Dysmorphic Research Articles

Assessing the Effectiveness of a Short Form Screening Tool (COPs) for Body Dysmorphic Disorder in Cosmetic Surgery Patients: A Study of Pre- and Post-Operative Outcomes

Assessing the Effectiveness of a Short Form Screening Tool (COPs) for Body Dysmorphic Disorder in Cosmetic Surgery Patients: A Study of Pre- and Post-Operative Outcomes

7.N. Round table: Social media & smartphones: Threats to child & adolescent health and public health solutions

Abstract The daily lives of children and adolescents in 2024 are heavily influenced by social media and smartphones, which is unprecedented in previous generations. While this technology offers undoubted benefits, there is strong evidence on the negative effects of social and cognitive development of infants and primary school aged children, and mental health impacts in adolescents including depression, anxiety, sleep disruption, addictive behaviours and self-harm. Internet companies are financially incentivised to maximise screen time of users to generate advertising revenue, and more time spent by young people on these devices in a largely unregulated online domain increases risk of consequences like bullying and harassment, body dysmorphia, gambling addiction, porn addiction, sexual predation and suicide. Comprehensive solutions are urgently needed to regulate the activities of social media and tech companies and support young people to protect themselves from serious harms. Governments have been slow to introduce policies such as smartphone bans or enhanced privacy laws, perhaps because they are perceived as unpopular infringements on the rights of adult users and/or due to a potential detrimental effect on commercial interests. Guidance can be disseminated to young people, schools, families and institutions on how to reduce screen time and smartphone addiction, and improve coping and self-regulation to mitigate these risks. Information campaigns with positive health messages in this area, to compete with the advertising dominance of social media companies, are another opportunity to improve behaviours and reduce adverse health effects. The objectives of this round table workshop are to share examples of strategies, guidance and policies from across Europe, and discuss with the audience how the public health community can collaborate to tackle this problem. Members of the EUPHA Child and Adolescent Public Health (CAPH) section will outline the latest available evidence on the negative impacts of social media and screens, present examples of innovative public health responses and strategies to protect children, and engage conference participants for their input and discussion. Five panellists will present. First, John will start with a quiz of the audience which will include presentation of current data and trends relating to social media and smartphone usage. The second presentation by Cecilia will highlight in detail evidence of both benefits and adverse effects of these technologies in the lives of young people. The third speaker Karin will discuss examples of effective policies to reduce this impact, with a focus on the role of schools. The fourth speaker Jean will give further examples of public health actions, and share recommendations directly from children and young people. The fifth panellist Silja will re-quiz the audience, to gauge the reaction and support of solutions that were covered, and this will lead into the interactive discussion. Key messages • Popularity of smartphones and social media has increased dramatically in recent years, particularly among minors, with significant impacts on mental and physical health. • Public health solutions are urgently needed, and this workshop will share examples of effective innovative responses in European contexts, followed by an interactive audience discussion.

Two familial cases of infantile epileptic spasms syndrome associated with UDP-glucose-6-dehydrogenase deficiency.

Developmental and epileptic encephalopathies (DEEs) are severe forms of epilepsy characterized by seizure onset in infancy or childhood. The seizures are typically drug-resistant and often accompanied by significant alterations in the electroencephalogram (EEG). DEEs are associated with neurodevelopmental impairment, which can arise from both the epileptic activity itself and the underlying etiology, which is most often genetic in origin. We present the clinical and molecular features of two patients with DEE associated with a pathogenic variant in the UGDH gene. This gene encodes a protein that converts uridine diphosphate (UDP)-glucose into UDP-glucuronate, which plays a crucial role in the biosynthesis of glycosaminoglycans, essential components of the connective tissue and extracellular matrix. Both patients started with epileptic spasms associated with a pattern of hypsarrhythmia in the EEG at 4 months of age. Both developed global developmental delay and the physical examination revealed hypotonia and mildly dysmorphic features. In both families, there was another affected sibling with a similar clinical presentation, although genetic studies were not performed in one of these children. A homozygous pathogenic variant in the UGDH gene, NM_003359.4:c.131C>T - p.(Ala44Val), previously reported to be associated with the described phenotype, was identified.

