MECP2 duplication syndrome

Title

Other Names:

MRXSL; Lubs X-linked mental retardation syndrome (formerly); XLMR syndrome, Lubs type; MRXSL; Lubs X-linked mental retardation syndrome (formerly); XLMR syndrome, Lubs type; Mental retardation, X-linked, Lubs type (formerly) See More

Categories:

Congenital and Genetic Diseases; Nervous System Diseases

Summary Summary

MECP2 duplication syndrome is a genetic condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual disability. Other signs and symptoms include infantile hypotonia; delayed motor milestones (i.e. sitting up, crawling); recurrent infections; poor or absent speech; seizures; and/or spasticity. MECP2 duplication syndrome occurs when there is an extra copy (duplication) of the MECP2 gene in each cell. This is generally caused by a duplication of genetic material located on the long (q) arm of the X chromosome. The condition is inherited in an X-linked manner. Treatment is based on the signs and symptoms present in each person.^[1]^[2]

Last updated: 7/23/2015

Symptoms Symptoms

MECP2 duplication syndrome is a condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual disability. Infants affected by this condition are generally diagnosed with severe hypotonia within the first few weeks of life. This reduced muscle tone can lead to feeding difficulties which may require a feeding tube. Trouble swallowing, gastroesophageal reflux, failure to thrive, and extensive drooling are also common symptoms. Distinctive physical features may be noticed shortly after birth which can include brachycephaly (abnormally flat back of the head), midface hypoplasia (underdevelopment of the middle of the face), large ears, deep-set eyes, prominent chin, and a depressed nasal bridge.^[1]^[2]

Due to hypotonia, affected children often have delayed development of motor milestones such as sitting up and crawling. Approximately, one third of affected people never walk independently and those who are able to walk may have an abnormal gait (style of walking). In most cases, hypotonia gives way to spasticity during childhood. Progressive spasticity, which is generally more pronounced in the legs, may lead to the development of mild contractures. Consequently, many affected adults require the use of a wheelchair.^[1]^[2]

The majority of affected people do not develop the ability to talk. Some may have limited speech during early childhood, but frequently this ability is progressively lost during adolescence.^[1]

Other signs and symptoms associated with MECP2 duplication syndrome may include seizures; autistic features; clinically significant constipation and bladder dysfunction.^[1]^[2]

Many people affected by MECP2 duplication syndrome have recurrent respiratory tract infections. These respiratory infections can be life-threatening and as a result, approximately half of affected people succumb by age 25.^[1]

In most cases, females with a duplication of the MECP2 gene do not have any symptoms, although depression, anxiety, and autistic features have been described in some. When affected, women with MECP2 duplication syndrome are generally less severely affected than males with the condition.^[1]

Last updated: 7/22/2015

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of chromosome segregation		0002916
Blepharophimosis	Narrow opening between the eyelids	0000581
Cryptorchidism	Undescended testes Undescended testis [ more ]	0000028
Delayed skeletal maturation	Delayed bone maturation Delayed skeletal development [ more ]	0002750
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Everted lower lip vermilion	Drooping lower lip Outward turned lower lip [ more ]	0000232
Hypospadias		0000047
Intellectual disability, severe	Early and severe mental retardation Mental retardation, severe Severe mental retardation [ more ]	0010864
Neurological speech impairment	Speech disorder Speech impairment Speech impediment [ more ]	0002167
Ptosis	Drooping upper eyelid	0000508
Severe global developmental delay		0011344
Short stature	Decreased body height Small stature [ more ]	0004322
Tented upper lip vermilion		0010804
30%-79% of people have these symptoms
Gait disturbance	Abnormal gait Abnormal walk Impaired gait [ more ]	0001288
Hernia of the abdominal wall		0004299
Pectus excavatum	Funnel chest	0000767
5%-29% of people have these symptoms
Joint stiffness	Stiff joint Stiff joints [ more ]	0001387
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis	Laboratory abnormality Metabolism abnormality [ more ]	0001939
Abnormality of the dentition	Abnormal dentition Abnormal teeth Dental abnormalities Dental abnormality [ more ]	0000164
Absent speech	Absent speech development Lack of language development Lack of speech No speech development No speech or language development Nonverbal [ more ]	0001344
Anxiety	Excessive, persistent worry and fear	0000739
Ataxia		0001251
Brachycephaly		0000248
Bruxism	Teeth grinding	0003763
Chorea		0002072
Constipation		0002019
Depressed nasal bridge	Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ]	0005280
Depressivity	Depression	0000716
Drooling	Dribbling	0002307
Dysphagia	Poor swallowing Swallowing difficulties Swallowing difficulty [ more ]	0002015
Facial hypotonia	Decreased facial muscle tone Low facial muscle tone Reduced facial muscle tone [ more ]	0000297
Gastroesophageal reflux	Acid reflux Acid reflux disease Heartburn [ more ]	0002020
Infantile muscular hypotonia	Decreased muscle tone in infant	0008947
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Low-set ears	Low set ears Lowset ears [ more ]	0000369
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Macrotia	Large ears	0000400
Malar flattening	Zygomatic flattening	0000272
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Midface retrusion	Decreased size of midface Midface deficiency Underdevelopment of midface [ more ]	0011800
Narrow mouth	Small mouth	0000160
Poor eye contact		0000817
Progressive		0003676
Progressive spasticity		0002191
Recurrent respiratory infections	Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ]	0002205
Rigidity	Muscle rigidity	0002063
Seizures	Seizure	0001250
X-linked recessive inheritance		0001419

