Childhood disintegrative disorder: part of the autism spectrum?

It has long been debated whether childhood disintegrative disorder (CDD) is sufficiently different from ‘classical’ autism to be set aside from the other disorders on the spectrum. Mehra et al. have carried out an exhaustive literature review, searching for cases of CDD (n=96) and comparing their clinical features with those found in two control groups: autism spectrum disorder without developmental regression (ASD) (n=1044) and autism spectrum disorder with developmental regression (ASD-R) (n=51). Most reported studies were cross-sectional. The clinical features were described in detail in all three groups, although the authors acknowledged that there was mainly low-quality information in the CDD cases. They found qualitative and prognostic differences between the CDD group and the two ASD control groups, with the ASD-R cases more like the CDD cases than were the ASD cases. Mehra et al. searched four databases to retrieve their cases. They mention briefly an earlier paper by Rosman and Bergia, in which the findings and conclusions were in close agreement with the present study. This earlier study reported six new cases of CDD and highlighted differences from findings in autistic disorder. As in the present paper, CDD was characterized by: (1) a greater male preponderance; (2) onset following a period of apparently typical development; (3) more global and more rapid regression than in ASD; (4) greater cognitive impairment than in ASD; (5) frequent loss of motor skills and continence, both rare in ASD; (6) a higher frequency of seizures than in ASD; and (7) a much poorer prognosis in CDD than in ASD. But unlike the earlier paper, Mehra et al. looked at two control groups: ASD and ASD-R, an important new contribution. They found a higher frequency of certain extra-diagnostic features (including fear/ anxiety, challenging behaviors, and in some instances, psychosis) than noted by Rosman and Bergia, but with only a paucity of pathogenetic insights from the few abnormal laboratory investigations found in the CDD cases in both studies. Because of the distinctive features seen in CCD that distinguish it from classical autism, Rosman wrote to the Committee responsible for revising the classification of the pervasive developmental disorders for the new edition (2013) of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), outlining the clinical data and arguments validating CDD as a distinct disorder, separate from the other pervasive developmental disorders, including ASD. The Committee felt, however, that because of the relatively small number of reported cases of CDD (since the first report of six cases by Heller in 1908) and incompleteness of clinical data in many of the reports, that CDD should be included in the broad grouping of autism spectrum disorder in DSM-5, rather than being placed separately in the DSM5 classification. Does the current study settle the issue? Mehra et al. did outline certain limitations of their study, including: (1) low-quality clinical evidence of CDD; (2) probable positive reporting bias, as most of the studies reviewed were cross-sectional; (3) lack of homogeneity in the control groups; and (4) lack of statistical tests of difference between the patients with CDD and the controls. Despite these limitations, this paper represents the largest and most detailed review of the CDD literature. It concludes by underscoring the need for additional genetic, immunological, neurocircuitry, and behavioral studies to explain phonotypical differences between CDD and ASD. If more differences are found, that will help to determine whether CDD should be placed as a separate diagnostic entity in future revisions of diagnostic manuals.