Biallelic germline DDX41 variants in a patient with bone dysplasia, ichthyosis, and dysmorphic features.

DDX41 (DEAD‑box helicase 41) is a member of the largest family of RNA helicases. The DEAD-box RNA helicases share a highly conserved core structure and regulate all aspects of RNA metabolism. The functional role of DDX41 in innate immunity is also highly conserved. DDX41 acts as a sensor of viral DNA and activates the STING-TBK1-IRF3-type I IFN signaling pathway. Germline heterozygous variants in DDX41 have been reported in familial myelodysplasia syndrome (MDS)/acute myeloid leukemia (AML) patients; most patients also acquired a somatic variant in the second DDX41 allele. Here, we report a patient who inherited compound heterozygous DDX41 variants and presented with bone dysplasia, ichthyosis, and dysmorphic features. Functional analyses of the patient-derived dermal fibroblasts revealed a reduced abundance of DDX41 and abrogated activation of the IFN genes through the STING-type I interferon pathway. Genome-wide transcriptome analyses in the patient's fibroblasts revealed significant gene dysregulation and changes in the RNA splicing events. The patient's fibroblasts also displayed upregulation of periostin mRNA expression. Using an RNA binding protein assay, we identified DDX41 as a novel regulator of periostin expression. Our results suggest that functional impairment of DDX41, along with dysregulated periostin expression, likely contributes to this patient's multisystem disorder.

Safety behavior reduction for appearance concerns: A randomized controlled trial of a smartphone-based intervention.

Appearance concerns are a core feature of multiple psychiatric disorders (i.e., body dysmorphic disorder, eating disorders, and social anxiety disorders). Individuals with these concerns commonly engage in appearance-related safety behaviors (ARSB), behaviors intended to avoid, prevent, or manage the negative evaluation of one's physical appearance. The present study evaluated a brief ARSB reduction intervention for appearance concerns. Women with elevated appearance concerns (N = 203) were recruited from across the United States and randomized to receive one of two 1-month smartphone-based interventions targeting ARSBs or unhealthy behaviors (UHBs). Both consisted of daily text messages with links to behavior checklists and reminders to avoid the respective behaviors. Participants in both treatments saw substantial reductions in symptoms. Though the UHB fading condition showed significantly better treatment adherence than ARSB fading, ARSB fading led to significantly lower appearance concerns (sr² = .028, p = .014) and eating disorder symptoms (sr² = .024, p = .020) at posttreatment, and lower appearance concerns (sr² = .041, p = .004), eating disorder symptoms (sr² = .029, p = .006), social anxiety (sr² = .048, p = .005), and appearance importance at 1-month follow-up (sr² = .042, p = .011), relative to UHB fading. Changes in ARSBs were found to partially mediate the effect of treatment on appearance concerns. These preliminary findings provide novel evidence for the efficacy of targeting ARSBs and suggest that this text-based intervention may be an efficacious and accessible intervention for women with elevated appearance concerns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neurodevelopmental Disorder Caused by Deletion of CHASERR, a lncRNA Gene

SummaryCHASERR encodes a human long noncoding RNA (lncRNA) adjacent to CHD2, a coding gene in which de novo loss-of-function variants cause developmental and epileptic encephalopathy. Here, we report our findings in three unrelated children with a syndromic, early-onset neurodevelopmental disorder, each of whom had a de novo deletion in the CHASERR locus. The children had severe encephalopathy, shared facial dysmorphisms, cortical atrophy, and cerebral hypomyelination — a phenotype that is distinct from the phenotypes of patients with CHD2 haploinsufficiency. We found that the CHASERR deletion results in increased CHD2 protein abundance in patient-derived cell lines and increased expression of the CHD2 transcript in cis. These findings indicate that CHD2 has bidirectional dosage sensitivity in human disease, and we recommend that other lncRNA-encoding genes be evaluated, particularly those upstream of genes associated with mendelian disorders. (Funded by the National Human Genome Research Institute and others.)

