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Disease Profile

MECP2 duplication syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q99.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

MRXSL; XLMR syndrome, Lubs type; Trisomy Xq28

Categories

Congenital and Genetic Diseases; Nervous System Diseases

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]

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]

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.

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]

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]

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

    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.

    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
    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.

    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

      Social Networking Websites

        Organizations Providing General Support

          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.

              References

              1. Esch HV. MECP2 Duplication Syndrome. GeneReviews. October 2014; https://www.ncbi.nlm.nih.gov/books/NBK1284/.
              2. MECP2 Duplication Syndrome. NORD. 2017; https://rarediseases.org/rare-diseases/mecp2-duplication-syndrome/.
              3. MECP2 duplication syndrome. Genetics Home Reference. March, 2017; https://ghr.nlm.nih.gov/condition/mecp2-duplication-syndrome.

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