Craniofacial Anomalies Research Articles

Prevalence of psychiatric and cognitive disorders in patients with Pierre-Robin sequence - a statistical analysis

IntroductionThe Pierre-Robin sequence (PRS), characterized by micrognathia, glossoptosis, and cleft palate, has long been a subject of clinical interest. Recent research suggests a potential association between PRS and cognitive or psychiatric disorders. This study explores this intriguing connection, shedding light on the complex interplay between craniofacial anomalies and mental health.ObjectivesThis study aims to establish a comprehensive understanding of the relationship between Pierre-Robin Sequence and psychiatric disorders. Specifically, our objectives include: assessing prevalence, evaluating impact and informing clinical practice. This research aims to improve the holistic care and mental well-being of individuals with craniofacial malformations, contributing to a more comprehensive approach in the field of psychiatry.MethodsThis cross-sectional study was conducted at a prominent referral hospital named Hospital de Clínicas de Porto Alegre, an international reference in Pierre-Robin Sequence, during the month of August 2023.Participant Selection: Patients with PRS. Inclusion criteria encompassed individuals of all ages and both genders.Data Collection: Trained medical personnel conducted structured interviews with participants to gather demographic information, medical history, and details of their craniofacial conditions.Medical Records Review: Medical records were reviewed to corroborate craniofacial diagnoses and identify any comorbid conditions.Statistical Analysis: Data were analyzed using appropriate statistical techniques to assess the association between PRS and psychiatric disorders.Ethical Considerations: The study adhered to all ethical guidelines, with informed consent obtained from participants or their legal guardians. Ethical approval was obtained from the hospital’s Institutional Review Board.Data Handling: Confidentiality and data security were ensured throughout the study, with all data anonymized to protect participant privacy.ResultsIn our study, we assessed 28 different patients with Pierre-Robin Sequence, comprising 13 females and 15 males. The youngest patient was 2 months old, while the oldest was 22 years old. The mean age of the patients was 4.75 years, with a median of 3 years and a standard deviation of 5.36 years.Among the patients, 6 exhibited psychiatric disorders, split between 4 males and 2 females. Their average age was 10 years, with a median of 9 years and a standard deviation of 4.2. The youngest patient with evidence of a psychiatric disorder was 5 years old.ConclusionsThis study underscores a concerning reality within the Pierre-Robin population, pointing to a high prevalence of psychiatric disorders. These findings highlight the urgent need for integrated care, emphasizing the importance of early psychiatric assessment and tailored interventions to enhance the overall well-being of individuals facing the challenges of PRS.Disclosure of InterestNone Declared

Radiographic Assessment Regarding the Pattern of Third Molar Impaction and its Association with Gender in the Population of Islamabad

Abstract 
 Objective: To analyze and document the gender-specific incidence of impacted third molars and elucidate the specific patterns associated with impacted third molars.
 Methodology: This retrospective cross-sectional study analyzed orthopantomograms (OPG) data from 278 patients, covering a total of 445 impacted third molars. A convenient sampling technique was used and the study was completed in three months from September 2023 and December 2023, Inclusion criteria: OPGs of individuals aged 25 years or older with fully formed third molar roots, Exclusion criteria: OPGs of individuals younger than 25, with craniofacial anomalies, prior orthodontic treatment, erupted third molars, or incomplete root formation in third molars.
 Results: Both males and females were almost equal in number. The majority 73.2% of OPG showed mandibular third molar impaction while 26.8% showed maxillary third molar impaction. In the maxillary arch, the distoangular type of impaction was observed in the majority, accounting for 48.7%. In the mandibular arch, mesioangular impaction prevailed, comprising 41.7%. In the maxillary arch, a statistically significant correlation (p=0.006) was found between gender and impaction type, with females exhibiting a distinct and more prevalent impaction pattern than males. In the mandibular arch, there was no statistically significant association between gender and impaction type (p=0.23).
 Conclusion: In conclusion, our study reveals noteworthy gender variations in the prevalence and types of third molar impactions. Mandibular third molars exhibit a higher prevalence than maxillary counterparts, with mesioangular impaction prevailing in the mandibular arch and distoangular impaction in the maxillary arch.

