Contents
What is Rett Syndrome?
Rett’s syndrome is a rare disorder of neurological development. It tends to affect girls, and the estimate tends to vary according to the place where it is born. For example, in the United States, one in 23,000 girls is believed to be born with the disease.
In Japan, a study was done with girls between 6 and 14 years old and the variation is that of one in 45 thousand, they suffer from Rett syndrome. The disease was discovered in the late 1950s, but it was not recognized until the 1980s, almost 30 years later.
Rett’s syndrome is characterized by the progressive loss of neurological and motor functions after a “normal” development from 6 to 18 months of age. After reaching 1 year and a half, the ability to walk, speak and use hands are lost over time and more and more noticeable. The repetitive and involuntary movement of the hands (manual apraxia) is the most striking feature of the syndrome.
Historical
The disease was first recognized by Dr. Andréas Rett, a pediatrician who identified the expression of neurological development after a normal period during early childhood.
The girls studied showed a slow head circumference, loss of functional use of hands and also of communication skills. The loss of manual movements caused the girls to tap, rub or put their hands to their mouths.
After these studies, Dr. Rett traveled across Europe to present the disease to other doctors at scientific meetings, but as they were written in German, there was not much repercussion.
At the same time, another doctor, known as Bengt Hagberg, also observed patterns very similar to those of Dr. Rett. Only in the late 1970s did they meet and discuss the disease. Thereafter, other doctors paid attention to the disease and the disease began to be diagnosed and researched.
In Brazil, in 1986, the first cases were diagnosed and, 4 years later, the Brazilian Rett Syndrome Association was founded in Rio de Janeiro. It was only in 1999 that the association of the disease with mutations in the MECP2 gene was established. After that, several researches and studies are carried out in order to reduce the symptoms and signs of the disease
Cause
The cause of Rett’s syndrome was unknown until 1999. The occurrence of the disease in females only showed a genetic basis known as a dominantly mutation in the X chromosome with a lethal effect in males.
The MECP2 gene encodes the MECP2 protein and has the function of inactivating other genes through mechanisms of transcription repression, involving the binding to methylated CpG regions.
One study identified mutations in the MECP2 gene in 80% of cases of classic Rett syndrome. The severity of the disease appears to be related to the type of mutation.
Mutations in the MECP2 gene represent an important proportion of the cases of the disease, but it is still possible that there are other factors that cause the disease and have not yet been identified.
Nowadays the discovery of mutations in MECP2 can confirm the disease early, making a prognosis and predicting a low risk of recurrence in siblings, which cannot be guaranteed if the diagnosis is not certain.
Rett syndrome in boys
Years ago, it was believed that boys with Rett syndrome suffered from premature death or else there was a miscarriage during pregnancy. This has changed, as it is known that they can also develop the disease in three different situations:
- Boys who have the typical karyotype for males (46, XY) and have mutations in the MECP2 gene. When there is no copy of the gene to counteract the allele mutation, severe symptoms occur in patients.
- Boys with a karyotype (47, XY), which characterizes Klinefelter Syndrome, with the mutation of the MECP2 gene allele on the X chromosome, the clinical picture may be that of Rett Syndrome.
- If some somatic cells in the individual have a mutated allele and others do not, somatic mosaicism may occur.
Stages of the disease
The disease can be divided into 4 stages, according to the symptoms and also the age of the girls.
1st phase
Affected children are usually between 6 and 18 months old. What most occurs is the delay in psychomotor development and head growth. Girls’ interest in recreational activities drops a lot.
2nd phase
Between 1 and 3 years is the average age of children in the second stage of the disease. The main characteristics are between the loss of voluntary use of the hands, the deterioration of behavior, rapid regression and the appearance of stereotypes (hand movements). Seizure crises, autistic manifestations, insomnia , clumsy motor skills and loss of speech are common in this phase.
3rd phase
The third stage of the disease appears between 2 and 10 years of age. Mental retardation is severe and social contact usually improves, but seizures continue to happen. Respiratory disorders, ataxia and apraxia can occur.
