Sunday, 4 May 2014

Autistic behaviours and Down's syndrome

I believe it is obligatory to say 'May the 4th be with you' today given that it is Star Wars Day. If you prefer the Chewbacca version of this greeting, well take yer pick from his many and varied vocalisations... Even better, ponder how Ming the Merciless might approach the greeting (no, really he's [the actor] gonna be in episode VII).
Pizza the Hutt @ cyclonebill @ Wikipedia 

Anyhow... today I want to talk about the paper by Georgina Warner and colleagues [1] and their quite stark finding that: "The pervasiveness of ASD [autism spectrum disorder] in children with DS [Down's syndrome] in England and Wales is substantially higher than in the general population". Indeed, their finding that over a third of children with Down's syndrome (also called Down syndrome) met the cut-off score for an ASD based on the Social Communication Questionnaire (SCQ) is particularly noteworthy. Alongside some related findings based on results from the Strengths and Difficulties Questionnaire (SDQ) suggestive of an ESSENCE-type scenario of comorbidity pertaining in relation to SCQ positive screen DS cases, there is definitely a need for further investigation in this area.

Down's syndrome (DS) is a condition I'm sure most people will have heard of. I've known about it since early childhood as a consequence of having an extended family member with DS. In more recent times, I've also become interested in John Langdon Down, the physician who gave his name to the condition and how science is progressing when it comes to issues like pregnancy screening for the condition and the implications thereafter (see here) (something which autism research may one day have to face).

Looking at some of the other peer-reviewed literature on the overlap between DS and ASD, a few other details caught my eye:

  • The Warner paper results, whilst interesting, have to be viewed with some caution insofar as their reliance on the SCD as a screening tool for autism; slightly different from making an actual diagnosis of autism. You may also argue that the presentation of DS might complicate matters when screening/assessing for ASD, but according to the results from Magyar and colleagues [2], the SCD in particular does seem fit for purpose.
  • Joanna Moss, one of the co-authors on the Warner paper, has previously looked into the presentation of ASD in DS [3], again relying on the SCD. Whilst the numbers reaching the SCD cut-offs for autism and ASD were quite a few percentage points lower on that occasion compared with the recent data, they are still eye-catching.
  • Just on the topic of the estimated prevalence of autism/ASD in DS, the paper by DiGuiseppi and colleagues [4] makes for some interesting reading: "Weighted prevalences of autistic disorder and total ASD were 6.4% (95% confidence interval [CI]: 2.6%-11.6%) and 18.2% (95% CI: 9.7%-26.8%), respectively". These figures aren't a million miles away from other data such as that reported by Lowenthal and colleagues [5] and the estimate by Kent and colleagues [6] who stated: "The comorbid occurrence of autism and DS is at least 7%". 
  • Perhaps one of the most useful research points to take from the suggestion of a heightened risk of autism in cases of DS is the possibility that there may be shared genetic or biological variables which predispose a person to both conditions. The paper by Ghaziuddin [7] kinda hints at this when reporting participants "with both DS and autism had an excess of first-degree relatives who met the description of the broader phenotype of autism". The fact however that autism is not universally detected in DS means that we have to be a little careful not to inflate this argument too much. That also autism has been linked to other genetic conditions such as NF1 (see here) and SLOS (see here) to name but a few [8], means that fragility is probably going to a bigger factor over and above certainty. That and the increasingly important pluralisation(?) of autism to take into account.

Outside of the requirement for further examination of the possible relationship between DS and autism, the Warner results also have some very practical implications such as the potential need for greater screening for autism in cases of DS. As the authors note: "the profile of their [DS] autism characteristics on the SCQ was atypical compared with individuals with idiopathic ASD" which might imply that similar to the topic of sex differences in autism presentation, a one-size-fits-all approach is probably not going to be particularly useful. Also, if at all possible, I'd also like to see if the prevalence of autism in DS is showing the same time trend differences as autism witnessed in the general population...?

Music to close. Did you know there ain't no flour in a hundred dollar bill... so said Tex Richman.


[1] Warner G. et al. Autism Characteristics and Behavioural Disturbances in ∼ 500 Children with Down's Syndrome in England and Wales. Autism Res. 2014. March 24. 10.1002/aur.1371

[2] Magyar CI. et al. An initial evaluation of the Social Communication Questionnaire for the assessment of autism spectrum disorders in children with Down syndrome. J Dev Behav Pediatr. 2012 Feb;33(2):134-45.

[3] Moss J. et al. Prevalence of autism spectrum disorder symptomatology and related behavioural characteristics in individuals with Down syndrome. Autism. 2013 Jul;17(4):390-404.

[4] DiGuiseppi C. et al. Screening for autism spectrum disorders in children with Down syndrome: population prevalence and screening test characteristics. J Dev Behav Pediatr. 2010 Apr;31(3):181-91.

[5] Lowenthal R. et al. Prevalence of pervasive developmental disorder in Down's syndrome. J Autism Dev Disord. 2007 Aug;37(7):1394-5.

[6] Kent L. et al.  Comorbidity of autistic spectrum disorders in children with Down syndrome. Dev Med Child Neurol. 1999 Mar;41(3):153-8.

[7] Ghaziuddin M. et al. Autism in Down's syndrome: a family history study. J Intellect Disabil Res. 2000 Oct;44 ( Pt 5):562-6.

[8] Zafeiriou DI. et al. Autism spectrum disorders: the quest for genetic syndromes. Am J Med Genet B Neuropsychiatr Genet. 2013 Jun;162B(4):327-66.

---------- Warner, G., Moss, J., Smith, P., & Howlin, P. (2014). Autism Characteristics and Behavioural Disturbances in ∼ 500 Children with Down's Syndrome in England and Wales Autism Research DOI: 10.1002/aur.1371