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ImportanceRecent reports have demonstrated a higher incidence of autism spectrum disorder (ASD) and substantially elevated autistic trait burden in individuals with neurofibromatosis type 1 (NF1). However, important discrepancies regarding the distribution of autistic traits, sex predominance, and association between ASD symptoms and attentional problems have emerged, and critical features of the ASD phenotype within NF1 have never been adequately explored. Establishing NF1 as a monogenic cause for ASD has important implications for affected patients and for future research focused on establishing convergent pathogenic mechanisms relevant to the potential treatment targets for ASD.ObjectiveTo characterize the quantitative autistic trait (QAT) burden in a pooled NF1 data set.Design, setting, and participantsAnonymized, individual-level primary data were accumulated from 6 tertiary referral centers in the United States, Belgium, United Kingdom, and Australia. A total of 531 individuals recruited from NF1 clinical centers were included in the study.Main outcomes and measuresDistribution of ASD traits (Social Responsiveness Scale, second edition [SRS-2], with T scores of ≥75 associated with a categorical ASD diagnosis); attention-deficit/hyperactivity disorder (ADHD) traits (4 versions of Conners Rating Scale, with T scores of ≥65 indicating clinically significant ADHD symptoms); ASD symptom structure, latent structure, base rate derived from mixture modeling; and familiality.ResultsOf the 531 patients included in the analysis, 247 were male (46.5%); median age was 11 years (range, 2.5-83.9 years). QAT scores were continuously distributed and pathologically shifted; 13.2% (95% CI, 10.3%-16.1%) of individuals scored within the most severe range (ie, above the first percentile of the general population distribution) in which the male to female ratio was markedly attenuated (1.6:1) relative to idiopathic ASD. Autistic symptoms in this NF1 cohort demonstrated a robust unitary factor structure, with the first principal component explaining 30.9% of the variance in SRS-2 scores, and a strong association with ADHD symptoms (r = 0.61). Within-family correlation for QAT burden (intraclass correlation coefficient, 0.73 in NF1-affected first-degree relatives) exceeded that observed in the general population and ASD family samples.Conclusions and relevanceThis study provides confirmation that the diversity of mutations that give rise to NF1 function as quantitative trait loci for ASD. Moreover, the within-family correlation implicates a high degree of mutational specificity for this associated phenotype. Clinicians should be alerted to the increased frequency of this disabling comorbidity, and the scientific community should be aware of the potential for this monogenic disorder to help elucidate the biological features of idiopathic autism.

Simple Summary: Difficulties in sensory processing are often found in neurodevelopmental disorders and can significantly impact how a child responds to and functions within their environment. Studies examining sensory processing in children with neurofibromatosis type 1 (NF1) are sparse. This cross-sectional study aims to address this gap by examining parent-reported sensory processing in a sample of 152 children with NF1. Approximately 61% of children with NF1 displayed differences in how they respond to sensory stimuli when compared to a typically developing control group. These difficulties were seen equally across ages and sex and were found to be associated with a higher degree of autistic behaviors, ADHD symptoms, lower adaptive skills, poorer social skills, and increased anxiety and affective symptoms. The results highlight the importance of accommodating multisensory processing difficulties at home and school when deciding how to support a child with NF1 across environments. Despite the evidence of elevated autistic behaviors and co-occurring neurodevelopmental difficulties in many children with neurofibromatosis type 1 (NF1), we have a limited understanding of the sensory processing challenges that may occur with the condition. This study examined the sensory profile of children and adolescents with NF1 and investigated the relationships between the sensory profiles and patient characteristics and neuropsychological functioning. The parent/caregivers of 152 children with NF1 and 96 typically developing children completed the Sensory Profile 2 (SP2), along with standardized questionnaires assessing autistic behaviors, ADHD symptoms, internalizing symptoms, adaptive functioning, and social skills. Intellectual functioning was also assessed. The SP2 data indicated elevated sensory processing problems in children with NF1 compared to typically developing children. Over 40% of children with NF1 displayed differences in sensory registration (missing sensory input) and were unusually sensitive to and unusually avoidant of sensory stimuli. Sixty percent of children with NF1 displayed difficulties in one or more sensory modalities. Elevated autistic behaviors and ADHD symptoms were associated with more severe sensory processing difficulties. This first detailed assessment of sensory processing, alongside other clinical features, in a relatively large cohort of children and adolescents with NF1 demonstrates the relationships between sensory processing differences and adaptive skills and behavior, as well as psychological well-being. Our characterization of the sensory profile within a genetic syndrome may help facilitate more targeted interventions to support overall functioning. [ABSTRACT FROM AUTHOR]

Duchenne and Becker muscular dystrophy are allelic X-linked disorders causing progressive muscle weakness in males. Duchenne muscular dystrophy is caused by absence of dystrophin in muscle and brain; boys with Duchenne muscular dystrophy have a static cognitive impairment with mean Full Scale lQ approximately I standard deviation below the mean. Less is known of the cognitive profile of males with Becker muscular dystrophy, which is associated with variable alterations in the amount or size of the dystrophin protein. The aim of this study was to describe the cognitive and psychological profile of males with Becker muscular dystrophy. This was a prospective cohort study. Clinical data collected included age at diagnosis and assessment, socioeconomic status, serum creatine kinase level, and site of gene deletion/mutation (by exon number). The following psychological tests were used to assess general intellectual functioning, academic achievement, incidence and nature of behavioral problems: The Wechsler Intelligence Scales, The Wide Range Achievement Test-Revised, The Developmental Test of Visual-Motor Integration, The Child Behavior Checklist, and The Conner's Parent Rating Scale. Twenty-four males were enrolled. The Wechsler Full Scale lQ was normally distributed with a mean of 95.6 (SD 23.3), which did not differ significantly from the population mean. The frequency of learning difficulties for reading was 21%, for spelling was 32%, and for arithmetic was 26%, significantly higher than the frequency in the general population. The frequency of total behavioral problems in the clinical range was 67%, and the frequency of autism was 8.3%. Patients with Becker muscular dystrophy demonstrate a less homogeneous cognitive phenotype than that seen in Duchenne muscular dystrophy. Males with Becker muscular dystrophy have a high incidence of learning Difficulties. Autism and behavioral and attention problems are also more common in Becker muscular dystrophy than in the general population. [ABSTRACT FROM AUTHOR]