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Chromosomal 1p duplications are a rarity, with minimal literature on the topic. As a result, it is useful to document patient presentations with this defect to help guide the management and treatment of future patients with this genetic abnormality. We present a successful case report of a patient with a chromosome 1p31.3p31.1 duplication, including her initial presentation, the path to genetic testing, and patient outcome. Chromosomal duplication was found on genetic testing performed for failure to thrive and inability to meet her developmental milestones. The patient was significantly undernourished due to her feeding difficulties, leading to her presentation of altered mental status, growth arrest, dehydration, and hypoglycemia. Intervention in the form of a gastrostomy tube and fundoplication led to a significant improvement in the stability seen in the patient at the time of discharge. Long-term cognitive-linguistic treatment is required for continued neurological development. Only 11 publications currently exist regarding chromosome 1p duplication. However, none are specific to the 1p31.3p31.1 duplication, making this case report the first of its kind. Overlapping chromosomal 1p duplications have been described in patients with low birth weight and growth delays, palate abnormalities, intellectual disability, microcephaly, heart defects, and ambiguous genitalia. Despite the rarity of this duplication, it is essential to document these cases because if some of these genetic abnormalities are identified in more significant numbers, they can be conclusively linked to the patient's phenotype. In addition, the treatment plan played an instrumental role in stabilizing our patient's condition. It is also helpful to report the treatment plans so future clinicians who encounter this situation can utilize the successful treatment plans that most align with their patient's clinical presentation.

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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.

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LAY ABSTRACT: Timely identification of autism spectrum conditions is a necessity to enable children to receive the most benefit from early interventions. Emerging technological advancements provide avenues for detecting subtle, early indicators of autism from routinely collected health information. This study tested a model that provides a likelihood score for autism diagnosis from baby wellness visit records collected during the first 2 years of life. It included records of 591,989 non-autistic children and 12,846 children with autism. The model identified two-thirds of the autism spectrum condition group (boys 63% and girls 66%). Sex-specific models had several predictive features in common. These included language development, fine motor skills, and social milestones from visits at 12-24 months, mother's age, and lower initial growth but higher last growth measurements. Parental concerns about development or hearing impairment were other predictors. The models differed in other growth measurements and birth parameters. These models can support the detection of early signs of autism in girls and boys by using information routinely recorded during the first 2 years of life.

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We present a case of a three-year-old African American male, born at term, who initially presented with bronchiolitis at six months and has since experienced recurrent episodes of respiratory distress and hospitalizations. The patient also has severe eczema, developmental delays, and recurrent viral illnesses. Despite thorough evaluations from various specialists, such as pulmonology, allergy, and gastroenterology, the underlying cause remained elusive. The differential diagnosis for this case is as follows: severe persistent asthma with a possible link to genetic mutations such as CDHR3, hyper-IgE syndrome, atypical presentation of Wiskott-Aldrich syndrome, and severe gastroesophageal reflux disease (GERD) with aspiration pneumonitis. This patient's chronic condition has contributed to several developmental consequences, including failure to gain weight and possible hypoxic encephalopathy, leading to delays in cognitive and motor milestones and speech delays. Aggressive medical management, especially long-term systemic steroids, raises concerns about future complications. Through this case, we highlight the importance of thorough workups and an interdisciplinary approach to diagnosing and managing an unknown immune condition, as well as consistent pediatric primary care follow-up to assess development and coordinate necessary support. Here, we aim to address a gap in research on the unique presentations of pediatric respiratory distress symptoms by formulating a comprehensive differential diagnosis and exploring the various ways that chronic respiratory illness can contribute to developmental deficits such as speech and cognitive delays in pediatric patients. This study calls for further research into genetic contributions to asthma, diverse presentations of GERD, prevention of viral illnesses, alternative treatments minimizing steroid use, and an understanding of the impact of chronic respiratory distress on cognitive and language development in children. Thorough workups and interdisciplinary approaches are essential for effective diagnosis and management.

