Rett syndrome is a highly complex disorder with a wide variety of symptoms and symptom severity. Always consult your physician to discuss specific medical concerns and questions pertaining to your child.
Rett Syndrome (RTT) is a rare neurodevelopmental disorder which is seen almost exclusively in females and more rarely in males. It is estimated to occur in 1 in 10,000 female births across all racial and ethnic groups. It is caused by an abnormality in the MECP2 gene, which is found on the X chromosome. Children with Rett syndrome experience regression or loss of previously acquired skills during infancy, often noticed at 6 to 18 months in age. They often lose their ability to walk and communicate and may experience breathing difficulties, cardiac issues, swallowing and digestion abnormalities, scoliosis and seizures. There is no approved treatment yet, though several potential treatments are in clinical trials.
Rett syndrome is most often misdiagnosed as autism, cerebral palsy, or non-specific developmental delay. While many health professionals may not be familiar with RTT, it is a relatively frequent cause of delayed development in girls. There is a simple blood test to confirm the presence of the MECP2 mutation, although that alone does not ensure an RTT diagnosis.
Rett syndrome is not a degenerative disorder, but rather is a neurodevelopmental disorder. Barring illness or complications, survival into adulthood is expected.
A blood test can confirm the presence of the MECP2 mutation; however, since MECP2 mutation is also seen in other disorders, the presence of the mutation itself is not enough for the diagnosis of Rett syndrome. It also requires a clinical diagnosis based on observed signs and symptoms.
In making the clinical diagnosis, specialists rely on an RTT Diagnostic Criteria Worksheet to assess early growth and development, evaluate medical history and physical and neurological status. Your child may be classified as Classic RTT, Atypical RTT or Male RTT.
In very rare cases, males are diagnosed with Rett syndrome. Most have very early onset of symptoms, with significant problems beginning at or shortly after birth. Aggressive medical intervention is needed for these patients. The diagnosis of Rett syndrome is based on clinical criteria (the abnormal MECP2 gene) and the clinical symptoms. Patients who have the abnormal gene but do not meet the clinical criteria for Rett syndrome are said to have “MECP2-related disorders”.
Many males diagnosed with Rett syndrome also have an unrelated genetic disorder known as Klinefelter syndrome Klinefelter syndrome is relatively common, appearing in roughly 1 in 500 males causing underdevelopment of the genitalia and underproduction of sex hormones. For more information on males and Rett syndrome, click HERE
Your child’s specific MECP2 mutation can be determined by a simple blood test. More than 200 different mutations in MECP2 that cause RTT have been identified. Yet, eight specific mutations are the most common and account for more than half of all individuals with RTT.
Click here for a list of labs that can do the MECP2 sequencing + deletion analysis if ordered by your physician.
No. Much more data needs to be collected by researchers in order for us to make predictions on the likelihood of developing certain symptoms based on mutation type. International Rett Syndrome Foundation actively supports an international database that collects, analyzes and shares this data with clinicians and researchers.
Stage I – Early Onset Stage
- Age: 6 months to 1.5 years
- Duration: Months
Stage II – Rapid Destructive Stage
- Age: 1 to 4 years
- Duration: Weeks to Months
Stage III – Plateau Stage
- Age: Preschool to adulthood
- Duration: Decades
Stage IV – Late Motor Deterioration Stage
- Age: When ambulation is lost (those who never ambulate move from Stage II to IV)
- Duration: Up to decades
No. The stages of Rett syndrome are guidelines provided to help understand the natural history of the disorder. The course and severity of RTT varies from one child to another.
Atypical Rett syndrome is diagnosed when a child has some of the symptoms of Rett syndrome but does not meet all the diagnostic criteria. Atypical Rett syndrome mostly affects girls and the symptoms can be either milder or more severe than those seen in Rett syndrome. Diagnostic criteria for typical and atypical RTT can be found HERE
Those with atypical Rett syndrome who do not have a [email protected] mutation may need to be evaluated for:
- CDKL5 Deficiency Disorder
CDKL5 deficiency disorder is caused by mutations in the CDKL5 gene which can cause an atypical form of Rett syndrome in some patients. CDKL5 deficiency disorder has been identified in males but primarily affects females. Patients generally experience early-onset, intractable epilepsy and neurodevelopmental delay that impacts cognitive, motor, speech and visual function. Although rare, it is one of the most common forms of genetic epilepsy. For more information, visit http://www.cdkl5.com/.
- FOXG1 Syndrome
FOXG1 Syndrome is caused by a mutation of the FOXG1 gene, which impacts brain development and function. It is characterized by seizures, inability to control body movements, and lack of speech. FOXG1 mutations can appear as atypical Rett syndrome in some patients. For more information, visit http://foxg1.com/.
