Facial Anomalies Research Articles

Novel compound heterozygous mutations in UHRF1 are associated with atypical immunodeficiency, centromeric instability and facial anomalies syndrome with distinctive genome-wide DNA hypomethylation.

Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is in most cases caused by mutations in either DNA methyltransferase (DNMT)3B, zinc finger and BTB domain containing 24, cell division cycle associated 7 or helicase lymphoid-specific. However, the causative genes of a few ICF patients remain unknown. We, herein, identified ubiquitin-like with plant homeodomain and really interesting new gene finger domains 1 (UHRF1) as a novel causative gene of one such patient with atypical symptoms. This patient is a compound heterozygote for two previously unreported mutations in UHRF1: c.886C > T (p.R296W) and c.1852C > T (p.R618X). The R618X mutation plausibly caused nonsense-mediated decay, while the R296W mutation changed the higher order structure of UHRF1, which is indispensable for the maintenance of CG methylation along with DNMT1. Genome-wide methylation analysis revealed that the patient had a centromeric/pericentromeric hypomethylation, which is the main ICF signature, but also had a distinctive hypomethylation pattern compared to patients with the other ICF syndrome subtypes. Structural and biochemical analyses revealed that the R296W mutation disrupted the protein conformation and strengthened the binding affinity of UHRF1 with its partner LIG1 and reduced ubiquitylation activity of UHRF1 towards its ubiquitylation substrates, histone H3 and proliferating cell nuclear antigen -associated factor 15 (PAF15). We confirmed that the R296W mutation causes hypomethylation at pericentromeric repeats by generating the HEK293 cell lines that mimic the patient's UHRF1 molecular context. Since proper interactions of the UHRF1 with LIG1, PAF15 and histone H3 are essential for the maintenance of CG methylation, the mutation could disturb the maintenance process. Evidence for the importance of the UHRF1 conformation for CG methylation in humans is, herein, provided for the first time and deepens our understanding of its role in regulation of CG methylation.

Fragile sites, chromosomal lesions, tandem repeats, and disease.

Expanded tandem repeat DNAs are associated with various unusual chromosomal lesions, despiralizations, multi-branched inter-chromosomal associations, and fragile sites. Fragile sites cytogenetically manifest as localized gaps or discontinuities in chromosome structure and are an important genetic, biological, and health-related phenomena. Common fragile sites (∼230), present in most individuals, are induced by aphidicolin and can be associated with cancer; of the 27 molecularly-mapped common sites, none are associated with a particular DNA sequence motif. Rare fragile sites ( 40 known), 5% of the population (may be as few as a single individual), can be associated with neurodevelopmental disease. All 10 molecularly-mapped folate-sensitive fragile sites, the largest category of rare fragile sites, are caused by gene-specific CGG/CCG tandem repeat expansions that are aberrantly CpG methylated and include FRAXA, FRAXE, FRAXF, FRA2A, FRA7A, FRA10A, FRA11A, FRA11B, FRA12A, and FRA16A. The minisatellite-associated rare fragile sites, FRA10B, FRA16B, can be induced by AT-rich DNA-ligands or nucleotide analogs. Despiralized lesions and multi-branched inter-chromosomal associations at the heterochromatic satellite repeats of chromosomes 1, 9, 16 are inducible by de-methylating agents like 5-azadeoxycytidine and can spontaneously arise in patients with ICF syndrome (Immunodeficiency Centromeric instability and Facial anomalies) with mutations in genes regulating DNA methylation. ICF individuals have hypomethylated satellites I-III, alpha-satellites, and subtelomeric repeats. Ribosomal repeats and subtelomeric D4Z4 megasatellites/macrosatellites, are associated with chromosome location, fragility, and disease. Telomere repeats can also assume fragile sites. Dietary deficiencies of folate or vitamin B12, or drug insults are associated with megaloblastic and/or pernicious anemia, that display chromosomes with fragile sites. The recent discovery of many new tandem repeat expansion loci, with varied repeat motifs, where motif lengths can range from mono-nucleotides to megabase units, could be the molecular cause of new fragile sites, or other chromosomal lesions. This review focuses on repeat-associated fragility, covering their induction, cytogenetics, epigenetics, cell type specificity, genetic instability (repeat instability, micronuclei, deletions/rearrangements, and sister chromatid exchange), unusual heritability, disease association, and penetrance. Understanding tandem repeat-associated chromosomal fragile sites provides insight to chromosome structure, genome packaging, genetic instability, and disease.

