Delays In Motor Skills Research Articles

Atypical procedural learning in children with developmental coordination disorder: A combined behavioral and neuroimaging study

While procedural learning (PL) has been implicated in delayed motor skill observed in developmental coordination disorder (DCD), few studies have considered the impact of co-occurring attentional problems. Furthermore, the neurostructural basis of PL in children remains unclear. We investigated PL in children with DCD while controlling for inattention symptoms, and examined the role of fronto-basal ganglia-cerebellar morphology in PL. Fifty-nine children (6–14 years; nDCD = 19, ncontrol = 40) completed the serial reaction time (SRT) task to measure PL. The Attention-Deficit Hyperactivity Disorder Rating Scale-IV was administered to measure inattention symptoms. Structural T1 images were acquired for a subset of participants (nDCD = 10, ncontrol = 28), and processed using FreeSurfer. Volume was extracted for the cerebellum, basal ganglia, and frontal regions. After controlling for inattention symptoms, the reaction time profile of controls was consistent with learning on the SRT task. This was not the case for those with DCD. SRT task performance was positively correlated with cerebellar cortical volume, and children with DCD trended towards lower cerebellar volume compared to controls. Children with DCD may not engage in PL during the SRT task in the same manner as controls, with this differential performance being associated with atypical cerebellar morphology.

Macular hypoplasia and high myopia in 48, xxyy syndrome: a unique case of 48, xxyy syndrome that presents with high myopia and macular dysplasia

BackgroundAmong sex chromosome aneuploidies, 48, XXYY syndrome is a rare variant. This condition is marked by the existence of an additional X and Y chromosome in males, leading to a diverse range of physical, neurocognitive, behavioral, and psychological manifestations. Typical characteristics include a tall stature and infertility. Other phenotypes include congenital heart defects, skeletal anomalies, tremors, obesity, as well as the potential for type 2 diabetes and/or peripheral vascular disease.Case presentationA 6-year-old boy, who had been experiencing progressive vision deterioration in both eyes for the past two years, presented with a history of poor vision, delayed motor skills. The patient was diagnosed with micropenis in the pediatric outpatient clinic. Sparse hair, an unusually tall stature and craniofacial dysmorphology characterized by ocular hypertelorism, depressed nasal bridge, and epicanthic folds were observed. Comprehensive ophthalmic examination revealed high myopia and grade 3 macular hypoplasia. Diagnostic investigations including karyotype analysis and whole-exome sequencing identified an anomalous male karyotype comprising two X and two Y chromosomes, confirming a diagnosis of 48, XXYY syndrome.ConclusionsThis study underscores the rare association of high myopia and grade 3 macular dysplasia with 48, XXYY syndrome. To our knowledge, this case marks the first recorded instance of macular dysplasia in a patient with 48, XXYY syndrome. This novel finding enhances our understanding of this syndrome’s phenotypic variability.

Protein restriction during pregnancy alters Cdkn1c silencing, dopamine circuitry and offspring behaviour without changing expression of key neuronal marker genes

We tracked the consequences of in utero protein restriction in mice throughout their development and life course using a luciferase-based allelic reporter of imprinted Cdkn1c. Exposure to gestational low-protein diet (LPD) results in the inappropriate expression of paternally inherited Cdkn1c in the brains of embryonic and juvenile mice. These animals were characterised by a developmental delay in motor skills, and by behavioural alterations indicative of reduced anxiety. Exposure to LPD in utero resulted in significantly more tyrosine hydroxylase positive (dopaminergic) neurons in the midbrain of adult offspring as compared to age-matched, control-diet equivalents. Positron emission tomography (PET) imaging revealed an increase in striatal dopamine synthesis capacity in LPD-exposed offspring, where elevated levels of dopamine correlated with an enhanced sensitivity to cocaine. These data highlight a profound sensitivity of the developing epigenome to gestational protein restriction. Our data also suggest that loss of Cdkn1c imprinting and p57KIP2 upregulation alters the cellular composition of the developing midbrain, compromises dopamine circuitry, and thereby provokes behavioural abnormalities in early postnatal life. Molecular analyses showed that despite this phenotype, exposure to LPD solely during pregnancy did not significantly change the expression of key neuronal- or dopamine-associated marker genes in adult offspring.