Case report: Adult patient with WWOX developmental and epileptic encephalopathy: 40 years of observation

WWOX developmental and epileptic encephalopathy is characterised by drug-resistant epilepsy with onset within the first year of life and severe psychomotor developmental delay. This report presents for the first time a clinical case of an adult patient with a homozygous likely pathogenic variant (p.Thr12Met) in the WWOX gene, with more than 40 years of follow-up. The patient had refractory epilepsy with various types of seizures during his life: mainly epileptic spasms, autonomic, myoclonic, tonic seizures, and absences. The patient had a prominent developmental delay with a lack of expressive speech, but by the age of 3, he had acquired the skills to sit, crawl, and walk with support. In adolescence, there was an acute regression of acquired skills to a total absence of independent motor activity. The patient had dysmorphic features, such as upslanting palpebral fissures, arched eyebrows, and hypertelorism. For many years, the patient was given a diagnosis of cerebral palsy; 38 years after the onset of the disease, he was given a molecular genetic diagnosis of WWOX-associated developmental and epileptic encephalopathy. Our observation illustrates the natural history of WWOX-DEE and the high clinical significance of early genetic diagnostics for identifying the cause of developmental delay and resistant epilepsy.

A Rare Cause of Recurring Lung Infection: Moebius Syndrome

Moebius syndrome is a rare congenital disorder characterized by bilateral paralysis of the VIth and VIIth cranial nerves, leading to facial diplegia and bilateral paralysis of ocular abduction, often associated with orofacial anomalies. This work reports a case collected at the pediatric infectious diseases and pneumo-allergology department of the Children's Hospital of Rabat, of a 9-month-old male infant, 6th of a family of six, of non-consanguineous parents, with a delay in psychomotor acquisitions. The examination shows facial dysmorphism with hypertelorism, epicanthus and right facial paralysis. Since birth, he has had swallowing disorders causing repeated respiratory infections, hence his hospitalization in our training. The etiopathogenesis of this disease remains controversial, with a great clinical heterogeneity whose observed signs are mainly due to the involvement of the VIth and VIIth cranial pairs, mainly resulting in various orofacial and ocular anomalies. The treatment remains symptomatic based on a multidisciplinary approach. The aim of this observation is to identify the particularities of this syndrome with a view to early diagnosis and effective management.

Dental abnormalities observed in the oculo-facio-cardio-dental (OFCD) syndrome present in two Czech families bearing novel de novo BCOR pathogenic variants

BackgroundThe oculo-facio-cardio-dental syndrome (OFCD) is an ultra-rare multiple congenital anomaly. This report describes clinical findings emphasising dental phenotype in five, molecularly confirmed, female cases from two Czech families.Case presentationDental examinations were carried out. An orthopantomogram was taken in three patients, and all patients’ intraoral cavities and teeth were photographed. Exome sequencing was performed in both probands. Results were validated by Sanger DNA sequencing which was also used to follow segregation of the variants in first-degree relatives. Dental abnormalities and congenital cataracts were present in all five cases, whilst other signs were variable and included facial dysmorphism, microphthalmia, and cardiac and skeletal abnormalities. Two individuals had cleft lip and/or cleft palate. Radiculomegaly occurred in three patients with permanent teeth and was diagnosed on orthopantomograms. Two patients had agenesis of permanent teeth. Malocclusion was also present in two patients due to crowding and a Class III malocclusion and mandibular overjet. De novo novel pathogenic variants in the BCOR gene were identified; c.2382del p.(Lys795Argfs*12) and c.3914dup p.(Gln1306Alafs*20) and co-segregated with the disease in each family.ConclusionsThe OFCD syndrome has a unique dental phenotype and dentists should be aware of signs of this ultra-rare genetic disorder. All patients with congenital cataracts and dental abnormalities, including those without a family history, should be referred for genetic testing and indicated to specialised dental care.

Clinical characteristics and genetic analysis of mental retardation disorder with TRIO gene variant

