About Rett syndrome
Rett syndrome (RTT) which is seen almost exclusively in females, is a genetic disorder in which the brain does not mature in the way it should. For most children, their early development appears normal but then slows down or suddenly halts. This time of their lives can be marked by most, if not all of, the following:non-purposeful repetitive hand movement reduced eye contact night laughter screaming problems with walking loss of communication ability seizures breathing problems (breath holding, fast breathing, and/or air swallowing) electroencephalogram (EEG) irregularities slowing of head growth varying degree of intellectual disability.
As the child grows, most, if not all of, the following, may become apparent:muscle stiffness cold bluish-red feet and legs and/or small feet chewing/swallowing difficulties abnormal sleep patterns teeth grinding constipation spinal curvature growth retardation decreased body fat and muscle mass tip-toe walking decreased mobility.
Apraxia (dyspraxia) i.e., where the brain has difficulty putting in place the automatic planning needed to carry out voluntary movement, is the most fundamental and severely handicapping aspect of RTT.
The degree of disability varies considerably among affected individuals, so much so that two individuals of the same age can present two totally different pictures of the disorder. The syndrome is not one involving continual degeneration of the brain. However, over time, gross motor ability is likely to deteriorate. Generally, the condition is not one in which there is a continuous downward trend but one where times of improvement alternate with periods of impairment and deterioration.
The disorder was first brought to the attention of the medical profession in 1966 by an Austrian doctor, Andreas Rett, but it wasn’t until 1983, following publication of an article by Swedish researcher Bengt Hagberg and others, that females in Australia and elsewhere began to be diagnosed.
Four stages have been suggested by scientists to describe how Rett syndrome presents itself over time.
Stage 1 is referred to as the ‘Early Onset ‘ stage. With a duration of months, the age group to whom it refers is from 6 to 18 months. This stage is usually overlooked as the symptoms of Rett syndrome (RTT) are just emerging and are somewhat vague. The affected infant may show less contact and a reduced interest in toys, and is often described as a “good” baby, being quite calm and placid. There may also be delays in reaching major movement milestones such as crawling or standing.
Stage 2 is called the ‘Rapid Destructive’ stage and can last from weeks to months. Children going through this stage can be as young as 1 year and as old as 4. Loss of purposeful hand use is usually apparent, and if talking, speech may cease. Repetitive hand movements begin to emerge and often include hand to mouth movements such as mid-line hand wringing or hand washing, and persist while the child is awake. Some children appear autistic-like because of their lack of social interaction and communication. Periods of shakiness may be obvious, especially when excited.
Stage 3 is termed the ‘Plateau’ stage. It begins in the pre-school or school years and, for some, most of their lifetime can be spent in this stage.
Apraxia (the brain experiences difficulty putting in place the usually automatic planning needed to perform voluntary movements) , movement problems and seizures, are more prominent. Improvement is seen in behavior with less irritability and crying, and less autistic features. The child shows more interest in surroundings, is more alert, attention span is better, and communication skills improve. Its almost as if the child has worked out how to partially get around the limitations that her body has placed upon her. In this stage, some lost skills might be regained, some may be acquired.
The ‘Late Motor Deterioration’ stage or Stage 4 of the syndrome begins when stage 3 ceases, be it at 5, 15, 25 years or older, and can be present for decades. Although eye gaze usually improves, mobility has reached the point where the individual is unable to walk. There is no further decline in cognition, communication or hand skills. Curvature of the spine is a common feature as is stiffness and dystonia (involuntary muscle spasms leading to body twisting, repetitive movement or abnormal posture). Repetitive hand movements and/or seizures may no longer be as frequent as in the past.
Rett syndrome results from a chain of events which begin with a genetic mutation at the time of conception.
In October 1999, it was discovered by researchers at the Baylor College of Medicine in Houston that mutations in the MECP2 gene are the main cause of Rett syndrome. To date, mutations in this gene have been found in 95% of individuals who have been diagnosed with the disorder. It is not known why these mutations occur.
The MECP2 gene contains instructions which enable genes to function properly. If the MECP2 gene is not functioning properly, it allows genes to turn on or off at inappropriate times, thus disturbing the precisely regulated sequence necessary for proper development of a human’s central nervous system.
