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• A new syndrome requires essential clinical and developmental descriptive data
  Eric Fombonne
  Published on: 27 May 2002

• Published on: 27 May 2002

  A new syndrome requires essential clinical and developmental descriptive data

  • Eric Fombonne, Canada Research Chair in Child and Adolescent Psychiatry

  Dear Editors

  The study by Ulhmann et al. published recently [1] is the third empirical article from Wakefield and colleagues supposedly describing a new syndrome of which a form of autism might be a component. Thus, it was surprising that Ulhmann et al. article did not contain a proper Subjects section providing the necessary background clinical characteristics which are required both for a pr...

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  Dear Editors

  The study by Ulhmann et al. published recently [1] is the third empirical article from Wakefield and colleagues supposedly describing a new syndrome of which a form of autism might be a component. Thus, it was surprising that Ulhmann et al. article did not contain a proper Subjects section providing the necessary background clinical characteristics which are required both for a proper evaluation of the significance of the results and for allowing replication by independent research groups. The behavioral and diagnostic characteristics of the 91 'affected' children included as patients in the paper are totally lacking. Nowhere in the paper the word 'autism' appears nor do the authors refer to regression in the developmental course of these children. Patients are vaguely described as being 'affected' with 'developmental disorders' (what is meant by this is unclear unless the disorders in question are further qualified) and the qualification of 'pervasive' for these disorders is not even used.

  Earlier reports by Wakefield and colleagues [2,3] have consistently lacked basic descriptive clinical information on the research subjects. Thus, the methods used to arrive at the diagnosis of pervasive developmental disorders in these reports were unstandardized, were not uniform across subjects, and no reliability data were ever provided. Furthermore, Wakefield et al. included in their earlier series of 60 children [3] with 'autistic enterocolitis', 1 child with attention deficit hyperactvity disorder (ADHD), 1 child with dyslexia, and 1 child with schizophrenia. Does the 'new syndrome' apply to a subgroup of children with an autistic-spectrum disorder or does it apply to any child whose behavior deteriorates irrespective of the underlying psychiatric or developmental status? Although this is not made explicit in the study description, one must assume that the sample of 91 children studied by Uhlmann et al. [1] includes those children described in the two earlier reports; if so, these questions about the sample diagnostic heterogeneity need answering for the reader to make sense of these findings.

  The first steps in the delineation of a new syndrome consist in a precise description of the semiological-clinical features of the syndrome in order to subsequently test for its validity using a range of epidemiological, therapeutic, genetic, or biological strategies. Wakefield and colleagues articulated that the distinctive features of the putative new syndrome ('autistic enterocolitis') were a combination of developmental regression and gastro-intestinal symptoms [3]. Yet, they have failed to provide basic descriptive clinical data on these features. In addition to provide the diagnostic breakdown of their sample, the authors should also provide clear answers to the following questions :

  · Did the 91 children in this sample have developmental regression?

  · If yes, how was regression assessed? And how was it established that the development was unambiguously normal prior to the loss ?

  · Which skills were lost (language? eye contact? pretend play ?)? And at what level were these skills before the loss occurred?

  · At which age did the loss occur (the initial claim that the regression occurred within 14 days of MMR first immunisation was apparently subsequently abandoned by Wakefield)? How long did the regression last, and what was the subsequent pattern of development?

  · What were the language and IQ levels (a basic requirement in all autism studies) of these children when assessed in Wakefield's protocol?

  · What were the actual type, age of onset, duration and severity of both gastro-intestinal symptoms and neurological signs indirectly alluded to in these reports? And what was their timing relative to developmental symptoms?

  One year ago, before one Institute of Medicine Committee and in other occasions,[4] we publicly requested from Dr Wakefield that he would provide clarification about the confused clinical picture generated in his articles and communications. More than one year later, it is remarkable that no beginning of an answer has been offered and how insensitive Wakefield and coauthors have generally been to requests of clarifications coming from their peers.[5] But it is the obvious failure of the review process, apparent in this new publication, that raises the most concerns. Whether or not autism experts were involved as reviewers of the manuscript, no care has ultimately been taken by reviewers and/or the editors to address this very basic issue of sample description, so essential for both the general readership and the scientific question. This seriously jeopardizes future attempts to replicate the findings by independent groups; and unfortunately, your decision to publish an article with such deficiencies has contributed to maintain the scientific uncertainty and confusion over this putative syndrome.

  The onus should now be firmly placed on Wakefield et al. to provide measurable, quantified evidence on clinical characteristics and symptom patterns in their samples, both for the recent Uhlmann et al.'s paper and for any future publication.

  Eric Fombonne, MD
  Canada Research Chair in Child and Adolescent Psychiatry
  Professor, McGill University
  Director of the Department of Psychiatry
  Montreal Children's Hospital
  4018 Ste-Catherine West
  Montreal H3Z 1P2
  Canada

  References

  [1] Uhlmann V, Martin CM, Sheils O, Pilkington L, Silva I, Killalea A, Murch SB, Wakefield AJ, O'Leary JJ. Potential viral pathogenic mechanism for new variant inflammatory bowel disease. J Mol Pathol 2002;55: 84-90.

  [2] Wakefield A, Murch S, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998;351:637-41.

  [3] Wakefield A, Anthony A, Murch S, et al. Enterocolitis in children with developmental disorders. Am J Gastroenterol 2000;95:2285-95.

  [4] Fombonne E, Chakrabarti S. No evidence for a new variant of measles- mumps-rubella-induced autism. Pediatrics 2001;108(4):E58.

  [5] Halsey NA. Publication by Uhlmann et al. and commentary [electronic response to Uhlmann et al. Potential viral pathogenic mechanism for new variant inflammatory bowel disease. molpath.com 2002 http://mp.bmjjournals.com/cgi/eletters/54/6/DC1 (accessed 27 May 2002)

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  Conflict of Interest:
  None declared.

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