Rett Syndrome

Joseph Lee

4th Period

Rett Syndrome is a disorder which affects the nervous system and is found almost exclusively in girls. One in 10,000-20,000 newborn babies are born with Rett Syndrome, making this disorder very rare. Rett Syndrome is often described as autism, cerebral palsy, Parkinson’s, epilepsy, and various anxiety disorders wrapped into one. In this paper, I will discuss what exactly Rett Syndrome is, who discovered it, how he discovered it, what its causes are, what the symptoms are, the disorder’s course, and possible treatments for the disorder. Said Dr. Rett at a conference regarding the disorder which bears his name:

These three words summarize best our task: To live, to love, and to learn. We are aware of the fact that many mysteries of this syndrome still remain undisclosed, and therefore, for the time being, we have no option but to live with it. However, the children with their very special ways give us enough impulse to share their lives. It is a further mystery of this syndrome that the affected children render it easy for us to love them. A dominating factor in the care of such children is that they understand us and we understand them. Their appearance and the sparkle in their eyes make it easy to love them. Daily care for them and working with them gives us grownups strength, enabling us to learn the special treatment required, thus furthering our own development. To live with them, to love them and to learn from them are the rudimentary principles of our work. (Hunter)

The disorder is named after Austrian pediatrician, Dr. Andreas Rett. One day in 1954, he “observed these children making the same repetitive hand-washing motions. Curious, he compared their clinical and developmental histories and discovered they were very similar” (History, IRSF). Rett continued his study of these, along with six other, curious children by filming their behavior and traveling throughout Europe in attempt to find others with similar symptoms. During his travels, Rett collected information from a total of 31 girls (Hagberg, Anvret, & Wahlström, 1993), and published his findings in 1966 in many German medical journals that were very popular within the region, but hardly popular among the global medical community. Meanwhile, in 1960, Swedish researcher Dr. Bengt Hagberg noticed similar behavior in young female patients. He gathered their files and set them aside for when he had more time to study these bizarre cases. Finally, in 1983, seventeen years after Dr. Rett published his initial findings, Dr. Hagberg published his research in an article in the main-stream journal Annals of Neurology. After this publication, Rett Syndrome was on the map and many investigators began researching the disorder.

Dr. Rett’s work was truly revolutionary. Since he worked in Austria, the National Socialist (Nazi) Party considered mentally retarded children social outcasts and refused them proper treatment or refused to allow the children to be studied to create a more proper treatment. “Dr. Rett’s work began over fifty years ago, after serving as a medic in a German navy hospital. After the war, he studied medicine in Innsbruck and Bonn and in 1948, went to Vienna. Realizing the great need for a children’s clinic, he approached the mayor and other local politicians, who were very difficult to persuade in a community where disabled children were considered social outcasts. His patience was finally rewarded when the 100 bed hospital, Rosenhugel (Rose Hill) opened its doors to patients from all over Europe. It was the first facility of its kind in the world, and he was the only physician in Austria caring for disabled children” (Hunter).

In 1999, scientists at Baylor University in Houston, Texas discovered that when the MeCP2 gene is mutated, it causes Rett Syndrome. The MeCP2 gene is found on the X chromosome. Since females have two X chromosomes, they generally can survive because the second chromosome is unaffected. A male with Rett Syndrome is such a rarity because they generally die in the womb as they have only one X chromosome (Rett Syndrome, NCBI). Although the disorder is genetic, less than one percent of all cases are inherited. The mutation of the MeCP2 gene occurs spontaneously between the ages of six and eighteen months.

The MeCP2 gene controls the making of proteins that promote normal brain development. When a child has Rett Syndrome, her brain is found to be about 30% smaller than a normal brain, although scientists have not found any obvious malformations or gross abnormalities. The MeCP2 protein makes the connections between nerves through which signals move. When the protein behaves normally, it controls other genes and prevents them from making proteins when they are not needed. MeCP2 also controls the making of messenger Ribonucleic Acid (mRNA) which acts as the blueprints for protein making. Girls with Rett Syndrome are found to have more than 200 mutations of the MeCP2 gene including deletions of DNA and a mutation which limits the making of MeCP2 protein, but there are eight specific mutations which are identified as the most common (Genetics Home Reference). Scientists have found that these mutations are the primary cause of Rett Syndrome, though they are unsure of other causes.

Rett Syndrome is characterized by normal development in the first 6-18 months, followed by a deterioration of motor skills, e.g. floppy arms and legs and loss of purposeful hand motions, loss of regular sleep patterns, scoliosis, etc. Because of these characterizations, Rett Syndrome is often misdiagnosed as autism or cerebral palsy which leads to many patients not getting proper treatment until later on. In the past, Rett Syndrome could take months or even years to properly diagnose as new symptoms developed (Testing, IRSF). Today, patients are given a blood test to check for the MeCP2 gene mutation; however, neither a positive nor a negative test confirms the diagnosis of Rett Syndrome. The MeCP2 mutation is also a leading cause of autism, etc. and a patient with normal MeCP2 genes can have what is called atypical Rett Syndrome (Rett Syndrome, NCBI). Ninety five percent of those with Rett Syndrome and fifty percent of those with atypical Rett Syndrome have the MeCP2 mutation (Doctors of USC).

