Cephalometric Evaluation of Children with Short Stature of Genetic Etiology: A Review.

Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of the quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological centre of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the keywords: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and "Turner syndrome"; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its aetiology. The angular and linear cephalometric measurements differ from the measurements of the average normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusions: The greater part of the existing literature regarding cephalometric measurements in short-statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature should be the focus of future studies. These quantitative data are required to potentially establish cut-off values for reference for genetic testing based on craniofacial phenotypes.

Early treatment for children with mental health problems and genetic conditions through a parenting intervention (The GAP): study protocol for a pragmatic randomized controlled trial.

BACKGROUND: Children with genetic conditions are at increased risk for mental health and neurodevelopmental problems, often accompanied by significant parental distress. Genetic and family factors can impact children and parents' mental health. Early parenting interventions, like the Incredible Years® programs, have demonstrated to improve parental distress and children's mental health. The recent version for young children with language delays or autism spectrum disorder (IY-ASLD®) has shown to be feasible and effective to support parents in their children's developmental trajectories. The effectiveness of treatments for children with genetic conditions and neurodevelopmental problems is largely unexplored, leaving significant gaps in evidence-based options. Clinicians lack guidance, especially when patients exhibit language or social communication impairments but do not meet diagnostic criteria for a full-blown autism spectrum disorder (ASD). We aim to fill this gap, providing evidence on the feasibility and effectiveness of the IY-ASLD® intervention for such patients. METHODS: We designed a prospective multicenter pragmatic randomized controlled trial including approximately 68 children aged 3 to 7 years, recruited from three tertiary care reference hospitals. Inclusion criteria will necessitate genetic confirmation of a neurodevelopmental disorder along with language, communication, or socialization difficulties. Individuals with an ASD diagnosis will be excluded. All subjects are included in a territorial register for rare conditions (ReMin, Registre de Malalties Minoritàries de Catalunya). Families will randomly be assigned to the intervention or the control group. The intervention will be held online by clinical psychologists and child and adolescent psychiatrists. DISCUSSION: Our group has recently piloted the online implementation of the IY-ASLD® intervention for the first time in Spain, for parents of children with language delays, socialization difficulties, or ASD, but not genetically determined. Our multicenter research consortium is well-positioned to recruit patients with rare conditions and implement efficient treatment pathways within the National Health System. Given the geographical dispersion of families affected by rare conditions, the online format offers logistical advantages and improved therapy access, enhancing homogeneity across all patients. The results of this study will inform clinicians and policymakers about evidence-based treatment options for this vulnerable and overlooked group of young children. TRIAL REGISTRATION: ClinicalTrials.gov NCT06125093 . Date of registration: first submitted 2023-10-23; first posted 2023-11-09. URL of trial registry record.

Persistent Urogenital Sinus Leading to Hydrometrocolpos in a Female Child With Features of McKusick-Kaufman Syndrome.

Persistent urogenital sinus (PUGS) presents as a solitary abnormality or is in association with syndromes, such as congenital adrenal hyperplasia (CAH), VACTERL association (common abbreviation for vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities), Bardet-Beidl syndrome, McKusick-Kaufman syndrome (MKS), and Townes-Brocks syndrome, to name a few. Those affected usually have overlapping phenotypic features of two or more syndromes. Because such children may grow up to be intellectually challenged with multiple other anomalies including gonadal hyperplasia, congenital heart defects, and sensorineural hearing loss, antenatal diagnosis becomes important. Moreover, those who survive into childhood may need a holistic approach to improve their quality of life. This is a rare case of an eight-year-old female child who is a postnatally diagnosed case of congenital heart disease, urogenital sinus with polydactyly, and bilateral hydroureteronephrosis at birth and who is now showing features of multiple overlapping syndromes.

Comment on Maghsoudlou et al. Titled "Uveitis Associated with Monogenic Autoinflammatory Syndromes in Children".

The work by Maghsoudlou et al. provides a comprehensive examination of monogenic autoinflammatory syndromes (MAIS) in children, with a specific focus on uveitis as a significant clinical manifestation. It meticulously details the genetic underpinnings, clinical features, diagnostic criteria, and current therapeutic strategies, including the use of biologics. This critique highlights the strengths of the review and suggests further exploration in areas such as long-term treatment outcomes, genotype-phenotype correlations, and the impact of MAIS on quality of life. Future research could benefit from longitudinal studies and enhanced predictive models to improve management and treatment personalization.

