Content

Introduction

Rett syndrome is a rare disease that predominantly affects women with a number of new cases (incidence) equal to one in 10,000 / 12,000 births. It rarely occurs in males.

Rett syndrome affects the central nervous system and is one of the most common causes of severe motor and cognitive disability.

Symptoms

The evolution and severity of Rett's syndrome are extremely variable. The age at which the first signs appear can also vary.

The classic form of Rett syndrome is described through four distinct stages, although these may overlap with each other. The main disorders (symptoms) present at each stage of the classical form are:

Stage 1 - Early signs

In the first six to eighteen months of life, the baby may show apparently normal development although some behavioral abnormalities may be present and the baby's development may appear to be slowed down.

During this first stage, generally referred to as period of stagnation, can be found:

  • hypotonia
  • difficulty in feeding
  • atypical repetitive movements of the hands or uncoordinated movements of the limbs
  • delay in speech development
  • difficulty in sitting, crawling and walking
  • lack of interest in the game

The first stage, in most cases, may not be recognized by parents and specialists because the changes occur gradually and can be minimal.

Stage 2 - Regression

In this stage, also referred to as regression, children experience the loss of previously acquired skills. It begins between the first and fourth years of life and can last from two months to more than two years.

The child gradually or suddenly manifests severe problems in language and communication, memory, use of the hands, mobility, coordination and brain functions.

Some aspects of behavior appear similar to those of autism spectrum disorder.

In this period can be found:

  • difficulty in intentional use of the hands, repetitive hand movements are often difficult to control and include twisting, washing, tapping, or hitting movements
  • crisis of distress, irritability and sometimes screams apparently for the absence of obvious reasons
  • social withdrawal, loss of interest in people and avoidance of gaze (eye contact)
  • instability and difficulty walking
  • sleep disorders
  • slowing of head growth
  • difficulty in feeding, in chewing, swallowing and sometimes constipation which can cause abdominal pain

Later, or during this time, the baby may experience periods of rapid breathing (hyperventilation) or slow breathing, including apneas. Air can also be swallowed causing abdominal swelling.

Stage 3 - The plateau

The third stage can begin between 2 and 10 years and can often last for a long time. Many children remain in this stage for a long period of their life.

In this phase, it is possible to observe an improvement of the problems manifested previously.For example, there may be an improvement in some behavioral problems with a reduction in irritability and crying.

Children may show more interest in people and the environment and progress in alertness, attention and communication skills may occur. Their walking ability may improve (or they may begin to walk if they were unable to walk). on the contrary, among the problems that begin at this stage, are included:

  • Seizures, which can become very common
  • worsening of breathing problems, for example shallow breathing followed by rapid deep breaths or apneas
  • teeth grinding (bruxism)
  • some children may develop abnormal heart rhythms

It can be very difficult to achieve and maintain the right weight.

Stage 4 - Deterioration of mobility

The last stage can last for years or decades. The main issues at this stage include:

  • development of curves in the spine known as scoliosis
  • reduction of muscle strength and spasticity (abnormal stiffness, particularly in the lower limbs)
  • loss of the ability to walk

Generally speaking, communication and language skills and brain function do not deteriorate. During this phase, repetitive hand movements may decrease and, generally, some improvement in eye contact is observed.

In addition to the typical form, at least 5 variants of Rett syndrome have been observed: the variant with preserved language, the variant with early onset seizures, the "whip forms" (in which the characteristic clinical signs are more nuanced), the congenital variant in which psychomotor retardation is evident from the first months of life and the late regression variant.

In the literature, some male patients have been described presenting symptoms similar to those of females with classic or atypical Rett syndrome and, rarely, male patients with severe encephalopathy with neonatal onset and significant alterations in breathing.

Causes

Rett syndrome is caused in most cases by a gene mutation MECP2 (Methyl CpG-binding protein 2) located on the X chromosome. The gene MECP2 it contains the information (coding) for the production of a protein necessary for proper brain development and its mutation, therefore, prevents regular brain development.

In most cases (99%) the onset of Rett's syndrome is sporadic, meaning the genetic mutation occurs spontaneously and is not present in healthy parents. This process is known as mutation de novo.

It has recently been shown that some variants of Rett syndrome are caused by mutations in two other genes, called CDKL5 and FOXG1.

Diagnosis

Diagnosis of Rett syndrome is based on observation of clinical signs, after excluding other more common conditions.

It may therefore not happen until the issues are clearly manifested.

To identify the mutation responsible for Rett syndrome, a genetic test must be done by taking a small amount (sample) of blood. However, the specific gene mutation is not present in all individuals with Rett syndrome.

The discovery of an alteration in the gene MECP2 it can help confirm the diagnosis but failure to find the genetic anomaly does not necessarily exclude the syndrome as it could be the result of other genetic mutations.

Therapy and treatment

There is currently no cure (therapy) for Rett syndrome.A parent who cares for a child with Rett syndrome may need support from a variety of professionals.

Interventions that may be indicated for the person with Rett syndrome include:

  • interventions for language and communication
  • therapies for respiratory problems and anti-epileptic therapies
  • Physiotherapy, with particular attention to the sitting position (to minimize the development of scoliosis) and frequent changes in posture
  • orthopedic bustsi, or surgery, in cases of severe scoliosis
  • use of braces in the lower leg (foot-ankle orthosis) for walking
  • use of orthoses (splint) to control hand movements (they are used for limited periods of time to prevent self-injury and encourage activity with the other hand)
  • high calorie diets for weight control, use of tubes or feeding aids
  • interventions to recover or maintain the development of autonomy in daily life
  • therapies for heart problems

Prospect

Although some people with Rett syndrome may have some degree of hand movement control, walking and communication skills, most will need ongoing care throughout their lives.

Many people reach adulthood although complications including heart rhythm abnormalities, pneumonia and epilepsy can cause premature death.

Tips for carers for someone with Rett syndrome

Caring for a child with Rett's syndrome can be psychologically very taxing. Social and psychological support may be needed.

Suggestions for family members or carers of a child with this disease include: taking care of yourself, staying fit and healthy, taking breaks in caring for the sick person, getting legal assistance, and support.

Some parents may find it beneficial to participate in support groups or to be involved in the activities proposed by the associations of family members of patients with this condition.

National Register

Specialists can refer children with Rett syndrome to the regional and national registers of rare diseases. Through this register, useful data can be collected for research on the causes and treatment of this condition.

Bibliography

Rare Diseases Observatory (OMaR). Rett syndrome: what it is

NHS. Rett syndrome (English)

Mayo clinic. Rett syndrome (English)

Orphanet. Rett syndrome

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