Developmental Profile Research Articles

Mid-childhood autism sibling recurrence in infants with a family history of autism.

Autism sibling recurrence in prospective infant family history studies is ~20% at 3 years but systematic follow-up to mid-childhood is rare. In population and clinical cohorts autism is not recognized in some children until school-age or later. One hundred and fifty-nine infants with an older sibling with autism underwent research diagnostic assessments at 3 years and mid-childhood (6 to 12 years (mean 9)). We report the autism sibling recurrence rate in mid-childhood and compare developmental and behavioral profiles at mid-childhood and 3 years in those with earlier versus later recognized autism, and those who had, or had not, received a community autism diagnosis. The autism recurrence rate in this sample in mid-childhood was 37.1%, 95% CI [29.9%, 44.9%] and higher in boys than girls. Around half of those diagnosed with autism in mid-childhood had not received a diagnosis at 3 years. Later, diagnosis was more common in girls than boys. While some had sub-threshold symptoms at 3, in others late diagnosis followed a largely typical early presentation. Sibling recurrence based on community clinical diagnosis was 24.5%, 95% CI [18.4%, 31.9%]. Those who also had a community diagnosis tended to be older, have lower adaptive function and higher autism and inattention symptoms. Notwithstanding limitations of a single site study, modest sample size and limits to generalisability, autism sibling recurrence in family history infants may be higher in mid-childhood than in studies reporting diagnostic outcome at 3 years. Findings have implications for families and clinical services, and for prospective family history studies.

Early developmental milestone clusters of autistic children based on electronic health records.

Autistic children vary in symptoms, co-morbidities, and response to interventions. This study aimed to identify clusters of autistic children with a distinct pattern of attaining early developmental milestones (EDMs). The clustering of 5836 autistic children was based on the attainment of 43 gross motor, fine motor, language, and social developmental milestones during the first 3 years of life as recorded in baby wellness visits. K-means cluster analysis detected four EDM clusters: mild (n = 1686); moderate (n = 1691); severe (n = 2265); and global (n = 194). The most prominent cluster differences were in the language domain. The global cluster showed earlier and greater developmental delay across domains, unique early gross motor delays, and more were born preterm via cesarean section. The severe cluster had poor language development prominently in the second year of life, and later fine motor delays. Moderate cluster had mainly language delays in the third year of life. The mild cluster mostly passed milestones. EDM clusters differed demographically, with higher socioeconomic status in mild cluster and lowest in global cluster. However, the severe cluster had more immigrant and non-Jewish mothers followed by the moderate cluster. The rates of parental concerns and provider developmental referrals were significantly higher in the global, followed by the severe, moderate, and mild EDM clusters. Autistic children's language and motor delay in the first 3 years can be grouped by common magnitude and onset profiles as distinct groups that may link to specific etiologies (like prematurity or genetics) and specific intervention programs. Early autism screening should be tailored to these different developmental profiles.

Parents reported language development and scholastic achievement in children with congenital heart diseases versus typically developed

BackgroundChildren with congenital heart diseases (CHD) may have developmental delays including delayed language development (DLD) and learning difficulties. The purpose of this study was to observe the effects of CHD on language developmental profile and scholastic achievement (SA) with particular emphasis on prevalence of DLD and SA, potential risks, and need for early intervention.ResultsThis case–control study included 158 children with CHD and 145 healthy children as controls. Participants’ ages ranged from 6 months to 15 years. Data were collected by reviewing clinical records and questionnaires covering potential risks, motor and language development, and SA. Potential risks were analyzed using the Fisher test, while language development and SA were compared using Mann–Whitney test. The incidences of parent consanguinity, family history of DLD, and neonatal cyanosis were higher than expected by chance in the CHD group with p-values which are < 0.001, 0.044, and < 0.001, respectively. The CHD group revealed more delay in babbling, first word production, two-word sentences, three-word sentences, narration, and SA than control group with significant differences. These comparisons’ p-values are 0.002, < 0.001, 0.009, 0.029, 0.03, and 0.042 respectively with mean effect size 0.3. The language development profile in cyanotic HD showed more delay than acyanotic HD with significant differences.ConclusionsThe DLD and affected SA were more prevalent in children with CHD. The risk for DLD in CHD children was multifactorial; however, the main predisposing factor was chronic hypoxia that starts in the intrauterine life in CHD. Neonates with CHD require early intervention through oxygen therapy before surgery. Early family counseling and language therapy are recommended to improve quality of life through achieving better communicative ability and academic skills. Further studies which concerned the effect of maternal oxygenation on prognosis of fetuses with CHD may be required. Also, duplication of the study including formal testing is recommended.