The Effect Of Sensory-Motor Virtual Reality On Balance In Children With Clinical Down Syndrome

Introduction: Down syndrome affects approximately one in every 800 live births and leads to musculoskeletal disorders and motor skill delays. Children with Down syndrome experience persistent deficits in balance and coordination. Virtual Reality (VR) offers an interactive and immersive approach to therapy and has gained popularity in rehabilitation. This study explores the effect of sensory-motor virtual reality (VR SenMor) on static and dynamic balance in children with clinical Down syndrome.Methods: A randomized controlled trial with a pre and post-test control group design was conducted with 20 children diagnosed with Down syndrome. Treatment group (n = 10) received VR SenMor therapy twice a week for four weeks, while the control group (n = 10) received no treatment. Balance assessments were conducted using the Pediatric Balance Scale (PBS) and Timed Up and Go (TUG) test before and after the intervention.Results: There were no significant differences in age, gender, or BMI between the intervention and control groups. The VR SenMor therapy resulted in significant improvements in the PBS and TUG test scores in the intervention group compared to the control group.Discussion: VR SenMor therapy enhanced balance in children with Down syndrome, with no confounding effects from age and gender. The VR system's sensory integration feedback and neuroplasticity mechanisms contributed to the improvements. The treatment's positive outcomes make it a promising approach for balance training at home.Conclusion: Sensory-motor virtual reality therapy shows promise in enhancing static and dynamic balance in children with clinical Down syndrome.Keywords: sensory-motor virtual reality; down syndrome

Using 2 Versions of the Test of Gross Motor Development to Classify and Screen Young Children's Motor Skills: A Comparison Study.

The purpose of this study was to examine comparability between 2 editions of the Test of Gross Motor Development (TGMD-second and TGMD-third edition) on (1) how children's motor skills were categorized as average or below average, and (2) how children are screened for being at-risk for motor delay or with delayed motor skills. Participants were 226 children (Mage = 53.4mo, 125 boys). All children completed full TGMD-2 and TGMD-3. Children were classified as average or above (>25th percentile) or below average (≤25th percentile) and, when applicable, as developmental delay (≤5th percentile) or at-risk for developmental delay (6-25th percentile). We compared children's classifications across TGMD editions using percent agreement and chi-squared tests. The TGMD-2 and TGMD-3 had moderate agreement when categorizing children as below average (72.2% for total skills, 76.0% for locomotor skills, and 73% for ball skills). The TGMD-3 was significantly more likely to categorize children's motor skill performance as average or above (all P < .01). TGMD-2 and TGMD-3 similarly screen children who demonstrate below average skills (≤25th percentile), but not for specific skill level classifications, including above average, at-risk for delays, and delayed.

Awareness and developments in the treatment of pompe disease : A review

Pompe disease is a hereditary, uncommon (one in every 40,000 births) and frequently deadly ailment that affects the heart and skeletal muscles. Mutations in a gene that produces an enzyme called acid alpha-glucosidase cause it (GAA). This article is meant to raise awareness among Pompe disease patients. We also talk about new future treatments on the market for the treatment of pompe illness. Pompe disease is an inherited disorder caused by the build-up of a complex sugar called glycogen in the body’s cells. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function normally. Researchers have described three types of pompe disease, which differ in severity and the age at which they appear. These types are known as classic infantile-onset, non-classic infantile-onset and late-onset. The classic form of infantileonset pompe disease begins within a few months of birth. Infants with this disorder typically experience muscle weakness (myopathy), poor muscle tone (hypotonia), an enlarged liver (hepatomegaly) and heart defects. Affected infants may also fail to gain weight and grow at the expected rate (failure to thrive) and have breathing problems. If untreated, this form of pompe disease leads to death from heart failure in the first year of life. The non-classic form of infantile-onset pompe disease usually appears by age 1. It is characterized by delayed motor skills (such as rolling over and sitting) and progressive muscle weakness. The heart may be abnormally large (cardiomegaly), but affected individuals usually do not experience heart failure. The muscle weakness in this disorder leads to serious breathing problems and most children with non-classic infantile-onset pompe disease live only into early childhood.