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Background Parents serve a fundamental role in monitoring developmental milestones and identifying potential delays during early childhood, enabling timely interventions. However, previous studies in Saudi Arabia have shown limited awareness among parents regarding age-specific norms and red flags across developmental domains. This knowledge gap can severely impact the detection and management of abnormalities. Hence, a comprehensive understanding of Saudi parental knowledge, attitudes, and practices concerning childhood developmental trajectories is imperative.  Methodology This cross-sectional study assessed developmental milestone awareness, beliefs, and behaviors among Saudi parents. A sample of 1,052 parents completed a validated 38-item questionnaire covering knowledge, attitudes, practices, and demographics. Knowledge was assessed across developmental domains using 22 multiple-choice questions, with scores categorized as excellent (≥75%), good (50%-75%), fair (40%-50%), or poor (≤39%). Attitudes and practices were captured on five-point Likert scales. Descriptive and chi-square analyses were conducted using IBM SPSS Statistics for Windows, Version 28.0 (IBM Corp., Armonk, NY).  Results The majority of participants were females (844, 80.2%), with a mean age of 38.8 years. Serious knowledge inadequacies existed regarding developmental timelines across domains, especially motor milestones like crawling (93, 29.4% correct), sitting unsupported (45, 27.6%), pointing at objects (278, 26.4%), and responding to names (440, 41.8%). Overall, 2 (0.2%) participants showed excellent and 281 (26.7%) showed good understanding, while 490 (46.6%) had poor knowledge. Significant sociodemographic variations were observed, with women and experienced parents demonstrating greater awareness (P < 0.001). Despite knowledge gaps, 542 (51.5%) actively sought developmental information themselves, and over 50% trusted pediatric guidance. Most participants expressed a willingness to undergo screenings if risk factors existed and reported spending a considerable amount of daily interaction time with their children, focusing on developmental needs. Conclusions Critical developmental milestone knowledge shortfalls and selective attitudes persist among Saudi parents, warranting public education and physician-parent communication that enhance interventions to enable impactful developmental monitoring and prompt responses to abnormalities in a timely manner.

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INTRODUCTION: Parents' ability to engage and raise their children in a safe and appropriate manner is largely influenced by their knowledge of child development and childrearing. This study aimed to evaluate the parenting and developmental milestone (MS) knowledge of Western region Saudi parents and identify the related elements that influence their knowledge. METHODS: This cross­sectional study was conducted for a period of six months. Ethical approval was duly sanctioned by the Institutional Review Board (IRB), and prior to participation, written informed consent was diligently procured from all the individuals involved in the study. In adherence to the paramount principles of privacy, rigorous measures were employed to de­identify the personal data of the participants, thereby safeguarding their confidentiality and anonymity. All research procedures were meticulously executed in strict compliance with the pertinent guidelines and regulatory standards governing research ethics. The study cohort consisted of Saudi parents from the Western Province of Saudi Arabia who had children aged up to six years and expressed a genuine willingness to participate in the research. This commitment was reaffirmed through their informed consent. Notably, the inclusion criteria for parental involvement did not impose any restrictions based on age or ethnic origin, ensuring a diverse and inclusive representation of this crucial demographic group. RESULTS: For assessing parental awareness and knowledge about children's developmental MSs, we examined a diverse sample of 873 participants, predominantly comprising females (77.00%). The age distribution revealed that a substantial portion of the respondents were below 30 (37.00%). Most respondents (62.40%) sought information from medical physicians and pediatricians. Gender had a significant effect, with males showing a lower awareness level compared to females (Beta = -0.582, 95% confidence interval (CI) [-0.890, -0.274], p-value < 0.001). Marital status demonstrated significance, where divorced individuals showed a lower awareness level than widowed participants (Beta = -1.641, 95% CI [-2.993, -0.288], p-value = 0.017). At the same time, no significant differences were found for singles or married individuals. CONCLUSION: Saudi parents lacked understanding of other parenting skills, such as a baby's personality and temperament, but they were well educated about some areas of childrearing, primarily physical safety precautions. It is advised that nurses and doctors give parenting advice to families at every step of their children's growth to educate and support them.

