Leading into the new millennium, scientists discovered the gene responsible for Rett syndrome. One year later, The Children’s Hospital at Westmead (CHW) opened its doors to Australia’s first and largest clinic dedicated to managing the incurable condition.  

Now, more than 20 years on, the CHW team have become international research leaders in the field and are looking towards gene therapy in the hope of changing the lives of those diagnosed.  

A/Prof Carolyn Ellaway, Clinical Geneticist, launched the clinic following the completion of her PhD on Rett syndrome, having gained significant experience diagnosing and managing girls with the condition.

She decided to give back to the small community of patients, families and careers who were committed and supportive of her studies through its establishment. 

“Starting a dedicated-clinic that’s a ‘one-stop shop’ seemed like the right thing to do. This service is now considered a gold-standard multidisciplinary clinic for children with rare genetic conditions,” A/Prof Ellaway said. 

Rett syndrome is a complex and rare genetic neurodevelopmental condition caused by variants in the MECP2 gene located on the X chromosome. It is one of the most common genetic causes of developmental and intellectual disability in girls. 

The condition is characterised by developmental regression with loss of normal movement and hand function, as well as loss of communication abilities and is coupled with features of cerebral palsy, autism, epilepsy and anxiety. 

There is currently no cure, with individuals needing lifelong personal care, assistance and support. 

The Rett syndrome multidisciplinary clinic at CHW has changed the lives of families like eight-year-old Abigail’s. 

Abigail was diagnosed with Rett syndrome just shy of her third birthday. A week later, Abigail and her family met A/Prof Ellaway and from that moment, mum, Mary, knew they were in good hands. 

“Dr Ellaway and the Rett Clinic at Westmead were an absolute lifeline for us when we first got the diagnosis of Rett Syndrome. She was so caring and understanding but also did not shy away from the hard conversations about the reality of Rett Syndrome,” Mary said. 

Rett syndrome now affects nearly all aspects of Abigail’s life. She is non-verbal, has limited hand function, breathing difficulties, gastrointestinal difficulties, handwringing, dystonia, as well as sleeping disturbances. The support of the team in managing Abigail’s needs though has made the world of difference.  

It gives me so much peace of mind to know that there is a fantastic clinic run by such experienced professionals who are committed to helping my child. It is truly wonderful,” Mary said. 

In a recent research paper, A/Prof Ellaway alongside colleagues, Lyndal Douglas, Sue Thompson, Jessica Newham, Robyn Kirkland, Gloria Tzannes, Dr Diane Tay, Sandra Vilvarajan and Madeleine McDonald at SCHN, analysed a cohort of females who attended the multidisciplinary clinic at CHW over a 20-year period.   

The paper provided a comprehensive review of their clinical features, comorbidities and multidisciplinary management and highlighted just how far research has come. 

I always hoped that one day I would be in a position to offer these girls an effective treatment and I am now very excited that this hope is quickly becoming a reality," A/Prof Ellaway said. 

"With increasing awareness and knowledge of Rett syndrome and access to diagnostic genetic technologies, children with the condition are now being diagnosed at a much younger age and previously unrecognised comorbidities are better managed." 

The demand and number of referrals to the clinic has grown year on year, and there is now significant awareness among the paediatric field in NSW. As soon as a new patient is diagnosed, or the diagnosis of Rett syndrome is considered, they are referred to the clinic at CHW.

As an Australian leader in the provision of care to children with the condition, the clinic is also at the forefront of clinical research.

In 2020, a clinical trial was launched, led by A/Prof Ellaway, to trial whether ANAVEX®2-73, a drug used to treat adults with Alzheimer’s, could help improve some of the devastating features of Rett syndrome for children like Abigail. 

The ANAVEX®2-73 trial was the first of its kind in Australia, with results now awaiting analysis. If successful, it will be the first time a treatment can be offered.  

"Hearing about the clinical trial was so exciting. Trials for medication to treat symptoms give us hope that someday soon there will be options for Abigail, and opportunities to make her, and our lives easier,” Mary said. 

I hope something positive comes from this trial and that I can tell Abigail she played an important role in helping other people with Rett syndrome. She will be so proud.”  

A/Prof Ellaway shares these hopes, with a vision to be able to provide treatment to even more children beyond the trial.  

"We hope the trial will show improvements in some of the features of Rett syndrome so we will then be in a position to extend this treatment beyond the extension phase of the trial and provide it to all of our patients,” A/Prof Ellaway said. 

The next stage of research is looking towards gene therapy, which A/Prof Ellaway says is at the core of future research and clinical trials. 

“There has been an increasing number of clinical trials particularly in the last few years, with gene therapy trials on the horizon. We are planning to participate in a gene therapy trial next year and as a result of this clinic, we have a cohort of patients who are trial ready.” 

“Gene therapy has the potential to change the natural history of not just Rett syndrome but may also open up the possibilities for other rare genetic diseases in the future.”

In Australia, around two million Australians live with a rare disease, making them collectively quite common.  

“Lessons learned from one rare disease drives innovative approaches that may be applicable to other rare diseases and sometimes more common diseases,” A/Prof Ellaway said. 

“Understanding causes and developing new interventions will improve the lives of people living with rare diseases, and ultimately identify preventative strategies.” 

Mary is excited by the developments in Rett syndrome research and is optimistic children like her daughter, Abigail, will have a brighter future. 

“I honestly believe there will be cure for Rett syndrome in Abigail’s lifetime and with the support of the community and the work of researchers such as Dr Ellaway and her peers, we are going to find it.” 

The ‘Multidisciplinary Management of Rett Syndrome: Twenty Years’ Experience’ paper was published in Genes last month.