What is Rett Syndrome?

Rett Syndrome is a postnatal neurological disorder, almost exclusively occurring in girls. The condition is genetic, but Rett Syndrome is rarely inherited. The Rett Syndrome disorder itself is rare (about 1 in 10,000 births results in Rett Syndrome), but the consequences are dire. Children and adults with Rett Syndrome experience challenges in almost all aspects of life – purposeful hand utilization, the ability to breathe, eat, walk, and speak are all affected.

The most telling sign of Rett Syndrome is the near-constant movement of the hands during waking hours, especially in repetitive motions. Rett Syndrome principally affects all aspects of motor control, but cognitive function of children and adults with the disorder is believed to be largely in-tact, notwithstanding the challenges inherent in non-verbal communication. Children with Rett Syndrome can express a wide range of emotions and moods, and have optimistic, attentive eyes which serve as their primary mode of communication.

Identifying current and accurate information will help jump-start your journey with a Rett Syndrome diagnosis in the right direction. The Rett Syndrome information below has been collected from trusted sources (including the National Institute of Neurological Disorders), with the intent to bring knowledge, awareness, and understanding to you and your family regarding this rare condition.

What Causes Rett Syndrome?

A confirmation of Rett Syndrome typically derives from a combination of clinical assessment coupled with a genetic profile (obtained by blood sample) that identifies the MECP2 gene mutation on the X-chromosome. MECP2 mutations are not unique to Rett Syndrome and can occur in other rare disorders. Clinical and symptomatic assessment by a neurological specialist is critical to diagnosis confirmation for Rett Syndrome.

Rett Syndrome presents on a spectrum from mild to severe, with symptoms manifesting in various degrees. Rett Syndrome severity is difficult to predict, and is determined by a number of complex inter-relating factors, including mutation type and location on the MECP2 gene, female X-chromosome inactivation status, X-chromosome skewing, and multiple other biological factors. This simply indicates that two children with the same mutation at the same age can present with distinct symptomatic profiles and severity of Rett Syndrome.

Even though it occurs at a much lower prevalence, males can be born with the MECP2 mutation and receive a Rett Syndrome diagnosis. Symptomatic Rett Syndrome severity tends to increase in males, and mortality rates are higher, largely attributable to their single X-chromosome genetic status. Ongoing advances in research and genetic sciences are leading to increased awareness, diagnosis, and a better understanding of what causes Rett Syndrome in both females and males.

Although Rett Syndrome brings about many difficulties and challenges, aggressive physical therapy, symptomatic drug interventions, diet protocols, and adaptive communication approaches (combined with love and understanding), can help Rett children thrive in their families and communities.

Typically, Rett Syndrome children grow well into middle ages, with the ability to experience a full range of moods and emotions. Their personality becomes well developed and defined, and they can engage in many recreational, educational, and social activities both in their homes and their communities.

Symptoms of Rett Syndrome

Children with Rett Syndrome ​are usually born after a normal and even healthy pregnancy and delivery. In most infants, from birth to about six months of age, there is healthy (normal) growth and development. Rett Syndrome symptom onset typically occurs between six and eighteen months of age, and may include generally impaired motor function, loss of functional hand use and acquired speech, breathing abnormalities, slowing growth patterns and other regressive characteristics.

The most visible Rett Syndrome symptoms begin to show up in this age range, with onset occurring over a period of weeks to months. Severity and range of symptoms can vary from child to child and differ depending on several factors.

Here’s what symptoms may look like for your child with Rett Syndrome:

• Unusual eye movements – Rett can cause abnormal eye movements in children, including crossed eyes, closing of one eye, and/or harsh blinking and staring.

• Irregular hand movements – Rett can cause irregular and repetitive hand movements that have no purpose. Changes can include tapping, clapping, hand-wringing, mouthing and rubbing but will likely differ from child to child.

• Slowed or stagnant growth – Growth of the Rett Syndrome brain slows or becomes stagnant after birth. Head size may be a first indicator, with repressed head growth (microcephaly) becoming evident before delayed growth in other areas of the body.

• Losing communication skills – Rett typically causes children to lose their ability to speak. Other meaningful communication modes (such as purposeful eye contact) may also be affected. This can cause isolation due to a disinterest in their toys, surroundings, and even people around them. Severity and final states are difficult to predict – some children may experience a sudden loss of speech, but over time, may regain the ability to make eye contact and develop other nonverbal communication abilities.