Structural connectivity matures along a sensorimotor-association connectional axis in youth.

Childhood and adolescence are associated with protracted developmental remodeling of cortico-cortical structural connectivity. However, how heterochronous development in white matter structural connectivity spatially and temporally unfolds across the macroscale human connectome remains unknown. Leveraging non-invasive diffusion MRI data from both cross-sectional (N = 590) and longitudinal (baseline: N = 3,949; two-year follow-up: N = 3,155) developmental datasets, we found that structural connectivity development diverges along a pre-defined sensorimotor-association (S-A) connectional axis from ages 8.1 to 21.9 years. Specifically, we observed a continuum of developmental profiles that spans from an early childhood increase in connectivity strength in sensorimotor-sensorimotor connections to a late adolescent increase in association-association connectional strength. The S-A connectional axis also captured spatial variations in associations between structural connectivity and both higher-order cognition and general psychopathology. Together, our findings reveal a hierarchical axis in the development of structural connectivity across the human connectome.

Developmental Assessment in Children at Higher Likelihood for Developmental Delays - Comparison of Parent Report and Direct Assessment.

Accurate assessment of cognitive development of young children is a vital component of developmental evaluations. Direct assessment of developmental skills is not always feasible, but there is limited information on the agreement between direct assessment and caregiver-reported cognitive skills. There is limited information regarding the accuracy of the parent-reported Developmental Profile 4 (DP-4) in comparison to the widely-used developmental measure, the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4). The purpose of the current study was to evaluate whether a standardized parent interview can effectively identify children at risk for cognitive developmental delays. We compared the agreement between the Bayley-4 Cognitive and the Developmental Profile 4 (DP-4) in young children being evaluated in-person for early developmental delays. 182 children (134 with an autism diagnosis), ages 6-42 months, completed both assessments. Results showed that Bayley-4Cognitive scores had a moderately strong correlation with DP4-Cognitive scores (r = 0.70, p < 0.001). A cutoff of 70 or 69 on the DP-4 Cognitive was determined as ideal for identifying developmental delay based on diagnosis of global developmental delay or the Bayley-4 Cognitive. Our analyses revealed good agreement between DP-4 and Bayley-4 Cognitive scores, even after controlling for confounding variables such as degree of ASD characteristics, age, and sex. These results suggest that caregiver-report measures can be a valid and useful tool in the assessment of young children, particularly when direct developmental assessment is not feasible.

Early Communication Skills Training for Infants and Toddlers with Cochlear ImplantEarly Communication Skills Training for Infants and Toddlers with Cochlear Implant

Background and Aim: Early communication skills in children with hearing loss depend on the quantity and quality of information received from parents. The present study aimed to investigate the effectiveness of early communication skills training in developing the communication skills of infants and toddlers with cochlear implants. Methods: To this end, 54 infants and toddlers at the age range of 8–24 months with sever to profound hearing loss fitted by Cochlear Implant (CI) with their mothers participated in this study. The experimental and wait list control groups had auditory verbal therapy as the main intervention after the CI; however, the experimental group received a systematic early communication skills program. All subjects were assessed using the Communication and Symbolic Behaviour Scales Developmental Profile as the pre-and post-tests. Results: Multivariate analysis of covariance indicated the effect of systematic training on the early communication development of subjects in intervention group. Conclusion: Teaching the parents how to interact with infants and toddlers with CI could improve the communication skills of the infants and therefore it’s recommended to be included in the auditory rehabilitation programs.