Neuroaesthetics in Plastic and Reconstructive Surgery: Opportunities for Interdisciplinary Collaboration.

Neuroaesthetics is a burgeoning discipline concerned with the neural basis for the perception and creation of art1 and neuroscientific mechanisms of human aesthetic experiences.2 Research in this field has combined principles of neurology, neuroanatomy, psychology, and art history to answer questions about the experience of beauty.2 Vision has received particularly close attention, especially human perception of faces, paintings, landscapes, and architecture.3 Neuroaesthetics has made meaningful contributions to unraveling neurologic mechanisms underpinning the aesthetic experience, previously regarded as a philosophical concept. Research has demonstrated aesthetic evaluations are important for human activity in consumer behavior, mate selection, and determination of morality.4 The field has identified neuroanatomic structures implicated in the perception of beauty broadly, notably the medial orbital frontal cortex, as well as cortical and subcortical structures specific to certain visual or auditory experiences.2 Within plastic surgery, neuroaesthetics overlaps with the specialty’s goal of characterizing optimal aesthetic outcomes for people. Plastic surgery research on aesthetic preferences may be augmented through collaboration with our colleagues in neuroaesthetics, who offer valuable expertise in neuroscience and aesthetic principles. In return, plastic surgery offers clinical, anatomic, and human aesthetic perspectives that may broaden the neuroaesthetic scope of inquiry. The fields complement one another to enhance the sophistication of questions posed, data generated, and analyses of those data. One example of such a collaboration is the University of Pennsylvania’s Center for Human Appearance, in which neuroaesthetics, plastic surgery, oral surgery, dermatology, oculoplastic surgery, and ear, nose, and throat play key complementary roles in designing studies that enhance understanding of appearance and clinical outcomes. Examples of the center’s initiatives include employing crowdsourcing to compare layperson aesthetic preferences, applying eye-tracking technology to characterize gaze patterns toward visual stimuli, and leveraging face databases to associate character traits to those with facial anomalies.1 Such studies have had an effect on understanding clinical outcomes in aesthetics, craniofacial surgery, and breast surgery. These clinical studies may be augmented with techniques common to the neuroaesthetics toolbox, including functional magnetic resonance imaging or magnetoencephalography to characterize brain activity in response to visual stimuli or convolutional neural networks to learn image features from datasets.5 Other efforts to leverage architectural and artistic principles are also poised to improve health care infrastructure and optimize the patient experience. Plastic surgery has not been regarded as a subdomain of neuroaesthetics inquiry. Plastic surgery would be an asset to the evolution of neuroaesthetics and should seek opportunities to foster relationships with colleagues in this nascent field. This convergence of interests is an exciting opportunity to continue plastic surgery’s history of collaboration to answer unique, multidisciplinary questions with implications for the outcomes of our patients. Disclosure The authors have no financial interest to declare in relation to the content of this article.

PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation.