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BACKGROUND: Developmental delays in children are assessed in four basic domains: gross motor, fine motor, social, and language. Early years of life are crucial in a child's development, so it is imperative that parents be aware of developmental milestones to facilitate early diagnosis and treatment in case of a developmental delay. This study assessed parental knowledge, attitude, and practices regarding children's developmental milestones and associated "red flags". METHODS: A cross-sectional study was conducted at the Department of Pediatrics at Liaquat National Hospital, Karachi. 390 parents, who had at least one child under 5 years of age, with no diagnosed developmental delay, were interviewed during outpatient clinic visits. The questionnaire consisted of three components to assess parental knowledge, attitude, and practices. RESULTS: 59% and 54% of parents had poor knowledge of gross and fine motor milestones respectively; In the social domain, 56% of the respondents had inadequate knowledge. 42% had inadequate knowledge of language milestones; 29% of parents strongly agreed that their pediatricians provide satisfactory information regarding red flags of developmental milestones. 60% of parents strongly agreed that their child's developmental delay would be a cause of concern for them. In the case of developmental delay, 55% of parents said they would consult a general pediatrician, 11% preferred a pediatric neurologist, 21% opted for a developmental pediatrician and 13% opted for a family physician. Residence and family systems were found to be associated with language-related milestones with significantly higher odds of knowledge among urban residents than rural ones and a significantly lower likelihood of language milestones knowledge among joint families than nuclear families. Female gender was found to be significantly associated with positive attitude. CONCLUSION: The majority of our respondents showed considerably poor knowledge regarding developmental milestones. This highlights the need to devise ways to educate parents on this subject to enable them to vigilantly monitor their child's developmental status and any associated abnormalities and ultimately facilitate the right course of action.

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Childhood is a period of construction of the organism, during which interactions with the environment and regular physical activity are necessary for the maturation of the neuronal networks. An atypical sensorimotor activity during childhood (due to bed-rest or neurodevelopmental disorders) impacts the development of the neuromuscular system. A model of sensorimotor restriction (SMR) developed in rats has shown that casting pups' hind limbs from postnatal day 1 (P1) to P28 induced a severe perturbation of motor behavior, due to muscle weakness as well as disturbances within the central nervous system. In the present study, our objective was to determine whether SMR affects the early postnatal ontogenesis. We explored the neuromuscular development through the determination of the age for achievement of the main neurodevelopmental reflexes, which represent reliable indicators of neurological and behavioral development. We also evaluated the maturation of postural control. Our results demonstrate that SMR induces a delay in the motor development, illustrated by a several days delay in the acquisition of a mature posture and in the acquisition reflexes: hind limb grasping, righting, hind limb placing, cliff avoidance, negative geotaxis. In conclusion, impaired physical activity and low interactions with environment during early development result in altered maturation of the nervous system.

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INTRODUCTION AND METHODS: We report two series of individuals with DDX3X variations, one (48 individuals) from physicians and one (44 individuals) from caregivers. RESULTS: These two series include several symptoms in common, with fairly similar distribution, which suggests that caregivers' data are close to physicians' data. For example, both series identified early childhood symptoms that were not previously described: feeding difficulties, mean walking age, and age at first words. DISCUSSION: Each of the two datasets provides complementary knowledge. We confirmed that symptoms are similar to those in the literature and provides more details on feeding difficulties. Caregivers considered that the symptom attention-deficit/hyperactivity disorder were most worrisome. Both series also reported sleep disturbance. Recently, anxiety has been reported in individuals with DDX3X variants. We strongly suggest that attention-deficit/hyperactivity disorder, anxiety, and sleep disorders need to be treated.

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This study had two aims. Aim one investigated achievement of 10 developmental milestones in children with Bardet-Biedl syndrome (BBS). Aim one data were derived from retrospective responses by caregivers of individuals with BBS who are enrolled in the Clinical Registry Investigating Bardet-Biedl syndrome (CRIBBS). CRIBBS is a natural history registry acquiring serial observations. Aim two investigated early adaptive skills using the Adaptive Behavior Assessment System (ABAS-II 0-5) completed by caregivers of children with BBS aged from 0 to 5. There were 652 individuals with milestone information (with some variability based on availability of information for specific milestones), and 101 individuals (including 95 among the 652) with ABAS-II information. Results revealed wide-ranging delays in adaptive skills, particularly in the domain of Self-Care. Expressive language appears to be the most frequently delayed developmental milestone. We found a difference by BBS genotype wherein individuals with BBS1 had higher adaptive/developmental scores than individuals with BBS10. Age also carried a significant association with adaptive skills diverging farther from a normative trajectory as children with BBS progress through early childhood.