Differences in the Development of Mathematics Motivation within and across Socioeconomic Status: Do Early Adolescents' Failure Beliefs Matter?

Interest in socioeconomic differences in academic motivation has been longstanding. However, previous research has often treated both low- and high-SES students as homogenous groups. This study aims to address this gap by investigating the developmental trajectory profiles of mathematics motivation during early adolescence, with a focus on variations within and across SES groups. Multigroup latent class growth analysis was used on a sample of 3718 early adolescents in China (initial Mage was 9.40 ± 0.52 years; 48.0% girls) across 2 years from grades 4 through 6. The analysis identified three distinct self-determined mathematics motivation trajectory profiles within each SES group: a good-quality profile (i.e., initially high autonomous but low controlled), a high-quantity profile (i.e., initially high both autonomous and controlled), and a low-quantity profile (i.e., initially low both autonomous and controlled). A greater proportion of low-SES students were observed within the low-quantity profile than within the good-quality profile. The study found that the failure-is-enhancing view was a protective factor against two relatively maladaptive motivational trajectory profiles (i.e., high-quantity profile and low-quantity profile), irrespective of socioeconomic background. These findings emphasize the importance of implementing motivational interventions for early adolescents that consider both structural factors (e.g., socioeconomic backgrounds) and psychological factors (e.g., failure beliefs), to foster students' academic development.

Profiles of Family and School Experiences and Adjustment of Adolescents During the Transition to High School.

Although family and school experiences play an important role in adolescents' adjustment during the transition to high school, most prior studies investigated the effects of these experiences in isolation; their joint implications for both adolescents' concurrent and long-term adjustment outcomes are less clear, and the potential role of individual characteristics within such associations remains understudied. Based on 525 10th graders (Mage = 15.48, SDage = 0.71, 43.6% boys) who participated in a longitudinal study, the present research aimed to identify distinct family and school experience profiles among first-year high school students and examine their associations with adolescents' internalizing problems and externalizing problems, both concurrently and 18 months later. Latent profile analysis revealed four distinctive profiles: thriving, low resources-moderate family risk, developmental stress-high parental conflicts, and developmental stress-high peer victimization profiles. The other three profiles (vs. the thriving profile) reported significantly higher levels of concurrent internalizing problems; while these differences diminished after 18 months. However, the enduring impacts of these profiles on internalizing problems persisted among adolescents with higher levels of environmental sensitivity. Additionally, adolescents characterized by two developmental stress profiles (vs. the thriving profile) exhibited significantly higher levels of externalizing problems both currently and longitudinally. Findings underscore the importance of identifying at-risk populations among adolescents during the transition to high school by including both family and school experiences when examining environmental influence on their adjustment, as well as the necessity to take individual environmental sensitivity into account when examining these associations.

Improving the care of children with GENetic Rare disease: Observational Cohort study (GenROC)—a study protocol

IntroductionAround 2000 children are born in the UK per year with a neurodevelopmental genetic syndrome with significantly increased morbidity and mortality. Often little is known about expected growth and phenotypes...

Developmental Profile in Children Aged 3-6 Years: Down Syndrome vs. Autism Spectrum Disorder.

This research aims to compare the developmental profiles of children with autism spectrum disorder (ASD) and children with Down Syndrome (DS) between the ages of 3 and 6 years. The study examines whether these developmental disorders share common developmental milestones or exhibit distinctive characteristics. A total of 43 children, 23 with DS and 20 with ASD, participated in the study. Cognitive and language skills were assessed using standardized tools, including the Battelle Developmental Inventory, Reynell Developmental Language Scales III, and NEPSY-II battery. The results indicated that children with ASD outperformed children with DS in the areas of fine motor skills, gross motor skills, and communication. Additionally, children with ASD demonstrated higher scores in language comprehension and expressive language, compared to children with DS. Significant correlations were found between motor skills and communication abilities. Neuropsychological evaluations revealed significant differences between the two groups in various tasks, such as the comprehension of instructions, body part naming and identification, and recognition of emotions. These findings contribute to our understanding of the similarities and differences between ASD and DS, shedding light on the dissociation between cognition and language and its impact on adaptive functioning in these populations.