The transcription of the main gene associated with Treacher–Collins syndrome (TCOF1) is regulated by G-quadruplexes and cellular nucleic acid binding protein (CNBP)

Treacle ribosome biogenesis factor 1 (TCOF1) is responsible for about 80% of mandibular dysostosis (MD) cases. We have formerly identified a correlation between TCOF1 and CNBP (CCHC-type zinc finger nucleic acid binding protein) expression in human mesenchymal cells. Given the established role of CNBP in gene regulation during rostral development, we explored the potential for CNBP to modulate TCOF1 transcription. Computational analysis for CNBP binding sites (CNBP-BSs) in the TCOF1 promoter revealed several putative binding sites, two of which (Hs791 and Hs2160) overlap with putative G-quadruplex (G4) sequences (PQSs). We validated the folding of these PQSs measuring circular dichroism and fluorescence of appropriate synthetic oligonucleotides. In vitro studies confirmed binding of purified CNBP to the target PQSs (both folded as G4 and unfolded) with Kd values in the nM range. ChIP assays conducted in HeLa cells chromatin detected the CNBP binding to TCOF1 promoter. Transient transfections of HEK293 cells revealed that Hs2160 cloned upstream SV40 promoter increased transcription of downstream firefly luciferase reporter gene. We also detected a CNBP-BS and PQS (Dr2393) in the zebrafish TCOF1 orthologue promoter (nolc1). Disrupting this G4 in zebrafish embryos by microinjecting DNA antisense oligonucleotides complementary to Dr2393 reduced the transcription of nolc1 and recapitulated the craniofacial anomalies characteristic of Treacher Collins Syndrome. Both cnbp overexpression and Morpholino-mediated knockdown in zebrafish induced nolc1 transcription. These results suggest that CNBP modulates the transcriptional expression of TCOF1 through a mechanism involving G-quadruplex folding/unfolding, and that this regulation is active in vertebrates as distantly related as bony fish and humans. These findings may have implications for understanding and treating MD.

Novel copy number variations and phenotypes of infantile epileptic spasms syndrome.

We summarize the copy number variations (CNVs) and phenotype spectrum of infantile epileptic spasms syndrome (IESS) in a Chinese cohort. The CNVs were identified by genomic copy number variation sequencing. The CNVs and clinical data were analyzed. 74 IESS children with CNVs were enrolled. 35 kinds of CNVs were identified. There were 11 deletions and 5 duplications not reported previously in IESS, including 2 CNVs not reported in epilepsy. 87.8% were de novo, 9.5% were inherited from mother and 2.7% from father. Mosaicism occurred in one patient with Xq21.31q25 duplication. 16.2% (12/74) were 1p36 deletion, and 20.3% (15/74) were 15q11-q13 duplication. The age of seizure onset ranged from 17 days to 24 months. Seizure types included epileptic spasms, focal seizures, tonic seizures, and myoclonic seizures. All patients displayed developmental delay. Additional features included craniofacial anomaly, microcephaly, congenital heart defects, and hemangioma. 29.7% of patients were seizure-free for more than 12 months, and 70.3% still had seizures after trying 2 or more anti-seizure medications. In conclusion, CNVs is a prominent etiology of IESS. 1p36 deletion and 15q duplication occurred most frequently. CNV detection should be performed in patients with IESS of unknown causes, especially in children with craniofacial anomalies and microcephaly.

Distinctive Craniofacial and Oral Anomalies in MN1 C-terminal Truncation Syndrome.

