The Prevalence of Neurofibromatosis Type 1 Among Children Identified with Autism Spectrum Disorders By the Autism and Developmental Disabilities Monitoring (ADDM) Network

Background: Neurofibromatosis Type 1 (NF1) is a neurocutaneous disorder characterized by café-au-lait spots, neurofibromas, and optic gliomas.   Neurodevelopmental disorders associated with NF1 include Autism Spectrum Disorders (ASD), learning disabilities, attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID).   Recent studies have identified ASD symptoms in up to 27% of patients with NF1. The frequency and pattern of DSM-IV criteria and associated ASD characteristics in children with co-occurring ASD and NF1 (ASD/NF1) have not previously been examined in a population-based sample.     

Objectives: (1) to determine the prevalence of NF1 in a population-based sample of 8 year-old children with ASD, and (2) to identify and compare patterns of ASD criteria and related characteristics between children with ASD/NF1 and ASD only.

Methods:  The Autism and Developmental Disabilities Monitoring (ADDM) Network identified 8-year-old children with ASD using validated population-based, multi-source records review methods during surveillance years 2000, 2002, 2004, 2006, and 2008.  The ASD/NF1 group included ASD cases for which a NF1 diagnosis and/or ICD9 code (237.71) were indicated in their records. Differences in characteristics between ASD cases with and without NF1 were tested using χ2 and t-tests.  Characteristics that were compared included sex, race/ethnicity, ID, ADHD, epilepsy, developmental regression, age of regression onset, ASD classification, ASD community diagnosis, and DSM-IV diagnostic criteria patterns.  For DSM-IV criteria and pre-existing ASD community diagnosis comparisons, samples were restricted to surveillance years 2000, 2006, 2008 for which complete data were available. 

Results: Among 12,271 children who met DSM-IV ASD diagnostic criteria, 22 (0.17%; 95% CI: 0.12%-0.27%) had NF1 /ASD. There was no difference in the distribution of sex or race/ethnicity between children with ASD/NF1 and ASD only.  There was no difference in the frequency of history of regression or the co-occurrence of ID, ADHD, or epilepsy with ASD, although a lower frequency of co-occurring ID in children with ASD/NF1 than with ASD only was nearly statistically significant (p=0.06). Significantly fewer (p=0.04) children with ASD/NF1 had a previous ASD community diagnosis (53%), compared to children with ASD only (76%).  Children with ASD/NF1 (58%) were significantly less likely (p=0.001) than those with ASD only (84%) to meet diagnostic criterion 1a (difficulty using or understanding non-verbal communication).  A small difference was observed between ASD/NF and ASD groups in mean number of DSM-IV criteria met (8.4 and 8.9 respectively, p=0.44); no difference between groups was found in the median number of criteria (9).  

Conclusions:  The estimated NF1 prevalence among 8-year-old children with ASD was approximately 5 to 7 times higher than published general population prevalence estimates (1-in-3000 to 1-in-4000).  The actual prevalence may exceed this because the presence of a co-morbid NF1 diagnosis is not consistently collected across ADDM sites.  Among children with ASD/NF1, the lower prevalence of co-occurring ID and likelihood of a previously established community ASD diagnosis suggest that those with ASD/NF1 may have milder ASD manifestations than children with ASD only.  These findings underscore the importance of regularly evaluating children with NF1 for ASD.