First report of Tunisian patients with CDKL5-related encephalopathy.

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) are associated with a wide spectrum of clinical presentations. Early-onset epileptic encephalopathy (EOEE) is the most recognized phenotype. Here we describe phenotypic features in eight Tunisian patients with CDKL5-related encephalopathy. We included all cases with clinical features consistent with CDKL5-related encephalopathy: infantile epileptic spasm, acquired microcephaly, movement disorders and visual impairment. We collected data about seizure types, electroencephalogram, magnetic resonance imaging, and metabolic analysis. The diagnosis of CDKL5 mutation was made thanks to Sanger sequencing with an ABI PRISM 3100-Avant automated DNA sequencer using a Big Dye Terminator Cycle Sequencing Reaction Kit v1.1. and Next Generation Sequencing (NGS) since the development of a gene panel responsible for DEE within the framework of "Strengthening the Sfax University Expertise for diagnosis and management of epileptic encephalopathies". We collected four boys and four girls aged meanly 6 years old with confirmed mutation on CDKL5 gene. Overall, we identified five de novo CDKL5 mutations including three Frame-shift mutations, one missense mutation, and a splicing variant. The mean age at first seizure onset was 4 months. The first seizure type was infantile epileptic spasm (4/8) followed by tonic (2/8) and myoclonic seizures (2/8). Out of eight cases, four exhibited two stages epileptic course while epilepsy in three other patients progressed on three stages. Regarding development, most cases (6/8) had psychomotor retardation from the start whilst the two others showed psychomotor regression with the onset of seizures. Additional clinical features included visual impairment (7/8), tone abnormalities (7/8), stereotypies (7/8), and acquired microcephaly (6/8). Our present report delineates an unusual phenotype of CDKL5-related encephalopathy with male gender predominance and delayed onset epilepsy. It interestingly described new phenotypic features and uncommon benign developmental profiles in boys, different patterns of CDKL5-epilepsy, neuroimaging findings, and CDKL5 mutational spectrum.

Preventative treatment of tuberous sclerosis complex with sirolimus: Phase I safety and efficacy results

AbstractObjectiveTuberous sclerosis complex (TSC) results from overactivity of the mechanistic target of rapamycin (mTOR). Sirolimus and everolimus are mTOR inhibitors that treat most facets of TSC but are understudied in infants. We sought to understand the safety and potential efficacy of preventative sirolimus in infants with TSC.MethodsWe conducted a phase 1 clinical trial of sirolimus, treating five patients until 12 months of age. Enrolled infants had to be younger than 6 months of age with no history of seizures and no clinical indication for sirolimus treatment. Adverse events (AEs), tolerability, and blood concentrations of sirolimus measured by tandem mass spectrometry were tracked through 12 months of age, and clinical outcomes (seizure characteristics and developmental profiles) were tracked through 24 months of age.ResultsThere were 92 AEs, with 34 possibly, probably, or definitely related to treatment. Of those, only two were grade 3 (both elevated lipids) and all AEs were resolved by the age of 24 months. During the trial, 94% of blood sirolimus trough levels were in the target range (5–15 ng/mL). Treatment was well tolerated, with less than 8% of doses held because of an AE (241 of 2941). Of the five patients, three developed seizures (but were well controlled on medications) at 24 months of age. Of the five patients, four had normal cognitive development for age. One was diagnosed with possible autism spectrum disorder.InterpretationThese results suggest that sirolimus is both safe and well tolerated by infants with TSC in the first year of life. Additionally, the preliminary work suggests a favorable efficacy profile compared with previous TSC cohorts not exposed to early sirolimus treatment. Results support sirolimus being studied as preventive treatment in TSC, which is now underway in a prospective phase 2 clinical trial (TSC‐STEPS).

