Cohen Syndrome

Abstract

Cohen syndrome was first described in 1973 by Dr. Michael Cohen and colleagues, when they reported three patients with severe learning problems and a similar dysmorphic facial appearance associated with microcephaly, truncal obesity, joint hyperextensibility, hypotonia, and specific ophthalmic abnormalities. More than 200 cases of Cohen syndrome have since been reported including two well-characterized, large patient cohorts from Finland (Kivitie-Kallio and Norio 2001) and the United Kingdom (Chandler et al. 2003a, 2003b) whose clinical presentation closely resembles that of the original patients. By comparison, a group of Jewish patients reported as having Cohen syndrome (Sack and Friedman 1986) were highly variable in their clinical phenotype and lacked the specific ocular and hematological anomalies associated with Cohen syndrome. A division of Cohen syndrome into “Jewish” and “Finnish” subtypes was suggested to explain this disparity (Kondo et al. 1990). The clinical variability among the Israeli patients made it impossible to define the distinguishing characteristics of the “Jewish” Cohen syndrome. Detailed analysis revealed that many patients had little to support the diagnosis of Cohen syndrome, and hence, the existence of a separate “Jewish” type of Cohen syndrome has been strongly disputed (Chandler and Clayton-Smith 2002). Instead, Cohen syndrome should be considered a single diagnostic entity with a distinctive clinical phenotype identifiable in patients worldwide. The discovery of the gene mutated in Cohen syndrome will facilitate this.Since the gene's identification, several studies involving patients from ethnically diverse populations have been published (Hennies et al. 2004; Kolehmainen et al. 2004; Mochida et al. 2004; Seifert et al. 2006). These studies have demonstrated a higher degree of clinical variability in Cohen syndrome patients with different gene mutations compared to those observed in the genetically homogeneous Finnish Cohen syndrome population. However, in all patient cohorts no clear genotype–phenotype correlation is apparent.