Pediatric cervical spine instability: evolving concepts.

The pediatric cervical spine is structurally and biomechanically unique in comparison to adults. Guidelines to assess for cervical spine instability and standard of care treatments in the pediatric population have yet to be delineated. This is due to the rarity of the condition and the lack of multicenter data published on the topic. Our review explores the biomechanics of the pediatric cervical spine and highlights evolving concepts/research over the last several decades, with special attention to the Down syndrome and complex Chiari malformation cohorts.

Cor Triatriatum Sinister in a Young Adult: An Unusual Cause of Syncope.

A 25-year-old male with no prior medical history presented with a one-month history of nausea, weight loss, and dyspnea that progressed to syncope. The initial echocardiogram showed a dilated right ventricle with signs of systolic failure. The patient was admitted for suspected pulmonary embolism, but chest computed tomography (CT) revealed interstitial pneumonia. A transthoracic echocardiogram on day 6 of admission diagnosed cor triatriatum sinister (CTS), severe pulmonary hypertension, chronic cor pulmonale, and reduced right ventricular function. The patient was managed conservatively in the intensive care unit (ICU) without the need for mechanical ventilation and discharged after clinical improvement. This case highlights the importance of the early diagnosis of rare congenital heart defects such as cor triatriatum sinister, which can present with nonspecific symptoms and rapidly progress to right heart failure.

Exploring an objective measure of overactivity in children with rare genetic syndromes.

BACKGROUND: Overactivity is prevalent in several rare genetic neurodevelopmental syndromes, including Smith-Magenis syndrome, Angelman syndrome, and tuberous sclerosis complex, although has been predominantly assessed using questionnaire techniques. Threats to the precision and validity of questionnaire data may undermine existing insights into this behaviour. Previous research indicates objective measures, namely actigraphy, can effectively differentiate non-overactive children from those with attention-deficit hyperactivity disorder. This study is the first to examine the sensitivity of actigraphy to overactivity across rare genetic syndromes associated with intellectual disability, through comparisons with typically-developing peers and questionnaire overactivity estimates. METHODS: A secondary analysis of actigraphy data and overactivity estimates from The Activity Questionnaire (TAQ) was conducted for children aged 4-15 years with Smith-Magenis syndrome (N=20), Angelman syndrome (N=26), tuberous sclerosis complex (N=16), and typically-developing children (N=61). Actigraphy data were summarized using the M10 non-parametric circadian rhythm variable, and 24-hour activity profiles were modelled via functional linear modelling. Associations between actigraphy data and TAQ overactivity estimates were explored. Differences in actigraphy-defined activity were also examined between syndrome and typically-developing groups, and between children with high and low TAQ overactivity scores within syndromes. RESULTS: M10 and TAQ overactivity scores were strongly positively correlated for children with Angelman syndrome and Smith-Magenis syndrome. M10 did not substantially differ between the syndrome and typically-developing groups. Higher early morning activity and lower evening activity was observed across all syndrome groups relative to typically-developing peers. High and low TAQ group comparisons revealed syndrome-specific profiles of overactivity, persisting throughout the day in Angelman syndrome, occurring during the early morning and early afternoon in Smith-Magenis syndrome, and manifesting briefly in the evening in tuberous sclerosis complex. DISCUSSION: These findings provide some support for the sensitivity of actigraphy to overactivity in children with rare genetic syndromes, and offer syndrome-specific temporal descriptions of overactivity. The findings advance existing descriptions of overactivity, provided by questionnaire techniques, in children with rare genetic syndromes and have implications for the measurement of overactivity. Future studies should examine the impact of syndrome-related characteristics on actigraphy-defined activity and overactivity estimates from actigraphy and questionnaire techniques.

Punctal Atresia As a Clinical Indicator of Systemic Genetic Anomalies.