Transcriptomic profiling across human serotonin neuron differentiation via the FEV reporter system

BackgroundThe detailed transcriptomic profiles during human serotonin neuron (SN) differentiation remain elusive. The establishment of a reporter system based on SN terminal selector holds promise to produce highly-purified cells with an early serotonergic fate and help elucidate the molecular events during human SN development process.MethodsA fifth Ewing variant (FEV)-EGFP reporter system was established by CRISPR/Cas9 technology to indicate SN since postmitotic stage. FACS was performed to purify SN from the heterogeneous cell populations. RNA-sequencing analysis was performed for cells at four key stages of differentiation (pluripotent stem cells, serotonergic neural progenitors, purified postmitotic SN and purifed mature SN) to explore the transcriptomic dynamics during SN differentiation.ResultsWe found that human serotonergic fate specification may commence as early as day 21 of differentiation from human pluripotent stem cells. Furthermore, the transcriptional factors ZIC1, HOXA2 and MSX2 were identified as the hub genes responsible for orchestrating serotonergic fate determination.ConclusionsFor the first time, we exposed the developmental transcriptomic profiles of human SN via FEV reporter system, which will further our understanding for the development process of human SN.Graphical

Developmental Trajectories of Mental Health in Chinese Early Adolescents: School Climate and Future Orientation as Predictors.

There is growing support for the dual-continua model of mental health, which emphasizes psychopathology and well-being as related but distinct dimensions. Yet, little is known about how these dimensions co-develop from childhood to early adolescence and what factors predict their different trajectories. The current study aimed to identify distinct patterns of mental health in Chinese early adolescents, focusing on both psychopathological symptoms (i.e., depressive symptoms and self-harm behaviors) and subjective well-being (i.e., life satisfaction and affect balance). This study also examined the contributions of school climate and future orientation to these trajectories. A total of 1,057 students (Mage = 11.88, SDage = 1.67; 62.1% boys) completed four assessments over two years, with six-month intervals. Using parallel-process latent class growth modeling, we identified four groups: Flourishing (32.5%), Languishing (43.8%), Troubled with Stable Depressive Symptoms (16.1%), and Troubled with Increasing Self-Harm Risk (7.6%). Furthermore, school climate and future orientation contributed to adolescents' membership in these trajectories, either independently or jointly. Specifically, higher levels of future orientation combined with higher school climate were associated with a lower likelihood of belonging to the Troubled with Increasing Self-Harm Risk trajectory, compared to the Flourishing group. Our findings identified four distinct mental health trajectories consistent with the dual-continua model, and demonstrated that the development of psychopathology and well-being were not always inversely related (e.g., the Languishing group). Adolescents with unique developmental profiles may benefit from tailored intervention strategies that build on the personal and environmental assets of the adolescent.

Assessing the Impact of E-Learning Adoption on Learning Behavior in Sierra Leonean Higher Education

This study aims to analyze the adoption of e-learning in higher education institutions in Sierra Leone and its impact on learning Behavior using the Technology Acceptance Model (TAM). The research employs a survey design, utilizing Structural Equation Modeling (SEM), to analyze the responses of students and lecturers. The study was conducted in Sierra Leone, involving ten universities. The duration of the study is not specified. 728 students and 327 lecturers were surveyed to assess their attitudes towards e-learning. The TAM was used to predict behaviors based on the perceived usefulness and ease of use of e-learning tools, such as mobile devices and social networking applications. The findings indicate that e-learning is more likely to be adopted if the tools are perceived as useful and easy to use. Additionally, prior experience with computers enhances the positive perception of e-learning's attributes and attitudes toward its utilization. The study highlights the potential of e-learning in developing countries like Sierra Leone. It provides insights for stakeholders in the education sector to develop strategies that can promote the adoption of e-learning in regions with similar developmental profiles.