Rett syndrome is not an hereditary condition, even though its cause is genetic. In 99% of diagnosed cases, the genetic mutation has been a spontaneous event which meant that it occurred randomly. However, this has not been the situation in 1% of recorded cases as the mutation was inherited or passed from one generation to the next.
Almost every person diagnosed with Rett syndrome is female.
The MECP2 gene, mutations of which are the main cause of Rett syndrome, lies within band Xq28 on the X chromosome. A female born with a MECP2mutation on her X chromosome has another X chromosome with an apparently normal copy of the MECP2 gene. On the other hand, a male with a mutated MECP2 gene on his X chromosome has no other X chromosome, only a Y chromosome, thus he does not have a normal MECP2 gene to fall back on. Male foetuses with an MECP2 mutation are believed to die before birth. However, there are a small number of live males with a genetic change in their MECP2 gene who have developed signs and symptoms like those seen in Rett syndrome, including intellectual disability, seizures, and movement problems, some of whom have been diagnosed with Rett syndrome.
The incidence of Rett syndrome in Australia is 1:9,000 live female births. The disorder is not restricted to any race or ethnic group.
Presently, there is no cure for Rett syndrome.
Treatment focusses on management of symptoms and can include medications for seizures, reflux, breathing problems and mood, and therapies aimed at improving movement and function. The latter include physical and occupational therapy, music therapy, sensory integration, speech therapy, hydrotherapy and horseback riding.
Surgery may be required to remedy curvature of the spine, foot deformities, swallowing difficulties or reflux.
The essential criteria for a medical diagnosis of Rett syndrome were redefined in 2010 and are as follows:
- A period of regression during the first 5 years of life followed by a relatively stable period
- Partial or complete loss of acquired purposeful hand skills
- Partial or complete loss of acquired spoken language
- An impaired ability to coordinate walking or an absence of the ability to walk
- Repetitive non-purposeful hand movements such as wringing/squeezing, clapping/tapping, mouthing, weashing/rubbing.
If all of these symptoms exist or existed, a label of ‘classic‘ or ‘typical‘ Rett syndrome is used.
In addition to all or some of the above, other symptoms that may be present or may have been experienced, can include:
- Breathing disturbances while awake
- Inappropriate laughing and/or screaming spells
- Teeth grinding
- Diminished response to pain
- Disturbed sleep pattern
- Intense eye contact, use of the eyes to communicate
- Abnormal muscle tone
- Small cold hands and feet
- Curvature of the spine or neck.
The presence of these additional symptoms support a diagnosis of Rett syndrome.
Where an individual has or had an early period of regression and at least two but not all of the above essential criteria, a label of ‘classic‘ or ‘typical‘ Rett syndrome does not apply. However, if this individual has or had at least five of the additional symptoms, a label of ‘variant‘ or ‘atypical‘ Rett syndrome is used.
A diagnosis of ‘typical’ or ‘classic’ Rett syndrome cannot be given if one or more of the following apply:
- Brain injury subsequent to trauma around or soon after birth;
- A neurometabolic disease;
- A severe infection that caused problems of the nervous system;
- The child’s attainment over time of skills that involve both mental and muscular activity, such as the ability to roll over, sit, crawl, walk, talk, is grossly abnormal (grossly abnormal to the point that normal milestones such as acquiring head control, swallowing, or developing a social smile are not reached within the first 6 months of life).
Please note that a genetic test which reveals a mutation in the MECP2 gene, confirms the diagnosis already determined or suspected by a medical or other health professional.
The outlook for Rett syndrome individuals is not all doom and gloom. Even though the condition is such that most will need lots of help to get through each day, some independent skills associated with eating, drinking, toileting and/or dressing, can be learnt. Communication is particularly important as there is strong desire on their part to interact with those around them, despite their lack of expressive language and impaired hand use. This desire is evident by their eye gaze, facial expressions, and/or body gestures.
