MECP2 Duplication Syndrome

Genetic MONDO:0010436 Neurodevelopmental Disorder X-linked Recessive Disorder

MECP2 Duplication Syndrome is a severe X-linked neurodevelopmental disorder caused by interstitial chromosomal duplications at Xq28 encompassing the MECP2 gene. It is 100% penetrant in males and is associated with infantile hypotonia, severe intellectual disability, poor speech development, recurrent respiratory infections, epilepsy, progressive spasticity, and in some cases developmental regression. Carrier females are typically asymptomatic but may exhibit neuropsychiatric phenotypes. The condition is distinct from Rett syndrome, which results from loss-of-function MECP2 mutations.

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👪

Inheritance

X-linked

X-linked inheritance with 100% penetrance in males. The majority of affected males inherit the MECP2 duplication from a heterozygous carrier mother, though de novo cases have been documented. Female carriers typically have skewed X-inactivation favoring the normal X chromosome and are usually asymptomatic, but may exhibit neuropsychiatric phenotypes including anxiety and mild cognitive features.

Show evidence (2 references)

PMID:20301461 SUPPORT Human Clinical

"MECP2 duplication syndrome is inherited in an X-linked manner. The majority of affected males have inherited the MECP2 duplication from a heterozygous mother; however, de novo genetic alterations have been reported."

GeneReviews confirms X-linked inheritance pattern.

PMID:20425814 SUPPORT Human Clinical

"Most of the reported cases are inherited, however, de novo cases have been documented. While carrier females have been reported to be unaffected, more recent research demonstrates that despite normal intelligence, female carriers display a range of neuropsychiatric phenotypes"

Documents carrier female neuropsychiatric phenotypes.

⚙

Pathophysiology

MECP2 Overexpression and Neurodegeneration

Duplication of the Xq28 region leads to overexpression of MECP2 protein, a multi-functional protein required for proper brain development and maintenance of brain function. MECP2 is dosage-sensitive; even a relatively modest increase causes severe neurological disease. Overexpression leads to neuronal death in specific brain regions including cortex, hippocampus, cerebellum, and spinal cord. Astrocytic dysfunction, including breakdown of glutamate homeostatic mechanisms, likely contributes to neuronal death.

Neuron link Astrocyte link Microglial cell link

Gene Expression Regulation link Neuron Apoptotic Process link Chromatin Organization link Synapse Organization link Neurotransmitter Transport link

Brain link Cerebral Cortex link Hippocampus link Cerebellum link Spinal Cord link

Show evidence (2 references)

PMID:33638179 SUPPORT Model Organism

"MDS is a neurodegenerative disorder in which neurons die in specific parts of the central nervous system, including the cortex, hippocampus, cerebellum, and spinal cord. Neuronal death likely results from astrocytic dysfunction, including a breakdown of glutamate homeostatic mechanisms."

Review of cell culture and mouse models shows MECP2 overexpression causes region-specific neurodegeneration via astrocytic dysfunction.

PMID:20425814 SUPPORT Human Clinical

"MECP2 duplication syndrome is 100% penetrant in affected males and is associated with infantile hypotonia, severe to profound mental retardation, autism or autistic features, poor speech development, recurrent infections, epilepsy, progressive spasticity, and, in some cases, developmental regression."

Comprehensive clinical review confirms the core phenotype resulting from MECP2 overexpression.

Immune Dysfunction

MECP2 overexpression is associated with immunodeficiency characterized by IgA and IgG2 deficiency, low antibody titers against pneumococci, and elevated acute-phase responses. This leads to recurrent and often life-threatening respiratory infections, particularly with encapsulated bacteria. The IRAK1 gene, encoding interleukin-1 receptor-associated kinase 1, is frequently co-duplicated with MECP2, but IRAK1 duplication does not increase canonical NF-kB-induced inflammation at baseline, suggesting the immune dysfunction mechanism is more complex than simple innate immune pathway overactivation.

B cell link

Immune Response link

Lung link

Show evidence (4 references)

PMID:25721700 SUPPORT Human Clinical

"increased susceptibility to infections in MECP2 duplication syndrome is associated with IgA/IgG2-deficiency, low antibody titers against pneumococci and elevated acute-phase responses"

First systematic immunological characterization of 27 MECP2 duplication patients showing specific humoral immune defects.

PMID:25721700 SUPPORT Human Clinical

"17/27 analyzed patients suffered from pneumonia, 5/27 from at least one episode of sepsis. Encapsulated bacteria (S.pneumoniae, H.influenzae) were frequently isolated."

Documents the infectious phenotype with predominance of encapsulated bacterial infections.

PMID:36319802 SUPPORT Human Clinical

"most patients with MECP2/IRAK1 duplication syndrome present with recurrent and severe infections, accompanied by strong inflammation. Respiratory infections are the most common cause of death."

Confirms recurrent severe infections and strong inflammatory responses in MECP2/IRAK1 duplication patients.

+ 1 more reference

●

Phenotypes

Digestive 2

Constipation FREQUENT Constipation (HP:0002019)

Constipation and gastroesophageal reflux are common gastrointestinal manifestations

Show evidence (1 reference)

PMID:20301461 SUPPORT Human Clinical

"gastrointestinal manifestations including gastroesophageal reflux and constipation"

GeneReviews identifies GI manifestations as characteristic features.

Feeding Difficulties FREQUENT Feeding difficulties (HP:0011968)

Show evidence (1 reference)

PMID:20301461 SUPPORT Human Clinical

"early-onset hypotonia, feeding difficulty, gastrointestinal manifestations including gastroesophageal reflux and constipation"

GeneReviews identifies feeding difficulty as a characteristic early feature.

Immune 1

Recurrent Respiratory Infections VERY_FREQUENT Recurrent respiratory infections (HP:0002205)

Major cause of morbidity and mortality; present in approximately 75% of affected individuals

Show evidence (2 references)

PMID:20301461 SUPPORT Human Clinical

"recurrent respiratory infections (in ~75% of affected individuals)"

GeneReviews entry provides frequency estimate for recurrent respiratory infections.

PMID:28938254 SUPPORT Human Clinical

"Respiratory infections are the main cause of early death in patients with MECP2 duplication syndrome."

Documents that respiratory infections are the primary cause of mortality.

Musculoskeletal 2

Infantile Hypotonia VERY_FREQUENT Floppy infant (HP:0008947)

Show evidence (1 reference)

PMID:20301461 SUPPORT Human Clinical

"MECP2 duplication syndrome is a severe neurodevelopmental disorder characterized by early-onset hypotonia"

GeneReviews entry identifies early-onset hypotonia as a characteristic feature.

Progressive Spasticity FREQUENT Progressive spasticity (HP:0002191)

Show evidence (1 reference)

PMID:33170557 SUPPORT Human Clinical

"Motor Dysfunction subscale (Figure 2) scores worsen with increasing age"

Natural history study demonstrates progressive motor dysfunction including spasticity worsening with age.

Nervous System 6

Severe Intellectual Disability VERY_FREQUENT Severe intellectual disability (HP:0010864)

Show evidence (1 reference)

PMID:20425814 SUPPORT Human Clinical

"MECP2 duplication syndrome is 100% penetrant in affected males and is associated with infantile hypotonia, severe to profound mental retardation"

Clinical review confirms severe to profound intellectual disability is a universal feature in affected males.