• Irregular movements, losing coordination – In addition to atypical hand movement in Rett Syndrome, other impaired motor functions may present, including the inability or impairment of ability to crawl and walk normally. When regression occurs, it can be rapid. Over time, other motor and physiological function may decline, such as decrease or weakening of muscle tone, irregular skeletal development (scoliosis), and other abnormal movement patterns.

• Crying and irritability – Although cause is unknown, children with Rett Syndrome may experience pronounced periods of crying and irritability as they get older (perhaps due to anxiety or fear, and the inability to verbalize feelings). Some children have long periods of screaming, crying, and irritability that can last hours.

• Breathing issues – Issues with breathing tend to be experienced during waking hours, and include breath holding (apnea), forcefully exhaling air and saliva, rapid breathing, and swallowing air. Children may also experience periodic or shallow breathing during sleeping periods.

• Irregular heartbeat – Rett Syndrome children may exhibit irregular heartbeats that can be life-threatening and in rare cases, fatal.

• Other abnormalities – Rett Syndrome children may experience other abnormal behaviors such as periods of laughter, grasping at clothing or hair, odd facial expressions, biting, hand-licking, and teeth grinding.

• Scoliosis – While onset is typically in later childhood (age 8 or later), many children with Rett Syndrome experience an abnormal curvature of the spine. Some may require surgical intervention to correct the most severe manifestations.

• Seizures – Epileptic-like seizures are common in children and adults with Rett Syndrome, often requiring pharmaceutical intervention to reduce frequency of occurrence and severity.
• Various other symptoms – Rett Syndrome children and adults may experience a multitude of other symptoms throughout their lifetimes, including but not limited to: small, cold hands and feet, difficulty chewing and swallowing, fragile bones with a propensity to fractures, irregular sleep patterns and disturbances, and more.

Diagnosis

While the MECP2 mutation occurs at conception, Rett Syndrome typically manifests postnatally, with first recognition occurring in early infancy. Mainly girls are affected, but boys can be diagnosed also. Rett Syndrome is often misdiagnosed, as symptoms can be erroneously attributed to those of cerebral palsy, autism, or non-specific developmental delays.

Rett Syndrome causes issues with brain function (and more specifically – synaptic transmission), leading to impairment of sensory, cognitive, autonomic, motor, and emotional functions. Speech, learning, sensory sensations, movement, mood, breathing, cardiac function, and even digestion, swallowing, and chewing are affected.

After apparently healthy early development, onset occurs between six and eighteen months of age. Though now classified as a “developmental” disorder (not degenerative), growth and skills stagnate or slow. As the affected child enters this regressive period, purposeful hand utilization and communication skills are lost.

Soon after, other symptoms manifest, such as the slowing of average head growth, gait disturbances, seizures, and disorganized breathing patterns during waking hours.

Children in the initial regressive periods of Rett Syndrome often experience sleep issues and commonly become isolated, suffering from periods of inconsolable crying and irritability. Typical communication methods are difficult or non-existent, and motor problems increase. Over time (weeks or months), communication and eye contact typically improve, and irritability stabilizes.

Genetic testing is an appropriate method of obtaining a trusted confirmation of Rett Syndrome.

When to Contact Your Doctor

The onset of symptoms associated with Rett Syndrome can be stressful and unnerving. Symptoms can be subtle and easily mistaken. If you notice any of the following signs, after a period of healthy growth and development, see your doctor as soon as possible. If appropriate, genetic testing can be performed to diagnose Rett Syndrome.

• Repetitive, non-deliberate hand movements
• Sudden, slowed growth in the head or other parts of your child’s body
• Marked mood swings and/or problematic behavior
• Deterioration of mobility or coordination
• Losing acquired abilities related to speech or communication
• Delays in new skills regarding speech, communication, or movement
• Decreased interest in toys, people, or traditional play
• Any apparent reduction or loss of previously acquired fine motor skills, or gross motor functioning

Stages of Rett

Rett Syndrome typically progresses through four distinct stages:

• Rett Syndrome Stage 1: Early Onset – Signs and symptoms in this stage can be prominent or easily overlooked, often occurring between six and eighteen months of age, lasting from several months to a year. Infants and toddlers in this stage may exhibit delays sitting or crawling, lose interest in toys, or show reduced eye contact.
• Rett Syndrome Stage 2: Rapid Deterioration – Typically experienced by children ages one to four, skills and abilities previously acquired may suddenly be lost. Changes can be gradual or rapid, taking place over several weeks to months. More pronounced symptoms become evident, including delayed head growth, screaming, crying, hyperventilating, abnormal hand movements, loss of coordination and movement, losing communication skills, and inhibited social interaction.
• Rett Syndrome Stage 3: Plateau – This stage can begin as early as age two and typically occurs up through age ten (but can last many years after). In this stage, a child with Rett Syndrome may have little or no improvement in behavior and continuing issues with motor movement. Intensive physical and occupational therapy, coupled with complex-learning techniques, may produce improvements in literacy, communication and use of hands. Some children may begin to experience seizures during this stage, though not typically before two years of age.
• Rett Syndrome Stage 4: Late Deterioration of Motor Skills – This stage occurs from age ten through adulthood, lasting decades for some. This period of life for those with Rett Syndrome may produce increased muscle weakness, scoliosis, joint contractures, and additional loss of mobility. Seizures may occur less often during this stage, while hand use and communication skills may improve.

Can Rett be Treated?

The National Institute of Health states that those facing Rett Syndrome can benefit from interventions at all ages, but superior results are realized by early intervention. There are multiple therapies, learning techniques, and assistance opportunities for those with Rett Syndrome leading to improved quality-of-life in many areas.

• Physical and hydrotherapies can help improve mobility and balance, delay scoliosis progression, and relieve other spasticity issues.
• Occupational therapy can help to improve purposeful hand use and reduce abnormal hand movements. Some patients may recover limited ability to self-feed and dress.
• Speech and language therapies may help improve nonverbal communication skills and social interactions.
• Pharmaceutical intervention can address issues of abnormal heartbeats, breathing problems, seizure control, and digestive issues (i.e. constipation and acid reflux). There are multiple treatments that have undergone clinical trials in the past or coming soon to clinical trials.
• Physical orthotics may include splints for hand movements and braces to correct or reduce scoliosis.
• Supplements, dietary programs and other nutritional intervention may help with maintaining healthy height and weight. Osteoporosis may be addressed and improved through diet and supplements. For those who have difficulty chewing or swallowing, feeding tube intervention may be required to ensure adequate nutrition and avoid aspiration of food into the lungs.

More information on Rett Syndrome can be found at the National Institute of Neurological Disorders and Stroke. Genetic testing information and work can be done at specialist organizations such as Boston Children’s Hospital for Rett Syndrome.

Can It Be Prevented?

According to Boston Children’s Hospital, there is no known prevention for Rett Syndrome. Typical Rett Syndrome is caused by a spontaneous mutation of the MECP2 gene at conception (“spontaneous mutation” indicating that the condition is genetic, but not inherited from a parent’s contributed DNA). The condition/mutation most often occurs in girls.

What Research Is Being Done?

Research into Rett Syndrome is being aggressively pursued and clinical trails of treatments are underway. Many organizations raise funds and sponsor grants for Rett research, with a goal to accelerate discoveries in therapeutic and cure-focused treatments. Multiple studies and clinical trials are in-progress, targeting improvements in the lives of those living with Rett Syndrome.

Research is being done to more fully understand what has gone wrong with the genetic biology. Researchers know that the spontaneously mutated MECP2 gene (and rarely inherited mutation) affects a critical protein process for brain function and development, but the exact cause of the mutation remains unknown. Clinical trials are underway to bring treatments to market and to better understand Rett Syndrome.

Further research is ongoing, developing new medications that may help improve the lives and biology of those with Rett Syndrome.

Rett Syndrome Facts

Here are several Rett Syndrome facts:

• Children diagnosed with Rett function cognitively at higher than previously thought levels
• Rett is caused by a single mutation of the MECP2 gene that affects the production of a critical brain protein
• Rett is potentially reversible through reintroduction of the affected protein
• Rett is as prevalent as Huntington’s Disease, Cystic Fibrosis, and ALS
• Rett is a debilitating neurological disorder
• Rett is most often found in girls but can affect boys too
• Children with Rett lose skills they’ve acquired between the ages of one and three years
• Most children affected by Rett can’t speak or use their hands, and over 50% lose their ability to walk and require mobility assistance
• A child is born with Rett Syndrome every 90 minutes

Rett Syndrome in Boys

Boys have a different chromosome combination (XY) than that found in girls (XX). Subsequently, the genetic mutation of Rett Syndrome is much more devastating for boys. Many boys who have Rett Syndrome will die in early infancy, if not before birth.

