Dr. Andreas Rett at his clinic in Vienna, Austria

Rett Syndrome (RS) is a neurological disorder seen almost exclusively in females, and found in a variety of racial and ethnic groups worldwide. First described by Dr. Andreas Rett, RS received worldwide recognition following a paper by Dr. Bengt Hagberg and colleagues in 1983. Rett Syndrome can be classified as an "Orphan Disease", that is, one that affects fewer than 200,000 citizens nationwide. Though the incidence of RS and other Orphan diseases may be significantly less than more well kown disorders, they are no less devestating to those afflicted and their families. Further, though originally thought to be very rare, with less than 200 cases worldwide, RS is now thought to be as prevalent as one in every 12,000 live female births, though the exact numbers are unknown due to misdiagnosis and lack of awareness in the medical community. My aim in presenting this page is to increase awareness of RS and facilitate early intervention for its victims.

The child with RS usually shows an early period of apparently normal or near normal development until 6-18 months of life. A period of temporary stagnation or regression follows during which the child loses communication skills and purposeful use of the hands. Soon, stereotyped hand movements, gait disturbances, and slowing of the rate of head growth become apparent. Other problems may include seizures and disorganized breathing patterns which occur when awake. Apraxia(dyspraxia), the inability to program the body to perform motor movements, is the most fundamental and severely handicapping aspect of RS. It can interfere with every body movement, including eye gaze and speech, making it difficult for the girl with RS to do what she wants to do. Due to apraxia and lack of verbal communication skills, an accurate assessment of intelligence is difficult. Most traditional testing methods require use of the hands and/or speech, which may be impossible for the girl with RS.

RS is most often misdiagnosed as autism, cerebral palsy or non-specific developmental delay. While many health professionals may not be familiar with RS, it is a relatively frequent cause of neurological dysfunction in females. The prevalence rate in various countries is from 1:10,000 to 1:23,000 live female births. Most researchers now agree that RS is a developmental disorder rather than a progressive, degenerative disorder as once thought. While there is strong evidence of a genetic basis, the origin and cause of RS remain unknown. Barring illness or complications, survival into adulthood is expected.

DIAGNOSTIC CRITERIA

Required for the recognition of Rett syndrome after the exclusion of other handicapping conditions

* Period of apparently normal development until between 6-18 months

* Normal head circumference at birth followed by slowing of the rate of head growth with age (3 mos-4yrs)

* Severely impaired expressive language and loss of purposeful hand skills, which combine to make assessment of receptive language and intelligence difficult

* Repetitive hand movements including one or more of the following:hand washing, hand wringing, hand clapping, hand mouthing, which can become almost constant while awake

* Shakiness of the torso, which may also involve the limbs, particularly when upset or agitated

* If able to walk, unsteady, wide-based, stiff-legged gait/toe-walking

SUPPORTIVE CRITERIA

Symptoms not required for the diagnosis, but which also may be seen.These features may not be observed in the young girl but may evolve with age.

* Breathing dysfunctions which include breath holding orapnea, hyperventilation and air swallowing which may result in abdominal bloating and distention

* EEG abnormalities -- slowing of normal electrical patterns, the appearance of epileptiform patterns and loss of normal sleep characteristics

* Seizures

* Muscle rigidity/spasticity/joint contractures which increase with age

* Scoliosis (curvature of the spine)

* Teeth grinding (bruxism)

* Small feet ( in relationship to stature)

* Growth retardation

* Decreased body fat and muscle mass (but tendency toward obesity in some adults)

* Abnormal sleep patterns and irritability or agitation

* Chewing and/or swallowing difficulties

* Poor circulation of the lower extremities, cold and bluish-red feet and legs

* Decreased mobility with age

* Constipation

All girls and women with RS do not display all of these symptoms, and individual symptoms may vary in severity. A pediatric neurologist or developmental pediatrician should be consulted to confirm the clinical diagnosis.