Epilepsy FREQUENT Seizure (HP:0001250)

Present in approximately 50% at baseline, increases with age; often treatment-refractory

Show evidence (2 references)

PMID:20301461 SUPPORT Human Clinical

"seizures (in ~50%)"

GeneReviews provides frequency estimate for seizures.

PMID:33170557 SUPPORT Human Clinical

"At baseline visit 28 participants had epilepsy. The average age of seizure onset was 8.96 years"

Natural history study shows 28/69 participants had epilepsy with mean onset at 9 years.

Poor Speech Development VERY_FREQUENT Delayed speech and language development (HP:0000750)

Show evidence (1 reference)

PMID:20425814 SUPPORT Human Clinical

"poor speech development"

Clinical review confirms poor speech development as a core feature.

Autistic Features FREQUENT Autistic behavior (HP:0000729)

Show evidence (1 reference)

PMID:20425814 SUPPORT Human Clinical

"autism or autistic features"

Clinical review identifies autistic features as a common manifestation.

Developmental Regression FREQUENT Developmental regression (HP:0002376)

Observed in 22% of participants at baseline in cross-sectional study (likely underestimate); mean age of regression 10.4 years

Show evidence (1 reference)

PMID:33170557 SUPPORT Human Clinical

"Twenty-two percent (n = 15 of 69 total) of the participants had regressed at the time of their visit, and average age of regression was 10.38 years"

Natural history study documents regression in 22% of participants at baseline, likely underestimate given cross-sectional design.

Global Developmental Delay VERY_FREQUENT Global developmental delay (HP:0001263)

Show evidence (2 references)

PMID:20301461 SUPPORT Human Clinical

"delayed psychomotor development leading to severe intellectual disability"

GeneReviews confirms global developmental delay as a core feature.

PMID:35313898 SUPPORT Human Clinical

"The key features of MDS include intellectual disability, developmental delay, hypotonia, seizures, recurrent respiratory infections, gastrointestinal problems, behavioural features of autism and dysmorphic features"

Comprehensive 20-year review confirms developmental delay as a key feature.

🧬

Genetic Associations

MECP2 (Causative)

Show evidence (4 references)

PMID:35313898 SUPPORT Human Clinical

"MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder caused by a duplication of the methyl-CpG-binding protein 2 (MECP2) gene"

Comprehensive review confirms MECP2 duplication as the causative genetic alteration.

PMID:20425814 SUPPORT Human Clinical

Documents inheritance pattern and carrier female phenotype.

PMID:39696717 SUPPORT Human Clinical

"Duplication sizes in the cohort ranging from 64.6 kb to 16.5 Mb were classified into four categories comprising of tandem duplications (48%), terminal duplications (22%), inverted triplications (20%), and other CGRs (10%)."

Largest genotype-phenotype study of 137 individuals characterizes structural variant heterogeneity.

+ 1 more reference

IRAK1 (Modifying)

Show evidence (2 references)

PMID:36319802 SUPPORT Human Clinical

"most patients with MECP2/IRAK1 duplication syndrome present with recurrent and severe infections, accompanied by strong inflammation. Respiratory infections are the most common cause of death."

Confirms IRAK1 co-duplication is a consistent feature and that immune dysfunction accompanies the duplication.

PMID:36319802 REFUTE In Vitro

"Patients with MECP2/IRAK1 duplication syndrome do not show increased canonical NF-κB signaling in immortalized fibroblasts, PBMCs, and whole blood."

Despite IRAK1 duplication, canonical NF-kB pathway activation is not increased, ruling out simple innate immune pathway overactivation as the mechanism.

💊

Treatments

Seizure Management

Action: Anticonvulsant agent therapy Ontology label: anticonvulsant agent therapy MAXO:0000167

Anticonvulsant medications for epilepsy control; seizures are often treatment-refractory.

Show evidence (1 reference)

PMID:20301461 SUPPORT Human Clinical

"Routine management of feeding difficulties, constipation, developmental and speech delays, spasticity, and seizures."

GeneReviews recommends routine seizure management as part of standard care.

Antibiotic Prophylaxis and Immunoglobulin Therapy

Action: antibiotic therapy Ontology label: Antibiotic Therapy NCIT:C15620

Agent: antibiotic ↗

Prophylactic antibiotics and immunoglobulin substitution for patients with IgA/IgG2 deficiency to prevent recurrent respiratory infections.

Show evidence (1 reference)

PMID:28938254 SUPPORT Human Clinical

"Immunoglobulin substitution, daily antibiotic prophylaxis with two agents and supportive measures reduced occurrence of pneumonia to four episodes in the following 6 2/12 years of life."

Case report demonstrates effectiveness of combined immunoglobulin replacement and antibiotic prophylaxis in reducing pneumonia episodes.

Physical Therapy

Action: Physical therapy Ontology label: physical therapy MAXO:0000011

Management of spasticity, maintenance of range of motion, and prevention of contractures.

Show evidence (1 reference)

PMID:20301461 SUPPORT Human Clinical

"Physical therapy to maintain range of motion to reduce likelihood of contractures."

GeneReviews recommends physical therapy for spasticity management.

Genetic Counseling

Action: Genetic counseling Ontology label: genetic counseling MAXO:0000079

Genetic counseling for families regarding X-linked inheritance, carrier testing for mothers and female relatives, and options for prenatal testing and preimplantation genetic testing.

Show evidence (1 reference)

PMID:20301461 SUPPORT Human Clinical

"Once the MECP2 duplication has been identified in an affected family member (and/or the mother of the proband is found to be a carrier of a balanced translocation), prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible."

GeneReviews details genetic counseling approach including prenatal and preimplantation testing options.