Background and Objectives: Pathogenic variants of PIGN are a known cause of multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). Many affected individuals have clinical features overlapping with Fryns syndrome and are mainly characterised by developmental delay, congenital anomalies, hypotonia, seizures, and specific minor facial anomalies. This study investigates the clinical and molecular data of three individuals from two unrelated families, the clinical features of which were consistent with a diagnosis of MCAHS1. Materials and Methods: Next-generation sequencing (NGS) technology was used to identify the changes in the DNA sequence. Sanger sequencing of gDNA of probands and their parents was used for validation and segregation analysis. Bioinformatics tools were used to investigate the consequences of pathogenic or likely pathogenic PIGN variants at the protein sequence and structure level. Results: The analysis of NGS data and segregation analysis revealed a compound heterozygous NM_176787.5:c.[1942G>T];[1247_1251del] PIGN genotype in family 1 and NG_033144.1(NM_176787.5):c.[932T>G];[1674+1G>C] PIGN genotype in family 2. In silico, c.1942G>T (p.(Glu648Ter)), c.1247_1251del (p.(Glu416GlyfsTer22)), and c.1674+1G>C (p.(Glu525AspfsTer68)) variants are predicted to result in a premature termination codon that leads to truncated and functionally disrupted protein causing the phenotype of MCAHS1 in the affected individuals. Conclusions: PIGN-related disease represents a wide spectrum of phenotypic features, making clinical diagnosis inaccurate and complicated. The genetic testing of every individual with this phenotype provides new insights into the origin and development of the disease.

Layperson Bias and Empathy Influence Visual Attention Toward Patients with Hemifacial Microsomia: A Prospective Eye-tracking Study

INTRODUCTION: Facial attractiveness influences our perceptions of others, with beautiful faces reaping societal rewards and anomalous faces encountering penalties. Previous work with functional magnetic resonance imaging (fMRI) has demonstrate implication of certain neuroanatomic structures in visual pathways when viewing others with facial anomalies. For example, laypersons with high levels of implicit bias toward those with facial anomalies demonstrated increased amygdala reactivity. This study aimed to characterize associations between visual attention patterns and implicit biases (attitudes toward groups of people without conscious awareness), explicit biases (attitudes toward groups of people with conscious awareness), and social dispositions toward people with facial anomalies. METHODS: Participants completed an implicit bias association test (IAT), an explicit bias questionnaire (EBQ), and several social disposition tests (e.g. empathic concern and perspective taking) prior to viewing publicly available images of pre- and postoperative patients with hemifacial microsomia (HFM). Eye-tracking was used to register visual fixations. Four areas of interest (AOIs) were defined on each face: cheek and ear, forehead and orbit, mandible and chin, and nose and lips. Linear mixed effects models (LMEMs) in R Studio tested whether locations of participant fixations were affected by surgical correction of HFM and influenced by IAT, EBQ, or social disposition scores. RESULTS: Sixty participants (38 women) were prospectively enrolled. LMEMs revealed participants with higher IAT scores fixated significantly less on the cheek and ear region preoperatively compared to postoperatively (β = 0.115, SE = 0.040, z = 2.855, p = 0.004). Participants with higher scores on empathic concern fixated more on the forehead and orbit preoperatively compared to postoperatively (β = -0.107, SE = 0.053, z = -2.007, p = 0.045) and participants with higher scores in perspective taking fixated more on the nose and lips (β = -0.085, SE = 0.038, z = -2.215, p = 0.027) preoperatively compared to postoperatively. EBQ scores and other social disposition scores did not significantly influence visual fixations in any AOIs based on better fit to the null models. CONCLUSION: Levels of biases, empathic concern, and other social dispositions may influence visual attention toward people with facial anomalies. Those with higher levels of implicit bias may avoid looking at anomalous anatomy, while those with higher levels of empathic concern and perspective taking do not show similar avoidance behaviors. These findings may have neural underpinnings with amygdala reactivity modulating visual activity in response to facial anomalies. This study has implications for the experience of patients with craniofacial anomalies and for characterizing neurologic mechanisms of the ‘beauty-is-good’ and ‘anomalous-is-bad’ biases.

A case of Potter sequence with WT1 mutation.

