Re:Alternative explanations for high rates of autism symptomatology in Neurofibromatosis Type 1

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We thank Walsh and Payne for their interest in our paper. They raise several important points deserving of response.Firstly they suggest that our detailed phase 2 phenotyping of ASD is not related back to the phase 1 data. On the contrary, we describe in the paper how the phase 2 phenotyping systematically sampled from each of three bands of parent-rated phase 1 SRS screening data, including screen negative cases. This methodology allowed a two-stage weighting procedure to calculate the population prevalence, which specifically adjusted for response biases at both phases of the epidemiological study.We discuss in our phase 1 paper (1) the discrepancy between parent and teacher screening ratings; this kind of discrepancy is common in psychopathology research - hence the key value of the in-person phase two phenotyping that we undertook. ADI-R and ADOS-G are known to give excellent sensitivity and specificity for ASD, particularly when their data is combined (2) and have been used internationally in numerous ASD phenotyping studies without evidence of high false positive rates. We are therefore confident in our population prevalence estimates for ASD.Walsh and Payne further raise issues of comorbidity and diagnostic overshadowing. We agree that children with severe ADHD can show social difficulties, however the nature and extent of such social problems are very different from those in full ASD. It was to illustrate this that we described the ASD phenomenology in our cases in detail across social communicative and repetitive and stereotyped behaviour domains (Table 1 in the paper), a profile quite different to that which could be accounted for by ADHD. We also demonstrate equivalent levels of rated ADHD symptoms across each of our ASD, Broad ASD and non-ASD groups, strongly suggesting the independent comorbidity of ASD and ADHD disorders in NF1. This is not unusual; comorbidity is generally common in psychopathology and research has specifically found comorbidity with ADHD in 28.2% cases of familial idiopathic ASD (3).We used the term 'diagnostic overshadowing' to refer to the clinical attribution of behaviours to one disorder without considering additional diagnosis and treatment of comorbid conditions. We agree that this is unlikely in relation to cognitive impairment, which was rare in the sample; instead we argue that previous under-recognition of ASD may well be due to presenting symptoms being attributed either to ADHD or to the NF1 disorder itself. For instance, children on our NF1 register who do not have major physical NF1 problems are generally followed in non- specialist paediatric clinics and our clinical information suggests that most behavioural problems in this context are assumed to be due to the NF1 itself rather than any specific co-morbidity; only 6 out of the 47 children (12.7%) in our phase 2 cohort for example had an independent prior diagnosis of ADHD.We acknowledge in our paper the importance of ADHD in NF1. Our findings show, however, additional independent high rates of ASD. The marked co-morbidity of these two neurodevelopmental disorders in NF1 does indeed deserve further study.
1. Garg S, Lehtonen A, Huson SM, et al. Autism and other psychiatric comorbidity in neurofibromatosis type 1: evidence from a population-based study. Dev Med Child Neurol. 2013;55(2):139-145 
2. Lord C, Petkova E, Hus V, et al. A multisite study of the clinical diagnosis of different autism spectrum disorders. Arch Gen Psychiatry. 2012;69(3):306-313 
3. Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. Psychiatric disorders in children with autism spectrum disorders: Prevalence, comorbidity, and associated factors in a population derived sample. Journal of American Academy of Child & Adolescent Psychiatry. 2008;47(8):921-929.
Conflict of Interest: Prof Evans and Dr Huson receive small amounts in royalties from a book entitled Handbook on Neurofibromatosis. The other authors have indicated they have no potential conflicts of interest to disclose.

Bibliographical metadata

Original languageEnglish
Publication statusPublished - 31 Mar 2014