Rett syndrome is a neurological condition classified in the autism spectrum disorders. An Austrian physician, Dr. Andreas Rett, identified the condition in 1966 but the disorder was not officially recognized until 1983. Rett syndrome is typically associated with females because the disorder is fatal to male children. Male children with Rett syndrome die before or shortly after birth because they have only one X chromosome. Females survive because they have a second X chromosome that compensates for the damaged one.
Rett Syndrome and Prognosis
Prognosis for children diagnosed with Retts varies but it is among the most severe of the five pervasive developmental disorders.
Prognosis and Gender
A girl may have a mutation on one X chromosome but the normal genes on the other chromosome compensate. The severity of the disorder depends on the number of cells affected by the mutation. For example, one girl may have healthy copies of the MECP2 genes in large numbers. This leads to a better prognosis, later development of problems and mild symptoms.A girl with a large percentage of cells affected, may "turn off" the normal MECP2 genes on the X chromosome. The prognosis in these cases are less promising. Prognosis for boys with Rett's disorder is bleak.
Boys have one X and one Y chromosome and when genetic problems occur on either, no backup copy exists to compensate for the dysfunction. Without genetic backup, there is no protection from the damaging effects of the condition. Boys with Retts typically do not survive long after birth. In extremely rare cases, boys can have a different MECP2 gene mutation that is not fatal but does lead to developmental delays and learning problems.
Symptoms of Rett Syndrome
Rett syndrome is currently one of the five pervasive developmental disorders outlined in the DSM-IV and it shares many of the symptoms of autism in children, particularity stereotyped repetitive movements.
Children who have the disorder seem to have normal early development followed by marked regression. Symptoms include:
- Hypotonia (muscle tone loss)
- Loss of speech
- Loss of fine motor skills
- Loss of gross motor skills
- Slowed brain growth
- Learning disability
- Diminishing eye contact
- Self-stimulatory behaviors
- Apraxia or loss of the ability to execute motor functions
The onset of the symptoms can appear abruptly with marked loss of skills occurring in a remarkably short period. Apraxia is perhaps the most severely disabling feature of Rett syndrome, interfering with every body movement, including eye gaze and speech.
Causes of Rett's Disorder
The notion that autism spectrum disorders have genetic components is supported by the causes of Rett disorder. The condition arises from a mutation in the MECP2 gene, pronounced meck-pea-two. The gene is present on the X chromosome.
The mutation is believed to interfere with the proper functioning of other genes. The MECP2 gene processes methyl cytosine protein. The protein serves as a biochemical switch that tells other genes to quit producing their specific proteins. The result is the production of abnormal or insufficient proteins.
Further research is required to determine how exactly the irregular proteins affect the body.
Four Stages of Rett Syndrome
The first stage of Retts is early onset, beginning between the ages of 6 and 18 months. Symptoms of this stage can be quite subtle, making it difficult to detect in many cases. Infants may exhibit:
- Loss of interest in toys
- Less eye contact
- Delay or regression in sitting
- Delay or regression gross motor skills
- Decreased head growth
- Hand movements like wringing and flapping
The early onset stage lasts the course of a few months or a little more than one year.
Stage II is rapid destructive, typically beginning between one and four years of age. During this stage, the toddler experiences rapid or gradual loss of language and social skills. Stereotyped repetitive movements replace purposeful hand movements. Marked regression appears along with sleep disturbances and slowed head growth.
The second stage lasts a few weeks or a few months. The loss of proper functioning begins to slow as the child enters Stage III.
Stage III is the plateau or pseudo-stationary, beginning between the ages of 2 and 10 years. The child may demonstrate improvements in behavior and an increased interest in her environment. Social and communication improvements may also surface. Problems in this stage include seizures and apraxia. Stage III is the longest, with many remaining in the phase for most of their lives. Some experience Stage IV.
Stage IV is the late motor deterioration that consists of mobility problems including weak muscles, abnormal posture, rigidity, and curvature of the spine. Cognition, fine motor skills and communication skills do not decline during this phase and there may be improvements in eye contact and self-stimulatory behaviors. Stage IV does not occur in every case of Rett's disorder. The phase lasts years or decades for girls and women who experience it.
Rett Syndrome Treatment
Today, Rett syndrome treatments are a combination of treating symptoms and assisting with daily life tasks. Since each person experiences Rett syndrome differently, treatment plans vary.
Treatment plans may involve a combination of the following:
- Physical therapy
- Speech therapy
- Occupational therapy
- Special education services
- Vocational services
- Life assistance equipment such as wheelchairs
Doctors prescribe medication to lessen the severity of symptoms. Many people with Rett syndrome have seizures. Medications, such as Tegretol and Lamictal, can help control seizures. Some children and adults may also receive Levodopa, which imitates the effects of dopamine on the body and can help with muscle rigidity in the later stages of Retts. Other medications can help with breathing irregularities and apraxia symptoms. Common medications for Rett syndrome symptoms include:
- Naltrexone (ReVia): ReVia is an opiate antagonist that can help regulate irregular breathing. Yet, a study suggests that the drug speeds up the progression of the disease.