Wilms tumor 1 (WT1) is the causative gene of Denys-Drash syndrome and Frasier syndrome, and in most cases, kidney failure develops after birth. We report an unusual case of Potter sequence due to fetal nephropathy and kidney failure with a WT1 mutation. The neonate was born at 37weeks of gestation, and had no distinctive facial appearance or anomalies of the extremities. The external genitalia were ambiguous. Presence of a penile-like structure or hypertrophic clitoris was noted, and the urethra opened at the base of the penis or clitoris. On ultrasonographic examination, the kidney sizes were small. No kidney cysts were noted, but the kidney parenchymal luminosity was increased. Although the neonate received mechanical ventilation because of severe retractive breathing after birth, he died of poor oxygenation due to air leak syndrome at 60h after birth. The congenital anomalies of the kidney and urinary tract (CAKUT) gene panel revealed a heterozygous missense mutation in WT1 [NM_024426.6:exon9:c.1400G > A, p.(Arg467Gln)]. In WT1, missense mutations are associated with earlier onset of nephropathy than nonsense or splicing mutations. However, severe cases of fetal onset and early neonatal death with WT1 mutations are rare, and only one severe case with the same missense mutation in WT1 has been reported. Therefore, WT1 mutation may be suspected in Potter sequence patients with external genital abnormalities, and the WT1 missense mutation in our case [NM_024426.6:exon9:c.1400G > A, p.(Arg467Gln)] may indicate a severe case with fetal onset of nephropathy and kidney failure.

Double Chambered Right Ventricle with Small Ventricular Septal Defect: Detection and Evaluation by Color Doppler Echocardiography - A Rare Case Report

Double-chambered right ventricle (DCRV) is a rare condition seen only in 0.5-2.0 % of all cases of congenital heart disease (CHD). 80-90 % of DCRV cases are associated with various other congenital heart defects. In particular, perimembranous large ventricular septal defect (VSD) is the most common anomaly associated with DCRV. Anomalous muscular bundle (AMB) typically divides the right ventricle (RV) into a proximal high pressure and distal low pressure chamber. This aberration is often diagnosed during childhood and adolescence. Here we are presenting an exceedingly rare case of asymptomatic DCRV in an adolescent female with a small perimembranous VSD. Keywords: Double Chambered Right Ventricle, small perimembranous VSD, DCRV in an adolescent, facial anomalies, cleft upper lip

Long-Surviving Adult Siblings With Joubert Syndrome Harboring a Novel Compound Heterozygous CPLANE1 Variant.

Background and ObjectivesWe describe 2 long-surviving siblings with a mild phenotype of Joubert syndrome (JBTS) harboring a novel compound heterozygous missense variant in the CPLANE1 gene.MethodsTargeted sequencing data of 2 middle-aged siblings (sister and brother) with JBTS were analyzed.ResultsThe patients were older than 60 years and presented with an inborn facial anomaly and ataxia, accompanied by a molar tooth sign on brain MRI. The male patient showed mild intellectual disability, abnormal eye movements, and progressive gait disturbance. Targeted sequencing revealed a compound heterozygous missense variant of CPLANE1 p.Arg1193Cys_Gln1223Pro; c.3577C>T_3668A>C. Multiple in silico assays predicted that the missense sites were pathogenic.DiscussionThe phenotype-genotype correlation of CPLANE1 remains controversial, although many cases have been previously reported in children and young adults. Our study revealed a novel pathogenic variant of CPLANE1 in patients, confirming the role of this gene in JBTS, thus providing an opportunity for neurologists to recognize JBTS as a differential diagnosis for chronic progressive ataxia in an aging society.

