Dysmorphic Research Articles

Fetal face shape analysis from prenatal 3D ultrasound images

3D ultrasound imaging of fetal faces has been predominantly confined to qualitative assessment. Many genetic conditions evade diagnosis and identification could assist with parental counselling, pregnancy management and neonatal care planning. We describe a methodology to build a shape model of the third trimester fetal face from 3D ultrasound and show how it can objectively describe morphological features and gestational-age related changes of normal fetal faces. 135 fetal face 3D ultrasound volumes (117 appropriately grown, 18 growth-restricted) of 24-34 weeks gestation were included. A 3D surface model of each face was obtained using a semi-automatic segmentation workflow. Size normalisation and rescaling was performed using a growth model giving the average size at every gestation. The model demonstrated a similar growth rate to standard head circumference reference charts. A landmark-free morphometry model was estimated to characterize shape differences using non-linear deformations of an idealized template face. Advancing gestation is associated with widening/fullness of the cheeks, contraction of the chin and deepening of the eyes. Fetal growth restriction is associated with a smaller average facial size but no morphological differences. This model may eventually be used as a reference to assist in the prenatal diagnosis of congenital anomalies with characteristic facial dysmorphisms.

Refining the 9q34.3 microduplication syndrome reveals mild neurodevelopmental features associated with a distinct global DNA methylation profile.

Precise regulation of gene expression is important for correct neurodevelopment. 9q34.3 deletions affecting the EHMT1 gene result in a syndromic neurodevelopmental disorder named Kleefstra syndrome. In contrast, duplications of the 9q34.3 locus encompassing EHMT1 have been suggested to cause developmental disorders, but only limited information has been available. We have identified 15 individuals from 10 unrelated families, with 9q34.3 duplications <1.5 Mb in size, encompassing EHMT1 entirely. Clinical features included mild developmental delay, mild intellectual disability or learning problems, autism spectrum disorder, and behavior problems. The individuals did not consistently display dysmorphic features, congenital anomalies, or growth abnormalities. DNA methylation analysis revealed a weak DNAm profile for the cases with 9q34.3 duplication encompassing EHMT1, which could segregate the majority of the affected cases from controls. This study shows that individuals with 9q34.3 duplications including EHMT1 gene present with mild non-syndromic neurodevelopmental disorders and DNA methylation changes different from Kleefstra syndrome.

Polyhydramnios associated with rare genetic syndromes: two case reports

BackgroundWe present two genetic causes of polyhydramnios that were challenging to diagnose due to their rarity and complexity. In view of the severe implications, we wish to highlight these rare genetic conditions when obstetricians consider differential diagnoses of polyhydramnios in the third trimester.Case presentationPatient 1 is a 34-year-old Asian woman who was diagnosed with polyhydramnios at 28 weeks’ gestation. First trimester testing, fetal anomaly scan, and intrauterine infection screen were normal. Subsequent antenatal ultrasound scans revealed macroglossia, raising the suspicion for Beckwith–Wiedemann syndrome. Chromosomal microarray analysis revealed a female profile with no pathological copy number variants. The patient underwent amnioreduction twice in the pregnancy. The patient presented in preterm labor at 34 weeks’ gestation but elected for an emergency caesarean section. Postnatally, the baby was noted to have a bell-shaped thorax, coat hanger ribs, hypotonia, abdominal distension, and facial dysmorphisms suggestive of Kagami–Ogata syndrome. Patient 2 is a 30-year-old Asian woman who was diagnosed with polyhydramnios at 30 weeks’ gestation. She had a high-risk first trimester screen but declined invasive testing; non-invasive prenatal testing was low risk. Ultrasound examination revealed a macrosomic fetus with grade 1 echogenic bowels but no other abnormalities. Intrauterine infection screen was negative, and there was no sonographic evidence of fetal anemia. She had spontaneous rupture of membranes at 37 + 3 weeks but subsequently delivered by caesarean section in view of pathological cardiotocography. The baby was noted to have inspiratory stridor, hypotonia, low-set ears, and bilateral toe polysyndactyly. Further genetic testing revealed a female profile with a pathogenic variant of the GLI3 gene, confirming a diagnosis of Greig cephalopolysyndactyly syndrome.ConclusionThese cases illustrate the importance of considering rare genetic causes of polyhydramnios in the differential diagnosis, particularly when fetal anomalies are not apparent at the 20-week structural scan. We would like to raise awareness for these rare conditions, as a high index of suspicion enables appropriate counseling, prenatal testing, and timely referral to pediatricians and geneticists. Early identification and diagnosis allow planning of perinatal care and birth in a tertiary center managed by a multidisciplinary team.