{ }

Source YAML

click to show

name: MECP2 Duplication Syndrome
creation_date: '2026-03-14T00:00:00Z'
updated_date: '2026-05-09T19:42:12Z'
category: Genetic
parents:
- Neurodevelopmental Disorder
- X-linked Recessive Disorder
disease_term:
  preferred_term: MECP2 duplication syndrome
  term:
    id: MONDO:0010436
    label: chromosome Xq28 duplication syndrome
prevalence:
- population: Global
  percentage: 1-9 / 1 000 000
  notes: >
    Estimated live birth prevalence of ~1/150,000 in males (~6.7 per million);
    global both-sex prevalence is lower given X-linked inheritance.
  evidence:
  - reference: PMID:35313898
    reference_title: "A brief history of MECP2 duplication syndrome: 20-years of clinical understanding."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MDS has an estimated live birth prevalence in males of 1/150,000."
    explanation: Epidemiological estimate from comprehensive 20-year review.
description: >
  MECP2 Duplication Syndrome is a severe X-linked neurodevelopmental disorder
  caused by interstitial chromosomal duplications at Xq28 encompassing the MECP2
  gene. It is 100% penetrant in males and is associated with infantile hypotonia,
  severe intellectual disability, poor speech development, recurrent respiratory
  infections, epilepsy, progressive spasticity, and in some cases developmental
  regression. Carrier females are typically asymptomatic but may exhibit
  neuropsychiatric phenotypes. The condition is distinct from Rett syndrome, which
  results from loss-of-function MECP2 mutations.
pathophysiology:
- name: MECP2 Overexpression and Neurodegeneration
  description: >
    Duplication of the Xq28 region leads to overexpression of MECP2 protein, a
    multi-functional protein required for proper brain development and maintenance
    of brain function. MECP2 is dosage-sensitive; even a relatively modest increase
    causes severe neurological disease. Overexpression leads to neuronal death in
    specific brain regions including cortex, hippocampus, cerebellum, and spinal
    cord. Astrocytic dysfunction, including breakdown of glutamate homeostatic
    mechanisms, likely contributes to neuronal death.
  cell_types:
  - preferred_term: Neuron
    term:
      id: CL:0000540
      label: neuron
  - preferred_term: Astrocyte
    term:
      id: CL:0000127
      label: astrocyte
  - preferred_term: Microglial cell
    term:
      id: CL:0000129
      label: microglial cell
  biological_processes:
  - preferred_term: Gene Expression Regulation
    term:
      id: GO:0010468
      label: regulation of gene expression
  - preferred_term: Neuron Apoptotic Process
    term:
      id: GO:0051402
      label: neuron apoptotic process
  - preferred_term: Chromatin Organization
    term:
      id: GO:0006325
      label: chromatin organization
  - preferred_term: Synapse Organization
    term:
      id: GO:0050808
      label: synapse organization
  - preferred_term: Neurotransmitter Transport
    term:
      id: GO:0006836
      label: neurotransmitter transport
  locations:
  - preferred_term: Brain
    term:
      id: UBERON:0000955
      label: brain
  - preferred_term: Cerebral Cortex
    term:
      id: UBERON:0000956
      label: cerebral cortex
  - preferred_term: Hippocampus
    term:
      id: UBERON:0002421
      label: hippocampal formation
  - preferred_term: Cerebellum
    term:
      id: UBERON:0002037
      label: cerebellum
  - preferred_term: Spinal Cord
    term:
      id: UBERON:0002240
      label: spinal cord
  evidence:
  - reference: PMID:33638179
    reference_title: "MECP2 and the biology of MECP2 duplication syndrome."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "MDS is a neurodegenerative disorder in which neurons die in specific parts of the central nervous system, including the cortex, hippocampus, cerebellum, and spinal cord. Neuronal death likely results from astrocytic dysfunction, including a breakdown of glutamate homeostatic mechanisms."
    explanation: Review of cell culture and mouse models shows MECP2 overexpression causes region-specific neurodegeneration via astrocytic dysfunction.
  - reference: PMID:20425814
    reference_title: "The MECP2 duplication syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MECP2 duplication syndrome is 100% penetrant in affected males and is associated with infantile hypotonia, severe to profound mental retardation, autism or autistic features, poor speech development, recurrent infections, epilepsy, progressive spasticity, and, in some cases, developmental regression."
    explanation: Comprehensive clinical review confirms the core phenotype resulting from MECP2 overexpression.
- name: Immune Dysfunction
  description: >
    MECP2 overexpression is associated with immunodeficiency characterized by
    IgA and IgG2 deficiency, low antibody titers against pneumococci, and
    elevated acute-phase responses. This leads to recurrent and often
    life-threatening respiratory infections, particularly with encapsulated
    bacteria. The IRAK1 gene, encoding interleukin-1 receptor-associated
    kinase 1, is frequently co-duplicated with MECP2, but IRAK1 duplication
    does not increase canonical NF-kB-induced inflammation at baseline,
    suggesting the immune dysfunction mechanism is more complex than simple
    innate immune pathway overactivation.
  cell_types:
  - preferred_term: B cell
    term:
      id: CL:0000236
      label: B cell
  biological_processes:
  - preferred_term: Immune Response
    term:
      id: GO:0006955
      label: immune response
  locations:
  - preferred_term: Lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: PMID:25721700
    reference_title: "Infectious and immunologic phenotype of MECP2 duplication syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "increased susceptibility to infections in MECP2 duplication syndrome is associated with IgA/IgG2-deficiency, low antibody titers against pneumococci and elevated acute-phase responses"
    explanation: First systematic immunological characterization of 27 MECP2 duplication patients showing specific humoral immune defects.
  - reference: PMID:25721700
    reference_title: "Infectious and immunologic phenotype of MECP2 duplication syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "17/27 analyzed patients suffered from pneumonia, 5/27 from at least one episode of sepsis. Encapsulated bacteria (S.pneumoniae, H.influenzae) were frequently isolated."
    explanation: Documents the infectious phenotype with predominance of encapsulated bacterial infections.
  - reference: PMID:36319802
    reference_title: "IRAK1 Duplication in MECP2 Duplication Syndrome Does Not Increase Canonical NF-κB-Induced Inflammation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "most patients with MECP2/IRAK1 duplication syndrome present with recurrent and severe infections, accompanied by strong inflammation. Respiratory infections are the most common cause of death."
    explanation: Confirms recurrent severe infections and strong inflammatory responses in MECP2/IRAK1 duplication patients.
  - reference: PMID:36319802
    reference_title: "IRAK1 Duplication in MECP2 Duplication Syndrome Does Not Increase Canonical NF-κB-Induced Inflammation."
    supports: REFUTE
    evidence_source: IN_VITRO
    snippet: "Patients with MECP2/IRAK1 duplication syndrome do not show increased canonical NF-κB signaling in immortalized fibroblasts, PBMCs, and whole blood."
    explanation: Despite IRAK1 co-duplication, canonical NF-kB pathway is not hyperactivated, suggesting immune dysfunction mechanism is more complex than simple innate immune overactivation.
phenotypes:
- name: Severe Intellectual Disability
  category: Neurological
  frequency: VERY_FREQUENT
  diagnostic: true
  phenotype_term:
    preferred_term: Severe intellectual disability
    term:
      id: HP:0010864
      label: Severe intellectual disability
  evidence:
  - reference: PMID:20425814
    reference_title: "The MECP2 duplication syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MECP2 duplication syndrome is 100% penetrant in affected males and is associated with infantile hypotonia, severe to profound mental retardation"
    explanation: Clinical review confirms severe to profound intellectual disability is a universal feature in affected males.
- name: Infantile Hypotonia
  category: Neurological
  frequency: VERY_FREQUENT
  diagnostic: true
