I read with interest the publication by Cooper et al,1 ‘Molecular and phenotypic expression of Beckwith–Wiedemann syndrome’. The article is well written, informative and documents important phenotypic information for a select group of patients. However, the study title does not accurately reflect the study methodology because the authors equate a syndrome diagnosis with a molecular defect. As stated on p.3 in the Methods section, the investigators ‘…analyzed only those cases with a proven molecular (my emphasis) diagnosis of BWS.’ The phrase ‘molecular diagnosis of BWS’ is a nonsequitur. Syndromes are clinical diagnoses, at least within the group of disorders defined by dysmorphology, and as such are defined by their specific pattern of malformation, not by their pattern on a Southern blot. To further cloud the issue, the original Cooper et al population from which the study group was culled were patients referred to the laboratory for ‘suspicion’ of BWS rather than from a population meeting specific diagnostic criteria. The author's concede this point in their results section, even noting two cases of isolated hemihypertrophy included in their N. They justify this approach because ‘97% of patients had at least two ‘major’ features of BWS…’. Unfortunately we are not given information as to which two major defects were present. Should a patient, for instance, with an umbilical hernia and a renal defect be considered to have BWS? As a result of not using specific diagnostic criteria and of reporting results only from patients with a molecular alteration, the authors have not categorized the molecular and phenotypic expression of BWS syndrome as the title indicates, but instead have categorized the phenotypic expression of a series of patient's with specific genetic and epigenetic alterations of the 11p15.5 region, and have done so quite nicely at that. The distinction is an important one. The era of gene discovery is winding down as we move into an exciting period of the search for modifying elements of human inheritance. Answering the question as to why two people with an identical genetic or epigenetic alteration have two distinctively different phenotypes is a next step in connecting the dots between gene mutation and pathogenesis. For example, we have recently showed that 1/3 of isolated hemihyperplasia (IH) patients have the same Lit1 and/or H19 methylation abnormalities as BWS.2 However, we have not gone back to those patients and labeled them with BWS. Clearly, lumping IH and other ‘suspicious’ BWS cases together and classifying them as BWS after a ‘BWS’ genetic alteration is found as Cooper et al did in this study dilutes the opportunity to understand why they are different. Their study methodology stands on its own and offers important information, so the title should say what it means and mean what it says.