- WDR45 mutations
Abnormalities in another gene on the X-chromosome known as WDR45 are associated with BPAN syndrome. WDR45 mutations have been found in a few girls who have a clinical diagnosis of Rett syndrome but test negative for a MECP2 mutation. For more information about this gene and screening for it click HERE.
Just as in any other disorder, the level of disability ranges from mild to severe. It is difficult to predict the intensity of symptoms in any individual child. Many children begin walking within the normal range, while others show significant delay or inability to walk independently. Some begin walking and lose this skill, while others continue to walk throughout life. Still others do not walk until late childhood or adolescence. The same range holds true for using their hands and other skills they may acquire.
The clinical features of a particular trait or disorder make up an individual’s phenotype. The gene for a given trait or disorder leads to the person’s genotype. By comparing the two, we are able to correlate the clinical features with a given mutation. In Rett syndrome, this may allow us in the future to make certain predictions on the likelihood of developing specific features such as scoliosis or epilepsy, but much data must still be collected before we can make these predictions.
One way to grow this the body of knowledge is to contribute to InterRett InterRett is the first-ever project collecting data on a global basis about Rett syndrome. Funded by the International Rett Syndrome Foundation, this international online database examines the clinical features and genetic characteristics of Rett syndrome.
This project collects information about the features of Rett syndrome from parents and clinicians. These details are then collated to form an online searchable database.
You will be sent details about entering your information online.
RTT results from a chain of events beginning with the MECP2 genetic mutation. This abnormality causes a shortage or absence of MeCP2 protein which is critical to developing and controlling regions of the brain responsible for sensory, emotional, motor and autonomic function (involuntary or unconscious actions, such as breathing and digesting). This development occurs rapidly during infancy and appears to be normal until the MeCP2 protein is needed. Without enough of the protein, regions of the brain do not develop properly. So, it is not until after the first few months of life that the effects of the lack of MeCPS protein become evident.
The chance of having more than one child with RTT is very small, much less than one percent. This means that more than 99.5% of the time, the mutation is sporadic, occurs only with this conception and is not repeated in a family. Both parents can be tested for mutations before deciding to have other children. To discuss your family’s situation, you should consult a skilled genetic counselor.
If a mother has a germline MECP2 mutation (no symptoms, just a positive blood test), then her daughters who do not have RTT may wish to be tested when they reach reproductive age to see if they might be asymptomatic or silent carriers. Prenatal testing of any babies conceived in a family where RTT has already occurred is also available. These options all need to be explored individually through a skilled genetic counselor.
Every child with RTT is unique and every family’s experience is equally unique. Often a child with RTT is diagnosed after they begin to lose communication skills and purposeful use of their hands. Soon after, stereotyped hand movements and gait disturbances begin. You may notice abnormal breathing patterns such as breath holding, and seizures may begin. Your child may have periods of isolation or withdrawal where they are irritable and cry inconsolably. Over time, motor skill problems may increase, which means your child will need assistance with most aspects of daily living and care. However, interaction and communication, breathing and seizures may very well improve over time.
Daily living and care include: feeding, bathing, dressing, and toilet assistance. Parents may need to lift and carry their child, or help them walk, and reposition them often for comfort. You and your child may need to learn to use a communication device. With support, you will learn how to find the right professionals, schedule appointments and therapies, search for the right schools or programs, and find special equipment. We encourage you to reach out to us and connect to other parents who are in this journey with you.
The level of disability with RTT ranges from mild to severe and it is difficult to predict the intensity of symptoms in any individual child. For example, many children are able to walk while others show significant delay or inability to walk. Some may not walk until late childhood or adolescence. The same holds true for using their hands and other skills they may acquire.
The most severely handicapping aspect of RTT is impaired motor function, which can interfere with all movement, including eye gaze and speech, making it difficult for the individual with RTT to do what they want to do.
Although children with RTT will need help for most activities of daily living, they can learn some independent skills. They can learn to feed themselves and use the toilet with some assistance. They can learn to use augmentative devices to communicate and can continue to learn and enjoy family and friends well into middle age and beyond. They express a full range of emotions and show their engaging personalities as they take part in social, educational and recreational activities at home and in the community.
Hyperventilation is breathing at a faster than normal rate. This type of fast or deep breathing expels more carbon dioxide from the body than usual, causing the carbon dioxide level to fall and making cells unable to function normally. Your child may feel dizzy and have tingling fingers when they hyperventilate.
Although episodes of breath holding produce great anxiety for parents, they are always followed by regular breathing. Observing the irregular breathing can cause great concern, it is important to stay calm. Experts in RTT recommend a low-key approach, taking comfort in the fact that regular breathing will soon return.