Cri Du Chat Syndrome: A Case Study

Cri du Chat syndrome (CdCS) is a chromosomal abnormality resulting from a deletion of variable size at the end of the short arm of chromosome 5 (5p), including a critical region located at p15.2. It is one of the most common chromosomal deletions, with an incidence in the general population of between 1:20,000 and 1:50,000. Clinical features include an acute monochromatic cry, microcephaly, characteristic craniofacial dysmorphia progressing with age and significant mental and psychomotor retardation. The size of the deletion varies, and treatment depends on the various symptoms. Parental chromosomal rearrangement is found in 12% of cases and the majority of deletions responsible for cri-du-chat disease occur de novo. We present an observation of a Cri du Chat syndrome, confirmed by metaphasic karyotype (46, XY,del(5)(p13) de novo). Through this observation we will update the scientific news of this rare syndrome, as well as the place of cytogenetic explorations in the precise diagnosis and genetic counselling of dysmorphic syndromes.

The Body Dysmorphic Disorder Questionnaire-Aesthetic Surgery: Are We Screening the Troublesome Patients?

This study aims to clarify the current concept of performing rhinoplasty in patients with possible body dysmorphic disorder (BDD). The primary objective was to investigate the validity and evolution over time of the Body Dysmorphic Disorder Questionnaire-Aesthetic Surgery (BDDQ-AS) before and after surgery. Together with the BDDQ-AS, also the Nasal Obstruction Symptom Evaluation scale, FACE-Q nose and nostrils, and Utrecht questionnaire (UQ) were used for convergent validation. In this prospective study, 187 patients completed these patient-reported outcome measures at four time points: at the preoperative consultation and postoperatively at 3, 6 and 12 months. The preoperative BDDQ-AS positivity rate was as high as 55.1%. Postoperatively, there was a highly significant decrease in the odds of scoring positive on the BDDQ-AS. At the preoperative consultation, positively screened patients were less satisfied with the esthetics of their noses with worse scores on UQ, FACE-Q nose, and visual analog scale. The preoperative differences in outcome measure ratings disappeared postoperatively, except for the FACE-Q nostrils, which surprisingly showed better values in BDDQ-AS positive patients. Younger age and absence of nasal trauma were statistically significant covariates associated with positive BDDQ-AS screening. Due to the overwhelming decrease in positive BDDQ-AS outcomes after surgery, a positive screening result on the BDDQ-AS should not be interpreted as a formal contraindication for surgery. Collaboration with psychologists or psychiatrists remains crucial to diagnose BDD conclusively.

A cohort study of neurodevelopmental disorders and/or congenital anomalies using high resolution chromosomal microarrays in southern Brazil highlighting the significance of ASD