RS PROFILE

The young girl with RS is well known for her attractive features, and as she grows older, her especially penetrating eyes. She typically sits independently and finger feeds at the expected time. Most girls do not crawl typically, but may "bottom scoot" or "combat crawl" without using their hands. Some children start to use single words and word combinations before they lose this ability. Predicting the severity of RS in any individual is difficult. Many girls begin independent walking within the normal age 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. Seizures can range from non-existent to severe, but do tend to lessen in their intensity in later adolescence. Breathing abnormalities may occur and also tend to decrease with age. While scoliosis is a prominent feature of RS, it can range from mild to severe. Despite these difficulties, girls and women with RS can continue to learn and enjoy family and friends well into middle age and beyond. They experience 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.

STAGE I

Early Onset Stage
Age: 6 months to 1 ½ years
Duration: months

This stage is usually overlooked, as the symptoms of RS are just emerging and are somewhat vague. The infant may show less eye contact and have reduced interest in toys. She is often described as a "good"baby, calm and placid. There may be delays in gross motor milestones.Non-specific hand wringing and decelerating head growth may be present.

STAGE IIRapid Destructive Stage
Age: 1 to 4 years
Duration: weeks to months

This stage can have a rapid onset or it can be more gradual as purposeful hand skills and spoken language are lost. Stereotyped hand movements begin to emerge, and often include hand-to-mouth movements as the first expression. Movements are most often midline hand wringing or hand washing, and persist while the girl is awake but disappear during sleep. Other hand movements include hand clapping or tapping. Hands are sometimes clasped behind the back or held at the sides in a specific pose, with random touching, grasping and releasing. Breathing irregularities may be noticed, and may include episodes of breathholding and hyperventilation associated with vacant spells. However,breathing is normal during sleep. Some girls appear autistic-like with loss of social interaction and communication. General irritability and sleep irregularity may be seen. Periods of tremulousness may be obvious, especially when excited. Gait patterns are unsteady, and initiating motor movements can be difficult. Slowing of head growth is usually noticed from 3 months - 4 years, when the girl's head circumference falls on a percentile chart (compared to children at the same age).

STAGE IIIPlateau Stage
Age: Preschool to school years
Duration: years

This stage, from 2-10 years, follows the rapid destructive period.Apraxia, motor problems and seizures are more prominent. However,improvement is seen in behavior with less irritability and crying and less autistic features. She shows more interest in her surroundings,and her alertness, attention span and communication skills improve. Many girls with RS remain in Stage III for most of their lifetime.

STAGE IV A (Previously ambulant)

STAGE IV B (Never ambulant)
Late Motor Deterioration Stage
Age: When stage III ceases, 5-15-25-? years
Duration: up to decades

This stage usually begins after age 10, and is characterized by reduced mobility. Some girls stop walking, while others have never walked. However, there is no decline in cognition, communication or hand skills.Repetitive hand movements may decrease. Scoliosis is a prominent feature. Eye gaze usually improves. Rigidity (stiffness) and dystonia(increased muscle tone with abnormal extremity or trunk positions) are characteristic. Puberty begins at the expected age in most girls.

GENETICS

There is convincing evidence that RS is a genetic disorder. This means that it is caused by a faulty or mutated gene, most likely, but not limited to the X chromosome. Researchers feel that there may be more than one gene involved, which would account for the wide expression of severity seen. Family studies have shown that while it has rarely recurred in families, the increased risk of having a second girl with RS is less than 0.4%.

TREATMENTS and THERAPIES

The course of RS can be improved by therapies aimed at slowing the progression of motor disability and improving communication skills.Physical therapy should be aimed at maintaining or improving ambulation and balance, maintaining full range of movement or at least functional movement, and at preventing deformities. Occupational therapy should be used to promote and improve the use of the hands. Studies have shown that decreasing the repetitive hand movements can lead to greater alertness and better focus, as well as helping to decrease agitation and self-injurious behavior. Intermittent use of hand or elbow splints maybe useful in reducing these hand movements and may encourage morepurposeful use of the dominant hand. Intermittent weighted immobilization of one hand can also be a useful approach. Music therapy is used as an adjunct to other therapies, and is useful in promoting communication and choice making. Horseback riding and hydrotherapy promote balance and help develop protective responses, in addition to being very relaxing and enjoyable.