Females with Rett syndrome have greater receptive language (i.e., what they hear and understand) than expressive language (speech). It is important for them that the activity and/or content of a conversation involves something that they find very stimulating. Communication methods vary considerably among the Rett syndrome population. Methods can include one or more of the following, eye pointing and blinking, use of yes/no, flash cards, pictures, switches, facilitation, communication boards, head pointers, voice output devices, computers (with touch windows, Intellikeys keyboard, switch activated mouse or eye gaze technology such as Tobii), and more recently, the Ipad. Abilities can also be influenced by such things as the extent of hand use, degree of mobility and/or stiffness, state of posture, level of intelligence and the listener’s appreciation of communication techniques to use, to name just a few.
Despite their difficulties, persons with Rett syndrome can continue to learn and enjoy family and friends, well into middle age and beyond. Survival data for the disorder has to be treated with caution as statistics on those affected by the condition and the number who die, do not include all such cases from around the world. The Australian Rett Syndrome Study has reported that 98% of Australian Rett syndrome girls born from 1976 onwards, would still be alive at 10 years of age and 75% at 25 years. Life expectancy data concerning an American Rett syndrome population was presented at the 7th World Congress on Rett Syndrome in New Orleans in June 2012 and stated that the odds of living for 10 years was the same as that of the general population of the United States living for 10 years. As for longer terms of survival, it was calculated that 90% of their Rett syndrome population would still be alive at age 20, 75% at age 30, 65% at age 40, and 50% at age 50 years.
Dr Andreas Rett, after whom Rett syndrome is named, was born in Nurnberg, Bavaria, in 1924. By the age of 15, he chose to develop his interest in medicine and, although his plans were interrupted by the Second World War, he did serve as a medic in a German naval hospital during that period.
Immediately following the war, he resumed his medical studies at the University of Innsbruck and gained his doctorate in medicine in 1949. He moved to Vienna the following year where he started medical school. He married fellow physician Jutta in 1952, qualifying as a paediatric specialist in 1955. They had two daughters, Barbara and Andrea.
It quickly became apparent to Dr Rett that there was an urgent need for a handicapped children’s clinic in Vienna and he immediately set about lobbying the local mayor and other politicians to have one established. After many difficulties, including being constantly reminded that he was wasting his time with such children, a 100 bed clinic was opened.
In his early years as a physician, he worked 16 hours a day and cared for every single child with an intellectual disability living in Vienna. At the time, there was no one else who would care for them. He almost lost his practice a couple of times because he refused to stop caring for them. Then came that day in 1960 which would eventually lead to international recognition of the syndrome which was to bear his name. He happened to notice two young girls sitting on their mothers laps in his clinic waiting room, both wringing their hands in the same way. He examined them one after the other, and found they had the same striking developmental histories – early normal development followed by regression, loss of purposeful hand use and compulsive hand movements that were constant. He found 4 other such girls in his practice, made a film of them and took it all over Europe trying to convince people that this must be a syndrome. He also published in obscure German journals which did not reach the attention of a wide scientific community.
At the same time, and unknown to Dr Rett, Dr Bengt Hagberg, from Sweden, had made the same “discovery” in several of his patients. Dr Hagberg discounted Rett’s earlier publications because the Swedish patients did not have elevated blood ammonia as Dr Rett’s patients did (this later turned out to be a mechanical error with the calibrating equipment used by Dr Rett).
The two met at a paediatric meeting in Toronto when Hagberg was at the lecturn talking about his new finding. Rett was in the audience and when he heard Dr Hagberg describe the syndrome, he jumped up from his seat and ran down the aisle to the stage, declaring “Ich Bin Rett “(I am Rett) over and over, delighted and excited to find the connection. He interrupted the meeting, the two men went offstage and discussed the matter. Dr Hagberg returned to the lecturn with the knowledge that the elevated blood ammonia was not correct and they were indeed, talking about the same disorder. In a rare and generous act, Dr Hagberg named the disorder Rett syndrome, changing the title of his ready-to-be published article.
Dr Rett called the Rett girls “his girls”. He longed for the discovery of the cause and worked tirelessly on their behalf. Andreas Rett died on 25 April 1997, two years before the discovery of mutations in the MECP2 gene as the main cause of Rett syndrome. He would have been so elated at this finding.
