Rett Syndrome: A Rare Neurological and Genetic Disorder

rett-syndrome

Rett Syndrome (RTT) is a rare neurological genetic disorder that almost exclusively affects baby girls. The disorder impairs every aspect of life: talking, walking, eating, and breathing easily.

The syndrome is caused by mutation in the MECP2 gene present on the X-chromosome. The mutation occurs randomly and the chances of passing the syndrome from one generation to another is rare.

Key Takeaways

  • Type: Neurodevelopmental disorder that almost exclusively affects baby girls.
  • Causal Gene: Mutation in the MECP2 gene. The gene is required for the development and functioning of the brain.
  • Inheritance Pattern: Rarely inherited, in rare cases which are inherited, are in X-linked dominant manner.
  • Main Symptoms: Loss of movement, coordination, and communication skills along with uncontrolled hand movements.
  • Diagnosis: Still based on Clinical Assessments and meeting the specific diagnostic criteria. Knowing the type of MECP2 mutation causing the disorder requires Genetic Testing.
  • Treatment: A Trofinetide drug is approved by the US FDA for the treatment of Rett Syndrome in Adults and children above 2 years.

Understanding Rett Syndrome

Rett Syndrome was originally described by an Austrian Pediatric Neurologist Dr. Andreas Rett in 1966.

What is Rett Syndrome?

Rett Syndrome is a rare genetic neurodevelopmental disorder. It affects almost every aspect of life like walking, talking, eating, and breathing easily.

The major feature of the disorder is the constant repetitive hand movements while the child is awake.

Children with Rett Syndrome shows normal development until around one year of age, but later the child starts losing the ability to use their hands purposefully.

Other development also slows down.

The child faces developmental challenges throughout their childhood. However, the challenges slow down in adulthood but do not go away.

Since the syndrome is not a degenerative disorder, people with Rett Syndrome live to middle age or even close to a typical lifespan.

How Prevalent is Rett Syndrome?

Rett Syndrome affects almost exclusively females and rarely boys. About 1 in 10,000 baby girls are born with this genetic disorder worldwide.

Symptoms of Rett Syndrome

The symptoms of Rett Syndrome can range from mild to severe depending on the type of mutation(s) present in the MECP2 gene.

Babies usually do not show symptoms for the first few months or years. But, later there is a delay in the child’s development along with the occurance of other symptoms.

The main symptoms of Rett Syndrome include:

  • Loss of movement. There is a decrease in the ability of the child to crawl or walk. Initially, the loss of ability is rapid but later it slows down. Eventually, the muscles become weak and stiff with uncontrolled movement.
  • Loss of communication abilities. The child loses the ability to speak, make eye contact, or communicate in other ways. Children lose interest in social activities. With time, children may regain non-verbal communication skills.
  • Uncontrolled hand movements. Children with Rett Syndrome show repetitive hand movements like hand wringing, clapping, tapping, squeezing, or rubbing.

Some of the other symptoms include:

  • Unusual eye movements
  • Unusual breathing
  • Intellectual disabilities
  • Swallowing and digestion abnormalities
  • Sleeping disorders
  • Irregular heartbeat
  • Seizures

Stages of Rett Syndrome

The course and severity of the Rett Syndrome varies from child to child. Rett Syndrome is divided into four stages. This is a general guideline provided to understand the disorder.

Four Stages of Rett Syndrome are:

  • Stage I (Early Onset Stage). Starts at 6 months to 1.5 years. There is a delay in the child’s development like crawling and making eye contact.
  • Stage II (Rapid Destructive Stage). Starts at 1 to 4 years old. The child loses some speaking and motor skills. There can be constant hand movements.
  • Stage III (Plateau Stage). Starts from Preschool to Adulthood. This stage may last for decades. The progression of symptoms slows down or might improve.
  • Stage IV (Late Motor Deterioration Stage). When a person loses the ability to walk. However, they still have some communication and thinking skills.

Genetics

What is the Genetic cause of Rett Syndrome?

Rett Syndrome is caused by genetic mutation (change) in the MECP2 gene present on the X-chromosome. There are more than 900 different mutations found in the MECP2 gene.

The MECP2 gene plays an important role in brain development and brain function. Shortage or absence of MeCP2 protein affects the development of the brain leading to the symptoms of Rett Syndrome.

How is Rett Syndrome Inherited?

Rett Syndrome is mainly caused by a random mutation in the MECP2 gene and is usually not inherited. However, in some rare cases it can be inherited in X-linked dominant manner.

Diagnosis and Testing

How to Diagnose Rett Syndrome?

Diagnosis of Rett Syndrome is still based on Clinical Assessments by specialists. It requires the fulfillment of specific diagnostic criteria.

The Main Criteria are:

  • Partial or complete loss of hand skills
  • Partial or complete loss of spoken language
  • Repetitive hand movements
  • Unable to walk properly

If Rett Syndrome is suspected, Genetic Testing is suggested. It is a blood test to check for any mutation in the MECP2 gene that causes Rett Syndrome.

The testing validates the clinical diagnosis and can help you know about the specific mutation causing the disease in your child.

Knowing about the type of mutation can help you get your child into clinical trials and inform you about the recurrence risks in future pregnancies.

Treatment, Cure, and Prevention

What is the Treatment for Rett Syndrome?

In 2023, the U.S. Food and Drug Administration (FDA) approved a Trofinetide drug to treat Rett Syndrome. The drug is marketed under the name DAYBUE.

It is the first FDA-approved treatment for Rett Syndrome in adults and children above 2 years. It works by reducing swelling in the brain and increasing the levels of protective protein in the brain.

Other medications focus on treating specific symptoms of Rett syndrome like breathing, movement problems, and seizures. Physical, Occupational, and Speech therapies are also suggested for people with Rett Syndrome.

Can Rett Syndrome be Cured?

To date, there is no cure for Rett Syndrome. However, the medication and therapies can help children to manage the symptoms effectively into adulthood.

How to Prevent Rett Syndrome?

You cannot prevent Rett Syndrome as the disorder occurs due to random mutations. There is nothing a parent can do before or during pregnancy to prevent Rett Syndrome.

FAQs

What is the life expectancy of a child with Rett Syndrome?

Rett Syndrome is a neurodevelopmental and not a neurodegenerative disorder. Therefore, people with Rett Syndrome can live to middle age or have a typical lifespan.

Do all children move through the different stages of Rett Syndrome?

No. The four stages of Rett Syndrome are only the guidelines provided to understand the disorder. The severity of Rett Syndrome varies from child to child and depends on the type of mutation present in the MECP2 gene.

Is Rett Syndrome seen predominantly in one race?

No. Rett Syndrome affects babies of all ethnicities and races.

Further Reading

  • Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study (2023) – Nature Medicine
  • Advanced genetic therapies for the treatment of Rett syndrome: state of the art and future perspectives (2023) – Frontiers in Neuroscience
  • Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study (2023) – BMC Neurology
  • Improving clinical trial readiness to accelerate development of new therapeutics for Rett syndrome (2022) – Orphanet Journal of Rare Diseases
  • Rett syndrome – biological pathways leading from MECP2 to disorder phenotypes (2016) – Orphanet Journal of Rare Diseases

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