October is Rett Syndrome Awareness Month, a time to foster understanding about this complex neurological disorder that impacts mostly females — one in 10,000 births globally. Rett syndrome affects multiple organ systems and can lead to severe impairments that disrupt key aspects of an individual’s life. “This condition is rare, but it places a heavy burden on families,” says Dr. Anita Datta, a pediatric neurologist, epileptologist, and investigator at BC Children's Hospital Research Institute (BCCHR). “Currently, there are many developments underway around the world focused on improving these patients’ quality of life, so this is a time of hope.”
With no cure, this syndrome results from mutations in the MECP2 gene, located on the X chromosome. This gene is crucial for brain development and activity, helping control how brain cells function and communicate. When it doesn’t work properly, MECP2 disrupts brain signaling, impacting control over important functions such as the ability to speak. In the Rett Syndrome Clinic located in the Neurological Care Centre at BC Children’s Hospital (BCCH), Dr. Datta, Dr. Gabriela Ana Horvath, and colleagues look after approximately 50 patients from across the province.
Most children diagnosed with Rett syndrome appear to be healthy at birth. However, as the months go by, the first signs start being noticed. There are core features associated with this condition, but there’s also a huge amount of variability and change over time. “Like with most neurodevelopmental conditions, parents typically will be the first ones to notice that something is different with their children,” says Dr. Datta, who is also a clinical associate professor in the Department of Pediatrics at the University of British Columbia. In that phase, patients may present low muscle tone, start saying a few words and lose their speech later on, and display unique movements such as hand wringing.
When parents or physicians notice something that concerns them, a referral is usually made to a pediatric neurologist or geneticist. “If the signs point to Rett syndrome, genetic testing is key to confirm the diagnosis,” says Dr. Datta. After the screening, it’s determined whether the patient needs to be referred to additional specialists. The average diagnosis happens between two and three years old.
Once diagnosed, patients go through different phases. Early on, the first signs of Rett syndrome point to a developmental delay. During regression, a second phase, caregivers notice a rapid deterioration in the patient’s health when they may lose skills they had already gained. In the plateau phase, where many patients spend most of their lives, seizures can be common, but the overall symptoms are relatively stable. Patients whose condition continues to advance could experience outcomes such as scoliosis and immobility, as part of a later phase. “We also may meet a young child who is not able to walk and an adult who is,” says Dr. Datta. “This is how extreme the variability can be between patients’ experiences.”
Nowadays, a diagnosis will have been made by the time patients start losing important functions, such as hand movement and speech, so they will be supported accordingly. Rett clinics and specialized programs are available in major hospitals in most provinces, and are essential to provide families with the necessary services. “The primary care will come from the pediatrician but, because this condition affects multiple organ systems, the clinic will make sure the patients are seeing the specialists they need,” says Dr. Datta.
The support required for patients diagnosed with Rett syndrome typically includes orthopedics to care for potential spine or hip problems, cardiology due to the risk of irregular heart rate, sleep medicine for disrupted sleep, gastroenterology to monitor reflux or severe constipation, and neurology to help manage seizures. Patients may also need support from additional areas such as physiotherapy, occupational therapy, and speech language pathology.
“Sometimes, for families, little changes make a big difference, so we’ll see patients more or less frequently, depending on their stability, and provide guidance,” says Dr. Datta.
Ideally, children diagnosed with Rett syndrome will be assisted by their health-care team and family support groups, such as the Rett Syndrome Society of British Columbia (RSSBC). In addition to raising awareness about the syndrome, they advocate for patients and help fund research aimed at finding a cure. “RSSBC is a strong support group, and different provinces will have others,” says Dr. Datta, noting that patients are immediately connected with a support group once the diagnosis is confirmed. “As these kids need a lot of care to accomplish their daily activities, the support groups can help with information, tips, and strategies.”
There’s no single treatment that can be prescribed to manage all symptoms related to Rett syndrome, but there have been important developments. Canada’s Drug Agency has recently approved trofinetide, a new medication specifically developed for Rett syndrome, but it’s not yet funded in Canada. “Studies show that, compared to placebo, this drug can improve functions such as communication and alertness,” says Dr. Datta. In addition, gene therapy trials are happening and have shown promising preliminary results related to various aspects of Rett syndrome, including improvements with mobility and communication, that are beyond the normal trajectory of the disorder. “It’s still very early, so there are still many questions to be answered, but it gives us hope.”
Dr. Datta has helped lead initiatives such as recent meetings with the Medical Allied Staff Engagement Society, formed by members and leaders of the Medical Staff Association of BC Children’s and Women’s Hospital. The initiative consists of educating staff about Rett syndrome and discussing ways to improve care to make a tangible difference.
“We’re also engaging health-care professionals who work in the community looking after patients and any experts we believe can help us advance care to these patients,” she says.
The treatment consists essentially of managing symptoms as they arise. Dr. Datta has also been involved with the Canadian Rett Syndrome Consortium, a national group that helps answer questions from physicians specialized in Rett syndrome. “It’s important for families to know that researchers are doing everything we can to find effective treatments and drugs not only to manage symptoms, but also improve our patients’ overall quality of life,” she says.