Down Syndrome Detection Through Graphical Analysis of Facial Dysmorphic Features in Newborn Children With Ethnicity/Racial Slicing: An AI/ML-Based Approach

Background Down syndrome (DS) is associated with high mortality in India, due to nondiagnosis/late-diagnosis caused by unavailability of qualified doctors and/or lack of access to expensive medical/diagnostic facilities, especially in rural India. Using artificial intelligence/machine learning graphical pattern recognition tools, relevant facial points can be extracted from children’s photographs, facial anomalies can be identified, and probability of DS affliction can be predicted. Methods: Trained Google’s Cloud Vision AutoML Image Classification model was employed with ~2,000 photographs of DS positive children and ~3,000 photographs of DS negative children. A subset of 300 images, 100 each of Asian, Caucasian, and Other-Race children, was used to train and test 3 race-specific models. These results were compared against a unified model trained and tested with same 300 images. Results: The CloudML model trained with ~5,000 images initially achieved: Sensitivity—94.6%, specificity—96.9%, and accuracy—96.0%. Upon optimizing confidence threshold to 0.1, model maximized sensitivity at 99.6%, specificity dropped to 93.8%, and accuracy maintained at 96.0%. Each of the race-specific models trained with 100 images each, after optimization, yielded perfect scores on sensitivity, specificity, and accuracy of 100% each. Against this, the unified model with 300 images yielded overall accuracy of 98% (100% sensitivity, 83% specificity for Caucasian children, and 100% sensitivity, 100% specificity for Asian/Other children). Conclusions: Post optimization, this model can be used as an effective postnatal screening tool for DS detection. Preliminary results indicate that race-specific models can achieve even higher accuracy, sensitivity, and specificity.

Case Report: Fortuitous discovery of a white matter signal abnormality in the context of Leopard syndrome

Multiple Lentigines syndrome is an autosomal dominant inherited disorder of variable expressivity also known by the acronym LEOPARD syndrome. A rare disease with multiple congenital anomalies, mainly characterized by skin, facial and cardiac anomalies. Other malformations can be encountered, in particular cerebral and dysmorphic. We report the case of a 40-year-old female patient known for a Leopard syndrome, who in the context of bilateral hypoacusis, the cerebral MRI carried out finds a lesion in flair hypersignal at the asymptomatic left occipital level, we do not note any evolution of this lesion after 10 years this could correspond to "unidentified shiny object: OFU". In conclusion, LEOPARD syndrome is a disease with a multi-systemic involvement, the discovery of a lesion corresponding to an OFU" is possible.

The Chromatin Remodeler HELLS: A New Regulator in DNA Repair, Genome Maintenance, and Cancer.

Robust, tightly regulated DNA repair is critical to maintaining genome stability and preventing cancer. Eukaryotic DNA is packaged into chromatin, which has a profound, yet incompletely understood, regulatory influence on DNA repair and genome stability. The chromatin remodeler HELLS (helicase, lymphoid specific) has emerged as an important epigenetic regulator of DNA repair, genome stability, and multiple cancer-associated pathways. HELLS belongs to a subfamily of the conserved SNF2 ATP-dependent chromatin-remodeling complexes, which use energy from ATP hydrolysis to alter nucleosome structure and packaging of chromatin during the processes of DNA replication, transcription, and repair. The mouse homologue, LSH (lymphoid-specific helicase), plays an important role in the maintenance of heterochromatin and genome-wide DNA methylation, and is crucial in embryonic development, gametogenesis, and maturation of the immune system. Human HELLS is abundantly expressed in highly proliferating cells of the lymphoid tissue, skin, germ cells, and embryonic stem cells. Mutations in HELLS cause the human immunodeficiency syndrome ICF (Immunodeficiency, Centromeric instability, Facial anomalies). HELLS has been implicated in many types of cancer, including retinoblastoma, colorectal cancer, hepatocellular carcinoma, and glioblastoma. Here, we review and summarize accumulating evidence highlighting important roles for HELLS in DNA repair, genome maintenance, and key pathways relevant to cancer development, progression, and treatment.