BACKGROUND: Punctal atresia or agenesis (PA) is a rare congenital anomaly characterized by the absence or closure of the tear duct puncta, potentially linked to systemic genetic anomalies. The necessity of a genetic workup based solely on the presence of PA remains uncertain. This study investigates a cohort of PA patients, examining the prevalence and types of associated syndromes. METHODS: A retrospective medical records review of all patients diagnosed with PA at the Children's Hospital of Philadelphia between 2009-2023 was conducted, analyzing medical histories and genetic testing results. Primary outcomes included the prevalence of systemic syndromes, while secondary outcomes focused on the variety of associated syndromes. RESULTS: Forty-four patients were included, of which 31 were male (70%) with a mean ± SD age 3.3 ± 3.3 years. Overall, 87 puncta in the study cohort were affected, and 26 cases (59%) were bilateral. Systemic abnormalities or genetic syndromes were identified in 19 patients (43%), with the most common being Ectodermal Dysplasia and Down syndrome. Additional rare syndromes were demonstrated. No significant association was found between systemic abnormalities and gender, bilaterality, or the number of puncta involved. CONCLUSIONS: A high incidence of systemic syndromes (43%) was observed in the study cohort. In individuals with PA who also exhibit extraocular disease, systemic evaluation and genetic workup should be considered. Syndromic diagnoses identified in our cohort also include: Branchio-oto-renal syndrome, 22q11.2 deletion syndrome, 1q21.1 microdeletion syndrome, NF1, monosomy 4q and trisomy 6q, which represent novel associations. The lack of correlation between PA's phenotypic severity and systemic abnormalities highlights the need to obtain a comprehensive medical history and consider a systemic workup in PA patients.

A Case Report of a Clinically Suspected Diagnosis of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) Syndrome With Cardiac Impairment.

This case report presents a description of a hypertrophic left ventricle with reduced ejection fraction in a man in his mid-twenties with clinical, radiologic, and biochemical features of a rare syndrome called mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). A literature review of this uncommon syndrome and MELAS cardiomyopathy has been conducted.

[Cancer in people with an intellectual disability in Germany: prevalence, genetics, and care situation]. / Krebserkrankungen bei Menschen mit einer Intelligenzminderung in Deutschland: Prävalenzen, Genetik und Versorgungslage.

Intellectual disability has a prevalence rate of approximately 1% of the population; in Germany, this is around 0.5-1 million people. The life expectancy of this group of people is reduced, with cancer being one of the most common causes of death (approx. 20%). Overall, the risk of cancer and mortality is increased compared to the general population.Certain genetic syndromes predispose to cancer in this vulnerable group, but associated comorbidities or lifestyle could also be risk factors for cancer. People with cognitive impairments are less likely to attend preventive check-ups, and challenges arise in medical care due to physical, communicative, and interactional characteristics. Optimized cooperation between clinical centers for people with disabilities and the respective cancer centers is required in order to tailor the processes to the individual.In Germany, there is a lack of data on the prevalence of cancer entities and the use and need for healthcare services. There is an urgent need to focus attention on cancer prevention, treatment, and research in the vulnerable and heterogeneous group of people with intellectual disabilities suffering from cancer in order to effectively counteract the increase in cancer-related deaths in this population group.The article summarizes specialist knowledge on cancer in people with an intellectual disability, identifies special features of treatment, presents care structures, and derives specific requirements for clinics and research.

Brain and spine malformations and neurodevelopmental disorders in a cohort of children with CAKUT.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) represent 20-30% of all birth defects and are often associated with extra-renal malformations. We investigated the frequency of brain/spine malformations and neurological features in children with CAKUT. METHODS: We reviewed the clinico-radiological and genetic data of 199 out of 1,165 children with CAKUT evaluated from 2006 to 2023 (99 males, mean age at MRI 6.4 years) who underwent brain and/or spine MRI. Patients were grouped according to the type of CAKUT (CAKUT-K involving the kidney and CAKUT-H involving the inferior urinary tract). Group comparisons were performed using χ2 and Fisher exact tests. RESULTS: Brain/spine malformations were observed in 101/199 subjects (50.7%), 8.6% (101/1165) of our CAKUT population, including midbrain-hindbrain anomalies (40/158, 25.3%), commissural malformations (36/158, 22.7%), malformation of cortical development (23/158, 14.5%), Chiari I anomaly (12/199, 6%), cranio-cervical junction malformations (12/199, 6%), vertebral defects (46/94, 48.9%), caudal regression syndrome (29/94, 30.8%), and other spinal dysraphisms (13/94, 13.8%). Brain/spine malformations were more frequent in the CAKUT-K group (62.4%, p < 0.001). Sixty-two subjects (62/199, 31.2%) had developmental delay/intellectual disability. Neurological examination was abnormal in 40/199 (20.1%). Seizures and/or electroencephalographic anomalies were reported in 28/199 (14%) and behavior problems in 19/199 subjects (9%). Developmental delay/intellectual disability was more frequent in kidney dysplasia (65.2%) and agenesis (40.7%) (p = 0.001). CONCLUSIONS: We report a relative high frequency of brain/spine malformations and neurodevelopmental disorders in children with CAKUT who underwent MRI examinations in a tertiary referral center, widening the spectrum of anomalies associated with this condition.