4th phase
The average age of people in this phase is 10 years. Motor capacity is lost, there is late motor deterioration, scoliosis, muscle atrophy and stiffness. Eye contact is improved, seizure crises become less than several, trophic changes may occur and pyramidal and extrapyramidal syndromes become common.
These phases are known as the classic Rett Syndrome. There is still the atypical Rett syndrome, which is characterized by not all symptoms appearing, in addition to the fact that the phases may appear at different times from those mentioned above.
Risk factors
It is known that in the case of boys there is little chance of surviving more than one or two years of age. When talking about girls, the average age changes a lot. They can live to be 60 or 70 years old. This difference is so big because they have 2 X chromosomes and they only one.
Syndrome of Rett Syndrome
The symptoms of Rett’s syndrome are defined in three parts: the very common, those that occur in some patients and those that are rare.
Very common:
- Normal prenatal and perinatal development;
- Normal head circumference at birth;
- After 6 months of age, there is a slowdown in the head circumference;
- Psychomotor development up to 6 months of age;
- Manual movements become stereotyped;
- There is a loss of words already learned, understanding is reduced and reasoning is reduced.
Present in some patients
- Bruxism;
- Abnormal muscle tone;
- Sleep disorders;
- Respiratory disturbances during wakefulness;
- Growth retardation;
- Scoliosis and progressive kyphosis ;
- Thin, small feet and hands.
Rare
- Organ sizes are increased;
- Brain damage evident before or after birth;
- Neurological disease resulting from severe infection or head trauma;
- Retinopathy, cataracts and optic atrophy;
- Enlarged organs.
Diagnosis
The specialized professionals to give this type of diagnosis are: neurologists, geneticists, pediatrician, psychiatrist, psychologist, cardiologist, pulmonologist, gynecologist, general practitioner and rheumatologist.
Observation of parents and guardians is essential for medical diagnosis. In case of changes in motor and speech skills, it is necessary to consult the doctor.
The doctor may order tests to detail the diagnosis, such as blood, urine, hearing and imaging tests. Genetic tests can be done for a more accurate diagnosis. This test is the patient’s analyzed DNA, in which a blood sample is collected so that it can be analyzed in the laboratory.
There are also criteria for diagnosing the variant forms of Rett syndrome. Experts say it is necessary to fulfill 3 of the 6 major criteria which are the most common symptoms, or else to fulfill 5 of the 12 minor criteria which are the symptoms present in some patients and the rare ones already mentioned in the topic above.
Treatment of Rett Syndrome
There is no cure or treatment for Rett Syndrome, but there are interventions that can improve patients’ quality of life. There are several forms of treatment, as the symptoms and severity of the disease are different and vary widely from patient to patient.
Despite this, there is a medical protocol that must be done by doctors. During childhood, the doctor who must accompany is the pediatrician and, after adolescence, the general practitioner must take control and guide the patient and her family.
In addition to these specialists, others must accompany the patient throughout her life.
Pediatricians and general practitioners should monitor:
- Evaluation and monitoring of vital signs, height, body mass index and the patient’s weight;
- Assess muscle tone, contractures and posture;
- Laboratory controls with the performance of exams and the use of medications;
- Assessment of the development of cognitive losses;
- Assessment of the resourcefulness of family members who care for the patient;
- Evaluate dermatitis , mucosal lesions and bedsores.
Pulmonologist
Oxygenation levels in patients with Rett Syndrome may be low, apneas, hyperventilation and pneumonia may occur in girls who suffer from the problem, so consultation with a pulmonologist can be important to ensure a good quality of life.
Neurologists
Visiting the neurologist systematically so that he can monitor the development of the disease is essential. The doctor will have the following functions:
- It monitors the patient’s neurological development, including motor development.
- Observing and medicating seizures, apnea attacks and epileptic seizures, working with sleep disorders is also a neurologist’s job.
Psychiatrist
The psychiatrist is indicated to guide the family to medicate patients in case of constant agitation and also how to behave in cases of self-harm.