Chromosomal abnormalities related to fever of unknown origin in a Chinese pediatric cohort and literature review

BackgroundFever of unknown origin (FUO) has been difficult to diagnose in pediatric clinical practice. With the gradual change in the disease spectrum, genetic factors have received increasing attention. Limited studies have shown an association between FUO and chromosomal abnormalities. In this study, we investigated the clinical and genetic characteristics of patients with FUO presenting with chromosomal abnormalities in a Chinese pediatric cohort.ResultsChromosomal abnormalities were detected in 5.5% (8/145) of the patients with FUO. Six patients with inflammatory fever presented with pharyngitis/amygdalitis (4/6), oral aphthous ulcer (2/6), digestive symptoms (3/6), developmental delay (4/6) and elevated C-reactive protein levels (6/6) during fever. These patients were often considered to have systemic inflammatory diseases, such as Behcet’s disease or systemic juvenile idiopathic arthritis. Trisomy 8, 7q11.23 dup, 3p26.3-p26.1 del/17q12 dup, 22q11.21 del, and 6q23.3-q24.1 del were identified in patients with inflammatory fever. The TNFAIP3 gene was included in the 6q23.3-q24.1 deletion fragment. Two patients with central fever were characterized by facial anomalies, developmental delay, seizures and no response to antipyretic drugs and were identified as carrying the de novo 18q22.3-q23 del. By performing a literature review, an additional 19 patients who had FUO and chromosomal abnormalities were identified. Trisomy 8, 6q23.2-q24.3 del and 18q22.3-q23 del were reported to present as fever, similar to the findings of our study.ConclusionsWe emphasized the important role of detecting chromosomal abnormalities in patients with FUO, especially in patients with systemic inflammatory manifestations or developmental delay. Identifying chromosomal abnormalities may change the diagnosis and management of patients with FUO.

Structure of DNMT3B homo-oligomer reveals vulnerability to impairment by ICF mutations

DNA methyltransferase DNMT3B plays an essential role in establishment of DNA methylation during embryogenesis. Mutations of DNMT3B are associated with human diseases, notably the immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome. How ICF mutations affect DNMT3B activity is not fully understood. Here we report the homo-oligomeric structure of DNMT3B methyltransferase domain, providing insight into DNMT3B-mediated DNA methylation in embryonic stem cells where the functional regulator DNMT3L is dispensable. The interplay between one of the oligomer interfaces (FF interface) and the catalytic loop renders DNMT3B homo-oligomer a conformation and activity distinct from the DNMT3B-DNMT3L heterotetramer, and a greater vulnerability to certain ICF mutations. Biochemical and cellular analyses further reveal that the ICF mutations of FF interface impair the DNA binding and heterochromatin targeting of DNMT3B, leading to reduced DNA methylation in cells. Together, this study provides a mechanistic understanding of DNMT3B-mediated DNA methylation and its dysregulation in disease.

Facial Nerve Anomalies as an Obscure Co-occurrence With External Ear Malformations: A Case Report

This study reports an infant with a rare triad of congenital facial palsy, bilateral aural atresia, and middle ear malformations. We highlight the audiological test battery in detail that led to identifying this obscure co-occurrence in a 6-month-old infant. The challenges associated with identifying such rare conditions, especially in infants, can be overcome only by incorporating a meticulous and vigilant approach. The infant was subjected to a series of subjective and objective audiological evaluations, through which rare asymmetric facial grimaces were vigilantly observed. This observation warranted radiologic investigation, which confirmed the suspicion that the anomaly may not be restricted to auditory structures alone. As facial nerve anomalies were confirmed, diversified recommendations, including speech, language, and swallow evaluation, were made apart from the auditory management. Hence in cases of external ear anomalies, although rare, it is essential to rule out facial nerve abnormalities as they can be a concealed problem.

FGD1 Variant Associated With Aarskog-Scott Syndrome.