MN1 C-terminal truncation (MCTT) syndrome was first reported in 2020 and only 28 patients have been recorded to date. Since MCTT syndrome is a newly defined and rare syndrome with many clinical features, the present study reviewed the manifestations and management of oral and dental anomalies. Gene variants of MCTT syndrome and their positive phenotypes were summarised. The phenotypes of variants in two exons differed from each other mainly in the craniomaxillofacial region, including brain MRI abnormalities and palatal morphology. Pathogenic mechanisms, especially in craniofacial and oral anomalies, were discussed. Appropriate treatments in the stomatology and respiratory departments could improve the symptoms of MCTT syndrome. The different sites of MN1 gene variants may influence the clinical symptoms and there may be racial differences in MCTT syndrome. We recommend oral and pulmonary evaluations for the multidisciplinary treatment of MCTT syndrome.

Digital Concepts for the Care of Newborns with Craniofacial Anomalies

The treatment of newborns with craniofacial abnormalities such as cleft lip and/or palate poses special challenges for healthcare providers. Often, the collaboration of an interdisciplinary team of pediatricians, orthodontists, and oral and maxillofacial surgeons is necessary. Therapy using feeding or stimulation plates can improve feeding and strengthen orofacial muscle tone. The treatment of patients with cleft lip and palate using conventionally manufactured feeding plates as well as the treatment of patients with reduced orofacial muscle tone through stimulation plates therapy are established and widely used methods. The conventional production of these plate appliances can lead to serious complications such as swallowing of impression material and airway obstruction due to aspiration. Through an innovative, entirely digital workflow using computer-assisted design and manufacturing of the appliances in a 3D printer, risks can be minimized and time and costs can be saved. This article aims to explain the digital workflow of treating newborns with 3D CAD/CAM feeding and stimulation plates through two case studies.

Transcriptomic analysis reveals mitochondrial dysfunction in the pathogenesis of Nager syndrome in sf3b4-depleted zebrafish

Nager syndrome (NS) is a rare acrofacial dysostosis caused by heterozygous loss-of-function variants in the splicing factor 3B subunit 4 (SF3B4). The main clinical features of patients with NS are characterized by facial-mandibular and preaxial limb malformations. The migration and specification of neural crest cells are crucial for craniofacial development, and mitochondrial fitness appears to play a role in such processes. Here, by analyzing our previously published transcriptome dataset, we aim to investigate the potential involvement of mitochondrial components in the pathogenesis of craniofacial malformations, especially in sf3b4 mutant zebrafish. We identified that oxidative phosphorylation (OXPHOS) defects and overproduction of reactive oxygen species (ROS) due to decreased antioxidants defense activity, which leads to oxidative damage and mitochondrial dysfunction. Furthermore, our results highlight that fish lacking sf3b4 gene, primarily display defects in mitochondrial complex I. Altogether, our findings suggest that mitochondrial dysfunction may contribute to the development of the craniofacial anomalies observed in sf3b4-depleted zebrafish.

A BMP-controlled metabolic/epigenetic signaling cascade directs midfacial morphogenesis.

Craniofacial anomalies, especially midline facial defects, are among the most common birth defects in patients and are associated with increased mortality or require lifelong treatment. During mammalian embryogenesis, specific instructions arising at genetic, signaling, and metabolic levels are important for stem cell behaviors and fate determination, but how these functionally relevant mechanisms are coordinated to regulate craniofacial morphogenesis remain unknown. Here, we report that bone morphogenetic protein (BMP) signaling in cranial neural crest cells (CNCCs) is critical for glycolytic lactate production and subsequent epigenetic histone lactylation, thereby dictating craniofacial morphogenesis. Elevated BMP signaling in CNCCs through constitutively activated ACVR1 (ca-ACVR1) suppressed glycolytic activity and blocked lactate production via a p53-dependent process that resulted in severe midline facial defects. By modulating epigenetic remodeling, BMP signaling-dependent lactate generation drove histone lactylation levels to alter essential genes of Pdgfra, thus regulating CNCC behavior in vitro as well as in vivo. These findings define an axis wherein BMP signaling controls a metabolic/epigenetic cascade to direct craniofacial morphogenesis, thus providing a conceptual framework for understanding the interaction between genetic and metabolic cues operative during embryonic development. These findings indicate potential preventive strategies of congenital craniofacial birth defects via modulating metabolic-driven histone lactylation.