Objective: To summarize the clinical and genetic characteristics of mental retardation disorder (MRD) with TRIO gene variant in children. Methods: Case series study. The data of 9 children with TRIO gene variants were collected retrospectively from August 2019 to March 2024 in Department of Neurology, Beijing Children's Hospital, Capital Medical University and Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University. The data included gender, age, intellectual and motor development, appearance, seizures, neuroimaging and genetic results. The clinical features and genotype-phenotype correlations were summarized. Results: Of the 9 children, 6 boys and 3 girls, 4 MRD63 children presented with moderate to severe developmental delays accompanied by macrocephaly; 5 MRD44 children had mild to moderate developmental delays with microcephaly. A total of 5 children had dysmorphic facial features (flat occiput, thick eyebrows, unibrow, large ears, short fingers, pale skin, yellow hair, and strabismus), 2 children experienced seizures (1 child with myoclonic seizure and 1 with absence seizure), 4 children had feeding difficulties, 1 child had congenital cataracts, 1 child had congenital heart disease, 1 child had recurrent infections, and 1 child had tiger-striped changes in the fundus examination. TRIO gene variants carried by the 9 children were all de novo, involving 8 variant sites, including 7 missense variants and 1 frameshift variant, c.3232C>T/p.R1078W (2 cases), c.3920A>G/p.Y1307C, c.4112A>T/p.H1371L, c.4283G>T/p.R1428L, c.4394A>G/p.N1465S, c.6041T>C/p.I2014T, c.6821G>A/p.R2274H, c.7027delC/p.Q2343Sfs*70. Among them, 2 sites are located in the Spectrin domain, 4 sites are in the GEFD1 domain, 2 sites are in the GEFD2 domain, and 1 site (frameshift variant) is in the PH2-SH3 domain. The individual with frameshift variant exhibit absence seizures, mild developmental delay, and the mildest phenotype. The child with myoclonic seizures was treated with valproic acid and levetiracetam for seizure control, while the child with absence epilepsy was treated with valproic acid and lamotrigine for seizure control. All 9 children underwent regular rehabilitation exercises, making slow progress. Conclusions: TRIO gene related MRD is characterized by varying degrees of developmental delay, and often accompanied by macrocephaly or microcephaly, dysmorphic facial features, and with or without seizures. The main variant types are missense variants, which are mostly concentrated in the Spectran domain and GEFD domain. p. R1078W may be a relative hotspot variant. The phenotype caused by the frameshift variant is relatively milder.

Phenotype of patients with late diagnosis of 22q11 deletion: a review and retrospective study.

Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, typically presenting in neonates with congenital cardiac anomalies, hypocalcaemia and thymic hypoplasia. Some patients are diagnosed later in adolescence and adulthood, with less known about the clinical phenotype of these patients. To summarise key clinical features in cases of 22q11DS diagnosed during adolescence and adulthood. This is a retrospective cohort study of 22q11DS patients diagnosed after 13 years of age over 2010-2021, with a literature review of published cases highlighting other late diagnoses. The study was performed in a large multicentre tertiary health network in Melbourne, Australia. Patients diagnosed with 22q11DS after the age of 13 years were included in the study. Main outcome measures were key clinical features in cases of late diagnosis of 22q11DS. A literature search yielded 53 published case reports and one cohort study for review (62 subjects). Additionally, 10 cases of late diagnosis of 22q11DS were identified through a retrospective electronic medical chart review. Findings suggest that intellectual disability and learning difficulties, hypocalcaemia with hypoparathyroidism and facial dysmorphism remain key features in patients with a late diagnosis of 22q11DS, with hypocalcaemia being the most common presentation leading to diagnosis. Patients diagnosed in adulthood may lack classical clinical features of congenital cardiac anomalies and thymic hypoplasia. Immunological consequences of 22q11DS are also an important late-onset consideration. Atypical features may include basal ganglia calcification. Chromosome 22q11DS has diverse clinical features and a highly variable phenotype, likely contributing to underdiagnosis and later diagnoses.

TRANSTORNO DISMÓRFICO CORPORAL:UMA REVISÃO INTEGRATIVA DO INSUSTENTÁVEL PESO DA BELEZA

This article explores the relationship between social media use and body dysmorphic disorder (BDD), contextualizing the increase in dissatisfaction with body image in an increasingly connected society. The objective was to understand the impact and influence of the search for beauty standards imposed by social media in relation to body dysmorphic disorder. The methodology used was an integrative literature review; the research was carried out through articles published in the last 10 years, in the PubMed, SciELO and Google Scholar databases; the search and selection path of the articles was arranged in an adapted flowchart. Four articles were included for the review and the results are presented in a summary table with the main elements of the studies. The discussion held understood that there is a strong correlation between the intensive use of social networks and the intensification of concerns about appearance, especially in relation to the face and belly. The discussions also revealed that the use of image-centered social media, such as Instagram and Snapchat, influences the perception of appearance, exacerbates comparative behaviors and fosters dysmorphic behaviors, and that constant exposure to idealized aesthetic standards and the use of filters and effects on published images contribute to increased body dissatisfaction with the consequent search for surgical and non-surgical aesthetic procedures. It was concluded that social media significantly influences the intensification of BDD, impacting individuals’ quality of life in the areas of physical and emotional health and social and professional relationships.

