Background: About a half of all children with a clinical diagnosis of Silver-Russell syndrome (SRS) have a detectable molecular genetic abnormality (maternal uniparental disomy of chromosome 7 or hypomethylation of H19). 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.
Objective and hypotheses: To evaluate the utility of four published clinical scoring systems for genetic testing in a cohort of patients referred to a clinical service laboratory.
Methods: Individuals with suspected SRS referred for molecular genetic testing of H19 methylation status or mUPD7 were scored according to published criteria. Anthropometric measures and clinical features were requested from the referring clinician using a custom-designed questionnaire.
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 (low birthweight, postnatal growth failure, relative macrocephaly and asymmetry) that performed similarly to the most sensitive and specific published scoring system (~80%).
Conclusions: 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 that are designed for use in a busy clinical practice rather than a research setting.
13 Nov 2013
British Society for Paediatric Endocrinology and Diabetes