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Background Monitoring children's acquisition of developmental milestones is integral to pediatric practice. Though pediatricians are responsible for evaluating children's development, parents have a crucial role in addressing delays as early as possible, where early detection of developmental delay can help in early intervention and ultimately potentiate a child's cognitive and social abilities toward an independent life. This study assesses parental knowledge of the warning signs denoting delayed developmental milestone acquisition, in addition to analyzing demographic variables that may influence their level of knowledge. Methods This cross-sectional study included 376 parents of children attending pediatric clinics in National Guard Health Affairs- King Abdulaziz Medical City, in Jeddah, Saudi Arabia. A two-section structured questionnaire was utilized. It included 16 option-based questions with one correct answer, while the other options were either an under or overestimate of the age at which the child should acquire a particularly significant milestone development across different domains. A score of 10 out of 16 was chosen as the minimum to show the appropriate level of knowledge. Results Most participants (n=282; 75%) were women, and 174 (46.27%) were between 29 and 39 years old. The highest reported level of education was college or higher (n=214; 56.91%). Only 41 (11%) parents had the required level of knowledge, while the remaining 335 (89%) fell short of meeting the passing level (mean 6.59, SD= 2.72). The motor domain had the highest level of accuracy, followed closely behind the cognitive domain. The language and social domains exhibited lower levels of accuracy. Conclusions Despite the majority of parents in this group possessing a college education and availing multiple health resources, there is a significant gap in their knowledge of typical trajectories of development milestones. Thus, there is a need for a nationwide initiative to promote the parent's proactive role in monitoring their children's growth.

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Despite the early onset of clinical signs suggestive of Duchenne muscular dystrophy (DMD), a diagnosis is often not made until four years of age or older, with a diagnostic delay of up to two years from the appearance of the first symptoms. As disease-modifying therapies for DMD become available that are ideally started early before irreversible muscle damage occurs, the importance of avoiding diagnostic delay increases. Shortening the time to a definite diagnosis in DMD allows timely genetic counseling and assessment of carrier status, initiation of multidisciplinary standard care, timely initiation of appropriate treatments, and precise genetic mutation characterization to assess suitability for access to drugs targeted at specific mutations while reducing the emotional and psychological family burden of the disease. This comprehensive literature review describes the early signs of impairment in DMD and highlights the bottlenecks related to the different diagnostic steps. In summary, the evidence suggests that the best mitigation strategy for improving the age at diagnosis is to increase awareness of the early symptoms of DMD and encourage early clinical screening with an inexpensive and sensitive serum creatine kinase test in all boys who present signs of developmental delay and specific motor test abnormality at routine pediatrician visits.

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Inadequate routine healthcare check-up visits for children aged three to five years impose substantial economic and social burdens due to morbidity and mortality. The absence of regular well-child visits and vaccinations leads to avoidable diseases, underscoring the need for a renewed emphasis on childhood immunizations and check-ups. Out of 160 articles initially screened after removing duplicates, 45 were chosen for full-text review following initial title and abstract screening by two independent reviewers. Afterward, 20 studies met the predefined inclusion criteria during the final assessment of full-text articles, and data were systematically extracted from these selected studies using standardized forms to ensure accuracy and consistency. Well-child visits promote holistic development, health, and well-being in children aged three to five years. Following established guidelines and evidence-based practices, healthcare professionals provide assessments, vaccinations, and guidance for a healthy future. Despite challenges, well-child visits are vital for preventive care, empowering informed decisions for children's growth and development. The benefits of well-child visits encompass growth monitoring, anticipatory guidance, and preventive measures, crucial for children with chronic illnesses. Key components include comprehensive assessments, developmental screenings, vision and hearing evaluations, immunizations, health education, and counseling. In the case of juvenile diabetes, parental education is paramount. Parents need to understand the intricacies of insulin administration, including proper dosage calculation based on glucose measurements, meal planning, and the importance of timing insulin injections. Implementing guidelines and principles by organizations such as Bright Futures and the American Academy of Pediatrics ensures holistic care, parent involvement, and evidence-based practices. This review explores best practices and guidelines for such visits, emphasizing their role in monitoring and promoting children's development.