Chromosomal microarray (CMA) is the reference in evaluation of copy number variations (CNVs) in individuals with neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and/or autism spectrum disorder (ASD), which affect around 3–4% of the world’s population. Modern platforms for CMA, also include probes for single nucleotide polymorphisms (SNPs) that detect homozygous regions in the genome, such as long contiguous stretches of homozygosity (LCSH). These regions result from complete or segmental chromosomal homozygosis and may be indicative of uniparental disomy (UPD), inbreeding, population characteristics, as well as replicative DNA repair events. In this retrospective study, we analyzed CMA reading files requested by geneticists and neurologists for diagnostic purposes along with available clinical data. Our objectives were interpreting CNVs and assess the frequencies and implications of LCSH detected by Affymetrix CytoScan HD (41%) or 750K (59%) platforms in 1012 patients from the south of Brazil. The patients were mainly children with NDDs and/or congenital anomalies (CAs). A total of 206 CNVs, comprising 132 deletions and 74 duplications, interpreted as pathogenic, were found in 17% of the patients in the cohort and across all chromosomes. Additionally, 12% presented rare variants of uncertain clinical significance, including LPCNVs, as the only clinically relevant CNV. Within the realm of NDDs, ASD carries a particular importance, owing to its escalating prevalence and its growing repercussions for individuals, families, and communities. ASD was one clinical phenotype, if not the main reason for referral to testing, for about one-third of the cohort, and these patients were further analyzed as a sub-cohort. Considering only the patients with ASD, the diagnostic rate was 10%, within the range reported in the literature (8–21%). It was higher (16%) when associated with dysmorphic features and lower (7%) for "isolated" ASD (without ID and without dysmorphic features). In 953 CMAs of the whole cohort, LCSH (≥ 3 Mbp) were analyzed not only for their potential pathogenic significance but were also explored to identify common LCSH in the South Brazilians population. CMA revealed at least one LCSH in 91% of the patients. For about 11.5% of patients, the LCSH suggested consanguinity from the first to the fifth degree, with a greater probability of clinical impact, and in 2.8%, they revealed a putative UPD. LCSH found at a frequency of 5% or more were considered common LCSH in the general population, allowing us to delineate 10 regions as potentially representing ancestral haplotypes of neglectable clinical significance. The main referrals for CMA were developmental delay (56%), ID (33%), ASD (33%) and syndromic features (56%). Some phenotypes in this population may be predictive of a higher probability of indicating a carrier of a pathogenic CNV. Here, we present the largest report of CMA data in a cohort with NDDs and/or CAs from the South of Brazil. We characterize the rare CNVs found along with the main phenotypes presented by each patient and show the importance and usefulness of LCSH interpretation in CMA results that incorporate SNPs, as well as we illustrate the value of CMA to investigate CNV in ASD.

Expanding the phenotype of PPP1R21-related neurodevelopmental disorder.

PPP1R21 encodes for a conserved protein that is involved in endosomal maturation. Biallelic pathogenic variants in PPP1R21 have been associated with a syndromic neurodevelopmental disorder from studying 13 affected individuals. In this report, we present 11 additional individuals from nine unrelated families and their clinical, radiological, and molecular findings. We identified eight different variants in PPP1R21, of which six were novel variants. Global developmental delay and hypotonia are neurological features that were observed in all individuals. There is also a similar pattern of dysmorphic features with coarse faces as a gestalt observed in several individuals. Common findings in 75% of individuals with available brain imaging include delays in myelination, wavy outline of the bodies of the lateral ventricles, and slight prominence of the bodies of the lateral ventricles. PPP1R21-related neurodevelopmental disorder is associated with a consistent phenotype and should be considered in highly consanguineous individuals presenting with developmental delay/intellectual disability along with coarse facial features.

Multiple central giant cell granuloma of the jaws: diagnostic signposts of Noonan syndrome and RASopathy.

Noonan syndrome (NS) is a phenotypically variable inherited multi-system disorder. Maxillofacial findings can be diagnostic, especially in the evaluation of discrete facial dysmorphia. Diagnostic landmark findings of therapeutic relevance for the jaws such as central giant cell granuloma (CGCG) are rare in NS. However, recent molecular genetic studies indicate that these rare, benign lesions are neoplasms and more common in specific syndromes grouped under the umbrella term RASopathies. A specialist surgical diagnosis can be helpful in identifying the underlying disease. This report outlines diagnosis and treatment of a case of CGCG for which jaw diagnosis became the key to identifying a syndromic disease.

Novel phenotype associated with homozygous likely pathogenic variant in the POP1 gene.

