renal agenesis (25%), closed spina bifida (21%), isolated cleft lip (14%) and talipes (11%). Specificity was > 99% for all anomalies. Secondary analysis showed that detection improved with advancing publication year, and that the use of imaging protocols had a statistically significant impact on screening performance (P < 0.0001). The accurate detection of congenital anomalies using first-trimester ultrasound is feasible, although detection rates and false-positive rates depend on the type of anomaly. The use of a standardized protocol allows for diagnostic performance to be maximized, particularly for the detection of spina bifida, facial clefts and limb-reduction defects. Highlighting the types of anomalies amenable to diagnosis and determining factors enhancing screening performance can support the development of first-trimester anomaly screening programs. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Paediatric Facial Cleft Treatment - Lessons Learned

The title of this publication includes the words “Lessons Learned” in order to emphasise the knowledge and experience gained in more than 4 decades in treating 5000+ patients with facial-oral cleft anomalies. The choice, timing and optimization of the most appropriate paediatric surgical and paediatric orthodontic treatments are reflected in the extremely satisfactory treatment outcomes. This paper delineates hierarchically the conceptual framework of treatment for the most profound to the least severe cleft anomaly. Over the years multiple treatment techniques, options and protocols have been published internationally and yet the young professionals often use the procedures and timing of interventions they have learned from their ‘masters’ or seniors, irrespective of whether these have been chosen based on the best long-term treatment outcomes. This paper advocates specific treatment protocols and techniques, based on the results of research, on observation, clinical evaluation, judgement of outcome and the ideal treatment of a specific type of cleft anomaly, in order to optimize long-term outcomes. The initial short-term result, as well as the long-term facial growth, functional and aesthetic influence or their combined influence, have been recorded until the onset of the adolescence age. The application of technique(s) appropriate for treatment of a particular type of cleft anomaly are described and motivated for use, without mention the so-called original or first person who applied or described or used a particular technique or procedure for the first time. Conversely, those treatment technique(s) utilized during the very important developmental phases of the neonate, the infant and the child and which have had a profoundly negative effect on function and/or facial growth and/or facial aesthetic in the long-term, are also described, without mention the name of the person(s) who advocated their use. Paediatric patients who have been treated by means of these latter surgical techniques or interventions which may lead to undesirable or insufficiently positive outcomes, may require extensive drawn-out surgical restructuring and orthodontic treatment during their adolescent’s years.

Atypical facial clefts: Tessier number 3 and 4 clefts.

Tessier number 3 and 4 clefts result from failed fusion of facial processes during embryogenesis, and cause functional, psychosocial, and cosmetic morbidity. Given their rarity and heterogeneity, they present a unique challenge to the reconstructive surgeon, with limited literature for guidance. The purpose of this update is to summarize Tessier number 3 and 4 clefts with a focus on recent literature and expert opinion. The incidence of atypical facial clefts has been estimated between 1.4 and 4.9 per 100 000 live births. Several retrospective chart reviews have been published in recent years; however, the epidemiologic data remains limited. Surgical management must be individualized and guided by classic reconstructive principles. The goal of surgery is to return the three soft tissue components (lip, nasomalar, and eyelid) to their proper anatomical location. Tessier number 3 and 4 clefts are rare, demonstrate a wide spectrum of clinical presentation, and remain challenging to gain a breadth of experience for any single surgeon. They are classified based on their location along well defined anatomical axes. Component repair is performed with attention to the lip, nasomalar, and eyelid regions to restore facial symmetry and function.

Reproductive and fetal toxicity studies of histamine H3 receptor antagonist DL76 used in mice to prevent maximal electroshock-induced seizure.

Introduction: Brain histamine is considered an endogenous anticonvulsant and histamine H1 receptor. H1R antagonists have, in earlier studies, been found to induce convulsions. Moreover, research during the last twodecades has provided more information concerning the anticonvulsant activities of histamine H3R (H3R) antagonists investigated in a variety of animal epilepsy models. Methods: Therefore, the in vivo anticonvulsant effect of the H3R antagonist DL76, with proven high in vitro affinity, in vitro selectivity profile, and high in vivo antagonist potency in mice against maximal electroshock (MES)-induced seizures in mice, was assessed. Valproic acid (VPA) was used as a reference antiepileptic drug (AED). In addition, DL76 was tested for its reproductive and fetal toxicity in the same animal species. Results and discussion: Our observations showed that acute systemic administration (intraperitoneal; i.p.) of DL76 (7.5mg/kg, 15mg/kg, 30mg/kg, and 60mg/kg, i.p.) provided significant and dose-dependent protection against MES-induced seizures in female and male mice. Moreover, the DL76-provided protective effects were comparable to those offered by the VPA and were reversed when animals were co-administered the CNS-penetrant selective H3R agonist R-(α)-methylhistamine (RAM, 10mg/kg, i.p.). Furthermore, the administration of single (7.5mg/kg, 15mg/kg, 30mg/kg, or 60mg/kg, i.p.) or multiple doses (3 × 15mg/kg, i.p.) of H3R antagonist DL76 on gestation days (GD) 8 or 13 failed to affect the maternal body weight of mice when compared with the control mice group. No significant alterations were detected in the average number of implantations and resorptions between the control and DL76-treated groups at the early stages of gestation and the organogenesis period. In addition, no significant differences in the occurrence of skeletal abnormalities, urogenital abnormalities, exencephaly, exomphalos, facial clefts, and caudal malformations were observed. The only significant abnormalities witnessed in the treated groups of mice were in the length of long bones and body length. In conclusion, the novel H3R antagonist DL76 protected test animals against MES-induced seizures and had a low incidence of reproductive and fetal malformation with decreased long bone lengths in vivo, signifying the potential therapeutic value of H3R antagonist DL76 for future preclinical as well as clinical development for use in the management of epilepsy.