BackgroundAarskog–Scott syndrome, a rare X-linked genetic disorder, is identified by combined clinical manifestations of short stature, facial, skeletal, and genital anomalies. Annually, two or three new cases are diagnosed with Aarskog–Scott syndrome, which is associated with FGD1 variants. However, there is no specific treatment for Aarskog–Scott syndrome due to its unclear mechanism.MethodsClinical data were collected when the patient first visited the hospital. Trio whole-exome sequencing and Sanger sequencing were performed for the genetic cause of disease. To evaluate the pathogenicity of the variants in vitro, stable cell lines were constructed using lentivirus infection in 143B cell. Furthermore, Western blot was used to verify the expression of signaling pathway-related proteins, and the transcription levels of osteogenic-related genes were verified by luciferase reporter gene assay.ResultsA 7-year-old boy was manifested with facial abnormalities, intellectual disability, and short stature (−3.98 SDS) while the growth hormone level of stimulation test was normal. Trio whole-exome sequencing and Sanger sequencing identified a variant (c.1270A>G, p.Asn424Asp) in FGD1 gene. The Asn424 residue was highly conserved and the hydrogen bond in the FGD1 variant protein has changed, which led to decrease in the interaction with CDC42 protein. In vitro study showed that the Asn424Asp variant significantly decreased the transcription levels of OCN, COL1A1, and ALP activity, and it activated the phosphorylation of JNK1.ConclusionMolecular biological mechanisms between abnormal expression of FGD1and Aarskog–Scott syndrome remain poorly understood. In our study, c.1270A>G variant of FGD1 resulted in Aarskog–Scott syndrome, and the analysis of pathogenicity supports the deleterious effect of the variant. Furthermore, we demonstrated the weakened affinity of the mutant FGD1 and CDC42. Decreased expression of osteogenic-related gene and abnormal activation of JNK1 were also shown in this work.

Tessier cranio-facial clefts presenting to a tertiary eye care center in Northern India: Ophthalmic features and a review of management.

Purpose:Tessier classification is used to classify congenital facial cleft disorders utilizing the anatomical location of the cleft and its extension. The orbital and ocular morbidities associated with the birth disorder are numerous. The authors decided to perform a retrospective analysis of the clinical features of the patients who presented to a tertiary care hospital with orbito-cranial clefts.Methods: The authors retrospectively evaluated the records of patients with craniofacial clefts who had presented to a tertiary eye care hospital in northern India in the last 2 years (January 2019–December 2020). The clinical features were studied, entered in MS Excel, and the data were evaluated.Results: The data of 40 patients with Tessier cleft were found. The majority of the patients were male and presented in the pediatric age group. Unilateral involvement was more common, with maxillary hypoplasia being the most common facial anomaly associated. Eyelid coloboma and euryblepharon was the most common periocular finding; lateral epibulbar dermoid and corneal opacity were the most common ocular surface anomaly. The majority of patients had presented for cosmetic correction. The syndromic association was with Goldenhar syndrome (n = 13), Fraser (n = 2), and one each of Treacher Collins, blepharocheilodontic, organoid nevus, and oculo-dento-digital syndrome. Combined clefts were also seen.Conclusion: Tessier cleft classification is a useful tool to classify cranio-facial left anomalies. Multitudes of ocular and orbital anomalies can be associated with their different forms. Better knowledge and understanding of the classification will aid immensely in predicting the ocular defects and planning their management.

Associations of Facial Proportionality, Attractiveness, and Character Traits.

Facial proportionality and symmetry are positively associated with perceived levels of facial attractiveness. The aims of this study were to confirm and extend the association of proportionality with perceived levels of attractiveness and character traits and determine differences in attractiveness and character ratings between "anomalous" and "typical" faces using a large dataset. Ratings of 597 unique individuals from the Chicago Face Database were used. A formula was developed as a proxy of relative horizontal proportionality, where a proportionality score of "0" indicated perfect proportionality and more negative scores indicated less proportionality. Faces were categorized as "anomalous" or "typical" by 2 independent reviewers based on physical features. Across the ratings for all faces, Spearman correlations revealed greater proportionality was associated with attractiveness ( ρ = 0.292, P < 0.001) and trustworthiness ( ρ = 0.193, P < 0.001), while lesser proportionality was associated with impressions of anger (ρ = 0.132, P = 0.001), dominance (ρ = 0.259, P < 0.001), and threateningness ( ρ = 0.234, P < 0.001). Mann-Whitney U tests revealed the typical cohort had significantly higher levels of proportionality (-13.98 versus -15.14, P = 0.030) and ratings of attractiveness (3.39 versus 2.99, P < 0.001) and trustworthiness (3.48 versus 3.35, P < 0.001). This study demonstrated that facial proportionality is not only significantly associated with higher ratings of attractiveness, but also associated with judgements of trustworthiness. Proportionality plays a role in evoking negative attributions of personality characteristics to people with facial anomalies.