Quantitative proteomics and phosphoproteomics of PP2A-PPP2R5D variants reveal deregulation of RPS6 phosphorylation via converging signaling cascades

Genetic germline variants of PPP2R5D (encoding: phosphoprotein phosphatase 2 regulatory protein 5D) result in PPP2R5D-related disorder (Jordan's Syndrome), which is characterized by intellectual disability, hypotonia, seizures, macrocephaly, autism spectrum disorder, and delayed motor skill development. The disorder originates from de novo single nucleotide mutations, generating missense variants that act in a dominant manner. Pathogenic mutations altering 13 different amino acids have been identified, with the E198K variant accounting for ∼40% of reported cases. However, the generation of a heterozygous E198K variant cell line to study the molecular effects of the pathogenic mutation has been challenging. Here, we use CRISPR-PRIME genomic editing to introduce a transition (c.592G>A) in a single PPP2R5D allele in HEK293cells, generating E198K-heterozygous lines to complement existing E420K variant lines. We generate global protein and phosphorylation profiles of WT, E198K, and E420Kcell lines and find unique and shared changes between variants and WT cells in kinase- and phosphatase-controlled signaling cascades. We observed ribosomal protein S6 (RPS6) hyperphosphorylation as a shared signaling alteration, indicative of increased ribosomal protein S6-kinase activity. Treatment with rapamycin or an RPS6-kinase inhibitor (LY2584702) suppressed RPS6 phosphorylation in both, suggesting upstream activation of mTORC1/p70S6K. Intriguingly, our data suggests ERK-dependent activation of mTORC1 in both E198K and E420K variant cells, with additional AKT-mediated mTORC1 activation in the E420K variant. Thus, although upstream activation of mTORC1 differs between PPP2R5D-related disorder genotypes, inhibition of mTORC1 or RPS6 kinases warrants further investigation as potential therapeutic strategies for patients.

Neurosurgical management of cervicomedullary compression, spinal stenosis, and hydrocephalus in pediatric achondroplasia: a systematic review.

Pediatric achondroplasia is often associated with conditions requiring neurosurgical intervention, including CSF diversion and multilevel spinal decompression. However, there is a lack of clinical guidelines and reliable estimates of the benefits and risks of these interventions. This study aimed to summarize the literature on the neurosurgical management of pediatric achondroplasia patients in order to aid in determining optimal treatment and standardization of care. A systematic review of peer-reviewed studies with an objective diagnosis of achondroplasia, patient demographic information, and available data on neurosurgical interventions performed before 18 years of age for cervicomedullary compression, spinal stenosis, and hydrocephalus was performed. Study quality and risks of bias were assessed using standardized scores. Independent patient data on surgical indications, outcomes, reoperations, and complication risks were aggregated using means and percentages. Of 204 records, 25 studies with 287 pediatric achondroplasia patients (mean age 25 ± 36 months) treated for cervicomedullary compression (n = 153), spinal stenosis (n = 100), and obstructive hydrocephalus (n = 34) were evaluated. Symptomatic cervicomedullary compression occurred early in life (mean age 31 ± 25 months), with apnea (48%), T2-weighted MRI cord signal (28%), myelopathy (27%), and delayed motor skills (15%) requiring foramen magnum decompression observed in 99% of patients, as well as cervical laminectomy in 65% of patients. Although 91% of treated patients had resolution of symptoms, 2% mortality, 9% reoperation, and 21% complication rates were reported. Spinal stenosis was treated in relatively older children (mean age 13 ± 3 years) with laminectomy (23%), as well as with instrumented fusion (73%) for neurogenic claudication (59%), back pain (15%), and sciatica (8%). Although 95% of patients had symptom resolution after surgery, 17% reported complications and 18% required reoperation. Of the hydrocephalus patients (mean age 56 ± 103 months), half were treated with endoscopic third ventriculostomy (ETV) and half had a shunt placed for progressive ventriculomegaly (66%), headaches (32%), and delayed cognitive development (4%). The shunted patients had a 3% mortality rate and an average of 1.5 shunt revisions per patient. None of the patients who underwent ETV as the primary procedure required a revision. Neurosurgical intervention for pediatric achondroplasia conditions, including cervicomedullary compression, spinal stenosis, and hydrocephalus, is associated with high recovery rates and good outcomes. However, complications and reoperations are common. Further studies with follow-up into adulthood are needed to evaluate the long-term outcomes.

