Turner syndrome: language profile of young girls at 12 and 24 months of age.

BACKGROUND: Turner syndrome (TS) is a genetic disorder associated with complete or partial absence of an X chromosome affecting approximately 1/2000 live female births. Available evidence suggests that, in the school-age years, girls with TS often require speech and language services; however, little is known about the language development of infants and toddlers. METHOD: This study (N = 31) explored the language profiles of 12- and 24-month-old girls with TS, as well as the percentage of girls who might be "at risk" for language delays. We also followed a subset of 12-month-old girls with TS to 24 months of age to determine the stability of the 12-month findings. RESULTS: Although all mean scores were within the average range at both time points, results revealed a higher prevalence of 24-month-old girls with TS "at risk" for receptive language difficulties. In addition, expressive language skills significantly exceeded receptive language skills at both time points. We found 12-month-old girls to be "at risk" for social and symbolic difficulties based on clinical assessment; only symbolic difficulties were significant based on caregiver report. At 24 months, clinical assessment indicated greater use of speech sounds and words than normative expectations. Caregivers reported greater use of speech sounds, and also, greater use of gestures. Although some changes occurred over a 1-year time span (12 to 24 months), all mean test scores remained within the average range and the changes in the percentage of girls manifesting "at risk" status on either the PLS-4 or CSBS-DP were non-significant. CONCLUSIONS: Although within normal limits, receptive language skills were found to be significantly lower than expressive language skills at both ages. Social and symbolic communication skills also were in the average range, with both showing significant improvement from 12 to 24 months based on clinical assessment. Caregiver report found that use of gestures and production of speech sounds not only improved from 12 to 24 months, but also exceeded normative expectations. Findings suggest the presence of relatively intact speech and language abilities during the first 2 years of life, with perhaps some emergent concerns for receptive language development. Ongoing developmental surveillance will be important.

Health Status and Health Care Use Among Adolescents Identified With and Without Autism in Early Childhood - Four U.S. Sites, 2018-2020.

Persons identified in early childhood as having autism spectrum disorder (autism) often have co-occurring health problems that extend into adolescence (1-3). Although only limited data exist on their health and use of health care services as they transition to adolescence, emerging data suggest that a minority of these persons receive recommended guidance* from their primary care providers (PCPs) starting at age 12 years to ensure a planned transition from pediatric to adult health care (4,5). To address this gap in data, researchers analyzed preliminary data from a follow-up survey of parents and guardians of adolescents aged 12-16 years who previously participated in the Study to Explore Early Development (https://www.cdc.gov/ncbddd/autism/seed.html). The adolescents were originally studied at ages 2-5 years and identified at that age as having autism (autism group) or as general population controls (control group). Adjusted prevalence ratios (aPRs) that accounted for differences in demographic characteristics were used to compare outcomes between groups. Adolescents in the autism group were more likely than were those in the control group to have physical difficulties (21.2% versus 1.6%; aPR = 11.6; 95% confidence interval [CI] = 4.2-31.9), and to have additional mental health or other conditions† (one or more condition: 63.0% versus 28.9%; aPR = 1.9; 95% CI = 1.5-2.5). Adolescents in the autism group were more likely to receive mental health services (41.8% versus 22.1%; aPR = 1.8, 95% CI = 1.3-2.6) but were also more likely to have an unmet medical or mental health service need§ (11.0% versus 3.2%; aPR = 3.1; 95% CI = 1.1-8.8). In both groups, a small percentage of adolescents (autism, 7.5%; control, 14.1%) received recommended health care transition (transition) guidance. These findings are consistent with previous research (4,5) indicating that few adolescents receive the recommended transition guidance and suggest that adolescents identified with autism in early childhood are more likely than adolescents in the general population to have unmet health care service needs. Improved provider training on the heath care needs of adolescents with autism and coordination of comprehensive programs¶ to meet their needs can improve delivery of services and adherence to recommended guidance for transitioning from pediatric to adult health care.

A Distinct Three-Factor Structure of Restricted and Repetitive Behaviors in an Epidemiologically Sound Sample of Preschool-Age Children with Autism Spectrum Disorder.

Prior studies investigating restricted and repetitive behavior (RRB) subtypes within autism spectrum disorder (ASD) have found varied factor structures for symptom groupings, in part, due to variation in symptom measurement and broad sample age ranges. This study examined RRBs among 827 preschool-age children, ages 35 to 71 months, through an exploratory factor analysis of RRB items from the Autism Diagnostic Interview-Revised (ADI-R) collected through the Study to Explore Early Development. The factor structures of RRBs among children with confirmed ASD versus those with non-autism developmental concerns were qualitatively compared. Correlations between RRB factors and participant characteristics were examined in the ASD group. Three conceptually well-defined factors characterized as repetitive sensorimotor behaviors (RSMB), insistence on sameness (IS), and a novel stereotyped speech (SPEECH) factor emerged for the ASD group only. Distinct factors were supported by different clinical correlates. Findings have implications for improving differential diagnosis and understanding of ASD symptomatology in this age range.

