Rett Syndrome

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Rett Syndrome

What Is Rett Syndrome?

Rett syndrome is a brain development disorder that affects mostly girls. In most cases, a change in a gene called MECP2 causes Rett syndrome.

Girls with Rett syndrome appear normal when born and as young infants. At around 6 to 18 months old, their learning slows down and they begin to lose language and motor skills. This loss eventually stops and their development stabilizes, but girls with Rett syndrome have serious, life-long problems with learning, speech, and movement.

One of the classic signs of Rett syndrome is making hand movements over and over, like hand wringing or clapping that has no purpose. Other signs include slowing head growth, autistic-like behaviors, severe communication problems, breathing irregularities, sleep disturbances, and seizures.

This combination of symptoms is called "classic" Rett syndrome. Sometimes the signs of Rett syndrome are more or less serious – or the signs start earlier or later than usual. These variations are called "atypical" or "variant" Rett syndrome. For example, in a milder variant of Rett syndrome, girls still have relatively normal speech. In a more severe variant, symptoms start near birth and cause serious seizures.

Rett syndrome may be misdiagnosed as autism, cerebral palsy, Angelman syndrome, or non-specific developmental delay.

Boys very rarely have Rett syndrome, but it is possible. The reason for this is explained in the  Genetics of Rett Syndrome. Boys who have a change in the MECP2 gene usually have such serious brain disease that they don't survive past one to two years old.

Next: Who Is at Risk for Rett Syndrome?

Why are you considering testing?

I am considering testing for my child who has signs of Rett syndrome.

My child has a Rett syndrome mutation and I'm considering testing for myself.

My child has a Rett syndrome mutation and I'm considering testing for a pregnancy.

I am a relative (but not a parent) of someone with Rett syndrome.

None of these

Rett syndrome genetic testing should be considered for anyone with diagnosed or strongly suspected Rett syndrome based on the medical signs. Testing will find an MECP2 gene mutation in 88% of girls with classic Rett syndrome and 43% of girls with variant Rett syndrome.

Rett syndrome testing may also be considered for people with some signs of Rett syndrome that aren't enough to make a diagnosis or for those who have uncommon signs of an MECP2 mutation. If your child doesn't have a clear diagnosis of classic or variant Rett syndrome, the chance that the test will actually find a mutation may be lower.

  • When testing finds a mutation, the results confirm that your child has Rett syndrome. This information can help you understand the reason for your child's condition, connect with people who may have a shared experience, and learn more about possible treatments. This information also allows reliable genetic testing for certain relatives who could also have the mutation. Rarely, mothers and sisters of a person with Rett syndrome also have a mutation and should consider testing. Even if no one else in the family is known to have a Rett syndrome mutation, there is a small increased chance to have another child with it. Knowing the mutation gives parents the option to have accurate prenatal diagnosis if desired. Other options, like preimplantation diagnosis or adoption, may also be considered.
  • When testing doesn't find a mutation, the results don't rule out Rett syndrome or another condition that causes symptoms like Rett syndrome. Depending on your child's specific symptoms, other genetic tests may be offered. For instance, a mutation in the CDKL5 gene can cause a variant kind of Rett Syndrome that starts earlier than usual and has serious seizures. Unless a diagnosis is found, it will be difficult to accurately predict if you or other family members have a higher chance for having another child with similar symptoms.

Once an MECP2 gene mutation has been found in a child, the mother is usually offered testing for just that one mutation. In very unusual circumstances, a father may also be offered testing. The laboratory will need to know the exact name of the mutation. If possible, it is best either to use the same laboratory that tested your child, or to give the laboratory a copy of the genetic test results.

More than 99% of the time, a person with Rett syndrome is the only person in the family with it. Usually, this is because a new gene change happened when that child was conceived – the mutation doesn't run in the family.

However, in rare cases, a mother can have the same MECP2 gene mutation and have mild or no signs of Rett syndrome. Women have two copies of the X chromosome and, therefore, two copies of the MECP2 gene. Each cell normally turns off one X chromosome because we only need the genetic information from one X. By luck, sometimes the X chromosome with the MECP2 gene mutation is turned off in a high percentage of cells. This means that most cells have an MECP2 gene that works normally, which is enough to keep the person from having Rett syndrome. In this case, a mother has a 50% chance to pass on the MECP2 mutation with each pregnancy. It is rare for a mother to have an MECP2 mutation, but it is important to rule out – especially if you have other children or plan to have more.

Fathers of girls with Rett syndrome may be offered testing if there are any signs that he might have a small percentage of cells that have an MECP2 gene mutation, or it isn't clear what kinds of symptoms the MECP2 gene mutation might cause.

Even if your results are normal, there is still a small chance to have another child with Rett syndrome. Prenatal diagnosis that looks for the MECP2 mutation is an option for any future pregnancy.

Once an MECP2 gene mutation has been found in a child, parents are offered genetic testing for that mutation in any future pregnancies. It is rare, but possible, that a parent has a small percentage of cells with the MECP2 mutation that can't be found by genetic testing. This is called mosaicism. Sometimes the gene mutation is only in the cells that make sperm or eggs. In this case, it is called germline mosaicism.

If you want some kind of testing, there are two main options:

  • Preimplantation genetic diagnosis (PGD) combines genetic testing with in vitro fertilization (IVF). Sperm from the father is combined with the mother's egg in the laboratory. Genetic testing is done on cells from very early developing embryos. Only the embryos that don't have the mutation based on genetic testing are placed into the mother to grow and develop as in a typical pregnancy.
  • Prenatal diagnosis is a way to get a small number of cells from the developing baby for genetic testing during pregnancy. Amniocentesis and CVS are the two main prenatal diagnosis tests. When the MECP2 mutation has already been found, prenatal diagnosis can reliably tell you if the pregnancy will have Rett syndrome. This allows you to make informed decisions about how you would like to proceed with the pregnancy. If a pregnancy is diagnosed with Rett syndrome, you can choose to continue the pregnancy and use the time to prepare yourself or decide to end the pregnancy.

More than 99% of the time, a person with Rett syndrome is the only person in the family with it. Usually, this is because a new gene change happened when that child was conceived – the mutation doesn't run in the family.

If an MECP2 gene mutation that causes Rett syndrome is found in a family member, the mother and sisters of that person may be offered genetic testing. If none of them has the same MECP2 mutation, less closely related family members aren't at risk. If a mother or sister does share the same mutation, it may make sense to test certain other relatives. Who should be tested depends on the relationship.

Your doctor or a genetic counselor can review your family history, the possible ways that an MECP2 gene mutation could be inherited in your family, and your personal risk. If appropriate, they can coordinate testing for you. The laboratory would need to know the exact name of the mutation found in your relative. If possible, it is best either to use the same laboratory that tested the relative, or to give the laboratory a copy of the genetic test results.

Importantly, several other conditions can cause symptoms that look like Rett syndrome. If Rett syndrome has not been confirmed by genetic testing in a relative, this kind of genetic testing isn't useful for other family members.

Rett syndrome genetic testing probably won't be useful for you if you don't have any of these reasons for testing.

There are much less common reasons to consider MECP2 gene testing. If you or a family member has symptoms that make you concerned about Rett syndrome or a related condition, you should talk to your doctor or a genetic counselor. These professionals can review your personal and family history, find any specific risks based on that history, and help you decide if genetic testing may be useful for you.