Most of the above information was originally compiled by Kathy Hunter, Founder and President of the former International Rett Syndrome Association and author of ‘The Rett Syndrome Handbook’.
History of Rett syndrome in Australia from 1983 to the present, follows –
1983 to 1989
Rett syndrome begins to be diagnosed in Australia in late 1983. Four years later, the first organised get-together of Rett families to be held in this country, takes place in Perth.
In 1989, RSAA publishes its brochure marking the first occasion that the words ‘Rett syndrome’ and ‘Australia’ appear together in print.
1990 to 1999
Two Rett syndrome research centres are established, one in Perth and the other in Sydney. Australian researchers and parents travel overseas to attend conferences on the syndrome.
The Rett Syndrome Australian Research Fund is formed and is based in New South Wales.
2000 to 2009
At the Baylor College of Medicine (Texas) in late 1999, it is discovered that mutations in the MECP2 gene are the main cause of Rett syndrome. The following year, screening of blood samples from persons diagnosed with the syndrome for MECP2 gene mutations, commence in Australia.
In 2001, scientists in Scotland and the United States reproduce Rett syndrome in mice.
Two international Rett syndrome internet databases are established, one in Perth and the other in Sydney, the funding for which is provided by the former International Rett Syndrome Association and its successor, the International Rett Syndrome Foundation.
Two Rett syndrome multidisciplinary management clinics are created, one in Melbourne and the other in Sydney.
|Blood samples from individuals suspected of or medically diagnosed as having Rett syndrome, begin to be screened for mutations in the MECP2 gene;|
Brett Aitken, father of Ashli who had Rett syndrome, wins a cycling gold medal at the Sydney Olympics and immediately sets about drawing public attention to the condition;
Gudrun Bachler, Chairperson of the Parents’ Support Group in Germany, meets families in Melbourne and rural Victoria;
Australian representation in Nagano for the 5th World Congress on Rett Syndrome;
Rett syndrome multi-disciplinary management clinics are established in Melbourne and Sydney.
|Brett Aitken completes a 585 kilometre bike ride from Adelaide to Broken Hill to fundraise and foster awareness.|
|Australian researchers are funded by the International Rett Syndrome Association (USA) to build and then maintain two databases, namely, InterRett (data on Rett syndrome children and adults worldwide) and RettBase (a register of MECP2 gene mutations).|
|Hungarian Rett syndrome father, Andor Kantas, and his co-pilot Csongor Latki, fly into Sydney in their single engine plane having just completed a 10 week 20,000 kilometre flight from Hungary to raise international awareness and funding for local research.|
At left: Andor Kantas (at right) a few days after landing in Sydney, is met at the Avalon International Show by RSAA President Bill Callaghan. Andor’s plane ‘Lucia’ emblazoned with the words ‘Fly4Rett’ on its fuselage, was an exhibit at the Show
|ANZACRett is created on the internet to assist parents in Australia and New Zealand; to communicate with one another.|
Discovery by the NSW Centre for Rett Syndrome that mutations in the CDKL5 gene cause a Rett syndrome-like condition.
|Rett syndrome information sessions are conducted at The Children’s Hospital at Westmead over two days for parents and others.|
|Hanne Blom-Bakke from the Norwegian Rett Syndrome Association, visits RSAA in Melbourne.|
|A two day talkfest ‘Let’s Talk Rett Syndrome’ takes place in Sydney, guest panelist for which is Kathy Hunter, Founder and President of the former International Rett Syndrome Association and author of ‘The Rett Syndrome Handbook’.|
|The Circle of Silent Angels Foundation is formed in Queensland;|
Australian representation in Paris for the 6th World Congress on Rett Syndrome;
Australian representation at Rett New Zealand’s conference in Wellington.