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.

The Psychology of Patients With Oral-Facial Clefts: A Review of Victor Hugo's The Man Who Laughs (L'homme qui rit).

In Victor Hugo's The Man Who Laughs, the protagonist has a facial cleft. The authors aimed to comprehend the psychological experience of a patient with a facial cleft by analyzing this novel. The novel concerns the life of a young nobleman, Gwynplaine, disfigured as a child, who travels with his protector and companion, the vagabond philosopher Ursus, and Dea, a baby girl he rescued. During the oppressive rule of the king, one of his adversaries was Lord Linnaeus Clancharlie, who had taken refuge in Switzerland. The tyrannical monarch ordered the execution of Gwynplaine's father and commissioned a surgeon, Dr Hardquannone, to carve the boy's face into a perpetual grin. The king declared that he should "laugh forever at his fool of a father." Subsequently, the king sold the boy to a group who specialized in the mutilation and disfigurement of children. On the psychology of a boy with an appearance giving the impression of laughing, Hugo wrote: "By laughing Gwynplaine made people laugh. However, he wasn't laughing. His face laughed, his thoughts did not." When Ursus met Gwynplaine, Ursus asked the boy: "What are you laughing at?" The boy replied: I'm not laughing. Ursus: Then you are terrible. Gwynplaine's unnatural laughter, which stems from an artificial deformation of the muscles, is a silent form of laughter. It represents the eternal laughter of those who do not truly laugh, signifying emotional emptiness and an accompanying sense of indifference. Plastic surgeons can restore an "unnatural laughing face" to a "natural smiling face."

A retrospective study of congenital anomalies and associated risk factors among children admitted at a tertiary hospital in northwestern Tanzania.

Congenital anomalies in Sub-Sahara Africa (SSA) are understudied despite the significant pediatric health burden. This retrospective longitudinal hospital-based study evaluated the records of 326 inpatient children under the age of two years with congenital anomalies at Bugando Medical Centre, a tertiary referral hospital in northwestern Tanzania. Classical logistic regression was used in the analysis of congenital malformation of muscles, gastrointestinal malformation, oral facial clefts, neural tube defects, and skeletal malformations. A modified poisson regression was used to model risk factors for Central Nervous System (CNS) hydrocephalus and congenital heart disease (CHD). A majority (78.8%) of children included in the study were less than six months of age. Nearly half (48.8%) were diagnosed with CHD followed by CNS hydrocephalus (10.4%) and congenital malformation of muscles (8.9%). Babies whose mothers missed periconceptual folic acid supplementation had 83% higher risk of hydrocephalus (aPR = 1.83, 95% CI = 1.11-1.96) and 78% higher for CHD (aPR = 1.78, 95% CI = 1.31-1.94). Male children had 1.67 higher odds of muscular congenital malformations (aOR = 1.67, 95% CI = 1.23-1.89). Less than 37 gestational age had a 1.86 higher odds of muscular congenital malformations (aOR = 1.86, 95% CI = 1.53-3.66). Our study highlights the critical need for folic acid supplementation and establishes a need for a registry and the potential for mapping.

Prenatal Diagnosis of a Case of Asyndromic Tessier Class-7 Bilateral Complete Transverse Facial Cleft: Case Report with Review of Literature

AbstractTransverse or lateral facial clefts are atypical and rare forms of facial clefts identified as Tessier type 7 in the classification system for orofacial clefts. They have an overall incidence of 1 in 60,000 to 300,000 live births. We report a case diagnosed at 22 weeks of gestation. The two-dimensional (2D) ultrasound examination revealed a single live fetus with a persistently open mouth, failure of visualization of lateral commissures, and mild retrognathia. The three-dimensional (3D) surface rendering of the fetal face demonstrated a bilateral horizontal facial cleft that extended from the lateral commissures to the ears. No additional anomalies were identified. Fetal karyotype and whole exome sequencing reports did not reveal any genomic imbalances. The case highlights the importance of 2D oblique and 3D imaging of the fetal face when subtle findings are detected in routine 2D views. A review of the literature is provided to enhance the understanding of the entity.