  phenotype_term:
    preferred_term: Infantile hypotonia
    term:
      id: HP:0008947
      label: Floppy infant
  evidence:
  - reference: PMID:20301461
    reference_title: "MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MECP2 duplication syndrome is a severe neurodevelopmental disorder characterized by early-onset hypotonia"
    explanation: GeneReviews entry identifies early-onset hypotonia as a characteristic feature.
- name: Recurrent Respiratory Infections
  category: Respiratory
  frequency: VERY_FREQUENT
  diagnostic: true
  notes: Major cause of morbidity and mortality; present in approximately 75% of affected individuals
  phenotype_term:
    preferred_term: Recurrent respiratory infections
    term:
      id: HP:0002205
      label: Recurrent respiratory infections
  evidence:
  - reference: PMID:20301461
    reference_title: "MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "recurrent respiratory infections (in ~75% of affected individuals)"
    explanation: GeneReviews entry provides frequency estimate for recurrent respiratory infections.
  - reference: PMID:28938254
    reference_title: "Antibiotic Prophylaxis, Immunoglobulin Substitution and Supportive Measures Prevent Infections in MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Respiratory infections are the main cause of early death in patients with MECP2 duplication syndrome."
    explanation: Documents that respiratory infections are the primary cause of mortality.
- name: Epilepsy
  category: Neurological
  frequency: FREQUENT
  notes: Present in approximately 50% at baseline, increases with age; often treatment-refractory
  phenotype_term:
    preferred_term: Seizures
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: PMID:20301461
    reference_title: "MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "seizures (in ~50%)"
    explanation: GeneReviews provides frequency estimate for seizures.
  - reference: PMID:33170557
    reference_title: "Phenotypic features in MECP2 duplication syndrome: Effects of age."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "At baseline visit 28 participants had epilepsy. The average age of seizure onset was 8.96 years"
    explanation: Natural history study shows 28/69 participants had epilepsy with mean onset at 9 years.
- name: Progressive Spasticity
  category: Neurological
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Progressive spasticity
    term:
      id: HP:0002191
      label: Progressive spasticity
  evidence:
  - reference: PMID:33170557
    reference_title: "Phenotypic features in MECP2 duplication syndrome: Effects of age."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Motor Dysfunction subscale (Figure 2) scores worsen with increasing age"
    explanation: Natural history study demonstrates progressive motor dysfunction including spasticity worsening with age.
- name: Poor Speech Development
  category: Neurological
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Poor speech development
    term:
      id: HP:0000750
      label: Delayed speech and language development
  evidence:
  - reference: PMID:20425814
    reference_title: "The MECP2 duplication syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "poor speech development"
    explanation: Clinical review confirms poor speech development as a core feature.
- name: Constipation
  category: Gastrointestinal
  frequency: FREQUENT
  notes: Constipation and gastroesophageal reflux are common gastrointestinal manifestations
  phenotype_term:
    preferred_term: Constipation
    term:
      id: HP:0002019
      label: Constipation
  evidence:
  - reference: PMID:20301461
    reference_title: "MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "gastrointestinal manifestations including gastroesophageal reflux and constipation"
    explanation: GeneReviews identifies GI manifestations as characteristic features.
- name: Autistic Features
  category: Neurological
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Autistic behavior
    term:
      id: HP:0000729
      label: Autistic behavior
  evidence:
  - reference: PMID:20425814
    reference_title: "The MECP2 duplication syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "autism or autistic features"
    explanation: Clinical review identifies autistic features as a common manifestation.
- name: Developmental Regression
  category: Neurological
  frequency: FREQUENT
  notes: Observed in 22% of participants at baseline in cross-sectional study (likely underestimate); mean age of regression 10.4 years
  phenotype_term:
    preferred_term: Developmental regression
    term:
      id: HP:0002376
      label: Developmental regression
  evidence:
  - reference: PMID:33170557
    reference_title: "Phenotypic features in MECP2 duplication syndrome: Effects of age."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Twenty-two percent (n = 15 of 69 total) of the participants had regressed at the time of their visit, and average age of regression was 10.38 years"
    explanation: Natural history study documents regression in 22% of participants at baseline, likely underestimate given cross-sectional design.
- name: Feeding Difficulties
  category: Gastrointestinal
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Feeding difficulties
    term:
      id: HP:0011968
      label: Feeding difficulties
  evidence:
  - reference: PMID:20301461
    reference_title: "MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "early-onset hypotonia, feeding difficulty, gastrointestinal manifestations including gastroesophageal reflux and constipation"
    explanation: GeneReviews identifies feeding difficulty as a characteristic early feature.
- name: Global Developmental Delay
  category: Neurological
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  evidence:
  - reference: PMID:20301461
    reference_title: "MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "delayed psychomotor development leading to severe intellectual disability"
    explanation: GeneReviews confirms global developmental delay as a core feature.
  - reference: PMID:35313898
    reference_title: "A brief history of MECP2 duplication syndrome: 20-years of clinical understanding."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The key features of MDS include intellectual disability, developmental delay, hypotonia, seizures, recurrent respiratory infections, gastrointestinal problems, behavioural features of autism and dysmorphic features"
    explanation: Comprehensive 20-year review confirms developmental delay as a key feature.
genetic:
- name: MECP2
  association: Causative
  gene_term:
    preferred_term: MECP2
    term:
      id: hgnc:6990
      label: MECP2
  notes: >
    Xq28 duplication encompassing MECP2; duplications range from 64.6 kb to
    16.5 Mb, classified as tandem duplications (48%), terminal duplications
    (22%), inverted triplications (20%), and other complex rearrangements
    (10%). 100% penetrant in males. Majority of cases are inherited from
    carrier mothers. Female carriers typically show skewed X-inactivation
    and are usually asymptomatic but may display neuropsychiatric phenotypes.
    Clinical severity correlates with MECP2 dosage and rearrangement
    structure, with triplications being most severe.
  evidence:
  - reference: PMID:35313898
    reference_title: "A brief history of MECP2 duplication syndrome: 20-years of clinical understanding."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder caused by a duplication of the methyl-CpG-binding protein 2 (MECP2) gene"
    explanation: Comprehensive review confirms MECP2 duplication as the causative genetic alteration.
  - reference: PMID:20425814
    reference_title: "The MECP2 duplication syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Most of the reported cases are inherited, however, de novo cases have been documented. While carrier females have been reported to be unaffected, more recent research demonstrates that despite normal intelligence, female carriers display a range of neuropsychiatric phenotypes"
    explanation: Documents inheritance pattern and carrier female phenotype.
  - reference: PMID:39696717