Expanding the novel MAPKAPK5-related developmental disorder's genotype-phenotype correlation: Patient report and 19months of follow-up.

This study aimed to widen the knowledge of a recently identified, autosomal‐recessive, multiple congenital anomalies syndrome to date observed in only other three children. This is the second report of biallelic mutations in MAPKAPK5 whose impairment during human development has been associated with neurological, cardiac, and facial anomalies combined with fingers and toes malformations. Through the affected patients' genetic and phenotypic features overlap, this report confirms MAPKAPK5 as causative gene and adds unique neurodevelopmental characterization. Moreover, based on the complex congenital genitourinary anomalies reported and MAPKAPK5 literature review, we also propose kidney and external genitalia involvement as a key syndromic feature whose expressivity may be more severe in males.

The Results of Cochlear Implantation in the Inner Ear Malformations.

Cochlear implants are arguably the most successful neural prosthesis today. Cochlear implantation has several difficulties in patients with internal ear anomalies. This study was performed to analyze intraoperative, postoperative findings, and auditory performance of 55 patients who had inner ear malformations and were treated with cochlear implants at Otorhinolaryngology Department of Çukurova University Hospital. Auditory performances were analyzed in 30 of 55 patients. Patients with cochlear anomalies were evaluated as group I, patients with vestibular malformation as group II, and patients with the normal bone labyrinth as group III. Listening progress profiles and meaningful auditory integration scale tests were used to determine performances. Comparison between the listening progress profiles test performance of the groups at 12th and 18th month of group I was significantly lower than other groups (P < .05) and reached at the same level after the 24th month. Comparison between the meaningful auditory integration scale test performance of groups at 24th and 36th month of group I was significantly lower than other groups (P < .05). Perilymph gusher was observed in 3 patients who had incomplete partition I malformation. Oozing was observed in 50% of incomplete partition II patients. Facial nerve traced a variant course in 4 of 55 patients and 6 patients had postoperative meningitis. Initially patients with inner ear anomalies showed that the level of language development was worse than patients with normal bone anatomy. However, it was shown that they both reached the same point as a result. Facial nerve anomaly and meningitis risk is higher in patients with inner ear malformations.

2021 Kazanjian Lecture: Caring for Children With Facial Anomalies—Inspiring the Next Generation

Varaztad Kazanjian stood for innovation in plastic surgery, serving as a founder of many of the craniomaxillofacial principles practiced today. However, we have seen attrition in career interest toward craniofacial and pediatric plastic surgery as trainees progress from medical school to early career. We explore several aspects of our specialty that could help reinvigorate enthusiasm for our specialty and the retention of young surgeons. We begin by judging career success and defining the patient population we wish to serve. We examine several areas by which our specialty can be perceived as more attractive to young surgeons, to include early mentorship and maintaining these mentoring relationships beyond the training period. We emphasize the need to diversify our trainees and include them in efforts to expand innovation in our specialty. We discuss the need to champion craniofacial and pediatric plastic surgery as mission-critical to our institutions, involve trainees and young surgeons in advocacy efforts on behalf of our patients, and involve trainees and young surgeons in global health efforts. We discuss how to structure our divisions to make craniofacial and pediatric plastic surgery an inviting environment that welcomes new participants, rather than making them feel they are working their way through an “old boys’ club.” Innovation alone will not sustain our specialty unless we mentor the next generation to want to continue in the line of innovation that drew us to this specialty.