METHODS AND INDICATORS FOR EVALUATING THE EFFECTIVENESS OF PHYSICAL THERAPY FOR PRESCHOOL CHILDREN WITH AUTISM

Autism spectrum disorder (ASD) is a developmental disorder that affects the way people perceive the world. The learning, thinking, and problem-solving abilities of people with ASD can range from gifted to very challenging. Some people with ASD need a lot of help in their daily lives, while others need less.&#x0D; Symptoms of ASD range from mild to severe. Children with ASD may have delays in developing basic skills. For example, some children with ASD may be able to talk. Others may communicate in other ways or have trouble relating to other people. People with ASD may also limit their behaviors or have repetitive behavioral patterns. Children with autism spectrum disorder (ASD) often have delayed motor skills, limited coordination, and poor postural control. They also have to work harder to learn imitation skills. This can make it difficult to develop social skills. The task of a physical therapist is to help children with ASD develop gross motor skills, basic motor skills and improve their quality of life. Intervention programs, including physical therapy, have benefits for children with ASD, but the lack of reliable diagnostic tools makes it difficult to assess children with ASD in the context of their holistic development and provide timely therapy. In order to design an effective rehabilitation program, a physical therapist needs to qualitatively assess physical development using standardized tools, so it is important to understand what assessment tools and indicators a physical therapist can use. Only after assessing and identifying impairments in movement or aspects of motor skills that are delayed in a child's development can a physical therapist set functional goals with the parents (guardians) of a child with ASD to optimize the child's functional mobility in the most effective way.&#x0D; The aim of the research: to determine which assessment tools and indicators are most commonly used by researchers to evaluate the effectiveness of physical therapy and rehabilitation of children with autism.&#x0D; Materials and Methods. A search for systematic reviews related to physical therapy, rehabilitation, exercise and physical activity in children with ASD in the Cochrane, PubMed and Pedro libraries over the past 10 years was conducted and 11 of them were selected, which included 225 scientific studies.&#x0D; Results. The analysis of scientific studies based on 11 systematic reviews ensured the use of high-quality data and the consideration of modern and relevant assessment tools for children with ASD. From the 286 assessment tools and indicators used, six groups of assessment criteria were formed in the following main areas: mental functions (97 assessment tools), motor development (127 tools and indicators), life activities (21 tools), quality of life (12 tools) and assessment of children with ASD (12 tools) and comprehensive assessment (17 tools). We divided motor development into three subgroups, which included questionnaires/observations of motor skills development (23 instruments), clinical tests for assessing motor skills and physical qualities (43 instruments), balance and vestibular function (61 instruments).&#x0D; Conclusions. In our study, the examination of children with ASD covered several areas that are important and allow a specialist to comprehensively assess the child, but since their large number and their repeatability in studies is insignificant, it is very difficult to choose those that will be effective in the use of a physical therapist.

Beyond Hand's Reach: Haptic Feedback Is Essential to Toddlers With Visual Impairments Achieving Independent Walking

Introduction: A toddler's ability to stand alone in the middle of a room (static standing) is an essential skill for independent walking and is accomplished visually or through haptic feedback. Toddlers who are blind or mobility visually impaired (hereafter, “visually impaired”) use haptic feedback to attain static balance as evidenced by their continued use of cruising furniture and walking with assistance long after it is age-appropriate. Methods: This study analyzed demographic data, motor skills, learning ability, mobility tool usage, and the solitary play activities of 562 learners who were visually impaired and born between 2012 and 2021. Results: A cross-sectional analysis of learners aged 8- to 180-months, found motor skill delays began at 12 months. The most frequent walking method reported was “walks with assistance” ( n = 274). The most frequent mobility tool provided was a gait trainer ( n = 131). A major reason for obtaining the pediatric belt cane was the child “does not use other tools correctly” ( n = 112). Discussion: The children received handheld mobility tools (e.g., long canes, gait trainers, push toys, and adaptive mobility devices) at 13 months of age. Adults were seeking belt canes for children aged 8 to 180 months because they did not benefit from handheld mobility tools. Physical therapists provided gait trainers to the children with visual impairments who had no motor impairments. PTs use gait trainers to provide the user with static and dynamic balance. Implications for Practitioners: Children who are born with visual impairments, as defined by the current study, acquire independent walking delays. These delays may be a function of how they learned to achieve static balance as toddlers, walking with assistance. Current instructional strategies and tools do not prevent these delays. The field of visual impairment must continue to search for new mobility tools and more effective strategies because the delayed achievement of independent walking appears to have long-lasting negative effects on development.