The biallelic variants of the POP1 gene are associated with the anauxetic dysplasia (AAD OMIM 607095), a rare skeletal dysplasia, characterized by prenatal rhizomelic shortening of limbs and generalized joint hypermobility. Affected individuals usually have normal neurodevelopmental milestones. Here we present three cases from the same family with likely pathogenic homozygous POP1 variant and a completely novel phenotype: a girl with global developmental delay and autism, microcephaly, peculiar dysmorphic features and multiple congenital anomalies. Two subsequent pregnancies were terminated due to multiple congenital malformations. Fetal DNA samples revealed the same homozygous variant in the POP1 gene. Expression of the RMRP was reduced in the proband compared with control and slightly reduced in both heterozygous parents, carriers for this variant. To our knowledge, this is the first report of this new phenotype, associated with a novel likely pathogenic variant in POP1. Our findings expand the phenotypic spectrum of POP1-related disorders.

Emanuel syndrome due to unusual pattern

BackgroundThe hallmarks of Emanuel syndrome are pre- and postnatal growth retardation, microcephaly, global developmental delay, ear anomalies, and in males, heart, kidney, and genital abnormalities.ResultsThis study describes the atypical features of Emanuel syndrome, a rare chromosomal disorder. The patient had several physical features that are common in Emanuel syndrome, such as microcephaly, hypotonia, and ear anomalies. However, he exhibited certain unusual characteristics, including the lack of a prominent forehead, epicanthic folds, and a downward slanting palpebral fissure. There was infratentorial brain involution with a minor infarction in the left cerebral hemisphere and cerebellar hypoplasia on the magnetic resonance imaging (MRI) scan of the brain. Additionally, the patient had bilateral mild hearing loss and an aberrant epileptogenic pattern on the electroencephalogram (EEG). Orodental examination showed a long philtrum, everted fissured thick lower lip, highly attached labial frenum, and prominent median palatine raphe. The karyotype revealed 45XY t(11;22)(p15.5;q11.22), which is different from the typical karyotype of Emanuel syndrome.ConclusionsThis case sheds light on the possibility of alternative genetic mechanisms, beyond chromosomal abnormalities, in patients presenting with multiple congenital anomalies and facial dysmorphism.

Hyperinsulinemia in Sotos Syndrome with a de novo NSD1 Deletion.

Sotos syndrome belongs to the group of diseases characterised by features such as facial dysmorphism, intellectual disability, hypotonia and overgrowth. Usually, Sotos syndrome is caused by heterozygous mutations in the NSD1 gene at chromosome 5q35 or by large genomic deletions of the same region. Genotype-phenotype correlations have mainly been reported as an association of significant or major abnormalities and presence of 5q35 deletions rather than intragenic deletions or point mutations in NSD1. The congenital hyperinsulinaemic hypoglycaemia (CHI) has been described as an uncommon feature in the presentation of Sotos syndrome. Most of the patients with Sotos syndrome and transient CHI were carriers of 5q35 deletions while persistent CHI has been recently reported in individuals with point mutations or small NSD1 deletions. We report the clinical features and medical treatment in a new-born child with Sotos syndrome and CHI that was present for almost two years. Genetic cause of Sotos syndrome in this case was a novel, large genomic deletion encompassing 24 OMIM genes including the entire NSD1 gene and 6 other Morbid genes. Our report shows challenges in diagnostics and management of this rare genetic condition. We propose, that in neonatal diagnostics, the phenotypic spectrum of Sotos syndrome should include CHI as a characteristic feature and molecular genetic testing should be done by whole genome analysis.

The COGINS: A New Measure of Cognitive Insight in Obsessive-Compulsive and Related Disorders.

