Rett syndrome is a rare developmental disorder, most often due to a mutation in the MECP2 gene on the X chromosome, but it’s not usually inherited. Advances in genetics have launched a new era in treatment research.
Rett syndrome is a rare, incurable genetic disorder that primarily affects people assigned female at birth.
Babies born with Rett syndrome usually appear healthy and grow and develop typically for the first 6 to 18 months. Afterward, head growth slows, eye contact and engagement decrease, and development stalls and begins regressing.
Children with Rett syndrome experience a rapid loss of developmental skills like crawling, sitting, and communicating. They lose purposeful hand use, developing abnormal hand movements and musculoskeletal problems. As they grow, seizures and heart and breathing complications can arise.
You may have previously heard Rett syndrome referred to as a form of female autism. But in
Further advances in the genetic understanding of Rett syndrome have enabled more accurate diagnosis and opened new frontiers in treatment research.
The genetics of Rett syndrome are complex. Scientists have identified at least 90 different mutations that can cause Rett syndrome.
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The MECP2 gene produces the MeCP2 protein, which helps “read” your DNA and regulate your cells’ production of many different molecules. MeCP2 protein exists in high concentrations in the brain.
But doctors still aren’t sure exactly how mutations in the MECP2 gene produce the symptoms of Rett syndrome.
Rett syndrome is an X-linked dominant condition. This means a mutation on just one X chromosome is enough to cause the disorder.
Females are generally born with two X chromosomes, while males have only one. For this reason, males developing Rett syndrome mutations in the MECP2 gene are very severely affected and often die before birth or in early infancy.
Because of this, doctors previously thought Rett syndrome only affected females. Now, scientists have identified a small number of cases of surviving males with Rett syndrome caused by less severe MECP2 or other gene mutations.
Rett syndrome is a very rare X-linked dominant disorder.
But unlike many other genetic diseases, the gene changes causing Rett syndrome appear spontaneously, usually in a random sperm cell. So, Rett syndrome generally does not run in families.
Over 99% of cases of Rett syndrome are caused by these random spontaneous mutations, usually in the MECP2 gene on one X chromosome.
In extremely rare cases, a female could carry MECP2 mutations but remain asymptomatic because her mutated gene copy is inactivated. In these cases, Rett syndrome-causing mutations may be inherited.
Yes, genetic testing for Rett syndrome is available.
If you or your doctor are concerned about your child’s development, your doctor will start by discussing your child’s birth, development, and family medical history.
Your doctor might order additional studies, such as blood tests or MRI scans. They may also refer you to a specialist in neurology or genetics.
If they suspect Rett syndrome, a doctor can order MECP2 gene analysis testing. Occasionally, testing doesn’t reveal the most common Rett syndrome-causing mutations, and a doctor may recommend further genetic testing.
There’s currently no cure for Rett syndrome. But scientists continue exploring treatments for this disorder.
In 2023, the Food and Drug Administration (FDA) approved
Multiple gene therapy trials are ongoing in 2024, as scientists attempt to introduce functional MECP2 genes (either full-length or shortened versions) in children with Rett syndrome using viral vectors.
Future research may also focus on reactivation of the healthy X-chromosome copy of MECP2 present in affected females.
Read more about ongoing clinical trials in Rett syndrome.
How common is Rett syndrome?
Rett syndrome occurs in approximately 1 per 10,000 to 20,000 live female births.
Rett syndrome is exceedingly rare in males, with about 60 reported cases in the medical literature.
At what age does Rett syndrome developmental regression start?
Depending on the gene mutation and severity, developmental regression (when a child starts to lose skills they previously gained) usually begins around 6 to 18 months of age.
Can you detect Rett syndrome before birth?
Yes, it’s possible to diagnose Rett syndrome prenatally, when pregnant people undergo testing for known gene mutations via procedures like amniocentesis.
But because Rett syndrome gene mutations usually occur spontaneously and are not generally inherited, prenatal diagnosis is uncommon.
Rett syndrome is a rare, X-linked neurodegenerative disorder seen mostly in females. Mutations in the MECP2 gene are responsible for most cases of Rett syndrome. MECP2 gene testing now provides many families with an earlier, more definitive diagnosis.
Advances in genetic research have since identified other causative mutations and can even help predict the outlook for some affected babies. Clinical trials of new treatments aimed at the underlying genetic cause of Rett syndrome are providing new hope for families.
If you have concerns about your child’s development or think your baby is losing skills they previously mastered, talk with your child’s pediatrician right away. Rett syndrome is quite rare, but early identification and treatment of developmental delays is helpful no matter the cause.