PubMed2006
The discovery of relevant causative genes has subdued the lumping versus splitting debate with respect to a growing number of syndromes. However, it remains paramount to define unknown genesis syndromes as precisely and appropriately as possible in order to provide accurate prognosis and to facilitate future research. The presentation of a 14-month-old girl, of normal intelligence, who had a colobomatous right eye with cyst, minor intracranial MRI variants, and an area of sparse scalp hair containing a 1 by 1.5 cm, soft, domed, and indented skin lesion suggested a diagnosis of mild oculocerebrocutaneous syndrome (OCCS). An initial exploration of the literature exposed the extreme variability in cases that have been reported as OCCS, and emphasized its possible relationship to encephalocraniocutaneous lipomatosis (ECCL), thus challenging the initial diagnosis. Cases reported, or discussed by others, as possible OCCS (40) and ECCL (44) were reviewed as completely as possible in an effort to determine whether diagnostic criteria could be developed for these syndromes, and to see whether or not evidence favored their continued separation as two syndromes. The approach used was to summarize the data for all cases, to select major and minor diagnostic criteria on the basis of the relative specificity and/or frequency of a sign, to then apply the criteria in a standard fashion and to review the outcome to see if the classification of cases made clinical sense, and to make appropriate adjustments. The criteria were not chosen so as to separate the syndromes and in some instances the same criteria could apply to either syndrome. An approach is outlined for handling reports of patients that purport to be variants or to expand the spectrum of a syndrome, and in the case of OCCS and ECCL this resulted in most such examples being excluded. Application of diagnostic criteria suggests that OCCS and ECCL are distinct, and that some case reports, including some purporting to expand the spectrum of OCCS, should be excluded, at least until such time as the etiology of these conditions is known and those cases can be tested. These diagnostic criteria were developed on the basis of literature reports that varied in their quantity and quality of detail. Furthermore, in many cases reliance had to be placed on copies of original studies with resultant degradation of photographic information. Modern ocular imaging, and histopathology of eye and skin malformations, will often clarify the specific nature of a malformation and, therefore, define exact diagnostic criteria and leave fewer uncertain cases. In the absence of anomalies in those systems, or if histopathology or appropriate imaging is unavailable, the diagnosis in some cases will continue to remain uncertain; this is not an argument for lumping the syndromes.