Research suggests that individuals with obsessive-compulsive and related disorders (OCRDs) with lower insight show a poorer response to cognitive behavioral therapy and might benefit from alternative treatments. However, there are inconsistencies in the literature regarding the definition and measurement of insight. This study endeavored to evaluate the psychometric properties of the Cognitive Obsessional Insight Scale (COGINS), a novel self-report measure of cognitive insight in OCRDs. The sample comprised 166 participants with a diagnosis of obsessive-compulsive disorder or body dysmorphic disorder enrolled in clinical trials. Participants completed the COGINS and a questionnaire battery at baseline and posttreatment. The COGINS demonstrated good internal consistency, test-rest reliability, convergent validity with other OCRD-specific measures of insight, positive associations with OCRD symptomatology, and had a moderating effect on treatment response. The COGINS is a valid and reliable practical tool to measure cognitive insight in OCRDs and might help toward clarifying the role of cognitive insight in this population.

An Evidence-based Pathway for Body Dysmorphic Disorder in Facial Aesthetics.

Aesthetic procedures should be avoided in patients with Body Dysmorphic Disorder (BDD) since they can negatively impact mental health and lead to further aesthetic dissatisfaction. There are no evidence-based patient pathways for BDD in facial aesthetics which can result in the failure to identify patients with BDD, leading to unsuitable treatments and suboptimal patient care. We aim to construct the first evidence-based patient pathway for BDD in surgical and non-surgical facial aesthetics. A systematic review was performed and articles that discussed screening or patient pathways for BDD in field of facial aesthetics were included. We extracted relevant information from each article on screening tools and pathways for BDD. Data were synthesised by summarising the data under column headings into a structured narrative and into new tables. Based on this synthesis, a practical pathway for BDD was constructed. Forty articles fulfilled the criteria for inclusion. Twenty-eight BDD screening tools were discussed in the included articles, and we provide an overview of these tools. Thirty-one articles discussed patient pathways for BDD, and we synthesised this information into a structured narrative. Combining these findings we present an evidence-based patient pathway for BDD for patients presenting for facial aesthetic treatments. This systematic review has resulted in the first, evidence-based, patient pathway for BDD in surgical and non-surgical facial aesthetics. This practical pathway can be used by aesthetic clinicians to identify patients with potential BDD and provide clear guidance for managing cases where BDD is suspected. It will help reduce the number of facial aesthetic procedures performed on patients with BDD, safeguard patient mental well-being and prevent further aesthetic dissatisfaction.

Impact of Psychiatric Symptoms on Nasal Perception in Septorhinoplasty Patients.

Psychological assessment plays a crucial role in the preoperative phase of septorhinoplasty (SRPL), exerting potential influence on both pre- and postoperative aspects of quality of life (QoL). In this prospective study, SRPL patients were systematically screened using two validated questionnaires for body dysmorphic disorder (BDD) and one each for anxiety, depression, and somatic symptom disorder (SSD). Nasal perception was evaluated utilizing two disease-specific, self-report instruments: The Rhinoplasty Outcomes Evaluation (ROE) and the Functional Rhinoplasty Outcome Inventory-17 (FROI-17). A total of 95 patients were enrolled. Positive screening rates were 40.4 and 28.3% for BDD, 37.3% for elevated anxiety, 16.4% for depression, and 22.4% for SSD. Mean scores on the ROE and FROI indicated lower QoL in all positive screening groups. Statistically significant differences were observed for anxiety (FROI total score: 47.1 ± 14.6 to 37.8 ± 16.2; p = 0.021) and BDD (ROE: 43.7 ± 15.7 to 32.5 ± 15.5; p = 0.003 and FROI total score: 47.4 ± 15.3 to 37.8 ± 17.1; p = 0.014). The Hospital Anxiety and Depression Scale exhibited a significant correlation with the preoperative FROI score (r = 0.34, p = 0.005). Patients with positive screenings for depression, anxiety, BDD, and SSD demonstrated compromised QoL during preoperative assessments compared with their negative counterparts, reflecting diminished nasal perception in both esthetic and functional dimensions. Surgeons must be cognizant of these psychological aspects during preoperative evaluations.

