Comparison of the clinical scoring systems in Silver-Russell syndrome and development of modified diagnostic criteria to guide molecular genetic testing

Background About half of all children with a clinical diagnosis of Silver-Russell syndrome (SRS) have a detectable molecular genetic abnormality (maternal uniparental disomy of chromosome upd(7)mat or hypomethylation of H19 differentially methylated region (DMR). The selection of children for molecular genetic testing can be difficult for non-specialists because of the broad phenotypic spectrum of SRS and the tendency of the facial features to mitigate during late childhood. Several clinical scoring systems for SRS have been developed by specialist researchers, but the utility of these for guiding molecular genetic testing in routine clinical practice has not been established. Objectives To evaluate the utility of four published clinical scoring systems for genetic testing in a cohort of patients referred to a clinical service laboratory. Patients Individuals with suspected SRS referred for molecular genetic testing of H19 DMR methylation status or upd(7)mat. Results 36 of 139 (25.9%) patients referred for testing had a genetic abnormality identified. Comparison of four published clinical scoring systems demonstrated that all included subjective criteria that could be difficult for the general clinician to assess. We developed a novel, simplified, scoring system utilising four objective, easily measured parameters that performed similarly to the most sensitive and specific published scoring system. Discussion Effective utilisation of genetic testing by clinicians without specialist clinical genetics training will be facilitated by the development of targeted testing protocols that are based on robust objective clinical features and are designed for use in a busy clinical practice rather than a research setting.