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OBJECTIVE: To determine whether an intervention addressing both logistical and knowledge barriers to early screening for autism spectrum disorder (ASD) increases evidence-based screening during 18-month well-child visits and PCPs’ perceived self-efficacy in caring for children with ASD. METHODS: Forty-six primary care providers (PCPs) from 10 diverse practices across four counties in Washington State participated. PCPs attended a two-hour training workshop on early recognition and care for toddlers with ASD and use of a REDCap-based version of the Modified Checklist for Autism in Toddlers–Revised with Follow-up (webM-CHAT-R/F) that provided automated presentation and scoring of follow-up questions. Data were collected at baseline and six-months following each county’s training window. PCPs’ screening methods and rates and perceived self-efficacy regarding ASD care were measured by self-report and webM-CHAT-R/F use was measured via REDCap records. RESULTS: At follow-up, 8 of the 10 practices were using the webM-CHAT-R/F routinely at 18-month visits. The proportion of PCPs reporting routine M-CHAT screening increased from 82% at baseline to 98% at follow-up (16% increase, 95% CI 3%–28%; McNemar exact p=.02). The proportion using the M-CHAT-R/F follow-up interview questions increased from 33% to 82% (49% increase, 95% CI 30%–68%, exact McNemar test, p

Background and ObjectivesDeletions and duplications at 16p11.2 (BP4 to BP5; 29.5–30.1 Mb) have been associated with several neurodevelopmental and neuropsychiatric disorders including autism spectrum disorder, intellectual disability (ID), and schizophrenia. Seizures have also been reported in individuals with these particular copy number variants, but the epilepsy phenotypes have not been well-delineated. We aimed to systematically characterize the seizure types, epilepsy syndromes, and epilepsy severity in a large cohort of individuals with these 16p11.2 deletions and duplications.MethodsThe cohort of ascertained participants with the recurrent 16p11.2 copy number variant was assembled through the multicenter Simons Variation in Individuals Project. Detailed data on individuals identified as having a history of seizures were obtained using a semistructured phone interview and review of medical records, EEG, and MRI studies obtained clinically or as part of the Simons Variation in Individuals Project.ResultsAmong 129 individuals with the 16p11.2 deletion, 31 (24%) had at least one seizure, including 23 (18%) who met criteria for epilepsy; 42% of them fit the phenotype of classic or atypical Self-limited (Familial) Infantile Epilepsy (Se(F)IE). Among 106 individuals with 16p11.2 duplications, 16 (15%) had at least one seizure, including 11 (10%) who met criteria for epilepsy. The seizure types and epilepsy syndromes were heterogeneous in this group. Most of the individuals in both the deletion and duplication groups had well-controlled seizures with subsequent remission. Pharmacoresistant epilepsy was uncommon. Seizures responded favorably to phenobarbital, carbamazepine, and oxcarbazepine in the deletion group, specifically in the Se(F)IE, and to various antiseizure medications in the duplication group.DiscussionThese findings delineate the spectrum of seizures and epilepsies in the recurrent 16p11.2 deletions and duplications and provide potential diagnostic, therapeutic, and prognostic information.

Expressive language impairment is one of the most frequently associated clinical features of 16p11.2 copy number variations (CNV). However, our understanding of the language profiles of individuals with 16p11.2 CNVs is still limited. This study builds upon previous work in the Simons Variation in Individuals Project (VIP, now known as Simons Searchlight), to characterize language abilities in 16p11.2 deletion and duplication carriers using comprehensive assessments. Participants included 110 clinically ascertained children and family members (i.e., siblings and cousins) with 16p11.2 BP4-BP5 deletion and 58 with 16p11.2 BP4-BP5 duplication between the ages of 2-23 years, most of whom were verbal. Regression analyses were performed to quantify variation in language abilities in the presence of the 16p11.2 deletion and duplication, both with and without autism spectrum disorder (ASD) and cognitive deficit. Difficulties in pragmatic skills were equally prevalent in verbal individuals in both deletion and duplication groups. NVIQ had moderate quantifiable effects on language scores in syntax and semantics/pragmatics (a decrease of less than 1 SD) for both groups. Overall, language impairments persisted even after controlling for ASD diagnosis and cognitive deficit. Language impairment is one of the core clinical features of individuals with 16p11.2 CNVs even in the absence of ASD and cognitive deficit. Results highlight the need for more comprehensive and rigorous assessment of language impairments to maximize outcomes in carriers of 16p11.2 CNVs.