Risk factors for infant hearing loss: a meta-analysis.

Hearing loss is a common disability in infants that significantly impacts their cognitive, language, and literacy development. This study aimed to systematically assess the risk factors for the early identification and intervention in infant hearing loss. Databases were searched for meta-analyses of observational studies until November 2023. The quality assessment was performed using the Cochrane risk of bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of the evidence. A meta-analysis identified 14 risk factors significantly associated with infant hearing loss. According to the GRADE approach, there were four factors with moderate-certainty evidence (low birth weight(LBW), congenital anomalies, craniofacial anomalies, intracranial hemorrhages), seven factors with low-certainty evidence (ototoxic medications, family history of hearing loss, mechanical ventilation > 5 days, intrauterine infection, admission to neonatal intensive care unit (NICU) > 5 days, mechanical ventilation and asphyxia) and six with extremely-low-certainty evidence (very low birth weight < 1500 g (VLBW), hyperbilirubinemia, sepsis or meningitis, male sex, premature birth, small for gestational age (SGA)). Nevertheless, no significant association was found between infant hearing loss and factors such as small for gestational age (SGA), male sex, and premature birth (P > 0.05). Conclusion: The identification of these 14 interrelated risk factors can prove advantageous in clinical practice, as these findings could guide hearing screening and parental counseling. Furthermore, prospective research could be conducted to develop risk-based scoring systems based on these factors. What is Known: • Infant hearing loss is a worldwide issue. • Risk factors for this condition are debated. What is New: • This is the first meta-analysis to comprehensively evaluate perinatal and postnatal risk factors for hearing loss in infants. • Intracranial hemorrhage, mechanical ventilation, and low birth weight are associated with infant hearing loss. However, no evidence of an association was found between premature birth, being small for gestational age, or male sex and hearing loss.

A homozygous SP7/OSX mutation causes osteogenesis and dentinogenesis imperfecta with craniofacial anomalies.

Osteogenesis imperfecta (OI) is a heterogeneous spectrum of hereditary genetic disorders that cause bone fragility, through various quantitative and qualitative defects of type 1 collagen, a triple helix composed of two α1 and one α2 chains encoded by COL1A1 and COL1A2, respectively. The main extra-skeletal manifestations of OI include blue sclerae, opalescent teeth, and hearing impairment. Moreover, multiple genes involved in osteoblast maturation and type 1 collagen biosynthesis are now known to cause recessive forms of OI. In this study a multiplex consanguineous family of two affected males with OI was recruited for genetic screening. To determine the causative, pathogenic variant(s), genomic DNA from two affected family members were analyzed using whole exome sequencing, autozygosity mapping, and then validated with Sanger sequencing. The analysis led to the mapping of a homozygous variant previously reported in SP7/OSX, a gene encoding for Osterix, a transcription factor that activates a repertoire of genes involved in osteoblast and osteocyte differentiation and function. The identified variant (c.946C > T; p.Arg316Cys) in exon 2 of SP7/OSX results in a pathogenic amino acid change in two affected male siblings and develops OI, dentinogenesis imperfecta, and craniofacial anomaly. On the basis of the findings of the present study, SP7/OSX:c. 946C > T is a rare homozygous variant causing OI with extra-skeletal features in inbred Arab populations.

Human split hand/foot variants are not as functional as wildtype human PRDM1in the rescue of craniofacial defects.