Showing of 48 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 4/1/2018

Cause Cause

MECP2 duplication syndrome occurs when there is an extra copy (duplication) of the MECP2 gene in each cell. This is generally caused by a duplication of genetic material located on the long (q) arm of the X chromosome. The size of the duplication can vary; however, this does not appear to affect the severity of the condition. People with larger duplications have signs and symptoms that are similar to people with smaller duplications.^[3]

The MECP2 gene encodes a protein that is important for normal brain functioning. Although it plays many roles, one of its most important functions is to regulate other genes in the brain by switching them on and off. A duplication of the MECP2 gene leads to the production of excess protein, which is unable to properly regulate the expression of other genes. This results in irregular brain activity, leading to the signs and symptoms of MECP2 duplication syndrome.^[3]^[2]

Last updated: 7/22/2015

Inheritance Inheritance

MECP2 duplication syndrome is inherited in an X-linked manner.^[3] A condition is considered X-linked if the genetic change that causes the condition is located on the X chromosome, one of the two sex chromosomes (the Y chromosome is the other sex chromosome). In males (who have only one X chromosome), a duplication of the MECP2 gene in each cell is sufficient to cause the condition.

In females (who have two X chromosomes), a duplication of one of the two copies of the gene typically does not cause the disorder. Early in the development of females, one of the two X chromosomes is randomly and permanently inactivated in each cell (called X-inactivation). X-inactivation prevents female cells from having twice as many functional X chromosomes as males. Because X-inactivation is usually random, the X chromosome inherited from the mother is active in some cells, and the X chromosome inherited from the father is active in other cells. However, when a female has an X chromosome with a duplicated copy of the MECP2 gene, the abnormal chromosome is often preferentially inactivated in many or all cells. This is called "skewed X-inactivation." It prevents some women with an MECP2 duplication from developing features of the duplication since the extra genetic material is not active.

In most cases, MECP2 duplication syndrome is inherited from a mother who has no signs or symptoms of the duplication. Rarely, the condition is not inherited and occurs due to a random event during the formation of the egg or sperm, or in early fetal development. When this happens, it is called a de novo duplication (occurring as a new genetic change for the first time in the affected person).^[3]^[2]

Last updated: 7/22/2015

Diagnosis Diagnosis

A diagnosis of MECP2 duplication syndrome is often suspected based on the presence of characteristic signs and symptoms. Genetic testing can then be ordered to confirm the diagnosis.^[1]

Last updated: 7/23/2015

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

Because MECP2 duplication syndrome affects many different systems of the body, medical management is often provided by a team of doctors and other healthcare professionals. Treatment for this condition varies based on the signs and symptoms present in each person. For example, infants with trouble swallowing and/or other feeding difficulties may require a feeding tube. Early developmental interventions may be recommended to help affected children reach their potential. This may include physical therapy, speech therapy and/or occupational therapy. Medications may be prescribed to treat seizures or spasticity. Recurrent infections are usually treated aggressively with appropriate antibiotics.^[1]^[2]

Please speak with a healthcare provider if you have any questions about your personal medical management plan or that of a family member.

Last updated: 7/23/2015

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Prognosis Prognosis

The long-term outlook (prognosis) for people with MECP2 duplication syndrome varies. Based on the few documented cases in the medical literature, approximately half of affected people succumb before age 25 years. This shortened life expectancy is largely due to immune system dysfunction and an increased risk for recurrent infections.^[1]

Last updated: 7/23/2015

Do you have updated information on this disease? We want to hear from you.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to MECP2 duplication syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Developmental Delay Resources (DDR)
5801 Beacon Street
Pittsburgh, PA 15217
Toll-free: 800-497-0944
Fax: 412-422-1374
E-mail: devdelay@mindspring.com
Website: http://www.devdelay.org
Rett Syndrome Research Trust
67 Under Cliff Road
Trumbull, CT 06611
Telephone: 203-445-0041
Fax: 203-445-9234
E-mail: info@rsrt.org
Website: http://reverserett.org/
The Arc of the United States
1825 K Street, NW
Suite 1200
Washington, DC, DC 20006
Toll-free: (800) 433-5255
Telephone: 202-534-3700
Fax: 202-534-3731
E-mail: info@thearc.org
Website: http://www.thearc.org
Unique – Rare Chromosome Disorder Support Group
G1, The Stables
Station Road West
Surrey
RH8 9EE
United Kingdom
Telephone: +44 (0)1883 723356
E-mail: info@rarechromo.org
Website: http://www.rarechromo.org

Organizations Providing General Support

American Association on Intellectual and Developmental Disabilities
501 3rd Street NW
Suite 200
Washington, DC 20001
Toll-free: (800) 424-3688
Telephone: (202) 387-1968
Fax: (202) 387-2193
Website: http://www.aaidd.org
The Society for Developmental and Behavioral Pediatrics
6728 Old McLean Village Drive
McLean, VA 22101
Telephone: 703-556-9222
E-mail: info@sdbp.org
Website: http://www.sdbp.org/index.cfm

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Education Resources

The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on MECP2 duplication syndrome. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
Unique is a source of information and support for families and individuals affected by rare chromosome disorders. Click on the link to view information about MECP2 duplication syndrome.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss MECP2 duplication syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

National DNA Day Reddit "Ask Me Anything" (AMA) Series
April 11, 2018

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I want to know if in this syndrome, people can have microcephaly. See answer
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