    reference_title: "Structural variant allelic heterogeneity in MECP2 duplication syndrome provides insight into clinical severity and variability of disease expression."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Duplication sizes in the cohort ranging from 64.6 kb to 16.5 Mb were classified into four categories comprising of tandem duplications (48%), terminal duplications (22%), inverted triplications (20%), and other CGRs (10%)."
    explanation: Largest genotype-phenotype study of 137 individuals characterizes structural variant heterogeneity.
  - reference: PMID:39696717
    reference_title: "Structural variant allelic heterogeneity in MECP2 duplication syndrome provides insight into clinical severity and variability of disease expression."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Genotype-phenotype analyses indicated a gradual worsening of phenotypic features, including overall survival, developmental levels, microcephaly, epilepsy, and genitourinary/eye abnormalities in the following order: Tandem duplications, Other complex duplications, Terminal duplications/Translocations, and Triplications encompassing MECP2."
    explanation: Demonstrates that clinical severity correlates with rearrangement structure and MECP2 dosage.
- name: IRAK1
  association: Modifying
  gene_term:
    preferred_term: IRAK1
    term:
      id: hgnc:6112
      label: IRAK1
  notes: >
    IRAK1 (interleukin-1 receptor-associated kinase 1) is frequently
    co-duplicated with MECP2 on Xq28. IRAK1 participates in innate immune
    signaling (Toll-like receptor/IL-1 pathway). Co-duplication may
    contribute to the immunologic phenotype, though baseline canonical
    NF-kB signaling is not increased.
  evidence:
  - reference: PMID:36319802
    reference_title: "IRAK1 Duplication in MECP2 Duplication Syndrome Does Not Increase Canonical NF-κB-Induced Inflammation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "most patients with MECP2/IRAK1 duplication syndrome present with recurrent and severe infections, accompanied by strong inflammation. Respiratory infections are the most common cause of death."
    explanation: Confirms IRAK1 co-duplication is a consistent feature and that immune dysfunction accompanies the duplication.
  - reference: PMID:36319802
    reference_title: "IRAK1 Duplication in MECP2 Duplication Syndrome Does Not Increase Canonical NF-κB-Induced Inflammation."
    supports: REFUTE
    evidence_source: IN_VITRO
    snippet: "Patients with MECP2/IRAK1 duplication syndrome do not show increased canonical NF-κB signaling in immortalized fibroblasts, PBMCs, and whole blood."
    explanation: Despite IRAK1 duplication, canonical NF-kB pathway activation is not increased, ruling out simple innate immune pathway overactivation as the mechanism.
inheritance:
- name: X-linked
  description: >
    X-linked inheritance with 100% penetrance in males. The majority of
    affected males inherit the MECP2 duplication from a heterozygous carrier
    mother, though de novo cases have been documented. Female carriers
    typically have skewed X-inactivation favoring the normal X chromosome
    and are usually asymptomatic, but may exhibit neuropsychiatric
    phenotypes including anxiety and mild cognitive features.
  evidence:
  - reference: PMID:20301461
    reference_title: "MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MECP2 duplication syndrome is inherited in an X-linked manner. The majority of affected males have inherited the MECP2 duplication from a heterozygous mother; however, de novo genetic alterations have been reported."
    explanation: GeneReviews confirms X-linked inheritance pattern.
  - reference: PMID:20425814
    reference_title: "The MECP2 duplication syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Most of the reported cases are inherited, however, de novo cases have been documented. While carrier females have been reported to be unaffected, more recent research demonstrates that despite normal intelligence, female carriers display a range of neuropsychiatric phenotypes"
    explanation: Documents carrier female neuropsychiatric phenotypes.
treatments:
- name: Seizure Management
  description: Anticonvulsant medications for epilepsy control; seizures are often treatment-refractory.
  treatment_term:
    preferred_term: Anticonvulsant agent therapy
    term:
      id: MAXO:0000167
      label: anticonvulsant agent therapy
  evidence:
  - reference: PMID:20301461
    reference_title: "MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Routine management of feeding difficulties, constipation, developmental and speech delays, spasticity, and seizures."
    explanation: GeneReviews recommends routine seizure management as part of standard care.
- name: Antibiotic Prophylaxis and Immunoglobulin Therapy
  description: >
    Prophylactic antibiotics and immunoglobulin substitution for patients with
    IgA/IgG2 deficiency to prevent recurrent respiratory infections.
  treatment_term:
    preferred_term: antibiotic therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: antibiotic
      term:
        id: NCIT:C258
        label: Antibiotic
  evidence:
  - reference: PMID:28938254
    reference_title: "Antibiotic Prophylaxis, Immunoglobulin Substitution and Supportive Measures Prevent Infections in MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Immunoglobulin substitution, daily antibiotic prophylaxis with two agents and supportive measures reduced occurrence of pneumonia to four episodes in the following 6 2/12 years of life."
    explanation: Case report demonstrates effectiveness of combined immunoglobulin replacement and antibiotic prophylaxis in reducing pneumonia episodes.
- name: Physical Therapy
  description: Management of spasticity, maintenance of range of motion, and prevention of contractures.
  treatment_term:
    preferred_term: Physical therapy
    term:
      id: MAXO:0000011
      label: physical therapy
  evidence:
  - reference: PMID:20301461
    reference_title: "MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Physical therapy to maintain range of motion to reduce likelihood of contractures."
    explanation: GeneReviews recommends physical therapy for spasticity management.
- name: Genetic Counseling
  description: >
    Genetic counseling for families regarding X-linked inheritance, carrier
    testing for mothers and female relatives, and options for prenatal
    testing and preimplantation genetic testing.
  treatment_term:
    preferred_term: Genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
  evidence:
  - reference: PMID:20301461
    reference_title: "MECP2 Duplication Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Once the MECP2 duplication has been identified in an affected family member (and/or the mother of the proband is found to be a carrier of a balanced translocation), prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible."
    explanation: GeneReviews details genetic counseling approach including prenatal and preimplantation testing options.
references:
- reference: PMID:20301461
  title: "MECP2 Duplication Syndrome."
  tags:
  - GeneReviews
  findings: []
- reference: DOI:10.1002/mgg3.1989
  title: Exploring the characteristics and most bothersome symptoms in <scp><i>MECP2</i></scp> duplication syndrome to pave the path toward developing <scp>parent‐oriented</scp> outcome measures
  found_in:
  - MECP2_Duplication_Syndrome-deep-research-falcon.md
  findings:
  - statement: MECP2 Duplication Syndrome (MDS), resulting from the duplication of Xq28 region, including MECP2, is a rare disorder with a nascent understanding in clinical features and severity.
    supporting_text: MECP2 Duplication Syndrome (MDS), resulting from the duplication of Xq28 region, including MECP2, is a rare disorder with a nascent understanding in clinical features and severity.
    evidence:
    - reference: DOI:10.1002/mgg3.1989
      reference_title: Exploring the characteristics and most bothersome symptoms in <scp><i>MECP2</i></scp> duplication syndrome to pave the path toward developing <scp>parent‐oriented</scp> outcome measures
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: MECP2 Duplication Syndrome (MDS), resulting from the duplication of Xq28 region, including MECP2, is a rare disorder with a nascent understanding in clinical features and severity.
      explanation: Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.
- reference: DOI:10.1093/hmg/ddae135
  title: Modeling antisense oligonucleotide therapy in <i>MECP2</i> duplication syndrome human iPSC-derived neurons reveals gene expression programs responsive to MeCP2 levels
