Joint hypermobility, gait and autism

I have already made mention of the paper by Maya Shetreat-Klein and colleagues [1] on this blog as part of a post on the potential usefulness of kata training for at least some people on the autism spectrum (see here). Based on an analysis of 38 children diagnosed with autism spectrum disorder (ASD) and a similar number of asymptomatic controls (all medication free), researchers set about recording "the characteristics of gait and prevalence of toe walking, the range of passive joint mobility, and age at walking" for their groups. They concluded that: "Children with ASDs had significantly greater joint mobility... more gait abnormalities... and on average walked 1.6 months later than their non-autistic peers". Ergo, much greater research focus should be directed to motor issues in cases of autism.

The cliff walk @ Wikipedia 

A few further details from the study might be useful:

• The analysis of movement such as gait and mobility is a science which I won't even pretend to understand. You get terms like goniometer fulcrum which probably makes a lot of sense to those in the know, but to me just sounds like a character from Game of Thrones. Suffice to say however that various measures were used to ascertain passive joint mobility - that is suppleness - across fingers, wrist, elbow and ankle. Gait was also analysed based on participants being "videotaped while walking and running barefoot up and down a hallway in the physician's office for 1-2 min".
• Results: as a group, participants with autism showed significantly greater values for maximum passive joint mobility angles across nearly all measured joints than controls. Taking one example, finger extension (or should that be 'finger metacarpo-phalangeal joint extension angle'), the authors present the very stark differences in angles obtained in histogram form between ASD and control participants. The majority of those with autism able to extend 110 degrees or over; such a feat only noted in 1 of the control participants. I might direct you to a post I wrote a while back on joint hypermobility (see here) which I'll talk about it moment.
• When it came to gait, the authors observed: "toe-walking was significantly more prevalent in children with autism" than controls (33% vs 3% observed on video only). I've talked about toe walking and autism in a previous post (see here) and what it may or may not mean for autism when present. Several other features of gait were also observed; 33% of children with autism were described as apraxic (an inability to execute learned purposeful movements) and 20% were described as clumsy. Both of these issues were not noted in any of the control group participants.

I found the Shetreat-Klein paper to be quite an intriguing read. Not only for the results obtained but because nestled in the paper introduction was reference to some of the original descriptions of autism by Leo Kanner, and how he "commented on the motor deficits in many of his patients". I've talked previously on this blog about how the seminal 1943 paper from Kanner [2] contained so much more than just descriptions of the triad (now dyad) of behaviours which make up the clinical diagnosis of the condition (see here). Aspects which we have perhaps ignored for too long...

The word 'hypotonia' - roughly translated as decreased or low muscle tone - is also a discussion point in the paper: "Our findings that passive joint mobility is on average increased in autism corroborates other studies that report a significantly increased proportion of clinically hypotonic children among those with ASD". Once again, I can't profess to be able to offer any great insight into this issue aside from some light reading around this concept and other uses in the research texts with autism in mind. Hypotonia seems to crop up quite a bit in various case reports detailing often rare genetic conditions with autism as part of presentation. Take for example the paper by Belengeanu and colleagues [3] reporting on a young child presenting with developmental delay and among other things, hypotonia. The paper by Shuvarikov and colleagues [4] talking about a potential HERV (human endogenous retrovirus) mediated genetic deletion with hypotonic features is another example; HERVs are another favourite talking point on this blog (see here).

That all being said, I'd also like to go back to the previous mention of joint hypermobility. Shetreat-Klein et al do talk about whether the descriptions of hyptonia in cases of ASD, or at least "joints with ligamentous laxity", might suggest "a disorder of elastin or collagen". Collagen issues immediately brought my mind back to the condition called Ehlers-Danlos syndrome (EDS), a heritable disorder of connective tissue. One of the primary features of EDS - accepting that there are various different presentations - is hyper-flexible joints. The literature looking at any overlap between autism and EDS is currently sparse, very sparse. I did happen upon the paper by Takei and colleagues [5] (open-access here) detailing a single case where "autistic disorder and EDS were diagnosed" concurrently. Takei et al describe a family history of EDS and as they note: "We speculate that associations exist between connective tissue diseases and autistic disorders, and that connective tissue abnormalities may contribute to autistic symptoms". I do wonder whether this might be an area requiring a little more scientific inspection.

The take home message from this post is that joint mobility and gait issues do seem to be quite apparent across the autism spectrum. Alongside other research in this area, one might start asking further questions about the hows and whys of such findings and whether it may offer further insight into some of the underlying issues potentially associated with at least some of the autisms?

To close, football (soccer). Now knowing that Germany are the 2014 World Cup Champions and this is the first lifting of the Jules Rimet trophy in a reunified Germany, I'm sure David Hasselhoff might have something to say...

----------

[1] Shetreat-Klein M. et al. Abnormalities of joint mobility and gait in children with autism spectrum disorders. Brain Dev. 2014 Feb;36(2):91-6.

[2] Kanner L. Autistic disturbances of affective contact. Nervous Child. 1943; 2: 217-250.

[3] Belengeanu V. et al. A de novo 2.3 Mb deletion in 2q24.2q24.3 in a 20-month-old developmentally delayed girl. Gene. 2014 Apr 10;539(1):168-72.