Improving care for rare genetic neurodevelopmental disorders: A systematic review and critical appraisal of clinical practice guidelines using AGREE II.

PURPOSE: Rare genetic neurodevelopmental disorders associated with intellectual disability require lifelong multidisciplinary care. Clinical practice guidelines may support healthcare professionals in their daily practice, but guideline development for rare conditions can be challenging. In this systematic review, the characteristics and methodological quality of internationally published recommendations for this population are described to provide an overview of current guidelines and inform future efforts of European Reference Network ITHACA (Intellectual disability, TeleHealth, Autism, and Congenital Anomalies). METHODS: MEDLINE, Embase, and Orphanet were systematically searched to identify guidelines for conditions classified as "rare genetic intellectual disability" (ORPHA:183757). Methodological quality was assessed using the Appraisal of Guidelines, Research, and Evaluation II tool. RESULTS: Seventy internationally published guidelines, addressing the diagnosis and/or management of 28 conditions, were included. The methodological rigor of development was highly variable with limited reporting of literature searches and consensus methods. Stakeholder involvement and editorial independence varied as well. Implementation was rarely addressed. CONCLUSION: Comprehensive, high-quality guidelines are lacking for many rare genetic neurodevelopmental disorders. Use and transparent reporting of sound development methodologies, active involvement of affected individuals and families, robust conflict of interest procedures, and attention to implementation are vital for enhancing the impact of clinical practice recommendations.

Gene Therapy for Genetic Syndromes: Understanding the Current State to Guide Future Care.

Gene therapy holds promise as a life-changing option for individuals with genetic variants that give rise to disease. FDA-approved gene therapies for Spinal Muscular Atrophy (SMA), cerebral adrenoleukodystrophy, ß-Thalassemia, hemophilia A/B, retinal dystrophy, and Duchenne Muscular Dystrophy have generated buzz around the ability to change the course of genetic syndromes. However, this excitement risks over-expansion into areas of genetic disease that may not fit the current state of gene therapy. While in situ (targeted to an area) and ex vivo (removal of cells, delivery, and administration of cells) approaches show promise, they have a limited target ability. Broader in vivo gene therapy trials have shown various continued challenges, including immune response, use of immune suppressants correlating to secondary infections, unknown outcomes of overexpression, and challenges in driving tissue-specific corrections. Viral delivery systems can be associated with adverse outcomes such as hepatotoxicity and lethality if uncontrolled. In some cases, these risks are far outweighed by the potentially lethal syndromes for which these systems are being developed. Therefore, it is critical to evaluate the field of genetic diseases to perform cost-benefit analyses for gene therapy. In this work, we present the current state while setting forth tools and resources to guide informed directions to avoid foreseeable issues in gene therapy that could prevent the field from continued success.

Lower Socioeconomic Status is Associated with an Increased Incidence and Spectrum of Major Congenital Heart Disease and Associated Extracardiac Pathology.

Several studies have suggested an inverse relationship between lower socioeconomic status (SES) and the incidence of congenital heart disease (CHD) among live births. We sought to examine this relationship further in a Canada-wide population study, exploring CHD subtypes, trends, and associated noncardiac abnormalities. Infants born in Canada (less Quebec) from 2008 to 2018 with CHD requiring intervention in the first year were identified using ICD-10 codes through the Canadian Institute for Health Information Discharge Abstract Database. Births of CHD patients were stratified by SES (census-based income quintiles) and compared against national birth proportions using X2 tests. Proportions with extracardiac defects (ED) and nonlethal genetic syndromes (GS) were also explored. From 2008 to 2018, 7711 infants born with CHD were included. The proportions of major CHD distributed across SES quintiles were 27.1%, 20.1%, 19.2%, 18.6%, and 15.0% from lowest to highest, with significant differences relative to national birth proportions (22.0%, 20.0%, 20.6%, 20.7%, and 16.7% from lowest (1) to highest (5)) (p < 0.0001). No temporal trends in the CHD proportions across SES categories were observed over the study period. The distribution across SES quintiles was different only for specific CHD subtypes (double-outlet right ventricle (n = 485, p = 0.03), hypoplastic left heart syndrome (n = 547, p = 0.006), heterotaxy (n = 224, p = 0.03), tetralogy of Fallot (n = 1007, p = 0.008), truncus arteriosus (n = 126, p < 0.0001), and ventricular septal defect (n = 1916, p < 0.0001)), with highest proportions observed in the lowest quintile. The proportion of the total population with ED but not GS was highest in lower SES quintiles (< 0.0001) commensurate with increased proportion of CHD. Our study suggests a negative association between SES and certain CHD lesions and ED.