The clinical spectrum and pathogenesis associated with KMT2B variants in Chinese pediatric patients

ObjectiveTo evaluate the clinical spectrum and pathogenesis associated with KMT2B variants in Chinese children with dystonia or developmental delay. MethodsWe reported twenty-seven (fourteen males and thirteen females) pediatric patients with KMT2B variants identified via next-generation sequencing from a single Chinese center. Moreover, transcriptomics and proteomics assays were performed on fibroblasts from patients with different genotypes to investigate the pathogenic mechanisms involved. ResultsTwenty-six patients had dystonia including generalized dystonia (n = 19), multifocal dystonia (n = 6), and segmental dystonia (n = 1), and one patient had nondystonic severe-developmental delay (DD). All the twenty-six patients had complex dystonia compounded with other manifestations of movement disorders (tremor (n = 6), myoclonus (n = 5), status dystonicus (n = 2), and tic (n = 1)) or dysmorphic features and developmental delay. The onset of dystonia was between 1 month and 13 years 8 months (median 4 years 4 months). Dystonia was aggravated by fever (n = 11), and diurnal and climate fluctuations (n = 4). Eleven patients underwent deep brain stimulation and experienced significant improvements in motor function and disability. We identified twenty-six intragenic heterozygous KMT2B pathogenic variants and one Chr:19q13.12 contiguous gene deletion. Sixteen variants were novel. Differentially expressed genes induced by KMT2B variants were significantly enriched for mitochondria-related biological processes in patient fibroblasts. As a result, mitochondrial morphology of mitochondria was altered, and aerobic respiration was impaired. ConclusionOur study reports the pediatric cases of KMT2B-related disorder from a single center in China. Additionally, our study highlights the role of KMT2B variants in mitochondrial dysfunction.

Epilepsy in Angelman syndrome and the most common electroencephalographic findings

Angelman syndrome is a genetic disorder characterised by severe mental retardation, subtle dysmorphic facial features, a characteristic behavioural phenotype, seizures and abnormalities in video electroencephalograms (video EEG). Angelman syndrome may be associated with genetic mechanisms involving the region of chromosome 15q11-13. Up to 90% of cases have epileptic seizures, usually in the early years of life. Videoelectroencephalography patterns with some typical characteristics associated with Angelman syndrome have been reported, although these are not specific to it, and as such it is also useful for early diagnosis, especially in the first months or years of life. To characterise the videoelectroencephalography findings of 17 patients diagnosed with Angelman syndrome, and compare them with previously published studies. We conducted a retrospective observational study of 34 video EEGs performed on 17 patients diagnosed with Angelman syndrome at the clinical neurophysiology service of the Puerta de Hierro University Hospital in Madrid between 2019 and 2022. The primary objective was to characterise the videoelectroencephalographic findings and compare them with previously published studies. As secondary objectives, we analysed the patterns proposed by Dan and Boyd, and other demographic, genetic and clinical data. Video EEG supported the clinical suspicion in our study, as baseline brain activity was altered in all the patients. We identified a pattern similar to those defined by Dan and Boyd in 88% of the cases, and the type III pattern was the most common in our series. These findings confirm that video EEG is highly sensitive for the diagnosis of Angelman syndrome, and very useful as a diagnostic biomarker in the early stages of life.

A Psychometric Evaluation of the Body Image Questionnaire Child and Adolescent Version.

