MECP2 duplication syndrome

Información en español Title

Other Names:

MRXSL; XLMR syndrome, Lubs type; Trisomy Xq28

Categories:

Congenital and Genetic Diseases; Nervous System Diseases

Summary Summary

MECP2 duplication syndrome is a severe neurological and developmental disorder. Signs and symptoms include low muscle tone (hypotonia) in infancy, developmental delay, severe intellectual disability, and progressive spasticity. Other signs and symptoms may include recurrent respiratory infections and seizures. Some people with MECP2 duplication syndrome may have autistic features, gastrointestinal problems, and/or mildly distinctive facial features. The syndrome is caused by having an extra copy (duplication) of the MECP2 gene, and inheritance is X-linked. The syndrome almost always occurs in males (who have one X chromosome), but some females with the duplication on one of their two X chromosomes have some signs or symptoms. Rarely, females may have severe signs and symptoms, similar to those in males with the syndrome.^[1]^[2]^[3]

Treatment is individualized and based on the signs and symptoms in each person. Treatment may involve routine management of feeding difficulties, infections, developmental delays, spasticity, and seizures.^[1]^[2] Respiratory infections are a major cause of death, with only half of people surviving past 25 years of age.^[3]

Last updated: 6/26/2018

Symptoms Symptoms

Signs and symptoms of MECP2 duplication syndrome may include:^[1]^[2]

Hypotonia (low muscle tone), which is usually apparent in infancy.
Delayed development of milestones.
Moderate to severe intellectual disability.
Inability to talk, or limited speech ability that may be lost with age.
Needing assistance to walk or inability to walk.
Progressive spasticity during childhood, which is generally worse in the legs. This may lead to the development of mild contractures.
Recurrent respiratory infections (in about 75% of people). Respiratory infections can be life-threatening and are a major cause of death.
Seizures (in about 50%).
Feeding difficulties which may require a feeding tube.
Distinctive head or facial features, such as 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.

Other signs and symptoms may include trouble swallowing, gastroesophageal reflux, failure to thrive, excessive drooling, autistic features, and bowel or bladder problems.^[1]^[2]

Most females with a MECP2 duplication generally do not have symptoms, although depression, anxiety, and autistic features have been described in some women with the duplication.^[1] Very rarely, females have severe signs and symptoms, similar to those in males with the syndrome.^[1]^[2]^[3]

Last updated: 6/26/2018

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 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	Short and broad skull	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
Hostility		0031473
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	Worsens with time	0003676
Progressive spasticity		0002191
Psychomotor retardation		0025356
Recurrent respiratory infections	Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ]	0002205
Rigidity	Muscle rigidity	0002063
Seizure		0001250
X-linked recessive inheritance		0001419

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

Last updated: 2/1/2021

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

Cause Cause

MECP2 duplication syndrome occurs when there is an extra copy (duplication) of genetic material that includes the MECP2 gene. The size of the duplication can vary (i.e. additional genes around the MECP2 gene may also be duplicated). However, it is unclear whether extra copies of other genes in this location affect the severity of the syndrome.^[3]

The MECP2 gene gives the body instructions for making protein needed for normal brain functioning. One of its most important functions is to regulate the activity other genes in the brain by "switching them on and off." A duplication of the MECP2 gene leads to the production of too much of the MECP2 protein, making it unable to regulate other genes properly. This disrupts normal brain activity, leading to the signs and symptoms of MECP2 duplication syndrome.^[2]^[3]

Last updated: 5/30/2018

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 usually does not cause the disorder. Early in the normal development of females, one of the two X chromosomes is randomly and permanently inactivated in each cell (called X-inactivation). This prevents females from having twice as many active X chromosome genes. Because this process 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 the one inactivated in many, or all, cells. This is called "skewed X-inactivation." X-inactivation prevents some females with a MECP2 duplication from developing features of the syndrome.

In most cases, MECP2 duplication syndrome is inherited from a mother who carries the duplication but has no symptoms. Rarely, the condition is not inherited. In these cases it may occur randomly during the formation of the egg or sperm, or shortly after the egg and sperm join together. When this happens, it is called a de novo duplication.^[3]^[2] The duplication can also arise from an unbalanced translocation involving the X chromosome (and the MECP2 gene).^[1]

Last updated: 5/30/2018

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 varies based on the signs and symptoms present in each person. For example, babies who have trouble swallowing and/or 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 must be treated with appropriate antibiotics.^[1]^[2]

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

Last updated: 5/30/2018

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

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 MedlinePlus Genetics.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include Prader-Willi syndrome and Alpha thalassaemia-mental retardation, X linked (ATR-X) syndrome (see these terms). Visit the Orphanet disease page for more information.

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.
The Rett Syndrome, MECP2 Duplications, & Rett-related Disorders Consortium is an integrated group of academic medical centers, patient support organizations, and clinical research resources dedicated to conducting clinical research into three disorders of the nervous system: Rett syndrome (RTT), MECP2 duplication disorder and RTT-related disorders. Major goals of the Consortium are to identify and understand the core clinical features of each disorder; identify factors that can modify the severity of the disorders; and understand the relationship between patients’ symptoms and their brain imaging and electroencephalography alterations. Click on the name of the study for more information.

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

MECP2 Duplication Foundation
E-mail: https://mecp2d.org/contact-us/
Website: https://mecp2d.org/
MECP2 Duplication UK
Telephone: 0770 420 1468
E-mail: http://mecp2duplicationuk.org.uk/#contact
Website: http://mecp2duplicationuk.org.uk/
Rett Syndrome Research Trust
67 Under Cliff Road
Trumbull, CT 06611
Telephone: +1-203-445-0041
E-mail: info@rsrt.org
Website: https://reverserett.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: https://www.rarechromo.org/

Social Networking Websites

Visit the following Facebook groups related to MECP2 duplication syndrome:
MECP2 Duplication Syndrome Family Talk
Females With MECP2 (Xq28) Duplication - Support Group

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 Arc of the United States
1825 K Street, NW
Suite 1200
Washington, DC, DC 20006
Toll-free: 1-(800) 433-5255
Telephone: +1-202-534-3700
Fax: +1-202-534-3731
E-mail: info@thearc.org
Website: https://www.thearc.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

MedlinePlus Genetics 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

Rare Disease Day at NIH 2021
March 1, 2021

GARD Answers GARD Answers

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I want to know if in this syndrome, people can have microcephaly. See answer
My teenage son has been diagnosed with MECP2 duplication syndrome. What can you tell me about this condition? See answer

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