There is a very small percentage of boys born with Rett Syndrome that will have a genetic mutation resulting in a less severe form of the condition, allowing them to live into child and even adulthood. Boys will still face the common difficulties and symptoms associated with Rett Syndrome and will likely have any number of developmental issues.

Risk Factors

Rett Syndrome is rare. The mutation occurring at the genetic level is random, and risk factors aren’t identified as of yet. There have been limited cases were inherited factors may have played a role, such as having a close family member who has Rett Syndrome.

Complications

Those facing Rett may have complications in the following areas:

• The need for lifelong assistance and care to maintain daily living activities
• Joint, muscle and bone problems
• Behaviors that may hinder social functioning, including anxiety and fears
• Difficulty eating and swallowing, leading to delayed growth, poor nutrition, and other issues
• Bladder and bowel difficulties, including gastroesophageal reflux disease (GERD), gall bladder disease, constipation, and bowel or urinary incontinence
• Sleep disturbances that cause significant difficulties for both the patient and parents/caregivers
• Pain that may be related to other issues such as gastrointestinal complications, weak bone fractures, and muscle spasticity
• Reduced lifespan – while many diagnosed with Rett Syndrome will live well into adulthood, complications from the condition tend to result in below-average lifespans. Availability of pharmaceutical intervention, physical therapies, and other factors contribute to life-expectancy for those suffering with Rett Syndrome

Rett Awareness

October is Rett Syndrome awareness month, and it’s the perfect time to make a difference in so many lives. For parents, a Rett diagnosis can be like walking blindly into a park. It is characterized by words they’ve never heard before, symptoms they cannot predict, and uncertain severity determined only by the passage of time.

Family, friends, and even many doctors can be unfamiliar with the diagnosis, making parents feel alone, in the dark, and unable to cope. Rett Syndrome occurs once per 10,000 live births, which may not sound like a lot, but results in significant numbers. A child is born with Rett Syndrome every 90 minutes, and estimates indicate over 350,000 cases worldwide.

With similar numbers to Huntington’s Disease, ALS and cystic fibrosis, Rett awareness is an important issue. Through major events like the Disney Princess Race Weekend, as well as dinners, runs, walks and other fundraising and family support, Girl Power 2 Cure works relentlessly to spread knowledge, awareness, and education that is so badly needed.

Rett Syndrome affects not just the children, but their parents, families and communities in immeasurable ways. As the leading genetic cause of severe motor impairment in girls, we must all work together to spread the story and advocate.

How Can I Donate / Support?

Donating to and supporting Rett organizations is easier than you might think. Substantive progress in understanding the condition, as well as treatments and the hope of potential cures can only continue with support from the broader community… people like you. Please visit any of the below pages to show your support, take action, and donate.

Donations go to helping fund research into the exact cause of Rett, finding better treatment or potential cure modalities, and development of better ways to help those with Rett live their lives to the fullest. Donations to Girl Power 2 Cure (https://www.girlpower2cure.org/donate/) not only support families directly, but also provides significant funding every year to leading research organizations such as the Rett Syndrome Research Trust (https://reverserett.org/donate/).

Getting the Support You Need

As the family member or caregiver of someone diagnosed with Rett Syndrome, the beginning stages can leave you reeling, not knowing where to turn or ask for help. We know it’s hard. That’s why we work every day at Girl Power 2 Cure and Rett University to provide resources and support services just for you.

Parents and caregivers embrace these organizations just like you; they’re substantially comprised of people who love and care about a person with Rett Syndrome, and who needed help at some point also.

These organizations include people who are willing to go the extra mile, share the latest medical news, pursue the next research topic, raise awareness with the public, and offer support in a meaningful way.

As advocates for those diagnosed or touched by Rett Syndrome, we want to help you in any way we can. Please register for our e-mail newsletter on the right side of this page.  We promise to help open your world to the help and resources available through international, state, and local organizations. Organizations that will partner with you to make sure that each parent, child, and family member touched by Rett has the resources they need.