Elsevier

The Journal of Pediatrics

Volume 167, Issue 3, September 2015, Pages 621-626.e1
The Journal of Pediatrics

Original Article
Distribution and Within-Family Specificity of Quantitative Autistic Traits in Patients with Neurofibromatosis Type I

https://doi.org/10.1016/j.jpeds.2015.04.075Get rights and content

Objective

To examine the distribution of quantitative autistic traits (QATs) in an independent neurofibromatosis type I (NF1) sample, the relationships between QAT, sex, and attention deficit hyperactivity disorder (ADHD) symptomatology, and to explore evidence for QAT mutational specificity within families.

Study design

Age-appropriate versions of the Social Responsiveness Scale, second edition and the Conners Adult ADHD Rating Scales were completed for 103 patients with NF1 from the Washington University Neurofibromatosis Center.

Results

Patients with NF1 exhibited a pathologically shifted unimodal distribution for QAT. Forty-four percent of the subjects exhibited a QAT burden at or above 1 SD from the population mean; 13% scored at or above the extreme first percentile of the general population distribution. Elevations in ADHD symptomatology exhibited a distinct bimodal distribution; however, mean ADHD index scores were equivalent in patients who had been diagnosed in the community with ADHD compared with those who had not. We observed striking within-family associations for QAT, reflected by an Social Responsiveness Scale, second edition intraclass correlation of 0.77 in pairings of first degree relatives with NF1.

Conclusions

Impairments in reciprocal social behavior and attention affect a large proportion of patients with NF1 throughout life and are often clinically unrecognized. Further exploration of genotype-phenotype correlation is strongly warranted for the purpose of gaining insights into mechanisms by which specific mutational variations in the NF1 gene may influence autistic trait severity.

Section snippets

Methods

The Washington University Neurofibromatosis Center actively follows 320 individuals from 253 families. Following review and approval of a separate protocol by the Washington University Human Research Protection Office, the families were contacted to request participation in the current behavioral phenotyping study. One hundred fifty-one individuals (47.2%) agreed to participate and were sent a study packet, which included age- and rater-appropriate versions of the Social Responsiveness Scale,

Results

The data for total SRS-2 scores for the full sample of patients with NF1 exhibited a continuous unimodal distribution, pathologically shifted by 0.6 SD in adults and 1.0 SD in children in comparison with general population norms (Figure 1, A).

DSM-5 subscale scores for social communication/interaction and repetitive behavior/restricted interests were similarly continuously distributed. SRS-2 total scores, DSM-5 subscale scores, and all treatment scale scores on the SRS-2 were elevated in

Discussion

We confirm prior reports of substantial autistic trait burden in individuals with NF1: 44% with QAT burden at or above 1 SD from the population mean, and 13% at or above the extreme first percentile of the general population distribution. These data also provide several fundamental new insights into the association between NF1, ADHD, and autistic symptomatology. First, although the distribution of total autistic trait scores appears fully continuous, there is marked bimodality in the

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    Research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under Award Number P30HD062171 to the Intellectual and Developmental Disabilities Research Center at Washington University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. J.C. receives royalties from Western Psychological Services for commercial sales and distribution of the Social Responsiveness Scale-2. The other authors declare no conflicts of interest.

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