Investigators: Amy Epstein, Helen Leonard, Jenny Downs, Jessica Mackay, Kingsley Wong, Sharolin Boban, Stephanie Smith, Yuka Mori
Project description
Rett syndrome is a rare neurological disorder affecting approximately 1:9000 females and is associated with a mutation in the MECP2 gene. Given the low number of cases at a national level, international collaboration and data collection are imperative. The InterRett database project allows clinicians and families caring for an individual with Rett syndrome to directly contribute to the global research effort by completing web or paper-based questionnaires.
This project, which is funded by Rettsyndrome.org (formerly the International Rett Syndrome Foundation), was established in 2002 and continues to grow and expand with online questionnaires available in Mandarin and six European languages. The database currently contains more than 2,600 cases representing more than 50 different countries. New participants register using a form on our project website. International support for the InterRett project continues to strengthen, particularly in Russia where we have had native speakers assisting families in submitting their information. The website also allows users to: generate graphs based on summary data; download clinical guidelines for the management of scoliosis and gastrointestinal issues; and to read snapshots of the over 20 peer-reviewed publications arising from analyses of the InterRett data. Our research has covered a wide range of topics such as: pain sensitivity; the characteristics that influence diagnosis; diagnostic challenges in China; the influence of mutation type or DNA variations in the BDNF gene on clinical severity; and ageing in Rett syndrome.
To allow families to contribute at all levels of the research process, from study design to the dissemination of findings, a Consumer Reference Group (CRG) has been established. In early 2017 we were awarded a further two years ongoing funding from Rettsyndrome.org to continue the management of the database.
The current aims of our project “The InterRett database: achieving international breadth and longitudinal depth in Rett syndrome” are:
- To continue to give families a strong voice in research about Rett syndrome,
- To expand data collection including a longitudinal component,
- To have a special focus on families who live in under-represented and low and middle income countries, including China, Russia and South America, and
- To further develop the InterRett infrastructure to enable linkage with other Rett syndrome and international rare disease database initiatives.
Our work in 2016 and 2017 focused on the profiling of and describing the impact of breathing and sleep disorders in Rett syndrome as well as the treatments being used to manage these disorders and ensuring that these results moved forward to publication within a timely manner.
We found that breathing irregularities such as hyperventilation and breath-holding affected girls and women of all ages and with most mutation types. However, the impact especially for breath-holding was worse for those with a p.Arg294* mutation, one of the generally milder mutations. In a paper published in 2018 we also found that a hospital admission for a lower respiratory tract infection over the previous five years was reported for slightly more than one fifth of individuals. For those with enteral feeding there was nearly twice the risk of an admission. Compared to those who walked independently, being unable to walk was associated with a six-fold increased risk of admission. Beyond the influence of mutation type, walking appears to have protective effects on respiratory health. We believe these findings have important implications for the day to day management and optimisation of health for those with Rett syndrome.
As a sequel to our earlier paper on the presence, nature and frequency of sleep problems, we found that better use of sleep hygiene practices was associated with less impact on the family and less sleep disturbance. Attention to sleep hygiene remains an important management strategy for sleep problems in Rett syndrome. However there is also an urgent need for research to investigate better pharmaceutical options to treat these symptoms. These findings were published in 2018.
Again using the web-based electronic data capture system Redcap we invited English-speaking families with whom we had recent contact, to fill out a further questionnaire in 2018 specifically designed to include the following:
- Previously used items in order to assess change over time in function and co-morbidity
- An oral health module
- Instruments to measure behaviour (e.g. anxiety, mood disorders and self-injury).
- A scoliosis bracing module, to determine when and how bracing is used for the management of scoliosis in Rett syndrome.
- The new quality of life measure – QI-Disability.
Study recruitment commenced in June 2018 and by year end we had already invited 240 families, 219 of whom had completed the questionnaire. Further recruitment and analysis of preliminary findings is planned for 2019.
External collaborators
- Svetlana Volgina (Kazan State Medical University)
Partners
- rettsyndrome.org