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Study shows link between neurofibromatosis, autism

Recent findings provided further evidence of associations between neurofibromatosis type 1 and autism spectrum disorder.

“Recent reports have demonstrated a higher incidence of autism spectrum disorder 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,” Stephanie M. Morris, MD, of Washington University School of Medicine, St Louis, and colleagues wrote. “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.”

To assess the quantitative autistic trait burden in individuals with NF1, researchers analyzed anonymized, individual-level primary data from six tertiary referral centers in the United States, Belgium, United Kingdom and Australia (n = 531). The cohort had a median age of 11 years.

Quantitative autistic trait scores were continuously distributed and pathologically shifted, according to researchers. Thirteen percent of the cohort scored within the most severe range, with a 1.6:1 male-to-female ratio relative to idiopathic ASD.

Among individuals with NF1, autism symptoms demonstrated a robust unitary factor structure, with the first principal component explaining 30.9% of the variance in Social Responsiveness Scale-second edition scores.

Within-family correlation with quantitative autistic trait burden was greater among individuals with NF1, compared with the general population and families with ASD.

“These data provide confirmation that the diversity of mutations that give rise to NF1 function as quantitative trait loci for ASD and, to our knowledge, are only the second demonstration using an adequately powered research sample (ie, Fragile X Mental Retardation) that a mutation in a single gene results in a neurodevelopmental syndrome of variable severity encompassing the complete ASD phenotype. Clinicians should be alerted to the high frequency of this disabling comorbidity of NF1, and the scientific community should recognize the potential for this monogenic disorder to provide new insights into the pathobiology of idiopathic autism,” the researchers concluded. – by Amanda Oldt

Disclosure: Morris reports no relevant financial disclosures. Please see the study for a full list of relevant financial disclosures.