Rett Syndrome in Males: How Boys Are Affected

Researchers once thought Rett syndrome affected only females. Now we know that males can also develop this condition, though it is rare. As genetic testing becomes more common, more males are being diagnosed. Scientists are still studying Rett syndrome in males and females to better understand the similarities and differences.

This article explains what we currently know about Rett syndrome in boys and men. It covers how this condition is inherited, when it can develop, and which symptoms to watch for.

Why Is Rett Syndrome So Rare in Males?

Rett syndrome is a rare genetic condition that affects the nervous system. According to the National Organization for Rare Disorders (NORD), Rett syndrome affects about 1 in 10,000 girls in the United States by age 12. Studies show that males make up only 3 percent to 5 percent of cases in the U.S. Researchers are still learning why, but they have a few theories.

Most cases of Rett syndrome are linked to mutations (changes) in the MECP2 gene, which is found on the X chromosome. Females typically have two X chromosomes, while males usually have one X chromosome and one Y chromosome. Because females have two X chromosomes, some of their cells can still use a healthy copy of the gene if the other copy has a mutation, according to NORD. Males typically have only one X chromosome, so they don’t have a second copy to help make up for a changed gene.

Some researchers think certain MECP2 mutations aren’t compatible with life. This may mean that many males who would have Rett syndrome don’t survive to birth. Males born with MECP2 mutations can develop severe symptoms of Rett syndrome early in life, according to the journal Rare. In some cases, these symptoms can be life-threatening.

A pediatrician or specialist may recommend genetic testing to look for MECP2 mutations. Finding one of these mutations is the first step in diagnosing Rett syndrome. Your child’s doctor will also look for other signs of the condition before making a final diagnosis.

Rett Syndrome Usually Develops Randomly

Most cases happen randomly because of spontaneous genetic mutations. These changes aren’t found in either parent’s DNA. Instead, they happen because of mistakes that occur when cells divide and copy their DNA.

Fathers pass either an X or a Y chromosome to their children. Because fathers pass their Y chromosome to their sons, they usually can’t pass on X-linked mutations that cause Rett syndrome. This is one reason the condition is so rare in males, according to a 2023 study in the journal Future Rare Diseases.

Males who develop Rett syndrome may inherit a mutation from their mothers or develop one randomly. In rare cases, they may also have an extra X chromosome. This condition, called Klinefelter syndrome, occurs when someone has two X chromosomes and one Y chromosome. If one of those X chromosomes carries a mutated copy of the MECP2 gene, Rett syndrome can develop.

Males can also develop Rett syndrome through a genetic change called mosaicism, in which some cells have the mutation while others do not. This can happen shortly after a sperm fertilizes an egg. In some cases, the X chromosome inherited from the mother has a healthy copy of the MECP2 gene at first. However, if a mutation occurs as the embryo’s cells grow and divide, some cells may develop a mutation in the gene. As a result, some cells carry the healthy copy of MECP2, while others carry the mutation. This mixture of cells can lead to Rett syndrome.

When Does Rett Syndrome Appear in Males?

Symptoms can begin at different ages in males with Rett syndrome. Because the condition is so rare in males, there’s limited information on how it develops. The International Rett Syndrome Foundation notes that some males with this condition begin showing symptoms between 6 and 18 months old. When children lose skills they had previously learned, this stage is called regression.

One 2025 study of 47 males with Rett syndrome found that many began missing developmental milestones early in life. About 34 percent showed signs between birth and 3 months of age. The rest began missing milestones between 4 months and 18 months.

On average, the children in the study were diagnosed with Rett syndrome around age 3. It took specialists about two years to make the final diagnosis.

It’s important to remember that every case of Rett syndrome is different. Children may develop symptoms at different times. If you’re concerned that your child is missing developmental milestones, talk with your pediatrician.

What Are Common Symptoms of Rett Syndrome in Males?

Children with Rett syndrome can experience a range of symptoms, from mild to more severe. Studies show males often develop repetitive hand movements (also called stereotypic hand movements) that may look like hand wringing, squeezing, rubbing, or clapping.

In the 2023 study, researchers examined 35 males diagnosed with Rett syndrome to better understand their health and symptoms. The researchers identified several common signs of the condition, including:

• Epilepsy causing seizures
• Sleep disorders
• Breathing problems
• Dysphagia (difficulty swallowing)
• Muscle weakness that affects motor skills
• Incontinence
• Scoliosis (an abnormal curve of the spine)

Children with Rett syndrome may also lose communication skills, such as speaking and making eye contact. Other symptoms may include frequent crying or irritability, as well as slowed head growth and brain development.

Rett Syndrome Is Often Misdiagnosed in Males

Rett symptoms can look similar to those of other health conditions. In the 2025 study of males with Rett syndrome, many had first received other diagnoses, including:

• Autism spectrum disorder
• Cerebral palsy
• Intellectual disability
• Sleep apnea
• Global developmental delay

How Does Rett Syndrome Differ Between Males and Females?

Only a few studies directly compare Rett syndrome in males and females, especially in people. Researchers are still learning how sex and genetics affect the condition.

Some scientists are using mouse models to study how Rett syndrome may affect males and females differently. One report examined specific changes in the MECP2 gene to see how they influence development. Researchers at the University of California, Davis, found that the male and female mice developed the condition differently.

These findings suggest there may be important differences between boys and girls with Rett syndrome. Some evidence suggests that males may develop more severe symptoms at an earlier age, according to UC Davis Health. However, more studies in humans are needed to better understand these differences.

What’s the Prognosis for Males With Rett Syndrome?

Because so few males are diagnosed with Rett syndrome, it’s hard to know the long-term prognosis (outlook). The 2025 study included 36 living participants and 11 who had died. Those who had died were between ages 1 and 16. The oldest participant was 31.5 years old.

Rett syndrome isn’t just a neurodevelopmental disorder — it can also affect a child’s ability to breathe, eat, and move independently. In the study, nearly half of the participants required breathing support, and most also needed feeding support to get enough nutrition. Many parents expressed frustration about not knowing how the condition might affect their child’s outlook.

Researchers are continuing to study how Rett syndrome affects males. Learning more about this rare condition may help doctors better understand what families can expect and how to provide the best care.

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