- Levodopa (L-dopa): L-dopa therapy, a synthetic dopamine drug, can help relieve muscle stiffness.
- Levocarnitine (L-carnitine): Some people with Rett syndrome who take anticonvulsants to prevent seizures experience carnitine deficiency. L-carnitine effectively treats the deficiency.
- Tyrosine (dopamine and noradrenalin) and tryptophan (serotonin): These amino acids can improve neurotransmitter levels in the brain.
- Bromocripitine (Parlodel): Parlodel can improve the brain's dopamine function. The drug helps with self-stimulatory hand movements.
- Antipsychotics and anticonvulsants are also sometimes used to treat various symptoms.
Physical and Occupational Therapy
A person with Rett syndrome can benefit from physical and occupational therapy to improve muscle coordination and rigidity and provide more purpose to hand and body movements. The therapy can relieve joint contracture, improve balance, build flexibility and help maintain an ability to walk. The therapy can also help an affected person gain some level of independence in caring for themselves.
Scoliosis is another concern for children with Retts and needs to monitored and checked for on a regular basis.
Special Diets and Nutritional Therapy
Rett syndrome may make it difficult for a person to gain weight and maintain a healthy weight. Special diets can help a person maintain an ideal weight and nutritional balance, which may contribute toward making symptoms less severe. Sometimes chronic constipation occurs and a high fiber diet works best. Some cases may also require additional liquid nutrients through feeding tubes. Many children with Rett syndrome need extra nutrition to maintain their weight and bodily functions. A high-fat, high-calorie diet can help a child put on weight and improve her growth. Some children take liquid nutrients through nasogastric or gastrostomy feeding.
Massachusetts Institute of Technology Study
In February 2009, MIT's Picower Institute for Learning and Memory and the Whitehead Institute for Biomedical Research announced the results of a study that successfully reduced the symptoms of Rett syndrome in mice using a molecule that improves brain development. The study was reported on the February 10 online edition of the Proceedings of the National Academy of Sciences.
Scientists gave daily injections of a peptide fragment of growth factor-1 (IGF-1), to mice who were genetically engineered to demonstrate Rett syndrome symptoms. Over a period of time, the injections eliminated a number of symptoms and lessened the severity of others.
The Study's Effect on Rett Syndrome
Some experts believe that Rett syndrome is largely due to a mutation in the methyl CpG-binding protein 2 (MECP2) gene on the X chromosome, which then produces less of a related protein, MeCP2, and can cause impairments in critical cell growth. The impairments cause cells to fail to mature and disrupts brain development. In a sense, some key brain developmental activity is turned off. When this happens, Rett syndrome symptoms can occur. IGF-1 can address deficiencies in MeCP2, help critical cell mature and activate important brain activity. IGF-1, which is used by the brain for neuronal and synaptic growth, is currently used as a growth disorder treatment and to control blood glucose imbalances. The molecule IGF-1 affects a large percentage of cells in the human body and regulates cell growth and nerve cell development.
During the study, the IGF-1 increased MeCP2 levels in treated mice and some impaired cells matured and symptoms such as motor performance and irregular breathing improved.
The results of the study indicate that a possible treatment using a form of IGF-1 can improve or eliminate certain Rett syndrome symptoms and possibly encourage healthy brain development.
Progress of the Possible Treatment
The MIT and Whitehead Institute scientists are in the process of developing a protocol to study the effect on IGF-1 on human beings with Rett syndrome. This is one of the first steps toward creating a possible treatment for Rett syndrome using IGF-1.
Typically, people with autism have normal life expectancy but Retts is a very rare condition. Few studies offer insight into lives of people with this condition. More studies in women over 40 with Retts is necessary to develop reliable estimates of life expectancy.
Resources for Parents
Parents faced with the diagnosis of Rett syndrome may be devastated by what this means for their child. Some things parents can do to cope are:
- Acknowledge and work through emotions, and recognize that there is a grieving process. Anger, disappoint and shock are normal responses after diagnosis.
- Support groups for families affected by Retts can help parents realize they are not alone, and it can also be helpful in finding treatment ideas and strategies that work.
- Respite for parents can alleviate some of the stress while giving them time to recharge and refocus.
- Take things one step at a time. Many parents may be preparing for the worst as they focus on what will happen when their child enters Stage IV of the disorder. It helps to recognize that not every child with Rett's experiences the fourth stage.
Several organizations provide information and support for a diagnosis of Rett syndrome, such as:
- International Rett Syndrome Foundation
- National Institute of Neurological Disorders and Stroke
- Easter Seals
Dealing with a diagnosis of Rett syndrome will be difficult, but there are many resources that can help parents and children live happy and full lives. Having a child with a disability is challenging but it is also very rewarding. Gathering information, support and services can help families grow stronger as they embark on their journeys.