Introduction 

Rett syndrome is a rare condition that affects the development of the brain. It can cause severe physical and mental disability that begins in early childhood.

The condition affects approximately one in every 10-12,000 females and is only rarely seen in males.

Signs and symptoms

Rett syndrome usually goes unnoticed for the first few months of the child's life, although parents often realise with hindsight that their child did show some features of the condition quite early on.

Parents tend first to become aware of the condition when their child’s development slows and she then begins to show some of the signs mentioned below.

Experts generally describe four stages of the disease, although symptoms will overlap between each stage. The main features of each stage are described below.

Stage one: early signs and slow development

Stage one describes the changes that typically appear in the first six to 18 months of the infant's life. These include:

  • a general slowness in development
  • floppiness (hypotonia)
  • difficulty feeding
  • abnormal hand movements (such as repeatedly making wringing, clapping or washing motions with the hands)
  • lack of interest in toys 
  • poor co-ordination of trunk and limbs

Stage two: regression

Stage two, known as 'regression' or the 'rapid destructive stage', is where a child starts to lose some of their abilities. This stage usually begins between the ages of one and four and may last for weeks or months.

Your child will gradually or suddenly start to develop severe problems with communication, language, learning, co-ordination and other brain functions.

Signs at this stage include:

  • no longer able to use the hands purposefully – repetitive and uncontrollable hand movements take over
  • periods of distress, irritability and sometimes screaming for no obvious reason
  • social withdrawal, a loss of interest in people and avoidance of eye contact (may be considered as resembling autism spectrum disorder)
  • unsteadiness and awkwardness when walking
  • rapid or slow breathing, including periods where the child holds their breath
  • problems sleeping
  • slowing of head growth/small head size
  • difficulty eating, chewing or swallowing and tummy aches, bloating and constipation

Stage three: plateau

Stage three of the condition usually begins between ages two and 10 and can last for years. At this stage, girls are considered to have emerged from the period of regression in stage two.

Prominent symptoms during this stage can include:

  • floppiness of the limbs and difficulty moving around
  • not being able to use their hands to hold, carry or manipulate objects, with the persistence of repetitive hand movements
  • teeth grinding and abnormal tongue movements
  • not gaining much weight

Many children will also develop seizures (epilepsy), irregular breathing patterns (for example, holding their breath or shallow breathing followed by rapid, deep breathing) and some may develop heart rhythm abnormalities (arrhythmias).

There may be some improvements in earlier problems during this stage as well, such as:

  • an improvement in behaviour, with less irritability and crying
  • increased interest in her surroundings
  • improvements in alertness, attention span, interest in people and communication
  • improvement in walking ability (or learning to walk, if previously unable to do so)

Many girls remain in this stage for most of their life.

Stage four: deterioration in movement

Stage four can last for years or even decades. The main symptoms at this stage are:

  • the spine bending to the left or right side (scoliosis)
  • spasticity (abnormal stiffness, especially in the legs)
  • loss of the ability to walk 

The repetitive hand movements may decrease by this stage and eye gaze usually improves. The seizures also usually become less of a problem in adolescence and early adult life, although they will normally be a lifelong problem to manage.

What causes Rett syndrome?

Most cases of Rett syndrome are caused by a mutation (change in the DNA) in the MECP2 gene, which is found on the X chromosome (one of the sex chromosomes), although mutations in other genes have been found in some cases where the symptoms don't quite follow the classic pattern described above.

The MECP2 gene contains instructions to make a particular protein (MeCP2) that is vital for brain development. The gene abnormality prevents nerve cells in the brain from developing properly.

Although Rett syndrome is caused by a genetic mutation, almost all cases are sporadic and occur without any family history of the condition. This is known as a 'de novo' mutation.

Why is Rett syndrome almost always seen in girls?

Each person normally has one pair of sex chromosomes in each cell – females have two X chromosomes and males have one X and one Y. However, only a single X chromosome is fully functional in any cell, in both males and females.

In females, one of the two X chromosomes is largely inactivated early in the embryo stage of development and the cells produced from these early cells then maintain the pattern of inactivating that particular X chromosome. Which chromosome is inactivated is chosen at random, so any female will have some areas where one X is active and other areas where the other X is active.

Rett syndrome results when half the cells in the child's brain are normal (make use of the X chromosome with an intact MECP2 gene) and half are abnormal, which means they survive but don’t work properly because they are using the X chromosome with a damaged MECP2 gene.

Rare exceptions of Rett syndrome in males occur when, for example, the male is born with an extra X chromosome so he has three sex chromosomes (XXY; known as Klinefelter's syndrome), or when the change is found in only some of the boy's cells (known as mosaicism). As in females, these situations result in a brain with a mix of functioning and impaired cells.

Males who carry the abnormal MECP2 gene on their only X chromosome will usually develop a serious condition known as infantile encephalopathy, which is often fatal at a very young age.

Males with less severe changes in their MECP2 gene can live a long life, although they may have some learning difficulties. Females who carry these milder changes on one of their two X chromosomes will often be perfectly healthy, as the unaffected X chromosome is able to compensate for this type of genetic fault on the affected chromosome.

Diagnosing Rett syndrome

A diagnosis of Rett syndrome is largely based on the symptoms your child has.

A genetic blood test can also be carried out to look for the genetic mutation responsible for the condition, although this is not found in every child with Rett syndrome. Finding a change in this gene can therefore help confirm the diagnosis, but failing to find it does not rule out the condition.

If you have a child with Rett syndrome and you are thinking about trying for another baby, it may be possible to test you and your partner to see if you carry one of the genetic faults that could be passed to your children. However, as the vast majority of cases occur randomly, the risk of having a second child with Rett syndrome is usually low (estimated at around 1%) but may be higher in some circumstances.

Read more about genetic testing and counselling.

Managing Rett syndrome

There is no cure for Rett syndrome and the symptoms can be very difficult to manage. You are likely to need help from a wide range of different health professionals.

Your child may benefit from some of the following treatments and aids:

  • anti-epileptic medicine to control the seizures
  • physiotherapy, posture changes, a back brace and possibly spinal surgery to prevent their spine from curving further (read more about treating scoliosis)
  • a high-calorie diet, with the use of a feeding tube and other feeding aids if necessary
  • occupational therapy to help them develop skills needed for dressing, feeding and other daily living activities
  • an ankle-foot orthosis (lower leg brace) to help them walk independently
  • a hand splint to help control their hand movements, if these are severe
  • beta-blocker medication or a pacemaker to control their heart rhythm
  • picture boards, eye gaze technology and other visual aids to help them communicate

Therapeutic horse riding, swimming, hydrotherapy and music therapy have also been reported to be beneficial. Ask your healthcare team where you can access these therapies.

Read more about caring for a disabled child and the aids and adaptations you may need if you're a parent carer.

Outlook

Although some people with Rett syndrome may retain a degree of hand control, walking ability and communication skills, most will be dependent on 24-hour care throughout their lives.

The lifespan of someone with the condition is generally shortened, often because of life-threatening arrhythmias, but many people live well into middle age and beyond.




Rett syndrome is caused by a genetic mutation 

Advice for carers

Caring for a child with Rett syndrome is mentally and physically challenging. Most carers will need social and psychological support.

The Care and support site provides lots of advice on how you can take time to look after yourself, including:

You may also find it useful to contact a support group, such as Rett UK, for information and advice about looking after a child with the condition.

Page last reviewed: 28/07/2014

Next review due: 28/07/2016