Genetics of Cardiac Tumours: A Narrative Review.

Cardiac tumours can occur in association with genetic syndromes. Rhabdomyomas have been reported in association with tuberous sclerosis, myxomas with Carney's complex, cardiac fibromas with Gorlin syndrome, and paragangliomas with multiple endocrine neoplasm syndrome. The presentation and prognosis of cardiac tumours associated with genetic syndromes differ compared with sporadic cases. Knowledge about the associated syndromes' genetic features and extracardiac manifestations is essential for the diagnosis, prognosis, and management of cardiac neoplasms. Moreover, identifying genetic mutations in benign and malignant cardiac tumours is needed to personalise management and improve treatment outcomes. Thus, this review discusses the genetic abnormalities associated with cardiac tumours, the current genetic screening recommendations, and the effect of those genetic mutations on the outcomes.

CanCHD Study of Hematopoietic Cancers in Children With and Without Genetic Syndromes.

BACKGROUND: Individuals with genetic syndromes can manifest both congenital heart disease (CHD) and cancer attributable to possible common underlying pathways. To date, reliable risk estimates of hematopoietic cancer (HC) among children with CHD based on large population-based data remain scant. This study sought to quantify the risk of HC by the presence of genetic syndrome among children with CHD. METHODS AND RESULTS: Data sources were the Canadian CHD database, a nationwide database on CHD (1999-2017), and the CCR (Canadian Cancer Registry). Standardized incidence ratios were calculated for comparing HC incidences in children with CHD with the general pediatric population. A modified Kaplan-Meier curve was used to estimate the cumulative incidence of HC with death as a competing risk. A total of 143 794 children (aged 0-17 years) with CHD were followed up from birth to age 18 years for 1 314 603 person-years. Of them, 8.6% had genetic syndromes, and 898 HC cases were observed. Children with known syndromes had a substantially higher risk of incident HC than the general pediatric population (standardized incidence ratio, 13.4 [95% CI, 11.7-15.1]). The cumulative incidence of HC was 2.44% (95% CI, 2.11-2.76) among children with a syndrome and 0.79% (95% CI, 0.72-0.87) among children without a syndrome. Acute myeloid leukemia had a higher cumulative incidence during early childhood than acute lymphoblastic leukemia. CONCLUSIONS: This is the first large population-based analysis documenting that known genetic syndromes in children with CHD are a significant predictor of HC. The finding could be essential in informing risk-stratified policy recommendations for cancer surveillance in children with CHD.

A Novel, Possibly Pathogenic, COL4A1 Gene Variant (c.3698G>A) in a Family With Childhood Epilepsy and Leukoencephalopathy.

This case report explores the clinical presentation and genetic findings of a 44-year-old male with a history of pediatric epilepsy. The patient's daughter, recently diagnosed with autism, underwent genetic testing, revealing a variant of uncertain significance (VUS) in the type IV collagen alpha 1 (COL4A1) gene. The male patient reported a spectrum of neurological symptoms, including chronic migraines, exertional weakness, and sensory disturbances. Detailed neurological examination findings were within normal limits, but a brain MRI unveiled confluent deep white matter T2/fluid-attenuated inversion recovery (FLAIR) signal abnormalities with basal ganglia involvement. Genetic testing identified a novel COL4A1 gene variant, c.3698G>A (p.Gly1233Glu), in the patient, which was also carried by his daughter. The nature and clinical implications of this VUS in the context of the family's clinical history are discussed in this case report, emphasizing the potential significance of this genetic variant in understanding the etiology of the patient's neurologic symptoms. Further research and correlation with clinical findings are needed to elucidate whether this is a pathogenic variant.

The use of eye-tracking technology as a tool to evaluate social cognition in people with an intellectual disability: a systematic review and meta-analysis.