There are many symptoms that range from mild and severe. According to the National Institution for Biotechnology Information, some of the symptoms of Rett Syndrome are Apraxia, breathing problems which tend to get worse with stress (breathing is usually normal during sleep and abnormal while awake because while awake, immature voluntary breathing control neurons are in control. While asleep, the automatic breathing control system prevails and allows for regular breathing patters (FAQ, IRSF)), change in development, excessive saliva and drooling, floppy arms and legs, intellectual disabilities and learning difficulties (assessing cognitive skills in those with Rett Syndrome, however, is difficult because of the speech and hand motion abnormalities), Scoliosis, seizures, slowing head growth beginning at approximately 5 - 6 months of age, loss of normal sleep patterns, loss of purposeful hand movements, loss of social engagement, ongoing, severe constipation and gastro esophageal reflux (GERD), poor circulation that can lead to cold and bluish arms and legs, and severe language development problems.

When a child has Rett Syndrome, the usual course is that general development will begin to slow. Motor skills such as gripping things with your hands and other purposeful movements will begin to be lost. Often a patient’s arms and legs will seem floppy and in a majority of cases, the patient will develop a repetitious hand gesture. The ability to speak, balance oneself, sit, and many other abilities may be lost. According to a pamphlet entitled Rett Syndrome, the severity and even development of any of these symptoms will vary from child to child and symptoms often reverse slightly when the child reaches mid-to-late adolescence, for example, seizures and breathing issues generally recede when the child becomes a teenager (NINDS, 2008). The life expectancy of a RS child is fairly unknown, though most patients live to ages comparable to a non RS child. Most cases of death related to Rett Syndrome are due to seizures, malnutrition, and accidents (NINDS, 2008).

Treatment for Rett Syndrome is really more of an attempt to mitigate the effects of the symptoms of the disorder. The treatment usually involves extensive physical therapy, hydrotherapy, and other types of therapy. Medication may be used to help prevent seizures, correct breathing irregularities, and help with keeping motor skills (NINDS, 2008). Specific methods of treatment include assistance with feeding, treating constipation and GERD, and, for those with scoliosis, weight bearing exercises. One hopeful treatment for Rett Syndrome is stem cell therapy, either alone or in conjunction with gene therapy. Recent studies have shown that the mutated MeCP2 gene which causes RS inhibits the growth of other genes on the affected X chromosome. Through gene and stem cell therapy, doctors would be able to replace the mutated MeCP2 gene with the normal gene. With the mutated genes replaced, the effects of Rett Syndrome be greatly reduced, if not completely cure the disorder.

As shown in the beginning paragraphs, Rett Syndrome is a rather new disorder. Much research is being done. Organizations like the International Rett Syndrome Foundation (IRSF), Rett Syndrome Research Trust (RSRT), National Institutes of Health (NIH), and many other medical institutions are dedicated to Rett Syndrome research and the finding of a cure. The IRSF has regional affiliates like the Southeaster Rett Syndrome Alliance (SRSA) which work with families on the local level, providing them with support. SRSA’s mission is “to develop understanding and awareness of Rett Syndrome; to promote the general welfare of those with Rett Syndrome; to assist in indentifying persons with Rett Syndrome; to support families in coping with the disorder, and conduct activities aimed at prevention, treatment and eradication of Rett Syndrome.” Through organizations like SRSA, the difficult and often daunting task of raising a Rett Syndrome daughter can be just a little easier.

Works Cited

"Rett Syndrome." PubMed Health. National Center for Biotechnology Information, 12 Nov 2010. Web. 16 Mar 2011. .

"Rett Syndrome Fact Sheet." National Institute of Neurological Disorders and Stroke. National Institutes of Health, 16 Feb 2011. Web. 10 Mar 2011. .

"Rett Syndrome History." About Rett Syndrome. International Rett Syndrome Foundation, n.d. Web. 10 Mar 2011.

Hunter, Kathy. "Tribute to Dr. Andreas Rett ." About Rett Syndrome. International Rett Syndrome Foundation, n.d. Web. 10 Mar 2011.

"Testing and Diagnosis." About Rett Syndrome. International Rett Syndrome Foundation, n.d. Web. 13 Mar 2011.

Wood, Debra. "Rett Syndrome." The Doctors of USC. University of Southern California, n.d. Web. 18 Mar 2011. .

Rett syndrome." Pamphlet by: National Institute of Neurological Disorders and Stroke. National Institute of Neurological Disorders and Stroke, 2008. Student Resource Center - Health Module. Web. 18 Mar. 2011.

Hagberg, Bengt, Maria Anvret, and Jan Wahlström.Rett Syndrome -- Clinical & Biological Aspects. 1. 27. Lavenham, England: MacKieth Press, 1993. 4-7. eBook.