Early Development of Infants with Turner Syndrome.

OBJECTIVE: To examine the early cognitive, temperament, and adaptive functioning of infants and toddlers with Turner syndrome (TS). METHODS: Cognitive abilities were measured using the Mullen Scales of Early Learning at 1 year of age for 31 girls with TS and compared with neurotypical female (N = 53) and male (N = 54) control groups. Temperament (Carey Toddler Temperament Scales) and adaptive functioning (Vineland Adaptive Behavior Scales-Second Edition) were measured at 1 year of age and compared with normative data. An exploratory analysis of cognitive/developmental trajectories was also conducted comparing age 12-month to 24-month time points for 22 TS subjects. RESULTS: Infants with TS performed largely within the average range for adaptive behavior, temperament, and early cognitive development with some increased risk for delays in language and significant increased risk for delays in motor skills (p < 0.001). Although exploratory, there was some suggestion of slower rates of progression in fine-motor and visual reception skills from 12 to 24 months of age. CONCLUSIONS: Infants and toddlers with TS exhibit a relatively positive neurodevelopmental profile overall, with some indication of an increasing gap in function in fine-motor and visual perceptual abilities as compared to neurotypical peers. It is unclear whether these apparent differences represent normal variability in this very young population or, perhaps, are early precursors of later phenotypic characteristics of TS in the school-age and young adult years.

DSM-5 criteria for autism spectrum disorder maximizes diagnostic sensitivity and specificity in preschool children.

PURPOSE: The criteria for autism spectrum disorder (ASD) were revised in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). The objective of this study was to compare the sensitivity and specificity of DSM-IV-Text Revision (DSM-IV-TR) and DSM-5 definitions of ASD in a community-based sample of preschool children. METHODS: Children between 2 and 5 years of age were enrolled in the Study to Explore Early Development-Phase 2 (SEED2) and received a comprehensive developmental evaluation. The clinician(s) who evaluated the child completed two diagnostic checklists that indicated the presence and severity of DSM-IV-TR and DSM-5 criteria. Definitions for DSM-5 ASD, DSM-IV-TR autistic disorder, and DSM-IV-TR Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) were created from the diagnostic checklists. RESULTS: 773 children met SEED2 criteria for ASD and 288 met criteria for another developmental disorder (DD). Agreement between DSM-5 and DSM-IV-TR definitions of ASD were good for autistic disorder (0.78) and moderate for PDD-NOS (0.57 and 0.59). Children who met DSM-IV-TR autistic disorder but not DSM-5 ASD (n = 71) were more likely to have mild ASD symptoms, or symptoms accounted for by another disorder. Children who met PDD-NOS but not DSM-5 ASD (n = 66), or vice versa (n = 120) were less likely to have intellectual disability and more likely to be female. Sensitivity and specificity were best balanced with DSM-5 ASD criteria (0.95 and 0.78, respectively). CONCLUSIONS: The DSM-5 definition of ASD maximizes diagnostic sensitivity and specificity in the SEED2 sample. These findings support the DSM-5 conceptualization of ASD in preschool children.

Associations between parental broader autism phenotype and child autism spectrum disorder phenotype in the Study to Explore Early Development.

The autism spectrum disorder phenotype varies by social and communication ability and co-occurring developmental, behavioral, and medical conditions. Etiology is also diverse, with myriad potential genetic origins and environmental risk factors. Examining the influence of parental broader autism phenotype-a set of sub-clinical characteristics of autism spectrum disorder-on child autism spectrum disorder phenotypes may help reduce heterogeneity in potential genetic predisposition for autism spectrum disorder. We assessed the associations between parental broader autism phenotype and child phenotype among children of age 30-68 months enrolled in the Study to Explore Early Development (N = 707). Child autism spectrum disorder phenotype was defined by a replication of latent classes derived from multiple developmental and behavioral measures: Mild Language Delay with Cognitive Rigidity, Mild Language and Motor Delay with Dysregulation (e.g. anxiety/depression), General Developmental Delay, and Significant Developmental Delay with Repetitive Motor Behaviors. Scores on the Social Responsiveness Scale-Adult measured parent broader autism phenotype. Broader autism phenotype in at least one parent was associated with a child having increased odds of being classified as mild language and motor delay with dysregulation compared to significant developmental delay with repetitive motor behaviors (odds ratio: 2.44; 95% confidence interval: 1.16, 5.09). Children of parents with broader autism phenotype were more likely to have a phenotype qualitatively similar to broader autism phenotype presentation; this may have implications for etiologic research.