Split hand/foot malformation (SHFM) is a congenital limb disorder presenting with limb anomalies, such as missing, hypoplastic, or fused digits, and often craniofacial defects, including a cleft lip/palate, microdontia, micrognathia, or maxillary hypoplasia. We previously identified three novel variants in the transcription factor, PRDM1, that are associated with SHFM phenotypes. One individual also presented with a high arch palate. Studies in vertebrates indicate that PRDM1 is important for development of the skull; however, prior to our study, human variants in PRDM1 had not been associated with craniofacial anomalies. Using transient mRNA overexpression assays in prdm1a-/- mutant zebrafish, we tested whether the PRDM1 SHFM variants were functional and could lead to a rescue of the craniofacial defects observed in prdm1a-/- mutants. We also mined previously published CUT&RUN and RNA-seq datasets that sorted EGFP-positive cells from a Tg(Mmu:Prx1-EGFP) transgenic line that labels the pectoral fin, pharyngeal arches, and dorsal part of the head to examine Prdm1a binding and the effect of Prdm1a loss on craniofacial genes. The prdm1a-/- mutants exhibit craniofacial defects including a hypoplastic neurocranium, a loss of posterior ceratobranchial arches, a shorter palatoquadrate, and an inverted ceratohyal. Injection of wildtype (WT) hPRDM1 in prdm1a-/- mutants partially rescues the palatoquadrate phenotype. However, injection of each of the three SHFM variants fails to rescue this skeletal defect. Loss of prdm1a leads to a decreased expression of important craniofacial genes by RNA-seq, including emilin3a, confirmed by hybridization chain reaction expression. Other genes including dlx5a/dlx6a, hand2, sox9b, col2a1a, and hoxb genes are also reduced. Validation by real-time quantitative PCR in the anterior half of zebrafish embryos failed to confirm the expression changes suggesting that the differences are enriched in prx1 expressing cells. These data suggest that the three SHFM variants are likely not functional and may be associated with the craniofacial defects observed in the humans. Finally, they demonstrate how Prdm1a can directly bind and regulate genes involved in craniofacial development.

Laryngomalacia and Obstructive Sleep Apnea in Children: From Diagnosis to Treatment.

The aim of this review is to investigate the state of the art among the association between Obstructive sleep apnea (OSA) and laryngomalacia, analyzing the epidemiology, the diagnostic tools, and the possible treatments available to affected patients. Laryngomalacia, characterized by the malacic consistency of the epiglottis with a tendency to collapse during inspiratory acts, producing a characteristic noise known as stridor, is a common condition in infants and particularly in those affected by prematurity, genetic diseases, craniofacial anomalies, and neurological problems. Congenital laryngomalacia, presenting with stridor within the first 15 days of life, is often self-limiting and tends to resolve by 24 months. OSA is not only a consequence of laryngomalacia but also exacerbates and perpetuates the condition. Currently, the treatments reported in the literature are based (i) on medical therapies (including watchful waiting) and (ii) on surgical treatments. Among the surgical techniques, the most described is supraglottoplasty, performed with the use of cold instruments, CO2 LASER, transoral robotic surgery, or the microdebrider.

Overjet in Infants: A Cross-Sectional Study.

The purpose of this study was to determine the normal ranges for overjet in healthy infants under 12 months of age. A cross sectional study of consecutive patients below 12 months of age. The study was conducted at a private practice in Tampa, FL that specializes in pediatric craniomaxillofacial disorders. All patients under the age 12 months were considered for entry into the study. Patients were excluded if they had temporomandibular joint pathology, sleep disordered breathing, facial trauma, or were diagnosed with a craniofacial anomaly. Measures of overjet, defined as the distance between the anterior surfaces of the alveolar ridges when in centric relation, were obtained. The primary study outcome was the overjet of the enrolled patients. A total of 152 infants were included in this study. Of these, 51 were female, and 40 were born prematurely (ranging from 32-37 weeks of gestation). In neonates below 1 month of age, the mean overjet was 2.25 mm (95% CI 1.31-3.19). Multivariate linear regression analysis showed overjet to significantly decrease with age, at a mean rate of approximately 0.1 mm per month (coefficient of -0.09, 95% CI -1.61 to -0.02, p = 0.01). When controlling for potential confounders, average overjet was not shown to vary significantly between the sexes, with prematurity, with race, or with primary diagnosis at presentation. This paper establishes normative values for overjet in infants below 12 months of age.