Body dysmorphic disorder (BDD) typically develops during adolescence, but there has been little research evaluating assessment tools for BDD in youth. This study sought to provide a comprehensive psychometric evaluation of a brief self-report questionnaire of BDD symptoms, the Body Image Questionnaire Child and Adolescent version (BIQ-C), in both clinical and non-clinical adolescent samples. Properties of the BIQ-C were examined in 479 adolescents recruited through schools and 118 young people with BDD attending a specialist clinic. Sensitivity to change was additionally examined in a subgroup of the clinical sample who received treatment (n = 35). Exploratory factor analysis indicated that a two-factor structure provided the best fit for the data in the non-clinical sample. The two-factor solution was corroborated through confirmatory factor analysis as the best solution in the clinical sample, although it did not fulfil predefined fit thresholds The first factor encompassed preoccupation and repetitive behaviours, while the second included items assessing functional impairment. The BIQ-C showed good internal consistency across both samples, and convergent validity with other measures of BDD. Among those in the clinical sample who received treatment, BIQ-C scores decreased significantly, and BIQ-C change scores were highly correlated with change scores on the gold-standard clinician-rated measure of BDD symptom severity. These findings indicate that the BIQ-C is a suitable tool for assessing BDD symptoms in young people and measuring change during treatment.

Prenatal alcohol exposure and associations with physical size, dysmorphology and neurodevelopment: a systematic review and meta-analysis

BackgroundFetal alcohol spectrum disorder (FASD) is a significant public health concern, yet there is no internationally agreed set of diagnostic criteria or summary of underlying evidence to inform diagnostic decision-making. This systematic review assesses associations of prenatal alcohol exposure (PAE) and outcomes of diagnostic assessments, providing an evidence base for the improvement of FASD diagnostic criteria.MethodsSix databases were searched (inception–February 2023). Case-controls or cohort studies examining associations between participants with/without PAE or a FASD diagnosis and the domains of physical size, dysmorphology, functional neurodevelopment and/or brain structure/neurology were included. Excluded studies were non-empirical, sample size < 10, PAE determined via biological markers only, or no suitable comparison group. Summary data were extracted and associations between outcomes and standardised levels of PAE or FASD diagnosis determined using random-effects meta-analyses. Certainty of the evidence was assessed using GRADE.ResultsOf the 306 included studies, 106 reported physical size, 43 dysmorphology, 195 functional neurodevelopment and 110 structural/neurological outcomes, with 292 different outcomes examined. There was a dose–response relationship between PAE and head circumference, as well as measures of physical size, particularly at birth. There was also an association between higher PAE levels and characteristic sentinel facial dysmorphology, as well as many of the current functional neurodevelopmental outcomes considered during diagnosis. However, data were often lacking across the full range of exposures. There was a lack of evidence from studies examining PAE to support inclusion of non-sentinel dysmorphic features, social cognition, speech-sound impairments, neurological conditions, seizures, sensory processing or structural brain abnormalities (via clinical MRI) in diagnostic criteria. GRADE ratings ranged from very low to moderate certainty of evidence.ConclusionsThis comprehensive review provides guidance on which components are most useful to consider in the diagnostic criteria for FASD. It also highlights numerous gaps in the available evidence. Future well-designed pregnancy cohort studies should specifically focus on dose–response relationships between PAE and dysmorphology, neurodevelopment and brain structure/neurological outcomes.Systematic review registrationPROSPERO: CRD42021230522.

Cohen Syndrome, A Case Report

Background: Cohen syndrome is a rare genetic disorder characterized by physical, developmental, and intellectual disabilities. It is primarily considered in children presenting with microcephaly, early-onset hypotonia, neutropenia, and global developmental delay. Results: A 16-day-old female infant with low birth weight and dysmorphic features was evaluated. This case highlights the importance of considering Cohen syndrome in the differential diagnosis of infants with similar clinical findings. Early recognition allows for timely intervention and support. Conclusion: While there is no cure for Cohen syndrome, early diagnosis and management can improve quality of life.Genetic counseling is essential for affected families.

ME2 Deficiency Is Associated With Recessive Neurodevelopmental Disorder.