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INTRODUCTION: Neurodegenerative diseases cause developmental delays and loss of milestones in infants and children. However, scalable outcome measures that quantify features meaningful to parents/caregivers (P/CGs) and have regulatory precedence are lacking for assessing the effectiveness of treatments in clinical trials of neurodegenerative disorders. To address this gap, we developed an innovative, blinded strategy for single-arm trials with external controls using expert panel review of home video. METHOD: We identified meaningful, observable, and objective developmental milestones from iterative interviews with P/CGs and clinical experts. Subsequently, we standardized video recording procedures and instructions to ensure consistency in how P/CGs solicited each activity. In practice, videos would be graded by an expert panel blinded to treatment. To ensure blinding and quality control, video recordings from interim time points would be randomly interspersed. We conducted a pilot study and a pretest of grading to test feasibility and improve the final strategy. RESULTS: The five P/CGs participating in the pilot study found the instructions clear, selected activities important and reflective of their children's abilities, and recordings at-home preferrable to in-clinic assessments. The three grading experts found the videos easy to grade and the milestones clinically meaningful. CONCLUSION: Our standardized strategy enables expert panel grading of developmental milestone achievements using at-home recordings, blinded to treatment and post-baseline time points. This rigorous and objective scoring system has broad applicability in various disease contexts, with or without external controls. Moreover, our strategy facilitates flexible, continued data collection and the videos can be archived for future analyses.

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BACKGROUND: Developmental surveillance, conducted routinely worldwide, is fundamental for timely identification of children at risk of developmental delays. It is typically executed by assessing age-appropriate milestone attainment and applying clinical judgment during health supervision visits. Unlike developmental screening and evaluation tools, surveillance typically lacks standardized quantitative measures, and consequently, its interpretation is often qualitative and subjective. OBJECTIVE: Herein, we suggested a novel method for aggregating developmental surveillance assessments into a single score that coherently depicts and monitors child development. We described the procedure for calculating the score and demonstrated its ability to effectively capture known population-level associations. Additionally, we showed that the score can be used to describe longitudinal patterns of development that may facilitate tracking and classifying developmental trajectories of children. METHODS: We described the Developmental Surveillance Score (DSS), a simple-to-use tool that quantifies the age-dependent severity level of a failure at attaining developmental milestones based on the recently introduced Israeli developmental surveillance program. We evaluated the DSS using a nationwide cohort of >1 million Israeli children from birth to 36 months of age, assessed between July 1, 2014, and September 1, 2021. We measured the score's ability to capture known associations between developmental delays and characteristics of the mother and child. Additionally, we computed series of the DSS in consecutive visits to describe a child's longitudinal development and applied cluster analysis to identify distinct patterns of these developmental trajectories. RESULTS: The analyzed cohort included 1,130,005 children. The evaluation of the DSS on subpopulations of the cohort, stratified by known risk factors of developmental delays, revealed expected relations between developmental delay and characteristics of the child and mother, including demographics and obstetrics-related variables. On average, the score was worse for preterm children compared to full-term children and for male children compared to female children, and it was correspondingly worse for lower levels of maternal education. The trajectories of scores in 6 consecutive visits were available for 294,000 children. The clustering of these trajectories revealed 3 main types of developmental patterns that are consistent with clinical experience: children who successfully attain milestones, children who initially tend to fail but improve over time, and children whose failures tend to increase over time. CONCLUSIONS: The suggested score is straightforward to compute in its basic form and can be easily implemented as a web-based tool in its more elaborate form. It highlights known and novel relations between developmental delay and characteristics of the mother and child, demonstrating its potential usefulness for surveillance and research. Additionally, it can monitor the developmental trajectory of a child and characterize it. Future work is needed to calibrate the score vis-a-vis other screening tools, validate it worldwide, and integrate it into the clinical workflow of developmental surveillance.

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Background The purpose of this study was to investigate if infants' age at attaining motor developmental milestones is associated with the big five personality traits 50 years later. Methods Mothers of 8395 infants from the Copenhagen Perinatal Cohort recorded a total of 12 motor developmental milestones during the first year of their infant's life. Information on at least one milestone was available for 1307 singletons with adult follow-up scores on the NEO-Five-Factor Inventory. The mean age at personality testing was 50.1 years. Results Slower attainment of motor milestones was associated with increased neuroticism and lower conscientiousness in midlife. All 12 motor developmental milestones explained a total of 2.4% of the variance in neuroticism, while they explained 3.2% of the variance in conscientiousness. These results remained significant after adjustment for the included family and perinatal covariates, as well as adult intelligence. Discussion The personality trait of neuroticism is a general risk factor for psychopathology and has in young adulthood been found to be associated with early motor development. However, evidence on associations of motor developmental milestones with other personality traits has been non-existent. These findings suggest that delays in early motor development may not only characterise individuals with later psychopathology, including schizophrenia, but may also be associated with personality traits such as neuroticism and conscientiousness through the life course.