  found_in:
  - MECP2_Duplication_Syndrome-deep-research-falcon.md
  findings:
  - statement: Genomic copy-number variations (CNVs) that can cause neurodevelopmental disorders often encompass many genes, which complicates our understanding of how individual genes within a CNV contribute to pathology.
    supporting_text: Genomic copy-number variations (CNVs) that can cause neurodevelopmental disorders often encompass many genes, which complicates our understanding of how individual genes within a CNV contribute to pathology.
    evidence:
    - reference: DOI:10.1093/hmg/ddae135
      reference_title: Modeling antisense oligonucleotide therapy in <i>MECP2</i> duplication syndrome human iPSC-derived neurons reveals gene expression programs responsive to MeCP2 levels
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Genomic copy-number variations (CNVs) that can cause neurodevelopmental disorders often encompass many genes, which complicates our understanding of how individual genes within a CNV contribute to pathology.
      explanation: Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.
- reference: DOI:10.1101/2023.02.07.527511
  title: A Cas9-fusion proximity-based approach generates an <i>Irak1-Mecp2</i> tandem duplication mouse model for the study of MeCP2 duplication syndrome
  found_in:
  - MECP2_Duplication_Syndrome-deep-research-falcon.md
  findings:
  - statement: MECP2 duplication syndrome (MDS) is a neurodevelopmental disorder caused by tandem duplication of the MECP2 locus and its surrounding genes, including IRAK1 .
    supporting_text: MECP2 duplication syndrome (MDS) is a neurodevelopmental disorder caused by tandem duplication of the MECP2 locus and its surrounding genes, including IRAK1 .
    evidence:
    - reference: DOI:10.1101/2023.02.07.527511
      reference_title: A Cas9-fusion proximity-based approach generates an <i>Irak1-Mecp2</i> tandem duplication mouse model for the study of MeCP2 duplication syndrome
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: MECP2 duplication syndrome (MDS) is a neurodevelopmental disorder caused by tandem duplication of the MECP2 locus and its surrounding genes, including IRAK1 .
      explanation: Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.
- reference: DOI:10.1111/cge.12814
  title: Expanding the clinical picture of the <i>MECP2</i> Duplication syndrome
  found_in:
  - MECP2_Duplication_Syndrome-deep-research-falcon.md
  findings:
  - statement: Individuals with two or more copies of the MECP2 gene, located at Xq28, share clinical features and a distinct facial phenotype known as MECP2 Duplication syndrome.
    supporting_text: Individuals with two or more copies of the MECP2 gene, located at Xq28, share clinical features and a distinct facial phenotype known as MECP2 Duplication syndrome.
    evidence:
    - reference: DOI:10.1111/cge.12814
      reference_title: Expanding the clinical picture of the <i>MECP2</i> Duplication syndrome
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Individuals with two or more copies of the MECP2 gene, located at Xq28, share clinical features and a distinct facial phenotype known as MECP2 Duplication syndrome.
      explanation: Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.
- reference: DOI:10.1111/jpc.14399
  title: The incidence, prevalence and clinical features of<i>MECP2</i>duplication syndrome in Australian children
  found_in:
  - MECP2_Duplication_Syndrome-deep-research-falcon.md
  findings:
  - statement: The incidence, prevalence and clinical features of<i>MECP2</i>duplication syndrome in Australian children
    supporting_text: The aim of this study was to assess the incidence and prevalence ofMECP2duplication syndrome in Australian children and further define its phenotype.MethodsThe Australian Paediatric Surveillance Unit was used to identify children withMECP2duplication syndrome between June 2014 and November 2017.
    evidence:
    - reference: DOI:10.1111/jpc.14399
      reference_title: The incidence, prevalence and clinical features of<i>MECP2</i>duplication syndrome in Australian children
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The aim of this study was to assess the incidence and prevalence ofMECP2duplication syndrome in Australian children and further define its phenotype.MethodsThe Australian Paediatric Surveillance Unit was used to identify children withMECP2duplication syndrome between June 2014 and November 2017.
      explanation: Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.
- reference: DOI:10.1186/s12920-024-01831-9
  title: Genetic analysis of a pedigree with MECP2 duplication syndrome in China
  found_in:
  - MECP2_Duplication_Syndrome-deep-research-falcon.md
  findings:
  - statement: MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder that primarily affects males.
    supporting_text: MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder that primarily affects males.
    evidence:
    - reference: DOI:10.1186/s12920-024-01831-9
      reference_title: Genetic analysis of a pedigree with MECP2 duplication syndrome in China
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder that primarily affects males.
      explanation: Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.
- reference: DOI:10.3233/trd-220055
  title: 'Current Status of Developmental Encephalopathies: Rett Syndrome, MECP2 Duplication Disorder, CDKL5 Deficiency Disorder and FOXG1 Disorder'
  found_in:
  - MECP2_Duplication_Syndrome-deep-research-falcon.md
  findings:
  - statement: 'Current Status of Developmental Encephalopathies: Rett Syndrome, MECP2 Duplication Disorder, CDKL5 Deficiency Disorder and FOXG1 Disorder'
    supporting_text: 'Current Status of Developmental Encephalopathies: Rett Syndrome, MECP2 Duplication Disorder, CDKL5 Deficiency Disorder and FOXG1 Disorder'
- reference: DOI:10.3389/fgene.2024.1332469
  title: MECP2-related disorders while gene-based therapies are on the horizon
  found_in:
  - MECP2_Duplication_Syndrome-deep-research-falcon.md
  findings:
  - statement: The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities.
    supporting_text: The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities.
    evidence:
    - reference: DOI:10.3389/fgene.2024.1332469
      reference_title: MECP2-related disorders while gene-based therapies are on the horizon
      supports: SUPPORT
      evidence_source: OTHER
      snippet: The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities.
      explanation: Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.
- reference: DOI:10.3390/children9050633
  title: 'Medical Comorbidities in MECP2 Duplication Syndrome: Results from the International MECP2 Duplication Database'
  found_in:
  - MECP2_Duplication_Syndrome-deep-research-falcon.md
  findings:
  - statement: Since the discovery of MECP2 duplication syndrome (MDS) in 1999, efforts to characterise this disorder have been limited by a lack of large datasets, with small case series often favouring the reporting of certain conditions over others.
    supporting_text: Since the discovery of MECP2 duplication syndrome (MDS) in 1999, efforts to characterise this disorder have been limited by a lack of large datasets, with small case series often favouring the reporting of certain conditions over others.
    evidence:
    - reference: DOI:10.3390/children9050633
      reference_title: 'Medical Comorbidities in MECP2 Duplication Syndrome: Results from the International MECP2 Duplication Database'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Since the discovery of MECP2 duplication syndrome (MDS) in 1999, efforts to characterise this disorder have been limited by a lack of large datasets, with small case series often favouring the reporting of certain conditions over others.
      explanation: Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.
- reference: DOI:10.1186/s13023-022-02278-w
  title: 'A brief history of MECP2 duplication syndrome: 20-years of clinical understanding'
  found_in:
  - MECP2_Duplication_Syndrome-deep-research-falcon.md
  findings: []
- reference: DOI:10.1186/s13073-024-01411-7
  title: Structural variant allelic heterogeneity in MECP2 duplication syndrome provides insight into clinical severity and variability of disease expression
  found_in:
  - MECP2_Duplication_Syndrome-deep-research-falcon.md
  findings: []