Advancing athlete development: How Percentile Comparison Methods (PCMs) can identify youth developmental profiles

ObjectivesInter-individual developmental differences confound the capability to accurately evaluate youth athletic performance, highlighting the need for considerate methodology and analytical approaches. The present study demonstrated how Percentile Comparison Methods (PCMs) were developed, tested, and applied to identify athlete developmental profiles in Australian youth swimming. DesignCross-sectional. MethodsParticipants were N = 866 female 100-metre (m) Front-Crawl swimmers, aged 9–15 years, competing at 36 Australian regional–national level long course events. At respective events, swim performance time was collated alongside, age, date of birth, and anthropometric measures to identify age group, relative age, and maturity status. Quadratic relative age and maturity status with 100-m performance regression trendlines were generated. Then, individual swim performances at a given relative age or maturity status were converted into percentile rank distributions and compared with raw (unadjusted) annual age-group performance percentile ranks. ResultsAt a cohort level, initial testing confirmed relative age and maturity-adjusted percentile rankings were associated with general rank improvements for relatively younger and later maturing swimmers compared to raw ranks (and vice versa). When assessing individual swimmer plots, where three percentile rank scores were compared and rank change threshold criteria applied, five Percentile Comparison Method profile types were identified, namely: ‘Early Developing’ (19 %); ‘Later Developing’ (18 %); ‘Consistent’ (15 %); ‘Mixed’ (38 %) and ‘Counteracting’ (10 %). Percentile Comparison Method plots helped identify developmentally (dis-)advantaged swimmers; specific factors leading to (dis-)advantage, and likely onward development trajectories. ConclusionsOverall and with practical considerations, Percentile Comparison Methods can improve the validity of youth athletic performance evaluation as well as inform athlete development programming.

Differential cognitive and behavioral development from 6 to 24 months in autism and fragile X syndrome

BackgroundSpecifying early developmental differences among neurodevelopmental disorders with distinct etiologies is critical to improving early identification and tailored intervention during the first years of life. Recent studies have uncovered important differences between infants with fragile X syndrome (FXS) and infants with familial history of autism spectrum disorder who go on to develop autism themselves (FH-ASD), including differences in brain development and behavior. Thus far, there have been no studies longitudinally investigating differential developmental skill profiles in FXS and FH-ASD infants.MethodsThe current study contrasted longitudinal trajectories of verbal (expressive and receptive language) and nonverbal (gross and fine motor, visual reception) skills in FXS and FH-ASD infants, compared to FH infants who did not develop ASD (FH-nonASD) and typically developing controls.ResultsInfants with FXS showed delays on a nonverbal composite compared to FH-ASD (as well as FH-nonASD and control) infants as early as 6 months of age. By 12 months an ordinal pattern of scores was established between groups on all domains tested, such that controls > FH-nonASD > FH-ASD > FXS. This pattern persisted through 24 months. Cognitive level differentially influenced developmental trajectories for FXS and FH-ASD.ConclusionsOur results demonstrate detectable group differences by 6 months between FXS and FH-ASD as well as differential trajectories on each domain throughout infancy. This work further highlights an earlier onset of global cognitive delays in FXS and, conversely, a protracted period of more slowly emerging delays in FH-ASD. Divergent neural and cognitive development in infancy between FXS and FH-ASD contributes to our understanding of important distinctions in the development and behavioral phenotype of these two groups.

Online Self-Disclosure and Self-Concept Clarity Among Chinese Middle School Students: A Longitudinal Study.

The relationship between online self-disclosure and self-concept clarity has been previously examined through cross-sectional studies. This study examined causal connections between online self-disclosure and self-concept clarity among Chinese middle school students using longitudinal data collected over 18 months. Participants were 535 seventh-grade students aged 12-14 years (Mage = 12.93, SD = 0.54, 43.18% girls), assessed four times, six months apart. In a random intercept cross-lagged panel model, self-concept clarity significantly predicted online self-disclosure. Latent growth mixture modeling identified two distinct growth trajectories for both online self-disclosure (Rapid change, 7%; Slow change, 93%) and self-concept clarity (Rapid change, 8%; No change, 92%). Multiple logistic regression analysis suggested that changes in self-concept clarity influenced the developmental trajectory profile of online self-disclosure. Although male and female students differed in online self-disclosure and self-concept clarity, gender differences in the developmental trajectory profiles of online self-disclosure and self-concept clarity were not significant. Supporting adolescents in developing a clear self-concept to mitigate risks associated with excessive online self-disclosure is important.