Association between Socioeconomic Status and Motor Skill Development among Preschool Children of Lekhnath, Pokhara: A Cross-Sectional Study

INTRODUCTION: Gross and fine motor skills are both necessary for healthy growth. According to studies, children from lower “Socioeconomic Status (SES)” families have delayed development of these fundamental motor skills, placing them at risk for delayed motor skill development. The current research’s objective was to study the occurrence of developmental risks and the variances between the gross as well as fine motor growth related to the SES of pre-schoolers in Pokhara. MATERIALS AND METHODS: One district preschool in the Lekhnath municipality of Pokhara was selected for the study. 102 elementary school students between 3-6 years were evaluated. Children’s fine and gross motor skill and SES of their parents were calibrated. The values were compared and evaluated for the various economic status and genders keeping p&lt;0.05 as significant. RESULTS: Particularly in the area of fine motor abilities, significant variations between the SES groups were found. Gross motor growth had a greater variation and was substantial than fine motor skill. Fine motor growth risk prevalence ranged from 1.9% to 21.0%, while gross motor growth risk prevalence peaked at 14.63%. Age and sex also affected the prevalence rates. CONCLUSIONS: In pre-schoolers aged three to six, fine motor skills are strongly correlated with socioeconomic level. A correlation in gross motor skills was not established. In this study, sex had a greater impact on motor development than SES

For the Love of Teaching: The Chronicles of Teachers Handling Students with Special Educational Needs

Teaching learners with special needs is a very different reality in the profession. This study aimed to determine the lived experiences of teachers who handle learners with special needs. Qualitative-phenomenological design was employed in order to explore their lived experiences. The participants were purposefully chosen based on pre-determined criteria and were interviewed in order to gather the needed data. Results showed that they encountered difficulty in communication and performing adaptive skills, denial of parents on their children’s condition, learners having delayed motor skills, lack of parental support, and the most recurring challenge that emerges is learners’ behavioral problems. With the educational practices that teachers employed that are suitable for the children’s needs, several outcomes were identified specifically increased participation in different activities, improvement of verbal and non-verbal skills, improvement of behavior through simple instructions, increased socialization with their classmates, and learners improved their skills in reading and writing. Furthermore, compassion, enthusiasm, good communication and leadership skills, patience, and resourcefulness and creativity were the skills necessary for teachers to possess in providing the most suitable learning experience to their learners.

An In Vivo Model of Echovirus-Induced Meningitis Defines the Differential Roles of Type I and Type III Interferon Signaling in Central Nervous System Infection.

Echoviruses are among the most common worldwide causes of aseptic meningitis, which can cause long-term sequelae and death, particularly in neonates. However, the mechanisms by which these viruses induce meningeal inflammation are poorly understood, owing at least in part to the lack of in vivo models that recapitulate this aspect of echovirus pathogenesis. Here, we developed an in vivo neonatal mouse model that recapitulates key aspects of echovirus-induced meningitis. We show that expression of the human homologue of the primary echovirus receptor, the neonatal Fc receptor (FcRn), is not sufficient for infection of the brains of neonatal mice. However, ablation of type I, but not III, interferon (IFN) signaling in mice expressing human FcRn permitted high levels of echovirus replication in the brain, with corresponding clinical symptoms, including delayed motor skills and hind-limb weakness. Using this model, we defined the immunological response of the brain to echovirus infection and identified key cytokines, such as granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6), that were induced by this infection. Lastly, we showed that echoviruses specifically replicate in the leptomeninges, where they induce profound inflammation and cell death. Together, this work establishes an in vivo model of aseptic meningitis associated with echovirus infections that delineates the differential roles of type I and type III IFNs in echovirus-associated neuronal disease and defines the specificity of echoviral infections within the meninges. IMPORTANCE Echoviruses are among the most common worldwide causes of aseptic meningitis, which can cause long-term sequelae or even death. The mechanisms by which echoviruses infect the brain are poorly understood, largely owing to the lack of robust in vivo models that recapitulate this aspect of echovirus pathogenesis. Here, we establish a neonatal mouse model of echovirus-induced aseptic meningitis and show that expression of the human homologue of the FcRn, the primary receptor for echoviruses, and ablation of type I IFN signaling are required to recapitulate echovirus-induced meningitis and clinical disease. These findings provide key insights into the host factors that control echovirus-induced meningitis and a model that could be used to test anti-echovirus therapeutics.