📚

References & Deep Research

References

PMID:20301461

MECP2 Duplication Syndrome.

No top-level findings curated for this source.

DOI:10.1002/mgg3.1989

Exploring the characteristics and most bothersome symptoms in <scp>MECP2</scp> duplication syndrome to pave the path toward developing <scp>parent‐oriented</scp> outcome measures

1 finding

MECP2 Duplication Syndrome (MDS), resulting from the duplication of Xq28 region, including MECP2, is a rare disorder with a nascent understanding in clinical features and severity.

"MECP2 Duplication Syndrome (MDS), resulting from the duplication of Xq28 region, including MECP2, is a rare disorder with a nascent understanding in clinical features and severity."

Show evidence (1 reference)

DOI:10.1002/mgg3.1989 SUPPORT Human Clinical

"MECP2 Duplication Syndrome (MDS), resulting from the duplication of Xq28 region, including MECP2, is a rare disorder with a nascent understanding in clinical features and severity."

Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.

DOI:10.1093/hmg/ddae135

Modeling antisense oligonucleotide therapy in MECP2 duplication syndrome human iPSC-derived neurons reveals gene expression programs responsive to MeCP2 levels

1 finding

Genomic copy-number variations (CNVs) that can cause neurodevelopmental disorders often encompass many genes, which complicates our understanding of how individual genes within a CNV contribute to pathology.

"Genomic copy-number variations (CNVs) that can cause neurodevelopmental disorders often encompass many genes, which complicates our understanding of how individual genes within a CNV contribute to pathology."

Show evidence (1 reference)

DOI:10.1093/hmg/ddae135 SUPPORT Human Clinical

Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.

DOI:10.1101/2023.02.07.527511

A Cas9-fusion proximity-based approach generates an Irak1-Mecp2 tandem duplication mouse model for the study of MeCP2 duplication syndrome

1 finding

MECP2 duplication syndrome (MDS) is a neurodevelopmental disorder caused by tandem duplication of the MECP2 locus and its surrounding genes, including IRAK1 .

"MECP2 duplication syndrome (MDS) is a neurodevelopmental disorder caused by tandem duplication of the MECP2 locus and its surrounding genes, including IRAK1 ."

Show evidence (1 reference)

DOI:10.1101/2023.02.07.527511 SUPPORT Model Organism

"MECP2 duplication syndrome (MDS) is a neurodevelopmental disorder caused by tandem duplication of the MECP2 locus and its surrounding genes, including IRAK1 ."

Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.

DOI:10.1111/cge.12814

Expanding the clinical picture of the MECP2 Duplication syndrome

1 finding

Individuals with two or more copies of the MECP2 gene, located at Xq28, share clinical features and a distinct facial phenotype known as MECP2 Duplication syndrome.

"Individuals with two or more copies of the MECP2 gene, located at Xq28, share clinical features and a distinct facial phenotype known as MECP2 Duplication syndrome."

Show evidence (1 reference)

DOI:10.1111/cge.12814 SUPPORT Human Clinical

"Individuals with two or more copies of the MECP2 gene, located at Xq28, share clinical features and a distinct facial phenotype known as MECP2 Duplication syndrome."

Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.

DOI:10.1111/jpc.14399

The incidence, prevalence and clinical features ofMECP2duplication syndrome in Australian children

1 finding

The incidence, prevalence and clinical features ofMECP2duplication syndrome in Australian children

"The aim of this study was to assess the incidence and prevalence ofMECP2duplication syndrome in Australian children and further define its phenotype.MethodsThe Australian Paediatric Surveillance Unit was used to identify children withMECP2duplication syndrome between June 2014 and November 2017."

Show evidence (1 reference)

DOI:10.1111/jpc.14399 SUPPORT Human Clinical

Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.

DOI:10.1186/s12920-024-01831-9

Genetic analysis of a pedigree with MECP2 duplication syndrome in China

1 finding

MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder that primarily affects males.

"MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder that primarily affects males."

Show evidence (1 reference)

DOI:10.1186/s12920-024-01831-9 SUPPORT Human Clinical

"MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder that primarily affects males."

Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.

DOI:10.3233/trd-220055

Current Status of Developmental Encephalopathies: Rett Syndrome, MECP2 Duplication Disorder, CDKL5 Deficiency Disorder and FOXG1 Disorder

1 finding

Current Status of Developmental Encephalopathies: Rett Syndrome, MECP2 Duplication Disorder, CDKL5 Deficiency Disorder and FOXG1 Disorder

"Current Status of Developmental Encephalopathies: Rett Syndrome, MECP2 Duplication Disorder, CDKL5 Deficiency Disorder and FOXG1 Disorder"

DOI:10.3389/fgene.2024.1332469

MECP2-related disorders while gene-based therapies are on the horizon

1 finding

The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities.

"The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities."

Show evidence (1 reference)

DOI:10.3389/fgene.2024.1332469 SUPPORT Other

"The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities."

Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.

DOI:10.3390/children9050633

Medical Comorbidities in MECP2 Duplication Syndrome: Results from the International MECP2 Duplication Database

1 finding

Since the discovery of MECP2 duplication syndrome (MDS) in 1999, efforts to characterise this disorder have been limited by a lack of large datasets, with small case series often favouring the reporting of certain conditions over others.

"Since the discovery of MECP2 duplication syndrome (MDS) in 1999, efforts to characterise this disorder have been limited by a lack of large datasets, with small case series often favouring the reporting of certain conditions over others."

Show evidence (1 reference)

DOI:10.3390/children9050633 SUPPORT Human Clinical

Deep research cited this publication as relevant literature for MECP2 Duplication Syndrome.

DOI:10.1186/s13023-022-02278-w

A brief history of MECP2 duplication syndrome: 20-years of clinical understanding

No top-level findings curated for this source.

DOI:10.1186/s13073-024-01411-7

Structural variant allelic heterogeneity in MECP2 duplication syndrome provides insight into clinical severity and variability of disease expression

No top-level findings curated for this source.

Deep Research

Falcon ▸

1. Disease Information

Edison Scientific Literature 22 citations 2026-05-09T11:54:46.571822

1. Disease Information

What is the disease?

Definition: A rare X-linked neurodevelopmental disorder caused by duplication (or triplication) of a chromosomal region on Xq28 that includes MECP2, producing MeCP2 overexpression and a characteristic syndromic phenotype. (ta2022abriefhistory pages 1-2, pehlivan2024structuralvariantallelic pages 1-2)

Key identifiers (from retrieved literature)

Disease OMIM/MIM: 300260 (MDS; also MRXSL). (ta2022abriefhistory pages 1-2, pehlivan2024structuralvariantallelic pages 1-2)
Gene OMIM (MECP2): 300005. (ta2022abriefhistory pages 1-2)
Orphanet / ICD-10 / ICD-11 / MeSH / MONDO: Not explicitly stated in the retrieved full-text evidence; requires external ontology lookups (OMIM/Orphanet/MeSH/MONDO/ICD) beyond this run.

Synonyms / alternative names

X-linked intellectual developmental disorder, Lubs type (MRXSL) (explicitly stated). (pehlivan2024structuralvariantallelic pages 1-2)
MECP2 duplication disorder (MDD) used in some reviews. (percy2023currentstatusof pages 11-15)

Evidence type note

Evidence in this report derives from: - Aggregated cohort resources/registries (e.g., International MECP2 Duplication Database; population epidemiology) (giudice‐nairn2019theincidenceprevalence pages 1-2, ta2022medicalcomorbiditiesin pages 6-7) - Prospective/retrospective natural history and caregiver-reported surveys (percy2023currentstatusof pages 11-15, ak2022exploringthecharacteristics pages 1-2) - Molecular/genomic cohort studies integrating omics and deep phenotyping (pehlivan2024structuralvariantallelic pages 1-2) - Mechanistic model systems (mouse and iPSC-derived human neurons) (maino2024anirak1mecp2tandem pages 23-26, bajikar2024modelingantisenseoligonucleotide pages 1-2)

2. Etiology

Disease causal factors

Primary cause: Germline copy-number gain (duplication/triplication; often complex rearrangements) spanning MECP2 at Xq28. (ta2022abriefhistory pages 1-2, pehlivan2024structuralvariantallelic pages 1-2)
Mechanistic principle (“Goldilocks” dosage paradigm): Under-expression (loss-of-function) causes Rett syndrome, whereas over-expression causes MDS. (percy2023currentstatusof pages 11-15)

Risk factors

Genetic: Having an Xq28 MECP2 duplication/triplication; most affected males inherit the duplication from carrier mothers, though de novo events occur. (ta2022abriefhistory pages 2-4, giudice‐nairn2019theincidenceprevalence pages 1-2)
Sex: Marked male predominance; females often asymptomatic due to skewed X-inactivation, but affected females exist. (ta2022abriefhistory pages 2-4, giudice‐nairn2019theincidenceprevalence pages 1-2)

Protective factors

No validated genetic or environmental protective factors were identified in the retrieved corpus.