Monitoring Educational Intervention Programs for Children and Young People with Disabilities through a Web Application

Early care professionals have to use instruments for assessing functional skills in children susceptible to early intervention that apply records and produce developmental profiles and personalized intervention proposals. The aims of the study were (1) to analyze the development of functional skills in users with an age range of 48–252 months attending school in a therapeutic intervention center for people with motor impairments; and (2) to analyze the development of functional skills in users with different impairments and ages ranging from 7 to 162 months participating in an early outpatient care program. Study 1 applied a sample of 50 users aged between 48 and 252 months all with motor disabilities and Study 2 included a sample of 71 users aged between 7 and 162 months with different disabilities. Factorial and descriptive–correlational designs were applied in both studies. The Student’s t-test for dependent samples, supervised machine learning techniques (linear regression analysis and logarithmic regression analysis), unsupervised machine learning techniques (k-means), ANOVA, and cross-tabulations were used as contrast tests. In Study 1, no significant changes were found in the development of users’ functional skills, except for a decrease in maladaptive behaviors. Likewise, the chronological age variable did not seem to be a determining factor in the results. In Study 2, significant differences were found in the development of all functional skills between the three measurement time points (initial–intermediate–final). In this group, the type of impairment explained 29% and chronological age 40% of the variance in functional development at the final measurement. This study found that intervention before four years old in outpatient mode produced better results in the acquisition of functional skills, with better results in users affected by rare diseases or communication and language delay at ages 49–60 months.

Neurobehavioral and developmental profiles: genotype–phenotype correlations in individuals with Cornelia de Lange syndrome

BackgroundCornelia de Lange (CdLS) is a rare genetic disorder that affects most body systems. Variants in multiple genes including NIPBL and SMC1A, can cause the syndrome. To date, literature on genotype–phenotype associations in individuals with CdLS is extremely limited, although studies suggest some differences in clinical phenotype severity across variants. This study aimed to examine and compare neurobehavioral differences and developmental variability across CdLS genes, specifically NIPBL and SMC1A, and identify genotype–phenotype correlations.Participants and methodsThis patient-reported outcomes study included accessing data from the Coordination of Rare Diseases registry at Sanford. Parents of a total of 26 children/adults with CdLS and a known variant in NIPBL (Mean age = 20.46 years, SD = 11.21) and 12 with a known variant in SMC1A (Mean age = 11.08 years, SD = 9.04) completed a series of questionnaires regarding their child’s developmental history. This included attainment of common language and motor milestones, intervention history, and behavior functioning. Developmental history and reported behavior regulation difficulties were compared across variant groups.ResultsOverall, individuals with a pathogenic variant in NIPBL or SMC1A were similarly delayed across motor and language milestones with about 70% not using phrase speech and 30–50% not walking by 5 years of age. However, those with NIPBL variants showed more severity in behavioral phenotype, namely with more repetitive behaviors, tantrums, and withdrawn behaviors. In addition, these individuals were more likely than those with SMC1A variants to demonstrate self-injurious behaviors, and anxiety. Both groups yielded a similar proportion of participants who participated in speech and occupational therapy, however those with SMC1A variants were more likely to engage in physical therapy. Both clinical groups report low rate of communicative or assistive device use despite a large proportion of participants never mastering single word or sentence use.ConclusionsStudy results are consistent with recent investigations highlighting more severe behavioral phenotype, particularly autistic features, anxiety, and behavior regulation challenges, among those with NIPBL variants albeit comparable developmental milestones. Both groups endorsed very elevated attention problems. Findings highlight importance of early interventions, including behavioral health services.