Tessier 7– Facial Cleft with Macrostomia: A Rare Case Report

The literature rarely reports unilateral Tessier no. 7 clefts. Tessier no. 7 craniofacial clefts, also called temporozygomatic or transverse facial clefts, are the most laterally located type of craniofacial clefts. History of the patient, clinical presentation, and Computed tomography (CT)scan were considered as the diagnostic criteria. The hasty analysis and surgical correction of craniofacial defect is essential because it may disturb the facial development of the patient.

Successful management of an unusual hypopigmented scar after surgical repair of a unilateral Tessier 7 cleft

Abstract Tessier No. 7 cleft is the most common atypical craniofacial cleft with an incidence of 1:3000–5642 births. This clinical report describes the successful management of a delayed, unusually hypopigmented postoperative facial scar following the surgical closure of a Tessier 7 cleft using the Pfeiffer wave line incision. In the absence of any other associated systemic lesions, the scar was treated as a localized leucoderma. The scar coloration improved dramatically with the chosen line of conservative medical treatment, and a surgical revision was not required. This report highlights the need for continuous follow up despite seemingly good short-term results. The medical management of the hypopigmented scar will aid fellow practitioners who may face similar dilemmas.

Bilateral Maxillary Duplication in Tessier No. 7 Cleft: An Uncommon Congenital Deformity with a Challenging Radiological Diagnosis.

Tessier No. 7 cleft, known as lateral facial cleft, is a rare and understudied entity with an incidence of 1/80,000-1/300,000 live births. Besides perioral tissue abnormalities manifesting as macrostomia, Tessier 7 cleft also involves anomalies of the underlying bony structures. It can appear as part of a syndrome, such as Treacher-Collins syndrome or Goldenhar/Orbito-Auriculo-Vestibular Spectrum, or as an isolated form (unilateral or bilateral) with variable expressions. Bilateral maxillary duplication in Tessier 7 cleft is considered extremely rare, accounting for only two previously presented cases. Given that the cases presented in the literature mainly focus on clinical appearance and surgical treatment, without providing sufficient imaging, we aim to present key radiological features of Tessier 7 cleft in terms of evaluating the involved structures, which is essential for the therapeutic approach and final outcome. A 17-year-old male with incompetent lips and orthodontic abnormalities was referred to our Radiology Department for orthopantomography (OPG) and CT examinations. Hetero-anamnestic data revealed a history of surgical treatment of the commissural cleft conducted 2 months after the birth to enable feeding. Intraoral examination showed a maxillary cleft and supernumerary teeth. Since the given clinical presentation was inconclusive, radiological diagnostics took precedence in elucidating this complex entity.

Facial Cleft in a Newborn.

A term newborn was detected for a rare facial defect in the delivery room. The defect arose due to malunion along the lines of facial development during fetal life. This embryonic defect is classified according to the areas of face involved and its associated structures.

Identification of a novel mutation of Platelet-Derived Growth Factor-C (PDGFC) gene in a girl with Non-Syndromic cleft lip and palate

BackgroundCleft lip with or without cleft palate (CL/CP) is a prevalent congenital malformation. Approximately 16 candidate loci for CL/CP have been identified in both animal models and humans through association or genetic linkage studies. One of these loci is the platelet-derived growth factor-C (PDGFC) gene. In animal models, a mutation in the PDGFC gene has been shown to lead to CL/CP, with PDGF-C protein serving as a growth factor for mesenchymal cells, playing a crucial role in embryogenesis during the induction of neural crest cells. In this study, we present the identification of a novel frameshift mutation in the PDGFC gene, which we hypothesize to be associated with CL/CP, within a consanguineous Iranian family. Case presentationThe proband was a 3-year-old girl with non-syndromic CL/CP. A history of craniofacial clefts was present in her family. Following genetic counseling, karyotype analysis and whole-exome sequencing (WES) were performed. Cytogenetic analysis revealed normal results, while WES analysis showed that the proband carried a homozygous c.546dupA (p.L183fs) mutation in the PDGFC gene. Sanger sequencing confirmed that her parents were carriers of the mutation. ConclusionThe c.546dupA (p.L183fs) mutation of PDGFC has not been previously reported and was not found in human genome databases. We speculate that the c.546dupA mutation of the PDGFC gene, identified in the Iranian patient, may be responsible for the phenotype of non-syndromic CL/CP (ns-CL/CP). Further studies are warranted to explore the specific pathogenesis of the PDGFC mutation in ns-CL/CP.