Orthopedists
As scoliosis is very common, monitoring by an orthopedist is essential. And because the problem is so serious, surgery is the best solution to avoid pain. Kyphosis can also occur.
Taking care of musculoskeletal deformities in the feet and hands, in addition to muscle contractures, is very common for orthopedists responsible for Rett Syndrome patients.
The treatment of osteopenia, osteoporosis is also done by orthopedists.
Gynecologist
Gynecological monitoring must be rigorous. The sexual maturity of SR patients is similar to that of healthy girls. Puberty may appear early in patients, but, on the other hand, menstruation takes longer in girls with the syndrome.
Knowing that the menstrual period of patients is the same as that of healthy women, it can cause discomfort for both the patient and family members, due to hygiene and PMS symptoms. A conversation with the specialist doctor may be recommended to interrupt the menstrual cycle.
Gastroenterologists
As patients with Rett Syndrome have intestinal constipation , gastroesophageal reflux, aerophagia, dysphagia , bloating as a symptom, medical monitoring by a gastroenterologist is necessary.
Physiatrist
Consultation with the physiatrist is important to develop an individualized therapeutic program for functional and motor deficiencies. This specialist assesses the need for wheelchairs, orthoses and other adaptations for the patient’s posture, movement and locomotion.
Nutritionist
As gastrointestinal disorders and musculoskeletal disorders are very common in patients with Rett syndrome, it is important to have a nutritionist monitor.
Cardiologist
After childhood and adolescence, it is important to consult the cardiologist, as heart problems are common in women with Rett Syndrome. These problems are usually cardiac arrhythmias and abnormal pauses between heartbeats.
Physiotherapy
Physiotherapy is essential for patients with RS. The physiotherapist should assess posture, movements, muscle and skeletal deformities, breathing, gait and muscle tone.
The goal of physiotherapy is to decrease, delay and prevent the onset of musculoskeletal manifestations of Rett Syndrome.
There are techniques that the physiotherapist can apply to improve the quality of life of the patient with Rett Syndrome.
Speech Therapy
In speech therapy, there are two aspects to be considered: communication and motor.
In communication, it is important to understand that blinking, looking, some words and babbling can have a communicative function. On the motor side, the speech therapist is responsible for promoting efficient sucking, with cups and straws, promoting efficient swallowing, drool control and other activities that may become specific to each case.
Complications
The main complications that can occur in Rett syndrome are:
- Severe seizures;
- Scoliosis that requires surgery;
- Difficulty eating, which can cause malnutrition;
- Movement problems, such as irregular hand movements;
- Osteoporosis and chances of fractures and falls;
- Short service life and sudden death;
- Sleep problems, sleeping during the day and waking up at night.
How to live with patients
As the disease has no cure, it is necessary to find solutions for the whole family, in addition to strictly following the recommendations made by the doctor. Often, support groups and psychological help may be needed to help the family.
Prognosis
The disease worsens gradually and slowly and can appear from early childhood to adolescence. Symptoms can stagnate and then improve, just as they can get worse over time.
During early childhood, girls with Rett syndrome tend to sit correctly, but have difficulty crawling. When it comes to walking, some children are able to perform the activity normally while others are unable to learn to walk. Patients who are able to walk may lose movement over time.
Life expectancy for Rett Syndrome
Life expectancy tends to vary widely from case to case. It is estimated that many women with the syndrome can live to be 40 to 50 years old or more.
In men, according to the International Rett Syndrome Foundation, this estimate may depend on the underlying mutation, in addition to other associated genetic problems. When mosaicism occurs, men may have a life expectancy similar to that of women. However, boys who have the typical male karyotype and mutation in the MECP2 gene usually live only until the end of childhood.
Prevention
There is no way to prevent the disease, as it is a genetic disease that involves mutations in the gene.
Staying informed is essential to always be able to help those in need. As you read this text, share it with your friends, colleagues and family so that they too are informed and can be better prepared to help others, if necessary.
