Diagnosis and management in Rubinstein-Taybi syndrome: first international consensus statement.

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.

The natural history of adults with Rubinstein-Taybi syndrome: a families-reported experience.

The existing knowledge about morbidity in adults with Rubinstein-Taybi syndrome (RTS) is limited and detailed data on their natural history and response to management are needed for optimal care in later life. We formed an international, multidisciplinary working group that developed an accessible questionnaire including key issues about adults with RTS and disseminated this to all known RTS support groups via social media. We report the observations from a cohort of 87 adult individuals of whom 43 had a molecularly confirmed diagnosis. The adult natural history of RTS is defined by prevalent behavioural/psychiatric problems (83%), gastrointestinal problems (73%) that are represented mainly by constipation; and sleep problems (62%) that manifest in a consistent pattern of sleep apnoea, difficulty staying asleep and an increased need for sleep. Furthermore, over than half of the RTS individuals (65%) had skin and adnexa-related problems. Half of the individuals receive multidisciplinary follow-up and required surgery at least once, and most frequently more than once, during adulthood. Our data confirm that adults with RTS enjoy both social and occupational possibilities, show a variegated experience of everyday life but experience a significant morbidity and ongoing medical issues which do not appear to be as coordinated and multidisciplinary managed as in paediatric patients. We highlight the need for optimal care in a multidisciplinary setting including the pivotal role of specialists for adult care.