[4] Shuvarikov A. et al. Recurrent HERV-H-mediated 3q13.2-q13.31 deletions cause a syndrome of hypotonia and motor, language, and cognitive delays. Hum Mutat. 2013 Oct;34(10):1415-23.

[5] Takei A. et al. High-functioning autistic disorder with Ehlers-Danlos syndrome. Psychiatry Clin Neurosci. 2011 Oct;65(6):605-6.

----------

Shetreat-Klein M, Shinnar S, & Rapin I (2014). Abnormalities of joint mobility and gait in children with autism spectrum disorders. Brain & development, 36 (2), 91-6 PMID: 22401670

Toe walking and autism

Whilst grazing, as one does, on the plains of the Internet savanna, I stumbled across an interesting article by Williams and colleagues* (open-access) describing a protocol for a study looking at toe walking. As what normally happens with me, memories of autism research times gone by started to flood back, culminating with the question: what ever happened to research looking at toe walking in cases of autism?

En Pointe @ Wikipedia  

Going back quite a few years now, I remembered one occasion when I had research reasons to be in contact with the family of a young girl diagnosed with autism. I quite vividly remember this youngster because of her almost ballet-like gait, hoisting her body weight (which it has to be said was only a very slender frame) on the front portion of her feet; her heels almost never touching the ground for the duration of my visit. The parents I recall, described how she would spend literally hours toe walking; her gait intertwined with various stereotypies depending on her mood and disposition at the time.

Most people will know about the links suggested between autism and issues with gait as per studies like the one from Fournier and colleagues** and the one from Green and colleagues***. Indeed just flicking through an old copy of the ADI (Autism Diagnostic Interview) which I have to hand, I note that in the general behaviours section there is an entry under gait and the words 'up on toes' and 'toe-walking' detailed as part and parcel of the schedule, even if not part of the diagnostic algorithm.

So what evidence is there for toe walking being linked to cases of autism?

• I was actually quite taken aback as to how few references there were for toe walking research in relation to autism as listed in PubMed. One the more important studies seems to be this one from Barrow and colleagues**** which was also discussed on a SFARI entry (see here). Barrow et al suggested that toe walking might be a facet of quite a few cases of autism - during childhood - and raised "the possibility of a secondary orthopedic deformity" to be present. Barrow also reported a disparity in results between the autisms (autism vs. Asperger syndrome) which might also tie into the various research looking at toe walking from a language point of view (see here) or the possibility of a cognitive developmental issue (see here).
• The possibility that toe walking might be a 'red flag' for the presentation of autism had been previously discussed as exemplified by the paper from Mandell and colleagues***** (open-access). As a parcel of behavioural presentations including 'hand flapping' and 'sustained odd play', they suggested that toe walking was associated with a decrease in the age of diagnosis. Someone it seems, has been taking its presence quite seriously.
• The paper by McDougle and colleagues****** (who is talking about some very interesting concepts these days) on tryptophan depletion in cases of autism offers some interesting links between everyone's favourite aromatic amino acid and behaviours such as toe walking. Their results, based on the very complicated area of tryptophan and serotonin chemistry in relation to autism, might have some connection back to more recent mouse model results (see here).

Of course there are other papers looking at toe walking and autism (even with a potential mitochondrial slant to them) but I'm not going to bore you with all the details. Obviously one has to keep in mind that toe walking is not an exclusively autism-linked trait and that some children can present with such a behaviour without presenting with other features linked to a diagnosis of autism or anything else.

I do wonder about a few things based on this collected work: whether we should, following Barrow's suggestion, be screening for orthopaedic issues where sustained toe walking presents in cases of autism, and indeed whether this heralds any link (or not) to things like joint hypermobility (see this post). Whether also toe walking might correlate with other signs and symptoms around either comorbidity (such as cerebral palsy) or even other slightly less well-defined motor-related behaviours are important questions too. That also, for the most part, examination of toe walking in cases of autism has tended to concentrate on the early years of childhood, leaves quite a wide gap into how far maturity acts on such behaviours, and indeed the extent to which toe walking persists into adulthood in cases of autism.

To close, I don't do advice on this blog. But if you really want some life advice, then how about listening to this chap and starting with wearing sunscreen.... (dancing is also a good idea).

----------

* Williams CM. et al. Do external stimuli impact the gait of children with idiopathic toe walking? A study protocol for a within-subject randomised control trial. BMJ Open. 2013; 3: e002389.

** Fournier KA. et al. Motor coordination in autism spectrum disorders: a synthesis and meta-analysis. J Autism Dev Disord. 2010; 40: 1227-1240.

*** Green D. et al. The severity and nature of motor impairment in Asperger's syndrome: a comparison with specific developmental disorder of motor function. J Child Psychol Psychiatry. 2002; 43: 655-668.

**** Barrow WJ. et al. Persistent toe walking in autism. J Child Neurol. 2011; 26: 619-621.

***** Mandell DS. et al. Factors associated with age of diagnosis among children with autism spectrum disorders. Pediatrics. 2005; 116: 1480–1486.

****** McDougle CJ. et al. Effects of tryptophan depletion in drug-free adults with autistic disorder. Arch Gen Psychiatry. 1996; 53: 993-1000.

---------

Barrow WJ, Jaworski M, & Accardo PJ (2011). Persistent toe walking in autism. Journal of child neurology, 26 (5), 619-21 PMID: 21285033