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Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomic microdeletion (7q11.23). WBS has been modeled by a mouse line having a complete deletion (CD) of the equivalent mouse locus. This model has been largely used to investigate the etiopathological mechanisms of WBS, although pharmacological therapies have not been identified yet. Surprisingly, CD mice were so far mainly tested in adulthood, despite the developmental nature of WBS and the critical relevance of early timing for potential treatments. Here we provide for the first time a phenotypic characterization of CD mice of both sexes during infancy and adolescence, i.e., between birth and 7 weeks of age. CD pups of both sexes showed reduced body growth, delayed sensory development, and altered patterns of ultrasonic vocalizations and exploratory behaviors. Adolescent CD mice showed reduced locomotion and acoustic startle response, and altered social interaction and communication, the latter being more pronounced in female mice. Juvenile CD mutants of both sexes also displayed reduced brain weight, cortical and hippocampal dendritic length, and spine density. Our findings highlight the critical relevance of early neurobehavioral alterations as biomarkers of WBS pathology, underlying the importance of adolescence for identifying novel therapeutic targets for this neurological disorder.

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Diagnosing rare developmental disorders using genome-wide sequencing data commonly necessitates review of multiple plausible candidate variants, often using ontologies of categorical clinical terms. We show that Integrating Multiple Phenotype Resources Optimizes Variant Evaluation in Developmental Disorders (IMPROVE-DD) by incorporating additional classes of data commonly available to clinicians and recorded in health records. In doing so, we quantify the distinct contributions of sex, growth, and development in addition to Human Phenotype Ontology (HPO) terms and demonstrate added value from these readily available information sources. We use likelihood ratios for nominal and quantitative data and propose a classifier for HPO terms in this framework. This Bayesian framework results in more robust diagnoses. Using data systematically collected in the Deciphering Developmental Disorders study, we considered 77 genes with pathogenic/likely pathogenic variants in ≥10 individuals. All genes showed at least a satisfactory prediction by receiver operating characteristic when testing on training data (AUC ≥ 0.6), and HPO terms were the best predictor for the majority of genes, though a minority (13/77) of genes were better predicted by other phenotypic data types. Overall, classifiers based upon multiple integrated phenotypic data sources performed better than those based upon any individual source, and importantly, integrated models produced notably fewer false positives. Finally, we show that IMPROVE-DD models with good predictive performance on cross-validation can be constructed from relatively few individuals. This suggests new strategies for candidate gene prioritization and highlights the value of systematic clinical data collection to support diagnostic programs.

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Joubert syndrome is a rare neurological and developmental malfunction represented by decreased muscle tone, ataxia, and delayed developmental milestones. Joubert syndrome-related disorders, besides central nervous system, can involve other systems and thus can lead to multi-organ malfunction. We report a case of pure Joubert syndrome who presented with developmental delay, decreased muscle tone, and ataxia. Identification of molar tooth sign on magnetic resonance imaging studies assisted to make a definitive diagnosis. Detailed examination revealed no other significant findings of any organ of the body. Patient was managed conservatively with symptomatic treatment. Although these types of cases are rarely encountered, they can lead to multiple organ disabilities. Therefore, clinicians should always keep this diagnosis in mind whenever an infant presents with the aforementioned neurodevelopmental symptoms.

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Early motor and sensory developmental delays precede Autism Spectrum Disorder (ASD) diagnosis and may serve as early indicators of ASD. The literature on sensorimotor development in animal models is sparse, male centered, and has mixed findings. We characterized early development in a prenatal valproic acid (VPA) model of ASD and found sex-specific developmental delays in VPA rats. We created a developmental composite score combining 15 test readouts, yielding a reliable gestalt measure spanning physical, sensory, and motor development, that effectively discriminated between VPA and control groups. Considering the heterogeneity in ASD phenotype, the developmental composite offers a robust metric that can enable comparison across different animal models of ASD and can serve as an outcome measure for early intervention studies.

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