Is it possible for Rett syndrome to occur in males?

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RTT is more likely to develop in people assigned as female at birth because its genetic transmission is linked with a person’s sex.

Sex-linked inheritance

A person assigned as female at birth typically has two X chromosomes, while those assigned as male usually have one X and one Y chromosome.

RTT most often develops due to an alteration in the methyl-CpG binding protein 2 (MECP2) gene, which is on the X chromosome. As they generally have two of these, females are more likely to develop this condition. Health experts refer to this as a sex-linked inheritance.

A person only requires one copy of this gene variation to display symptoms. This is called X-linked dominant inheritance.

Chromosomal alterations

Females with RTT usually possess one X chromosome variation and one typical X chromosome.

Only one X chromosome in each cell remains active throughout a person’s life. Determining which X chromosome remains active is complex, and researchers are still investigating how this process works.

If the cells have an active gene alteration more often than the typical gene, the person’s RTT symptoms will be more severe. This random process allows most females with RTT to survive infancy.

Because males typically only have one X chromosome, if they possess this gene variation and do not have a second X chromosome without the alteration, they will most likely be stillborn or not live past infancy.

Rett syndrome is most common in females. However, in some very rare cases, it does affect males. Males with Rett syndrome usually experience more severe symptoms than females.

Because males usually only have one X chromosome, it is rare for males with RTT to live past infancy. However, some males with RTT do live past infancy. If they do, it is most likely due to one of the following reasons:

• Mosaicism: Mosaicism is a condition that causes individual cells within the same person to have a different genetic makeup. This means a person could have some X chromosomes featuring the alteration that causes RTT and some that do not.
• Klinefelter syndrome: Klinefelter syndrome is a condition that causes males to have two X chromosomes and one Y chromosome. If one of the X chromosomes carries the variation that causes RTT, then the male can develop symptoms of the condition. The more cells with active X chromosome alteration, the more severe their symptoms.
• A less severe gene alteration: If the genetic variation is less severe than in other forms of RTT, then the male may live past infancy.
• Duplication of the MECP2 gene: In some rare cases, a duplication of the MECP2 gene can occur. This can affect intellectual and physical function.

According to the National Institute of Neurological Disorders and Stroke, the age of onset and severity of RTT symptoms vary between children.

It states that while infants with RTT often display typical early growth and development, there may be subtle differences in early infancy and toddlerhood compared with children who do not have the condition.

These may include:

• loss of muscle tone, also known as hypotonia
• difficulty feeding
• jerky limb movements
• problems crawling or walking
• reduced eye contact
• loss of functional use of their hands followed by compulsive hand movements, such as hand wringing

Later, they will typically display more obvious symptoms of RTT, including:

• slowed development
• loss of mobility or function in their hands
• distinctive hand movements
• slowed growth of the brain and head
• issues with walking, such as walking on their toes or a wide-based gait
• seizures
• cognitive issues
• digestive issues
• trouble with motor functions, such as speaking and controlling eye movements
• difficulty breathing
• sleep problems
• teeth grinding
• difficulty chewing

A doctor will often diagnose RTT by observing the child’s signs and symptoms. They will then conduct ongoing evaluations of the child’s physical and neurological status.

There is a genetic test that medical professionals can carry out to find the specific MECP2 alterations to help confirm their diagnosis. A medical professional will carry out a blood test and send the sample to a lab, where a professional will analyze it to look for the gene variation.

Currently, there is no cure for RTT and the cause of the genetic variation that causes it is largely unknown.

This means that most treatments for RTT aim to reduce symptoms. Options include:

• Speech and language therapy: This can help children develop nonverbal communication methods and support them with social interaction.
• Medications: There are some medications a child can take to help with breathing and mobility problems. They may also take anti-epileptic medicines to manage seizures.
• Physical therapy: This can help improve a child’s mobility and sitting posture to minimize their chances of developing scoliosis.
• Dietary changes: A medical professional may suggest a high calorie, low carbohydrate diet to help a child maintain sufficient weight. This may also help manage seizures. Medical professionals may help with the use of a feeding tube and other feeding aids if necessary.
• Occupational therapy: This can help the child develop skills to assist with their daily activities. This can include learning how to dress and feed themself.
• Braces: A child may wear braces to help correct the effects of scoliosis or wear a lower leg brace to help them walk independently.
• Splints: A medical professional may suggest using splints to adjust hand movements.

Rett syndrome (RTT) is a rare genetic condition that can cause mental and physical disabilities. Although it most commonly affects females, in rare cases, it can affect males.

The condition develops due to an alteration in the MECP2 gene on the X chromosome. It most commonly affects females because they generally have two X chromosomes, while males typically have one.

Males with the gene variation that causes RTT do not typically live past infancy. However, in some rare cases, males with the variation can survive beyond this if they have mosaicism, Klinefelter syndrome, or a less severe form of the gene variation.