BACKGROUND: Relatively little is known about social cognition in people with intellectual disability (ID), and how this may support understanding of co-occurring autism. A limitation of previous research is that traditional social-cognitive tasks place a demand on domain-general cognition and language abilities. These tasks are not suitable for people with ID and lack the sensitivity to detect subtle social-cognitive processes. In autism research, eye-tracking technology has offered an effective method of evaluating social cognition-indicating associations between visual social attention and autism characteristics. The present systematic review synthesised research which has used eye-tracking technology to study social cognition in ID. A meta-analysis was used to explore whether visual attention on socially salient regions (SSRs) of stimuli during these tasks correlated with degree of autism characteristics presented on clinical assessment tools. METHOD: Searches were conducted using four databases, research mailing lists, and citation tracking. Following in-depth screening and exclusion of studies with low methodological quality, 49 articles were included in the review. A correlational meta-analysis was run on Pearson's r values obtained from twelve studies, reporting the relationship between visual attention on SSRs and autism characteristics. RESULTS AND CONCLUSIONS: Eye-tracking technology was used to measure different social-cognitive abilities across a range of syndromic and non-syndromic ID groups. Restricted scan paths and eye-region avoidance appeared to impact people's ability to make explicit inferences about mental states and social cues. Readiness to attend to social stimuli also varied depending on social content and degree of familiarity. A meta-analysis using a random effects model revealed a significant negative correlation (r = -.28, [95% CI -.47, -.08]) between visual attention on SSRs and autism characteristics across ID groups. Together, these findings highlight how eye-tracking can be used as an accessible tool to measure more subtle social-cognitive processes, which appear to reflect variability in observable behaviour. Further research is needed to be able to explore additional covariates (e.g. ID severity, ADHD, anxiety) which may be related to visual attention on SSRs, to different degrees within syndromic and non-syndromic ID groups, in order to determine the specificity of the association with autism characteristics.

Short report: Behavioural characterisation of SOX11 syndrome.

BACKGROUND: SOX11 syndrome is a rare condition caused by deletions or de novo point mutations of the SOX11 gene. SOX11 is a transcription factor gene that plays an important role in brain development. AIMS: The aim of this study was to quantitatively evaluate the behavioural profiles of individuals with SOX11 syndrome. METHODS AND PROCEDURES: The Vineland Adaptive Behaviour Scales 3 (VABS-3) and the Social Responsiveness Scale 2 (SRS-2) were completed by parents of 21 children and young adults with SOX11 syndrome. OUTCOMES AND RESULTS: Most were found to have borderline (33 %) or mild (39 %) impairment in adaptive behaviour, with more difficulties in communication and daily living than socialisation in the cohort overall. Most (90 %) were found to exhibit clinically relevant levels of autistic traits, with 62 % scoring in the "severe" range, though social motivation was observed to be a relative strength in the cohort overall. CONCLUSIONS AND IMPLICATIONS: This study presents the first standardised evaluation of adaptive behaviour and autistic traits of individuals with SOX11 syndrome. This will improve clinicians, educators and parents' understanding of SOX11 syndrome.

The Impact of Artificial Intelligence on Optimizing Diagnosis and Treatment Plans for Rare Genetic Disorders.

Rare genetic disorders (RDs), characterized by their low prevalence and diagnostic complexities, present significant challenges to healthcare systems. This article explores the transformative impact of artificial intelligence (AI) and machine learning (ML) in addressing these challenges. It emphasizes the need for accurate and early diagnosis of RDs, often hindered by genetic and clinical heterogeneity. This article discusses how AI and ML are reshaping healthcare, providing examples of their effectiveness in disease diagnosis, prognosis, image analysis, and drug repurposing. It highlights AI's ability to efficiently analyze extensive datasets and expedite diagnosis, showcasing case studies like Face2Gene. Furthermore, the article explores how AI tailors treatment plans for RDs, leveraging ML and deep learning (DL) to create personalized therapeutic regimens. It emphasizes AI's role in drug discovery, including the identification of potential candidates for rare disease treatments. Challenges and limitations related to AI in healthcare, including ethical, legal, technical, and human aspects, are addressed. This article underscores the importance of data ethics, privacy, and algorithmic fairness, as well as the need for standardized evaluation techniques and transparency in AI research. It highlights second-generation AI systems that prioritize patient-centric care, efficient patient recruitment for clinical trials, and the significance of high-quality data. The integration of AI with telemedicine, the growth of health databases, and the potential for personalized therapeutic recommendations are identified as promising directions for the field. In summary, this article provides a comprehensive exploration of how AI and ML are revolutionizing the diagnosis and treatment of RDs, addressing challenges while considering ethical implications in this rapidly evolving healthcare landscape.