Isolated Sagittal Craniosynostosis: A Comprehensive Review.

Sagittal craniosynostosis, a rare but fascinating craniofacial anomaly, presents a unique challenge for both diagnosis and treatment. This condition involves premature fusion of the sagittal suture, which alters the normal growth pattern of the skull and can affect neurological development. Sagittal craniosynostosis is characterised by a pronounced head shape, often referred to as scaphocephaly. Asymmetry of the face and head, protrusion of the fontanel, and increased intracranial pressure are common clinical manifestations. Early recognition of these features is crucial for early intervention, and understanding the aetiology is, therefore, essential. Although the exact cause remains unclear, genetic factors are thought to play an important role. Mutations in genes such as FGFR2 and FGFR3, which disrupt the normal development of the skull, are suspected. Environmental factors and various insults during pregnancy can also contribute to the occurrence of the disease. An accurate diagnosis is crucial for treatment. Imaging studies such as ultrasound, computed tomography, magnetic resonance imaging, and three-dimensional reconstructions play a crucial role in visualising the prematurely fused sagittal suture. Clinicians also rely on a physical examination and medical history to confirm the diagnosis. Early detection allows for quick intervention and better treatment outcomes. The treatment of sagittal craniosynostosis requires a multidisciplinary approach that includes neurosurgery, craniofacial surgery, and paediatric care. Traditional treatment consists of an open reconstruction of the cranial vault, where the fused suture is surgically released to allow normal growth of the skull. However, advances in minimally invasive techniques, such as endoscopic strip craniectomy, are becoming increasingly popular due to their lower morbidity and shorter recovery times. This review aims to provide a comprehensive overview of sagittal craniosynostosis, highlighting the aetiology, clinical presentation, diagnostic methods, and current treatment options.

Genetic Associations of Oral Clefts in Arabs.

This study aims to investigate genetic association between Non-syndromic Cleft lip with or without palate (NCLP) and 14 specific Single Nucleotide Polymorphism (SNPs) reported to be associated with NCLP from previous Genome Wide Association Studies (GWAS). A prospective case-control study. Ministry of Health (MOH) Cleft and Craniofacial Clinic and Kuwait University. One hundred sixty-four NCLP patients were recruited from MOH Cleft and Craniofacial clinic, and 491 controls from the Kuwait DNA bank established at Kuwait University. Total gDNA was extracted from whole blood withdrawn from patients and genotyped by real time PCR. Hardy-Weinberg Equilibrium was tested, and the set p value for significance (p < 0.05) was adjusted using the Benjamini - Hoochberg procedure to achieve 5% false discovery rate. Logistic regression multivariate analysis was used to test statistically significant differences between cases and controls. Genotyping both groups for the variants was determined through the allele discrimination software program. There was statistically significant difference between cases and controls in relation to two SNPs; LOC102724968 (rs13041247) (MAF cases/control = C (0.28/0.39) OR Homozygous = 1.30; 95% CI = 1.09-1.56, p = 0.0041) and PVT1 (rs987525) (MAF cases/control = A (0.41/0.27) OR heterozygous = 1.48; 95% CI =1.12-1.95, p = 0.0073), increasing the susceptibility to NCLP. Genetic variations are associated with the occurrence of oral clefts. Customized Next Generation Sequencing (NGS) panel to the Arab ethnicity is encouraged. In Addition, national preconception genetic carrier screening tests should expand to include common craniofacial anomalies.