At left: Among the attendees at Rett New Zealand’s conference in Wellington were (from left to right): John Forman ((NZ Organisation for Rare Diseases), Rob Pakes and Gillian Deane (Rett NZ), John Christodoulou (NSW Centre for Rett Syndrome Research), Kathy Hunter (Founder and President of the former International Rett Syndrome Association, USA), Mark Campbell and Doug Laing (Rett NZ), and Bill Callaghan (RSAA)
|A group of kayakers paddle their way from Port Welshpool in Victoria to the north eastern tip of Tasmania to raise awareness and funds for research;|
Mari Kondo, a researcher from the Howard Florey Institute (now called the Florey Neuroscience Institutes) in Melbourne, publishes findings from her study on the benefits of environmental stimulation in Rett syndrome.
2010 to the present
A two day conference for Australian families takes place in Brisbane;
The work of the Rett Syndrome Australian Research Fund comes to an official end in 2011 after having donated $1.8 million to research and, from 2004 to 2009, financially supporting the Rett syndrome clinic at The Children’s Hospital, Westmead;
The Australian Rett Syndrome Study celebrates its 20th anniversary.
|A third Rett Syndrome multidisciplinary management clinic is established, this time in Brisbane;|
Australian representation at Rett New Zealand’s conference in Auckland;
The booklet ‘It Takes Two Girls’ is released by Heather Jennings and Jodie Brodie, both of whom live in Brisbane and have daughters with Rett syndrome.
|The Rett Syndrome Australian Research Fund ceases to be having donated $1.8 million to Australian research;|
Athel Hockey, a geneticist with the Disability Services Commission of Western Australia, dies. In 1987, she organised the first gathering of Rett syndrome families to be held in Australia and maintained her support for them and RSAA from then on.
|A 2 day Rett syndrome family conference is held in Brisbane;|
RSAA President, Bill Callaghan, is awarded an Order of Australia Medal;
Australian representation in New Orleans for the 7th World Congress on Rett Syndrome.
|Australian representation in Maastricht for the 3rd European Rett Syndrome Conference;|
The Australian Rett Syndrome Study celebrates its 20th anniversary.
|The ‘Beyond Respite Family Forum’ for Rett syndrome families in Queensland who are participating in the|
‘Respite Plus Initiative’ takes place at Maroochydore;
RSAA representation at Rett New Zealand’s bi-annual conference in Auckland;
RSAA Committee for 2014/15 consists of members who live in New South Wales, Queensland, South
|RSAA’s first national conference ‘The Rett Syndrome Journey: Pathways to Follow’ takes place in Geelong;|
Visit of Pam Mayo-Roman, Founder and Head of ‘Rett Syndrome Philippines’;
‘Service to Rett syndrome’ awards are presented by the Association to Kathy Hunter (USA), Janelle Lillis (New South Wales), Peter Werchon and Bill Callaghan (both Victoria).
|Australian representation at Rett syndrome conferences in Kazan (World Congress), Auckland and Vienna.|
Susan Norwell (USA), a specialist on communication and Rett syndrome, conducted 2 all day forums in Brisbane in May 2016. One was for families and the other, for professionals. Copies of these presentations can be obtained directly from Equity Works via the following link
‘Our Lives with Rett syndrome’
A 35 minute video which was produced in 2014, begins with Dr Helen Leonard, Principal Researcher for the Australian Rett Syndrome Study, briefly describing the current work of her team. The remaining 30 minutes of this presentation sees parents and siblings talking openly about their lives with Rett syndrome.
The video is a professional production, its content both relevant and informative, and is a valuable resource on the syndrome, particularly for a family whose young child receives a diagnosis. It can be viewed by clicking on the following link http://vimeo.com/110741678
Furthering one’s knowledge of Rett syndrome
World Congress on Rett Syndrome – June 2012 – New Orleans, USA
In June 2012, the 7th World Congress on Rett Syndrome was held in New Orleans. Organised by the International Rett Syndrome Foundation, topics referred to in a report prepared by RSAA’s representative at the Congress, include eye gaze technology, communication, therapies, health issues, education and research. Please click on World Congress on Rett Syndrome June 2012 to view the report.