COMMUNICATION

Most girls with RS show an intense desire to communicate through their eyes, gestures and body language. There is often a delay in response to stimuli. A speech therapist's evaluation of communication should include parent/teacher/care giver observations of responses to cause and effect, choice-making, following directions and recognition of objects and people. There are reports of some girls who use augmentative(non-speech) communication techniques demonstrating good receptive language. Possible alternative communication methods include eye-gaze response, picture, letter and word boards and touch or switch operated voice output devices. These should be investigated for the type best suited to the individual to allow for active and fulfilling participation in everyday life. Lack of obvious communication skills should not deter the pursuit of academic skills using alternative methods. The girl or woman with RS should always be spoken to as an intelligent person, despite her often unresponsive appearance. Not being able to talk doesn't mean she has nothing to say!

EDUCATION

Early exposure to age-appropriate books, toys and music is important,even if she does not appear to show much interest or make appropriate responses. It can require several minutes for her to process information and respond. Even when she does respond, it may not be inconventional ways. Always allow enough time for her to take in information, and enough room for her to respond in her own way. Great fluctuations in her motor ability, attention span and behavior may be seen, even within a short period of time. Apraxia makes it difficult for her to perform motor movements by following directions. The more she has to think about the process, the more difficult it becomes. However, when she is emotionally motivated, movements are automatic (i.e. reaching for food, scratching an itch, etc.). Providing environments and situations that are strongly motivating will make it easier for her to show what she understands, resulting in greater success and satisfaction. Girls with RS can be seen in classrooms of all types, ranging from self-contained special education units to full inclusion in regular schools. The goal in education should be to provide her with the most stimulating program in the least restrictive environment, taking into account each girl's own special needs.

SOME FACTS ABOUT RETT SYNDROME

Scoliosis develops in a considerable number of girls with RS and may progress rapidly during ages 8-14. In some, bracing and/or surgery maybe required. However, many girls do not show rapid progression. The likelihood of worsening scoliosis seems to be increased in girls who do not walk and those who have early low muscle tone or dystonia.Weight-bearing exercise and frequent evaluation are recommended.

Seizures are reported in a high number of girls with RS, but the incidence of true clinical seizures is felt to be overestimated. Many common RS motor behaviors are mistaken for seizures(shown during polygraphic monitoring). It is felt that many of these events are non-seizure, while actual seizures may be under-recognized and occur during sleep. Video-EEG monitoring may be necessary to determine appropriate treatment. Drugs to control seizures are very effective in most cases.

Growth in RS is usually slowed, with most girls and women quite small for their age. Studies have shown that despite what appears to be voracious appetite, many girls meet the criteria for moderate to severe malnutrition. This may come about due to swallowing difficulties,inadequate intake of food, energy expenditure imbalance, or inadequate utilization of nutrients. Evaluation for swallowing difficulties and gastroesophageal reflux is indicated for many girls with RS. A program of supplemental feeding (oral feeding with high-calorie/high-fat diet, NG tube or gastrostomy button) has been shown to bring about significant weight and height gains, which may improve alertness and interaction.

Bone fractures are seen more often in RS than in other motor disorders.This is due to low bone-mineral content and decreased bone density, in spite of adequate calcium intake. Weight bearing exercises and a high calcium diet may be helpful.

Agitation is often thought to result from frustration over the inability to communicate. It is helpful to keep a detailed log including a list of the girl's behaviors and activities, in an attempt to determine and remedy factors that influence agitation. Physical causes for crying should always be considered. Once physical factors are ruled out, strategies such as warm baths, massage, music or a quiet,less stimulating environment can be helpful. Small frequent meals during the day with added carbohydrates may help. Agitation at bedtime can be treated with various medications.

Constipation is common and can result in severe discomfort. Adequate fluid intake, high-fiber foods and exercise are important. It is preferable to avoid long-term use of laxatives, suppositories and enemas, but stool softeners, mineral oil and Milk of Magnesia are often helpful.