Are Rates of Autism and Autism Symptoms Raised Among Children with Neurofibromatosis Type-1?

Poster Presentation
Friday, May 3, 2019: 5:30 PM-7:00 PM
Room: 710 (Palais des congres de Montreal)
E. Fombonne1, H. Morotti2, S. Mastel3, R. Barnard4, K. Keller5, T. Hall2, A. Barnes6 and B. J. O'Roak7, (1)Psychiatry, Pediatrics & Behavioral Neurosciences, Oregon Health & Science University, Portland, OR, (2)Oregon Health & Science University, Portland, OR, (3)Institute on Development and Disability, Oregon Health and Science University, Portland, OR, (4)Oregon Health and Science University, Portland, OR, (5)Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, (6)Knight Cancer Institute, Portland, OR, (7)Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR

NF1 is associated with several developmental and behavioral challenges including ADHD, and intellectual/learning disabilities. It was recently reported that up to 50% of NF1 subjects also meet diagnostic criteria for autism spectrum disorder. However, it is unclear if the increase in autism diagnosis and symptomatology is accounted for by confounding psychiatric features, especially ADHD symptoms.


This study reexamined the association between ASD diagnosis, ASD symptomatology, and NF1.


We selected participants aged 5-13 with NF1 (mean age = 9.2; 50% male). Control subjects were matched on age and sex on each participant in a 4:1 ratio to create two control groups of 180 ASD subjects and 180 typically developing (TD) siblings. Participants were evaluated with the CBCL, NICHQ Vanderbilt, Vineland-II, SRS-2, RBS-R, and SCQ. We performed an EPIC search on ICD-10 diagnoses of NF1 and PDD; additionally, medical records of NF1 subjects were abstracted. Comparisons were also performed with data published by the International NF1-ASD Consortium.


In the OHSU EPIC database, there were 968 patients with an NF1 diagnosis, of whom 20 (2.07%) had a PDD diagnosis and 85 (8.8%) had an ADHD diagnosis.

On measures of autistic symptomatology, the NF1 group scored significantly lower than the ASD group, on both SRS-2 total score (55.8 vs 81.1; p = .001), SCQ total score (6.1 vs 20.6; p = .001) and RBS-R total score (10.4 vs 27.6; p = .001). On the two available measures of autism symptoms in the TD group, TD subjects scored lower than NF1 participants (SRS-2: 44.6 vs 55.8; p = .001; SCQ: 6.1 vs 1.9; p = .001), though the magnitude of the differences were small in comparison to the NF1/ASD contrast. Both groups’ means fell under the published thresholds on these two instruments. Moreover, differences were attenuated on all measures when 11 NF1 participants with a comorbid ADHD diagnosis were removed from analysis.

The same pattern emerged with the total externalizing and internalizing scores of the CBCL, with the NF1 group falling between the ASD and TD groups. NF1 participants did not differ from TD siblings for adaptive behavior on the Vineland ABC (99.7 vs 102.3; NS), Daily Living Skills (102.7 vs 100.4; NS), and Socialization (104.8 vs 101.4; NS). However, NF1 subjects had significantly lower scores than TDs on the Vineland Communication score (97.0 vs 106.7; p = .001) although their mean scores were very close to the population mean and were significantly higher than in the ASD group (97.0 vs 75.3; p = .001).

Compared to published consortium data, the mean SRS scores for NF1 were slightly lower (55.8 vs 58.2); remarkably, both means fell well within the normal range of SRS norms.


This study does not support an association of ASD diagnosis with NF1. There was no evidence of an increased rate of clinically diagnosed ASD in our sample or hospital electronic medical records. Our NF1 sample showed mild elevation of autistic symptomatology on standardized measures, but average scores remained below published cutoffs on these measures.

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