Sixty Years of Innovation in Biomechanical Orthognathic Surgery: The State of the Art and Future Directions

Craniofacial surgery is proposed and performed for a variety of reasons, ranging from congenital or acquired malformations to emotional disorders and parafunctions of the masticatory, respiratory, auditory, and visual systems. Surgery of the mandible and its orthostatic repositioning is the most common of these corrections of craniofacial anomalies. Throughout the history of these procedures, various techniques have been proposed and perfected, but always with a high rate of minor and major complications. The recurrence rate of mandibular malposition is high, as is the temporary loss of facial sensitivity and motor skills. These outcomes are often related to the choice of surgical technique rather than the skill of the surgeon, which is considered to be one of the most important factors in the final outcome. Surgical techniques involving direct manipulation of the vascular-nervous bundles, such as bilateral sagittal split osteotomy, clearly present the possibility of major or minor complications. In this study, an orthognathic surgical technique, performed by the same team for over 40 years and now available through a 20-year postoperative patient follow-up study, is presented with a literature review relating it to biomechanical concepts and bone remodeling to analyze the evolution of orthognathic surgery since it became common practice to correct maxillofacial discrepancies. In this review, we also present a case report in which previous orthodontic treatment prepared a patient for surgical correction of mandibular bone discrepancy without the need for combined maxillary and/or genioplasty, and we describe the most commonly used techniques today, as well as their advantages and disadvantages. The combination of established concepts together promotes favorable stability of mandibular osteotomies, functional anatomical positioning of the temporomandibular joint, reduced risk of injury to the mandibular vasculo-nervous bundle, and good aesthetics with positive patient acceptance and no relapse, thus these are the objectives for proposing innovative treatments that combine the technologies available today.

Foucault and Clinical Photography: An Analysis and Mitigation of the Clinical Gaze in Pediatric Craniofacial Plastic Surgery

While objectification in medicine has been extensively critiqued as a philosophical concept dating back to the Ancient Greeks and contemporarily popularized by Michel Foucault, the impact of objectification through clinical photography in plastic surgery is often overlooked. Plastic surgery patients are by necessity subjected to the clinical gaze through clinical photography, which may lead to experiences of dehumanization and alienation from their physicians and surgeons. In this essay, we explore the concept of the clinical gaze in clinical photography from a structured philosophical lens, and offer one potential answer to this problem. First, we draw upon Foucault’s well-known and monumental critique of contemporary Western medical practice from Birth of the Clinic alongside a brief history of clinical photography to illustrate the problem of the “clinical gaze.” Then, we argue that mitigating the clinical gaze is critical for the flourishing of patients in general and plastic surgery patients in particular. Finally, we offer our attempt to mitigate the clinical gaze that was conducted by the Craniofacial Anomalies Program at the University of Michigan in 2014 as a demonstration of an upending of the power dynamic usually at play.

Variants in KMT2A in Three Individuals with Previous Suspicion of 22q11.2 Deletion Syndrome.

The condition known as 22q11.2 deletion syndrome (MIM #188400) is a rare disease with a highly variable clinical presentation including more than 180 features; specific guidelines for screening individuals have been used to support clinical suspicion before confirmatory tests by Brazil's Craniofacial Project. Of the 2568 patients listed in the Brazilian Database on Craniofacial Anomalies, 43 individuals negative for the 22q11.2 deletion syndrome were further investigated through whole-exome sequencing. Three patients (6.7%) presented with heterozygous pathogenic variants in the KMT2A gene, including a novel variant (c.6158+1del) and two that had been previously reported (c.173dup and c.3241C>T); reverse phenotyping concluded that all three patients presented features of Wiedemann-Steiner syndrome, such as neurodevelopmental disorders and dysmorphic facial features (n = 3), hyperactivity and anxiety (n = 2), thick eyebrows and lower-limb hypertrichosis (n = 2), congenital heart disease (n = 1), short stature (n = 1), and velopharyngeal insufficiency (n = 2). Overlapping features between 22q11.2 deletion syndrome and Wiedemann-Steiner syndrome comprised neuropsychiatric disorders and dysmorphic characteristics involving the eyes and nose region; velopharyngeal insufficiency was seen in two patients and is an unreported finding in WDSTS. Therefore, we suggest that both conditions should be included in each other's differential diagnoses.