Malate is an important dicarboxylic acid produced from fumarate in the tricarboxylic acid cycle. Deficiencies of fumarate hydrolase (FH) and malate dehydrogenase (MDH), responsible for malate formation and metabolism, respectively, are known to cause recessive forms of neurodevelopmental disorders (NDDs). The malic enzyme isoforms, malic enzyme 1 (ME1) and 2 (ME2), are required for the conversion of malate to pyruvate. To date, there have been no reports linking deficiency of either malic enzyme isoforms to any Mendelian disease in humans. We report a patient presenting with NDD, subtle dysmorphic features, resolved dilated cardiomyopathy, and mild blood lactate elevation. Whole exome sequencing (WES) revealed a homozygous frameshift variant (c.1379_1380delTT, p.Phe460fs*22) in the malic enzyme 2 (ME2) gene resulting in truncated and unstable ME2 protein in vitro. Subsequent deletion of the yeast ortholog of human ME2 (hME2) resulted in growth arrest, which was rescued by overexpression of hME2, strongly supporting an important role of ME2 in mitochondrial function. Our results also support the pathogenicity and candidacy of the ME2 gene and variant in association with NDD. To our knowledge, this is the first report of a Mendelian human disease resulting from a biallelic variant in the ME encoding gene. Future studies are warranted to confirm ME2-associated recessive NDD.

The Relationship Between Body Dysmorphic Disorder and Depressive Symptoms with Health-Related Quality of Life in Women with Vitiligo

Background: Vitiligo is a common skin disorder characterized by the loss of skin pigment, which can significantly impact individuals' health-related quality of life (HRQoL), particularly in women. Body dysmorphic disorder (BDD) and depressive symptoms are common psychological comorbidities associated with vitiligo. Objectives: This study aimed to investigate the relationship between BDD, depressive symptoms, and HRQoL in women with vitiligo. Methods: A cross-sectional study was conducted in Ahvaz, Iran, in 2023, involving a sample of 152 women with vitiligo. The study population included all women with vitiligo who presented to dermatology or cosmetic clinics in Ahvaz during that year. Data were collected using the MOS 36-item Short-Form Health Survey (SF-36), the Multidimensional Body-Self Relations Questionnaire (MBSRQ), and the Beck Depression Inventory (BDI). Pearson's correlation and regression analyses were used to assess the relationships between variables. Data analysis was conducted using SPSS-27 software. Results: Women with vitiligo had a mean health-related quality of life score of (58.13 ± 11.50). Their mean score on the body dysmorphic disorder assessment was (99.61 ± 37.33), and the mean depressive symptom score was (20.25 ± 4.47). Significant negative correlations were found between BDD and HRQoL, as well as between depressive symptoms and HRQoL, in women with vitiligo (P &lt; 0.001). Multiple regression analysis showed that BDD and depressive symptoms independently predicted HRQoL (P &lt; 0.001). Conclusions: Body dysmorphic disorder and depressive symptoms are significantly associated with impaired HRQoL in women with vitiligo. Screening for and treating BDD and depressive symptoms may improve HRQoL in this population.

Radiculomegaly as a key clinical feature in oculo-facio-cardio-dental (OFCD) syndrome: a case report with a novel truncating variant in BCOR gene.

Radiculomegaly is a rare dental anomaly characterised by the enlargement of the root canals of teeth. It is usually associated with oculo-facio-cardio-dental (OFCD) syndrome due to truncating variants in BCL-6 transcriptional corepressor (BCOR) (MIM*300485). We present the case of a 21-year-old female patient who was referred to genetics for a polymalformative syndrome including bilateral glaucoma and dental anomalies, especially radiculomegaly. Some others dysmorphic features were right superior lip notch, ogival palate, long philtrum, difficulty in pronation, café-au-lait spots, II-III toe bilateral syndactyly, and macrocephaly. Cone-beam CT confirmed radiculomegaly. The genetic analysis identified a heterozygous pathogenic variant NM_001123385.1:c.2093del (p.Pro698Glnfs*17) in the BCOR gene. After genetic diagnosis of OFCD syndrome, cardiac CT-scan revealed a large asymptomatic atrial septal defect that was subsequently surgically closed. Reviews of the literature have previously highlighted the prevalence of radiculomegaly in OFCD syndrome with a positive predictive value of 88.23% and a sensitivity of 75.94%. This case report highlights the importance of radiculomegaly as a clinical sign of OFCD syndrome, emphasising the rarity of non-syndromic radiculomegaly and the benefits of its diagnosis in clinical management, especially in cardiac screening.