Reliability of the Modified Star Excursion Balance Test in individuals with Down Syndrome

Neuromotor problems such as hypotonia, incoordination, impaired sensory-motor integration lead to significant delays in motor skills and balance development in individuals with Down Syndrome (DS). Balance control is essential for performing many motor skills independently and safely. Standardised testing of balance control can contribute significantly to the rehabilitation of individuals with DS. The purpose of this study was to determine intrarater and interrater reliability of the Modified Star Excursion Balance Test (SEBT) for individuals with DS. Thirteen individuals with DS were recruited in this study. Intraclass correlation coefficients (ICC [3,1]) with 95% confidence intervals, standard error of measurement (SEM), the smallest detectable difference (SDD) and the Spearman rank correlation coefficient were calculated. In all directions of the Modified SEBT, no statistically significant difference was found between two raters’ first and second measurements (p > 0.05). Interrater reliability for all reach directions of the Modified SEBT was high, with ICC ranging from 0.990 to 0.998.95% confidence intervals, SEM and SDD ranged from 0.924 to 0.999, 0.180–2.434 and 3.270–6.747, respectively. The Modified SEBT are reliable for evaluating dynamic balance in individuals with DS aged between 6 and 24 years.

Celiac crisis with thrombocytopenia and coagulopathy in a child

Celiac disease rarely presents with edema, hypoalbuminemia, acute metabolic deterioration, and electrolyte imbalances. This life-threatening condition is defined as a celiac crisis and may mimic disorders with metabolic derangement and sepsis. The crisis may present at onset or develop in celiac disease patients with poor compliance to a gluten-free diet. The fluid resuscitation and replacement of electrolyte deficits are life-saving modalities. A 14-month-old girl was admitted with fever, lethargy, severe dehydration, edema, hypotension, and commenced sepsis therapy. However, the patient had a growth delay and loss of weight with diarrhea and delayed motor skills. On admission, laboratory evaluation showed anemia, coagulopathy, hypoalbuminemia, electrolyte disturbances, and metabolic acidosis and developed thrombocytopenia during follow-up. The celiac serological tests and upper gastrointestinal endoscopic duodenal mucosa appearance, and duodenum histopathology findings suggested celiac disease. This case highlights that a celiac patient may present with a severe illness like sepsis and may be associated with cytopenia and coagulopathy in the celiac crisis.

Fundamental Motor Skill Delays in Preschool Children With Disabilities: 2012 National Youth Fitness Survey

Delays in fundamental motor skill (FMS) competency have been observed in a variety of children with disabilities. However, evidence of FMS delays is largely limited to small, geographically specific, limitedly diverse, and non-representative samples. The purpose of this study was to examine the association between FMS competency and reported disability status among pre-school children, ages 3–5 years, using the 2012 National Youth Fitness Survey (NYFS). In total, 329 preschool children (49% female; 4.00 ± 0.04 years of age) from the 2012 NYFS completed the Test of Gross Motor Development−2, including 43 preschoolers identified with a disability based on parental report (44% female; 4.20 ± 0.16 years). Associations were examined with logistic regression using sampling weights. Poor FMS competency, defined as gross motor quotient scores ≤ 79, was observed in significantly more children with disabilities (29%) than children without disabilities (10%, OR = 3.5, p = 0.04). While not statistically significant, there was a growing disparity in FMS competency at age 5 (41 vs. 11%) compared to age 3 (15 vs. 9%, OR = 1.80, p = 0.30). The results provide additional evidence for poor FMS competency among pre-school children with disabilities. FMS should be an early part of comprehensive assessments for all children suspected of disability or development delay as it is critical to identify and intervene upon FMS delays before discrepancies can widen.