Prenatal incidence of cleft lip/palate and cocaine abuse in parents: a systematic review and meta-analysis.

The study aimed to investigate the association between maternal cocaine abuse during pregnancy and the prevalence of cleft lip/palate (CL/P) in offspring, synthesizing existing evidence through a systematic review and meta-analysis. CL/P is a congenital craniofacial anomaly with complex etiology, and prior research has suggested potential links between maternal cocaine use and CL/P. However, these associations remain inconclusive. A comprehensive literature search was conducted to identify relevant studies published up to the study's cutoff date in September 2021. Several databases were systematically searched using predefined search terms. Inclusion criteria were set to encompass studies reporting on the prevalence of CL/P in infants born to mothers with a history of cocaine use during pregnancy, with a comparison group of non-cocaine-using mothers. Data were extracted, and a meta-analysis was performed using a random-effects model to calculate pooled odds ratios (OR) and relative risks (RR) with their respective 95% confidence intervals (CI). The review included data from 4 studies that met the inclusion criteria. The combined OR from two studies was 0.05 (95% CI: 0.00, 4.41), which does not suggest a statistically significant association between prenatal cocaine exposure and the incidence of CL/P due to the confidence interval crossing the null value. Additionally, the combined RR was 0.17 (95% CI: 0.04, 0.66), indicating a statistically significant decrease in the risk of CL/P associated with prenatal cocaine exposure. These results, with an OR that is not statistically significant and an RR suggesting decreased risk, should be interpreted with caution due to considerable heterogeneity and variability among the included studies' findings. Further research is needed to clarify these associations. The findings from this systematic review and meta-analysis suggest that maternal cocaine use during pregnancy is not a statistically significant independent risk factor for the development of CL/P in offspring. These results underscore the multifactorial nature of CL/P etiology and emphasize the importance of considering other genetic, environmental, and nutritional factors in understanding the condition's origins. While the study provides important insights, limitations such as data heterogeneity and potential confounders should be acknowledged. Future research should adopt rigorous study designs and explore a broader range of potential risk factors to comprehensively elucidate CL/P development.

Investigating the dynamic relationship of sleep-disordered breathing, orthodontic treatment needs, and dental esthetics in the general population.

Sleep-disordered breathing (SDB) is characterized by upper airway dysfunction and is linked to severe health issues. Individuals with SDB have distinct craniofacial morphology for which orthodontists are most suitable for the management due to their dental expertise. This study aims to discern key differences in dental parameters between individuals with and without SDB. The present study is a cross-sectional observational study conducted for 12 months. Out of 70 participants, 35 were placed in the SDB group as per the Berlin questionnaire (BQ) and 35 in the control aged 18-22 years. Criteria excluded individuals with preexisting illnesses, missing teeth, tonsillectomy, orthodontic or jaw surgeries, cleft lip/palate, or craniofacial anomalies. Dental assessments included interdental width, palatal vault depth and shape, molar relation, overjet, and overbite. In addition, self-perceived orthodontic treatment needs were evaluated as a secondary measure. In the SDB group, interdental distances were significantly reduced in the canine, first premolars, second premolars, and molar regions by 2, 3, 4, and 1.8 mm, respectively. A noticeable V-shaped arch was observed. Overjet and overbite increased by 42.85% and 31.42%, respectively, with Class 1 malocclusion more prevalent than Class 2. The Berlin questionnaire identified 54.3% as high-risk SDB. The Index of Orthodontic Treatment Need-Esthetic Component (IOTN-AC) revealed that 68.6% of snoring participants required orthodontic treatment. Individuals with SDB exhibit a constricted maxilla and reduced interdental measurements, indicating a moderate risk. The Berlin questionnaire proves valuable in assessing SDB severity. Moreover, individuals displaying signs of SDB often present a high prevalence of orthodontic treatment needs, as indicated by the IOTN-AC.