Episodes of apnea, hyperventilation and disordered breathing are found in approximately 70 percent of patients with Rett syndrome at some stage of their life. For the majority of individuals, irregular breathing patterns become less noticeable as they get older. Abnormal breathing episodes can resemble epileptic seizures, but they are not. Although alarming to watch, abnormal breathing episodes are not believed to cause permanent damage.
In Rett syndrome, irregular breathing occurs only when they are awake and does not usually occur during sleep. When they are awake, the periods of abnormal breathing result from probable immaturity of the neurons that regulate voluntary breathing mechanisms. During periods of sleep, involuntary breathing systems take over, allowing them to breathe regularly and continuously. When abnormal breathing is seen with RTT during sleep, it is of the obstructive type, usually from enlarged adenoid/tonsils. Airway obstruction may be caused by mechanical problems in the breathing passages. Mouth breathing, snoring and frequent ear infections may be signals that your child has a problem which should be evaluated by an ear, nose, and throat specialist.
If your child’s upper abdomen is distended shortly after they eat it could be that they are swallowing air during feedings. If the child is unable to burp or pass gas, the bowel wall may become thin over time. This is especially true in individuals who have a poor nutritional status.
If you suspect that they are swallowing air, you can:
- Decrease the length of mealtimes
- Sit them upright position after eating to help them burp
- Prevent and treat constipation so that gas does not accumulate in the mid intestine.
If these measures are not adequate and the abdominal distention is severe, consult your physician. Early detection and consultation with a gastroenterologist are extremely important to avoid progression of the problem and to manage it as early as possible, thus preventing more severe complications.
By age 5, your child should have an ECG performed. If normal, it should be repeated every other year. If abnormal, a cardiologist expert in electrical function of heart should be consulted. Nonspecific ECG changes probably do not warrant medications, but prolonged QT syndrome may require attention.
Due to the rarity of RTT, very little has been published about life expectancy. Data from the Natural History Study have determined that a girl with RTT has a 100% chance of reaching age 10, a 90% chance of reaching age 20, a greater than 75% chance of reaching age 30, a greater than 65% chance of reaching age 40, and a greater than 50% chance of reaching age 50. As improved nutrition and overall care are provided, these probabilities are expected to improve.
The most frequently reported causes of death (one-quarter of deaths) are variations of sudden, unexplained death, most suspected due to cardiorespiratory compromise. The factors most strongly associated with an increased risk of sudden unexplained death in RTT are uncontrolled seizures, swallowing difficulties, and lack of mobility. Swallowing difficulties or poor esophageal motility are suspected to increase the risk for aspiration pneumonia. The increased risk of death by pneumonia are compromised lung function due to scoliosis. Overall severity, seizures frequency and severity, immobility, and reduced weight are all risk factors.
Although they may be at higher risk for life-threatening events, it is very likely that your child will live a long life. However, when that time inevitably comes, researchers and International Rett Syndrome Foundation are ready to listen, to learn, and to share. You can participate in research studies that will help us further understand RTT. Consider making the precious gift of brain and other tissue donation to the Harvard Brain Resource Center Rett syndrome tissue bank.
While Rett syndrome may not be well known among the general public, know that it is in the forefront of research happening across the globe. International Rett Syndrome Foundation is building a better understanding of RTT and its potential treatments through the Natural History Study. We are implementing a research model that is focused on exploring the development of drugs that can treat RTT and developing speech, physical and neurological therapies to help reset the neurological development in Rett syndrome. Our research model also focuses on the critical early work needed to lay the foundation for gene therapies. For more research information, click here.
No. The incidence of RTT in the African-American and Hispanic population in the United States is comparable to that in Caucasian Americans.
Some children with MECP2 gene mutations may exhibit features typically seen in autism. While RTT occurs primarily in girls, autism occurs much more frequently in boys. RTT symptoms include reduced rate of head growth, loss of purposeful hand skills, loss of mobility and irregular breathing patterns which are not seen in autism. The child with RTT almost always prefers people to objects and enjoys affection, but the opposite is seen in autism. Children with RTT often have autistic-like features at an early age, but these disappear as they grow.
MECP2 duplication syndrome is a condition that occurs more in males than females, and it is characterized by moderate to severe intellectual disability. Those affected often have weak muscle tone in infancy, feeding difficulties, poor or absent speech, seizures, muscle stiffness (spasticity), delayed development of motor skills and recurrent respiratory infections. These respiratory infections are a major cause of death in affected individuals.
Contact International Rett Syndrome Foundation at 1 800 818 RETT or visit www.rettsyndrome.org. We can connect you with many types of informational resources: online, print, video, audio, as well as connect you with others in your local area.