Prenatal Alcohol Exposure in Relation to Autism Spectrum Disorder: Findings from the Study to Explore Early Development (SEED).

BACKGROUND: Prenatal alcohol exposure can affect neurodevelopment, but few studies have examined associations with autism spectrum disorder (ASD). METHODS: We assessed the association between maternal alcohol use and ASD in the Study to Explore Early Development, a multi-site case-control study of children born between September 2003 and August 2006 in the US Regression analyses included 684 children with research clinician-confirmed ASD, 869 children with non-ASD developmental delays or disorders (DDs), and 962 controls ascertained from the general population (POP). Maternal alcohol exposure during each month from 3 months prior to conception until delivery was assessed by self-report. RESULTS: Mothers of POP children were more likely to report any prenatal alcohol use than mothers of children with ASD or DD. In trimester one, 21.2% of mothers of POP children reported alcohol use compared with 18.1% and 18.2% of mothers of children with ASD or DD, respectively (adjusted OR for ASD vs. POP 0.8, 95% confidence interval 0.6, 1.1). During preconception and the first month of pregnancy, one to two drinks on average per week was inversely associated with ASD risk. CONCLUSIONS: These results do not support an adverse association between low-level alcohol exposure and ASD, although these findings were based on retrospective self-reported alcohol use. Unmeasured confounding or exposure misclassification may explain inverse associations with one to two drinks per week. Pregnant or potentially pregnant women should continue to follow recommendations to avoid alcohol use because of other known effects on infant health and neurodevelopment.

Homogeneous Subgroups of Young Children with Autism Improve Phenotypic Characterization in the Study to Explore Early Development.

The objective of this study was to identify homogenous classes of young children with autism spectrum disorder (ASD) to improve phenotypic characterization. Children were enrolled in the Study to Explore Early Development between 2 and 5 years of age. 707 children were classified with ASD after a comprehensive evaluation with strict diagnostic algorithms. Four classes of children with ASD were identified from latent class analysis: mild language delay with cognitive rigidity, mild language and motor delay with dysregulation, general developmental delay, and significant developmental delay with repetitive motor behaviors. We conclude that a four-class phenotypic model of children with ASD best describes our data and improves phenotypic characterization of young children with ASD. Implications for screening, diagnosis, and research are discussed.

The Broader Autism Phenotype in Mothers is Associated with Increased Discordance Between Maternal-Reported and Clinician-Observed Instruments that Measure Child Autism Spectrum Disorder.

Autism spectrum disorder (ASD) diagnosis relies on parent-reported and clinician-observed instruments. Sometimes, results between these instruments disagree. The broader autism phenotype (BAP) in parent-reporters may be associated with discordance. Study to Explore Early Development data (N = 712) were used to address whether mothers with BAP and children with ASD or non-ASD developmental disabilities were more likely than mothers without BAP to 'over-' or 'under-report' child ASD on ASD screeners or interviews compared with clinician observation or overall impression. Maternal BAP was associated with a child meeting thresholds on a maternal-reported screener or maternal interview when clinician ASD instruments or impressions did not (risk ratios: 1.30 to 2.85). Evidence suggests acknowledging and accounting for reporting discordances may be important when diagnosing ASD.

Methods for assessing neurodevelopment in lysosomal storage diseases and related disorders: a multidisciplinary perspective.

UNLABELLED: Lysosomal storage diseases and related disorders (LSRDs) are a heterogeneous group of rare diseases caused by genetic mutations that result in deficiencies of specific lysosomal enzymes. Some of these enzymes are necessary for normal development of the central and peripheral nervous systems. Because of the heterogeneity in clinical presentation and complexity of these disorders, evaluation of disease progression poses unique challenges. In recent years, recombinant enzyme replacement therapy and haematopoietic stem cell transplantation have been developed to treat some of these diseases. With the development of specific therapies and screening programmes, there is a need to systematically follow the natural course and effects of treatment in these disorders with standardized and validated tools. This review describes the limitations of currently available neurobehavioural tools in longitudinally tracking disease outcomes in patients with neurodegenerative LSRDs. A multidisciplinary team reviewed over 750 evaluations in 274 patients. These patients were found to have neurological, sensory and somatic problems that considerably influence the results of neurobehavioural testing. CONCLUSION: Treatment effects in patients with neurodegenerative LSRDs are best evaluated by repeated measures and longitudinal analysis of each domain of function.