Predictive value of the early clinical signs in Rett disorder

The British Isles Survey for Rett has registered 1,159 cases over up to 20 years. Indicators of health and severity, recorded at intervals throughout life, are drawn from clinical examinations, reports and postal questionnaires. This study aimed to establish the stability and predictive value of an early severity score based on muscle tone, locomotor ability, feeding difficulty, scoliosis and epilepsy. Data from people with clinically documented classic or non-classic Rett and health records over 20-30 years indicate that severity scores tend to increase throughout the first 15 years and then to stabilise in mild and severe, classic and non-classic Rett. Severity scores before regression reflect later severity scores within relatively wide inter-quartile ranges. In general, the adult severity level is around 40 points above the pre-regression level for classic Rett and around 20 points for non-classic Rett. High early severity scores are associated with reduced cumulative survival. Used with caution, early signs are helpful in diagnosis and prognosis. The mutations T158M, R255X and R168X are generally associated with more severe and R306C and R133C with less severe disease but exceptions make these unreliable predictors of outcome.