Growth in achondroplasia including stature, weight, weight-for-height and head circumference from CLARITY: achondroplasia natural history study\u2014a multi-center retrospective cohort study of achondroplasia in the US

BackgroundAchondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments from birth through 18 years for clinical use and research for achondroplasia patients.MethodsAll available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population.ResultsOver 37,000 length/height, weight and head circumference measures from 1374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves.ConclusionAchondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth.

Early trajectories of motor skills in infant siblings of children with autism spectrum disorder.

Delays in motor development are not considered a core feature of autism spectrum disorder (ASD). Yet, recent studies of infant siblings of children with ASD suggest that early delays in motor skills may be associated with later delays in developmental areas considered to be core features of an ASD diagnosis. While these studies demonstrate the longitudinal association between core features and motor delays observed at single time points, there is considerable interest in studying the trajectories of motor development over the first 3 years of life. To accomplish this, we investigated early trajectories of motor development in a cohort of 499 infant siblings of children with ASD and 176 children with no family history of ASD. Data for the current study were drawn from the prospective, multi-site, Canadian Infant Sibling Study. We evaluated trajectories of fine and gross motor development over the first 3 years using group-based trajectory modeling. Our results show that membership for both fine and gross motor trajectory groups was related to expressive language skills, receptive language skills, ASD symptom severity scores, and diagnostic classification at age 3. These results provide evidence that the trajectory of a child's early motor development may have important prognostic implications in ASD.

Impairment of motor skills in children with achondroplasia-usefulness of brain and cranio-cervical junction evaluation by quantitative magnetic resonance imaging: a case-control study.

Most infants and children with achondroplasia show delayed motor skill development; however, some patients may have clinical consequences related to cranio-cervical junction stenosis and compression. To assess, using brain magnetic resonance imaging (MRI), quantitative variables linked to neuromotor impairment in achondroplasic children. In total, 24 achondroplasic children underwent pediatric neurological assessment and were grouped in two cohorts according to relevant motor skill impairment. Achondroplasic children with (n=12) and without (n=12) motor symptoms were identified, and brain MRI scans were quantitatively evaluated. 3D fast spoiled gradient echo T1-weighted images were used to assess: supratentorial intracranial volumes (SICV); supratentorial intracranial brain volume (SICBV); SICV/SICBV ratio; posterior cranial fossa volume (PCFV); posterior cranial fossa brain volume (PCBFV); PCFV/PCFBV ratio; ventricular and extra-ventricular cerebrospinal fluid (CSF) volumes; foramen magnum (FM) area; and jugular foramina (JF) areas. In both groups, SICV/SICBV ratio, supratentorial ventricular and extra-ventricular space volumes were increased while SICBV was increased only in the asymptomatic group (P < 0.05). PCFV/PCFBV ratio, IV ventricle, infratentorial extra-ventricular spaces volumes were reduced (P < 0.05) in the symptomatic group while PCFBV was increased only in the asymptomatic group (P < 0.05). Foramen magnum (FM) area was more reduced in the symptomatic group than the asymptomatic group (P < 0.05) but no correlation between FM area and ventriculomegaly was found (P > 0.05). Evaluation of the FM area together with infratentorial ventricular and extra-ventricular space volume reduction may be helpful in differentiating patients at risk of developing motor skill impairment. Further investigation is needed to better understand the temporal profile between imaging and motor function in order to propose possible personalized surgical treatment.

PRO39 Caregiver Perspectives on the Humanistic Burden of Creatine Transporter Deficiency

Creatine Transporter Deficiency (CTD) is a rare, X-linked, recessive disorder resulting in creatine deficiency, primarily in the brain. Patients with CTD can experience significant developmental delays in motor skills, speech, and cognition, as well as seizures and behavioral issues. The objective of this research was to gather data on the burden of CTD from the caregiver perspective.