MECP2 duplication syndrome

One syndrome, several names

MDS

Lubs syndrome

Atypical Rett Syndrome

OMIM #300260

Xq28-duplication

MRXSL

The syndrome

MECP2 duplication syndrome is a rare and severe genetic disorder. Also known as Lubs syndrome, Xq28 duplication or atypic Rett syndrome, the syndrome is results from the duplication of the MECP2 gene on the X chromosome. This gene plays a crucial role in brain development and function, and its duplication leads to an overproduction of the MECP2 protein, which disrupts normal neurological processes.

This condition primarily affects males, as they have only one X chromosome. Females can also be affected, but typically exhibit milder symptoms due to the presence of a second, normal X chromosome.

Prevalence

MECP2 duplication syndrome is considered rare, with an estimated prevalence of 1 in 50,000 to 1 in 100,000 live births. However, as awareness and genetic testing improve, more cases are being identified, suggesting that the condition might be underdiagnosed (Daniel Ta et al., Orphanet J Rare Dis 17, 131 (2022)).

Research and Support

Ongoing research is essential to better understand MECP2 duplication syndrome and develop more effective treatments. Various associations around the world are here to support caregivers and families with MECP2 duplication syndrome. Don’t hesitate to contact them for local support.

Symptoms and Characteristics

Individuals with MECP2 duplication syndrome often present with a range of symptoms, which can vary in severity. Common characteristics include:

Developmental Delays: Delays in reaching developmental milestones such as sitting, walking, and talking.
Intellectual Disability: Most individuals have moderate to severe intellectual disability.
Recurrent Infections: Frequent respiratory infections are common due to immune system dysfunction.
Motor Skills Impairment: Poor muscle tone (hypotonia) and coordination issues.
Seizures: Many affected individuals develop seizures or epilepsy.
Behavioral Issues: Some may exhibit autistic-like behaviors, including repetitive movements and social interaction difficulties.

Diagnosis and Management

Diagnosis of MECP2 duplication syndrome is typically confirmed through genetic testing, which identifies the duplication of the MECP2 gene. Early diagnosis is crucial for managing the condition and improving quality of life.

There is no treatment available to cure MECP2 duplication syndrome yet. Management strategies often involve a multidisciplinary approach, including:

Medical Care: Regular monitoring and treatment of infections, seizures, and other medical issues.
Therapies: Physical, occupational, and speech therapies to support development and improve daily functioning.
Support Services: Access to educational and social support services tailored to the needs of the individual and their family.

Comparison to Rett Syndrome

While MECP2 duplication syndrome and Rett syndrome both involve the MECP2 gene, they are distinct conditions. Rett syndrome is primarily caused by mutations in the MECP2 gene and predominantly affects females. In contrast to MECP2 duplication syndrome, where there is an overexpression of the MECP2 protein, patients with Rett syndrome do not have enough functional MECP2 protein. This deficiency disrupts normal brain development and function.

It leads to severe cognitive and physical impairments, with symptoms typically emerging between 6 to 18 months of age. These symptoms include loss of purposeful hand skills, repetitive hand movements, slowed growth, and difficulties with motor coordination and communication.