Surgical Rhinoplasty in Mild Forms of Body Dysmorphic Disorder: Safety, Protocols, and Long-Term Outcomes

AbstractBody dysmorphic disorder (BDD) is an obsessive–compulsive disorder concerning body image which negatively distorts the patient's perception of their appearance. In rhinoplasty, surgery on patients with severe BDD is considered contraindicated as patients are often dissatisfied and their BDD symptoms rarely improve. For patients with borderline to mild BDD, however, there has been some preliminary evidence to show that they can benefit from surgical rhinoplasty. In our first article on this series of BDD in rhinoplasty, we presented our two-specialist protocol using mandatory psychiatric evaluation (MPE) to assess patient's suitability. In this present article, we used this protocol to identify a group of borderline to mild BDD patients, performed surgical rhinoplasty on this group, and evaluated the outcome using a visual analog scale (VAS) and a five-point Likert scale. From 2010 to 2023, 1,602 patients attended our practice seeking cosmetic rhinoplasty, out of which, 892 were sent for MPE to the same psychiatrist. The MPE identified 2.5% (22/892) patients as having mild BDD, out of which, 15 were considered suitable for surgical intervention and underwent successful rhinoplasty (follow-up 6–95 months, M = 54.13 months). Five of 15 patients scored 10/10 on the VAS and were very happy, 8 of 15 patients scored 7 to 9/10 on the VAS and were happy, and 2 of 15 patients scored 6/10 on the VAS but were still happy. Although all patients were happier, 3 of 15 patients requested revision rhinoplasty which was not offered as was planned and discussed before the initial intervention. This study shows that in the presence of safe protocols, including a two-specialist model, safe outcomes can be expected even in the long term. Further, the request for revision surgery appears to be common in borderline to mild BDD cases, and we like to warn the patients against it before surgery.

Body Dysmorphic Disorder: A Decade of Mandatory Psychiatric Evaluation in Cosmetic Rhinoplasty Aspirants

AbstractThe aim of rhinoplasty is to make the patient happier with their nose. The patient's perception plays a substantial role in their outcome satisfaction. Body dysmorphic disorder (BDD) is an obsessive-compulsive disorder concerning body image, which negatively distorts the patient's perception, rendering them dissatisfied with the outcome even if the results are close to the defined objectives. In this paper, we present a protocol with a two-specialist approach (rhinoplasty surgeon and a psychiatrist) to standardize BDD diagnosis using the DSM-5 criteria. The patients deemed suitable for cosmetic rhinoplasty by the rhinoplasty surgeon's first consultation were sent for Mandatory Psychiatric Evaluation (MPE) for further consultation and second opinion. MPE was employed with a semi-structured clinical interview by a psychiatrist incorporating the Cosmetic Procedure Screening Questionnaire and Appearance Anxiety Inventory. From 2010 to 2023, 1,602 patients attended our practice seeking cosmetic rhinoplasty, out of which, 892 were sent for MPE to the same psychiatrist. The MPE identified 2.5% (22/892) patients as having mild BDD; out of which, 15 were considered suitable for surgical intervention and underwent successful rhinoplasty (follow up: 1–10 years, M = 4.33 years). Although BDD is considered a contraindication in rhinoplasty, our experience shows that borderline and mild BDD can be offered surgery with good insight and support system. Moderate to severe BDD in our practice was filtered out at the first stage and was not offered surgical intervention. BDD among rhinoplasty aspirants is not as prevalent as previously reported. Standardized diagnostic protocols and studying the severity of BDD when present has clarified management of BDD in rhinoplasty aspirants in our practice. MPE is not easy to incorporate in every rhinoplasty practice, but we aim to present guidelines arising from our ongoing experience to help management of BDD in rhinoplasty.

The first case of a point pathogenic variant in the RREB1 gene in Noonan-like Rasopathy.

