Phenotype and natural history in 101 individuals with Pitt-Hopkins syndrome through an internet questionnaire system

BACKGROUND: Pitt-Hopkins syndrome (PTHS; MIM# 610954) is a genetically determined entity mainly caused by mutations in TransCription Factor 4 (TCF4). We have developed a new way to collect information on (ultra-)rare disorders through a web-based database which we call ‘waihonapedia’ (waihona [meaning treasure in Hawaiian] encyclopaedia). METHODS: We have built a waihonapedia system in a collaboration between physicians, social scientists, and parent support groups. The system consists of an initial extensive questionnaire for background cross-sectional data, and subsequent follow-up using small questionnaires, with a particular focus on behavioural aspects. The system was built to be used through the internet, ensuring a secure environment, respecting privacy for participants, and acting automated to allow for low costs and limiting human mistakes in data handling. Recruitment of participants is through the patient support groups. In addition, as a sub-study, we used the data from the waihonapedia system to compare the two proposed diagnostic classification systems for PTHS. RESULTS: We present here the results of the initial, cross-sectional questionnaire in which early development, physical health, cognition and behaviour are interrogated, and to which modules specific for PTHS were added on epilepsy and breathing patterns. We describe 101 individuals with a molecularly confirmed diagnosis of PTHS. Comparison of the two classification systems aimed at helping the clinical diagnosis was performed in 47 of the present PTHS individuals, with disappointing results for both. Internationally accepted clinical diagnostic criteria are needed. CONCLUSION: The present cross-sectional data on the natural history of PTHS have yielded useful information which will further increase when follow-up data will be added. No doubt this will improve both care and research.