Key Clinical Message 16p11.2 deletions and duplications are commonly associated with autism spectrum disorder and linked to mirrored phenotypes of physical characteristics and higher penetrance for deletions. A male with a rare 16p11.2 triplication demonstrated a similar phenotypic presentation to deletion carriers with neurocognitive and adaptive skill deficits and above‐average physical growth.

Introduction Medicaid-enrolled children with autism spectrum disorder (ASD) encounter significant barriers to dental care. Iowa's I-Smile Program was implemented in 2006 to improve dental use for all children in Medicaid. This study compared dental home and preventive dental utilization rates for Medicaid-enrolled children by ASD status and within three time periods (pre-implementation, initial implementation, maturation) and determined I-Smile's longitudinal influence on ASD-related dental use disparities. Methods Data from 2002–2011 were analyzed for newly Medicaid-enrolled children aged 3–17 years (N=30,059); identified each child's ASD status; and assessed whether the child had a dental home or utilized preventive dental care. Log-linear regression models were used to generate rate ratios. Analyses were conducted in 2015. Results In 2003–2011, 9.8% of children with ASD had dental homes compared with 8% of children without ASD; 36.3% of children with ASD utilized preventive care compared to 45.7% of children without ASD. There were no significant differences in dental home rates by ASD status during pre-implementation, initial implementation, or maturation. There were no significant differences in preventive dental utilization by ASD status during pre-implementation or initial implementation, but children with ASD were significantly less likely to utilize preventive care during maturation (rate ratio=0.79, p p =0.54 and p =0.71, respectively). Conclusions Among newly Medicaid-enrolled children in Iowa's I-Smile Program, those with ASDs were not less likely than those without ASD to have dental homes but were significantly less likely to utilize preventive dental care.

Background The recurrent ∼600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. Objective To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. Methods We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. Results When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. Conclusions The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.

OBJECTIVE. We have previously described patterns of neonatal brain injury that correlate with global cognitive and motor outcomes. We now examine, in survivors of neonatal encephalopathy (presumed secondary to hypoxia-ischemia) without functional motor deficits, whether the severity and neuroanatomical involvement on neonatal MRI are associated with domain-specific cognitive outcomes, verbal and performance IQ, at 4 years of age. METHODS. In this prospective study, neonatal MRIs of 81 term infants with neonatal encephalopathy were scored for degree of injury in 2 common patterns: watershed distribution and basal ganglia distribution. Follow-up evaluation at 4 years of age by examiners blinded to clinical history and MRIs included a 5-point neuromotor score and the Wechsler Preschool and Primary Scale of Intelligence–Revised. In 64 subjects with no functional motor impairment, test of trend was used to examine the association of ordered watershed-distribution and basal ganglia-distribution MRI scores with mean verbal and performance IQ. RESULTS. Lower verbal and performance IQs were seen with increasing degree of injury on both watershed-distribution and basal ganglia–distribution scales in univariate analyses. When each MRI pattern score was adjusted for the other, only the association of decreasing verbal IQ with increasing watershed-distribution injury remained significant. A suggestion of decreasing verbal IQ with increasing basal ganglia–distribution injury was also seen in the multivariate model, whereas no association was seen between performance IQ and severity of injury in either MRI pattern. CONCLUSIONS. In survivors of neonatal encephalopathy without functional motor deficits at 4 years of age, an increasing severity of watershed-distribution injury is associated with more impaired language-related abilities.

Klinefelter (47, XXY) syndrome (KS), the most common form of sex-chromosomal aneuploidy, is characterized by physical, endocrinologic, and reproductive abnormalities. Individuals with KS also exhibit a cognitive/behavioral phenotype characterized by language and language-based learning disabilities and executive and attentional dysfunction in the setting of normal general intelligence. The underlying neurobiologic mechanisms are just now beginning to be elucidated through structural and functional neuroimaging. Here, we review the literature of structural and functional neural findings in KS identified by neuroimaging and present preliminary results from a functional magnetic resonance imaging study examining brain activity during a verb generation task in KS.

Apraxia traditionally refers to impaired ability to carry out skilled movements in the absence of fundamental sensorimotor, language, or general cognitive impairment sufficient to preclude them. The child neurology literature includes a much broader and varied usage of the term developmental dyspraxia. It has been used to describe a wide range of motor symptoms, including clumsiness and general coordination difficulties, in various developmental disorders (including autistic spectrum disorders, developmental language disorders, and perinatal stroke). We argue for the need to restrict use of the term developmental dyspraxia to describe impaired performance of skilled gestures, recognizing that, unlike acquired adult-onset apraxia, coexisting sensory and motor problems can also be present.