MECP2 Duplication Syndrome

MECP2 duplication syndrome is a rare neurodevelopmental condition caused by an extra copy (duplication) of the MECP2 gene. The disorder can cause a wide range of symptoms with varying severity. The most common symptoms include differences in muscle tone, epilepsy and neurodevelopmental impairment that affects cognitive, motor and speech function.

MECP2 duplication syndrome is a condition whose cardinal features include low muscle tone (hypotonia) from infancy, delayed development and abnormal gait. About half of affected children develop epilepsy. The majority of children also have recurrent infections (often respiratory infections) as well as gastrointestinal dysmotility problems with significant constipation. Additional symptoms include stereotypic hand movements, decreased pain sensitivity and scoliosis, and characteristic facial features can be seen in some individuals.  Increased muscle tone can become a problem later in life. 

Most children with MECP2 duplication syndrome will have moderate to severe intellectual disability. Many children do learn to sit and walk independently, though some may eventually lose the ability to walk at an older age. Most have limited or absent speech, but they may be able to communicate in other ways. 

The MECP2 gene creates a protein (methyl-CpG-binding protein 2) that regulates the activity of other genes in the body. When the protein level is altered either because of a faulty gene or an extra copy of the gene, it causes other genes in the body to malfunction, and ultimately affects normal brain development. Individuals with MECP2 duplication syndrome have an extra copy of the MECP2 gene and therefore produce too much MECP2 protein. Rarely, an individual may have two or three extra copies of the gene; these individuals are more severely affected.

MECP2 duplication syndrome primarily affects males, but in rare cases, females may also be affected. The MECP2 gene is located on the X chromosome, one of the two chromosomes that determine a person’s sex. Females have two X chromosomes, while males have one X and one Y. Although in some cases MECP2 duplication syndrome can happen sporadically, in most cases an affected boy inherits the MECP2 duplication from his mother. Females typically do not manifest symptoms, as they are able to turn off or silence the copy of their X chromosome that is carrying the duplication so that the correct amount of MECP2 protein is produced. 

Diagnosis of MECP2 duplication syndrome is initially suspected based on symptoms, medical history and a physical exam. In some cases, there may also be a family history of the condition. The diagnosis is confirmed by molecular genetic testing that can usually be performed by either a blood or saliva sample that is sent to a laboratory for genetic testing. Results typically take several weeks.

At CHOP, treatment is focused on managing symptoms, providing support to children and their families, and maximizing each child’s abilities and skills. In our clinic, children meet with an interdisciplinary team of specialists that provides a personalized treatment plan to guide the child’s local medical, therapeutic and educational teams. Children with MECP2 duplication syndrome are typically followed by multiple providers, including dedicated specialists in neurogenetics, genetic counseling, gastroenterology, rehabilitation medicine, orthopaedics, pulmonology, immunology and physiotherapy.

For children with seizures, anti-seizure medications are used. Seizure control in MECP2 duplication syndrome is challenging, and seizures are often the most difficult health issue to manage. No single anti-seizure medication has been found to be uniformly effective to treat MECP2 duplication syndrome. In some individuals, the presence of seizures can lead to a worsening of overall developmental skills including speech, hand use and ambulation. For children who develop increased muscle tone, medications may be helpful, or in some cases, surgical intervention may be needed. 

Physiotherapy (also known as physical therapy) helps improve overall muscle tone, trunk stability, strength, balance and foot alignment, prevents foot deformities, and keeps heel cords lengthen. Early intervention in the form of physical therapy, occupational therapy, vision therapy, and speech and augmentative communication therapy is key. We provide psychosocial support for families caring for a loved one with MECP2 duplication syndrome to help them navigate the complexities of raising a child with a lifelong neurodevelopmental disorder.

The outlook for children with MECP2 duplication syndrome is varied and largely depends on the progression and severity of symptoms that are present in each individual. For individuals with a history of recurrent infections and other risk factors, this can unfortunately lead to a reduced lifespan.

Although children with MECP2 duplication syndrome will need help with most daily activities, many can learn some independence skills, such as feeding or toileting with assistance. While verbal communication is typically limited, many children can learn to communicate in other ways, such as by using augmentative communication devices. 

The majority of individuals with MECP2 duplication syndrome are not able to live independently because of their significant needs, and will remain with their families or in another setting where they can receive appropriate care into adulthood. Therefore, it is important to maintain a dialogue with your child’s healthcare providers and to coordinate a plan for transitioning from pediatric to adult care. Despite these limitations, individuals with MECP2 duplication syndrome can continue to learn and be engaging members of their families and communities. 

CHOP has been an active site for MECP2 duplication syndrome research, primarily through the National Institutes of Health-funded Natural History Study, aiming to develop a better understanding of MECP2 duplication syndrome and develop new biomarkers to aid in future research or clinical trials.

Children’s Hospital of Philadelphia has unique experience caring for children with MECP2 duplication syndrome and has been active in clinical research for this rare condition.

Our team consists of experts from a variety of specialties, including epilepsy, genetics, gastroenterology, physical medicine, rehabilitation and palliative care, with neurology as the coordinating specialty.

• MECP2 Duplication Foundation
• Rett Syndrome Research Trust
• National Organization for Rare Diseases (NORD) MECP2 Duplication Syndrome Information
• Medline Plus MECP2 Duplication Syndrome Information