The RREB1 is a zinc finger transcription factor that plays a role in regulating gene expression and inactivating MAPK signalling components. To date, no pathogenic variant in the RREB1 gene has been associated with any disease, but several cases of 6p terminal deletions affecting the RREB1 gene have been reported. In this study, we report the first case of RREB1-associated Noonan-likeRASopathycaused by a pathogenic variant within this gene. Genetic testing included whole-genome sequencing (WGS) of the proband and Sanger sequencing of the proband, his parents, and his sibling. The proband had a de novo c.2677del, p.(Ala893Argfs*20) variant, likely resulting in RREB1 haploinsufficiency. Comparative analysis of patients with microdeletions, including in the RREB1 gene, confirmed shared clinical traits while highlighting unique features, such as blue sclerae and absence of cardiac anomalies. This study reinforces previous data on RREB1 haploinsufficiency as the driver of a new Noonan-like RASopathy variant, which includes intellectual disability, delayed motor skills, short stature, short neck, and distinctive facial dysmorphisms as key clinical indicators. These findings shed light on this RREB1-related syndrome and underscore the necessity for further investigation into the functional consequences of RREB1 mutations.

ALDH18A1‐related hereditary spastic paraplegia and developmental and epileptic encephalopathy with spike‐wave activation in sleep: Expanding the clinical phenotype

AbstractObjectiveWe present the cases of two sisters, both harboring the same ALDH18A1 gene mutations, who presented with a complex clinical phenotype characterized by spastic paraparesis with ataxia, epileptic encephalopathy, severe psychomotor deficits, and behavioral abnormalities.MethodsCase description of two sisters with ALDH18A1 gene mutations.ResultsThe older patient, a 12‐year‐old girl, exhibited spastic paraparesis with ataxia, microcephaly, facial dysmorphisms, and severe intellectual disability, with an absence of verbal language. An electroencephalogram (EEG) revealed marked spike‐and‐wave activation during sleep (SWAS), although no clinically documented seizures were observed. The younger sister, who was 9 years old, displayed a similar clinical presentation, including spastic paraparesis with ataxia, microcephaly, dysmorphisms, however, she displayed slightly more severe intellectual deficits and polymorphic seizures. EEG revealed a SWAS pattern in this case. Magnetic resonance imaging scans in both cases showed only a thin corpus callosum. Whole exome sequencing unveiled the presence of two likely pathogenic variants in compound heterozygosity within the ALDH18A1 gene. Specifically, these variants included the splice site variant c.88 + 1c.88+1G&gt;A of paternal origin and the variant c.1364c.1364T&gt;C (p.Leu455Ser) of maternal origin. Both sisters displayed normal blood levels of ammonia, ornithine, citrulline, arginine, and other amino acids.InterpretationThese findings were compatible with ALDH18A1‐related HSP complicated with a clinical and EEG pattern reminiscent of DEE‐SWAS. We present the first report of DEE‐SWAS in ALDH18A1‐related HSP, expanding the clinical manifestations of this complex neurodevelopmental condition.

Body dysmorphic disorder in adult orthodontic treatment candidates according to the index of treatment need

Objectives: Body image perception plays an important role in seeking orthodontic treatment. Body dysmorphic disorder (BDD) is a psychological condition where an individual constantly focuses on flaws in their appearance. This study aimed to assess BDD in adult orthodontic treatment candidates according to the index of treatment need (IOTN) in Qazvin city in 2020. Material and Methods: This descriptive study was conducted on 404 eligible patients over 18 years of age presenting to dental clinics in Qazvin seeking orthodontic treatment. The patients were categorized according to their IOTN (grades 1–5) and filled out the Body Deformation Metacognition Questionnaire (BDMCQ). Data were analyzed by t-test and Analysis of Variance using the Statistical Package for the Social Sciences. Results: Of all the patients, 50.2% were grade 1 (no need for treatment),and 1.5% were grade 5 (very great need for treatment). Furthermore, 54.5% of patients had severe BDD. BDD had no significant correlation with gender or marital status (P &gt; 0.05). BDD was significantly correlated with age, educational level, and IOTN grade (P &lt; 0.05). Conclusion: The present results revealed that over 50% of patients seeking orthodontic treatment did not need treatment, according to the IOTN. Dental clinicians are advised to be more careful in accepting patients with a history of psychological problems and numerous surgical procedures who seek cosmetic treatments.

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.