European Conference on Rett Syndrome – October 2013 – Maastricht, the Netherlands
In October 2013, the 3rd European Conference on Rett Syndrome took place in Maastricht, the theme of which was “Research Update and Preventive Management”. It was the first occasion that the RSAA had been represented at a conference organised for the European Rett syndrome community. Topics referred to in a report prepared by RSAA’s representative in Maastricht include communication, research, aging, therapies, curvature of the spine and dental care. Please click on European Rett Syndrome Conference – Oct 2013 to view that report.
Rett New Zealand’s bi-annual conference, Auckland 16-18 May 2014 – A summary
Topics include communication, education, orthopaedics and research. The report has been prepared by Phil Creswell who represented RSAA at the conference. Please click the following link to view 2014 RettNZ Conference Report
RSAA President recipient of an Order of Australia medal (2012)
Bill Callaghan, who has been President of RSAA since its formation in 1989, was awarded the Medal of the Order of Australia in the Honours announced by the Commonwealth Government of Australia on the Queen’s Birthday in June 2012. Bill’s daughter, Joanne, was diagnosed with Rett syndrome in 1986. She died in 2004, 11 days before her 33rd birthday. Please click here for further information on Bill’s award
Emily Osborne is awarded Northern Territory Young Australian of the Year (2014)
Northern Territory (NT) Young Australian of the Year 2014, was 19 year old Nhulunbuy resident, Emily Osborne, for her work as a youth advocate.
A passionate advocate for young carers, Emily Osborne understands the responsibilities that rest on the shoulders of young carers. She looks after her older sister Kaia, who suffers from Rett syndrome. Emily said that Kaia has taught her to cherish every moment, and had motivated her to be the best person she can be. Additional information on Emily’s award can be obtained by clicking on the following link
Insulin-Like Growth Factor 1 (IGF-1) – A potential treatment in Rett syndrome?
Research conducted at the Massachusetts Institute of Technology saw Rett syndrome mice being treated with an active peptide fragment of Insulin-Like Growth Factor 1 (IGF-1). As a result, they were found to live longer, move better, and both their heart rates and breathing patterns,mproved. A study into the treatment of Rett syndrome individuals with IGF-1 is being conducted the Children’s Hospital, Boston.
Phase 1 of a trial with IGF-1 directly involving individuals with Rett syndrome, began at the Children’s Hospital, Boston (USA), in December 2010, and basically just looked at dosage and side effects.
An update on the trial was provided in September 2012 by Dr Steven Kaminsky, Chief Scientific Officer of the International Rett Syndrome Foundation. He advised that “The initial trial was a four week phase 1 study of safety and tolerability of IGF-1 in Rett syndrome. This initial phase 1 trial was followed by a 20 week open label (i.e., everyone received IGF-1) extension of the study. During this period, the patients were monitored for safety and potential long term side-effects of IGF-1. New technologies which may be useful to demonstrate efficacy of the drug during the phase 2 trial, were also tried.
After analyzing data from phase 1 and the open label extension, the Boston team decided to narrow the inclusion criteria for phase 2. The upper age limit was reduced to 10 years, while the lower age limit was increased to 5 years. A press release at that time by the International Rett Syndrome Foundation advised that “the phase 1 trial has deemed that IGF-1 is safe and well tolerated in girls diagnosed with Rett syndrome, and the data also suggests that certain breathing and behavioral symptoms associated with Rett syndrome were ameliorated after IGF-1 treatment.”http://localhost/rettaustralia/2012/09/insulin-like-growth-factor-1-igf-1-a-potential-treatment-in-rett-syndrome/
Phase 2 is a double-blinded trial, meaning that neither the families nor the researchers know which participants are receiving IGF-1. The cross-over design of the trial means that each subject received 20 weeks of either a placebo or IGF-1 and then, after a 6-week washout period, participants received another 20 weeks of treatment but taking the drug they did not take on the first occasion. In other words, all girls enrolled in phase 2 received 20 weeks of treatment with IGF-1. The most recent announcement about Phase 2 was made in May 2014 by the Boston Children’s Hospital, a copy of which can be viewed by clicking on the following file
This announcement was sourced from the website of Rettsyndrome.org (the International Rett Syndrome Foundation). In March 2017, a check of the Boston Children’s Hospital website by RSAA, could not find any new information about the IGF-1 trial.