Gene–environment interactions

Not specifically delineated in the retrieved evidence; respiratory infections and aspiration risk likely interact with hypotonia, dysphagia, reflux, and seizure severity as downstream clinical-pathophysiologic interactions rather than established etiologic GxE. (ta2022medicalcomorbiditiesin pages 6-7, lim2017expandingtheclinical pages 10-13)

3. Phenotypes (with quantitative data where available)

Core neurodevelopmental phenotype

Early developmental delay: In a US natural history cohort (n=69), 70% had developmental delay in the first 6 months. (percy2023currentstatusof pages 11-15)
Hypotonia: 88% in the same cohort. (percy2023currentstatusof pages 11-15)
Speech: Little-to-absent speech described as near-universal in reviews; specific quantified rates not extracted from the retrieved pages. (allison2024mecp2relateddisorderswhile pages 4-5)

Suggested HPO terms (examples): - Global developmental delay (HP:0001263) - Intellectual disability (HP:0001249) - Hypotonia (HP:0001252) - Absent speech (HP:0001344) / Severely impaired speech (HP:0002465)

Epilepsy

Seizures: In International MECP2 Duplication Database cohort, >60% (90/148) had seizures; median onset ~8 years in males and ~9.8 years in females. (ta2022medicalcomorbiditiesin pages 6-7)
Treatment refractoriness: 69% had treatment-refractory seizures; 31% had status epilepticus; 25% had Lennox–Gastaut syndrome. (ta2022medicalcomorbiditiesin pages 6-7)
Caregiver survey study found epilepsy in 58.4% of participants and 75% of those were drug-resistant. (ak2022exploringthecharacteristics pages 1-2)

Suggested HPO terms: - Seizures (HP:0001250) - Epileptic encephalopathy (HP:0200134) - Status epilepticus (HP:0002133) - Lennox-Gastaut syndrome (HP:0007180)

Respiratory infections / aspiration and pulmonary complications

Australian childhood cohort: ~75% had a history of pneumonia. (giudice‐nairn2019theincidenceprevalence pages 1-2)
Registry cohort: aspiration is common—55% (81/147) aspirated occasionally/frequently; 23% (33/146) aspirated into lungs in the past 12 months; 53% (78/146) could not effectively clear chest secretions. (ta2022medicalcomorbiditiesin pages 6-7)
Cardiac/pulmonary: pulmonary hypertension is described as a rare but life-threatening complication with reported early death; authors recommend early cardiac assessment and ongoing monitoring. (giudice‐nairn2019theincidenceprevalence pages 1-2)

Suggested HPO terms: - Recurrent respiratory infections (HP:0002205) - Pneumonia (HP:0002090) - Aspiration (HP:0002835) - Pulmonary hypertension (HP:0002092)

Gastrointestinal and feeding phenotype

Constipation common: in US cohort (n=69) 81% constipation. (percy2023currentstatusof pages 11-15)
Caregiver survey: ~85% constipation, and ~1/3 required enemas/suppositories. (ak2022exploringthecharacteristics pages 1-2)
GI dysfunction is highlighted as a major domain in MDS and a target for improving QoL. (lim2017expandingtheclinical pages 10-13, allison2024mecp2relateddisorderswhile pages 7-8)

Suggested HPO terms: - Constipation (HP:0002019) - Gastroesophageal reflux (HP:0002020) - Intestinal dysmotility (HP:0002572)

Autonomic/vasomotor and related features

Registry cohort: autonomic disturbance 81% (119/146); cold peripheries 70%, temperature dysregulation 57%, breath holding 38%, hyperventilation 13%. (ta2022medicalcomorbiditiesin pages 6-7)
US cohort review reports vasomotor disturbances 73%. (percy2023currentstatusof pages 11-15)

Suggested HPO terms: - Autonomic nervous system abnormality (HP:0012332) - Cold extremities (HP:0002046) - Breath-holding spells (HP:0002598)

Sleep-disordered breathing and pain sensitivity

Sleep apnoea: 43% (61/143). (ta2022medicalcomorbiditiesin pages 9-10)
Abnormal pain sensitivity: 59% (85/143), with decreased pain sensitivity 55% (79/143). (ta2022medicalcomorbiditiesin pages 9-10)

Suggested HPO terms: - Sleep apnea (HP:0010535) - Abnormality of pain sensation (HP:0004305)

Musculoskeletal/bone health

Bone fractures: 32% (46/142); osteopenia/osteoporosis 13% (19/143). (ta2022medicalcomorbiditiesin pages 9-10)

Suggested HPO terms: - Osteopenia (HP:0011002) - Fractures (HP:0002659)

Quality of life impact

Higher clinical severity in MDS correlates with lower physical health QoL in the reviewed US natural history cohort analyses. (percy2023currentstatusof pages 11-15)

4. Genetic / Molecular Information

Causal gene(s)

MECP2 (Xq28) dosage gain is the core driver. (ta2022abriefhistory pages 1-2, pehlivan2024structuralvariantallelic pages 1-2)
A commonly implicated minimal duplicated region includes MECP2 and IRAK1, supporting potential multi-gene contributions to phenotype. (ta2022abriefhistory pages 2-4, maino2024anirak1mecp2tandem pages 1-5)

Variant class / chromosomal abnormality

Structural class heterogeneity: In a 2024 cohort (n=137), duplication sizes ranged 64.6 kb–16.5 Mb, with tandem duplications 48%, terminal duplications 22%, inverted triplications 20%, and other complex rearrangements 10%. (pehlivan2024structuralvariantallelic pages 1-2)
Terminal duplications often involve translocations (65%); de novo events enriched in terminal duplication group. (pehlivan2024structuralvariantallelic pages 1-2)

Functional consequence

Pathogenic mechanism is increased MECP2 dosage (gain of function via overexpression), with higher dosage (triplication) associated with greater severity/early lethality. (pehlivan2024structuralvariantallelic pages 1-2)

Modifier genes

Co-duplicated genes (e.g., IRAK1, FLNA, HCFC1, GDI1, RAB39B) have been associated with differences in severity in cohort analyses/reviews. (percy2023currentstatusof pages 11-15)

5. Environmental Information

No primary environmental toxins, lifestyle risks, or infectious agents as causal triggers were identified; infections are prominent complications in the disease course. (ta2022medicalcomorbiditiesin pages 6-7, lim2017expandingtheclinical pages 10-13)

6. Mechanism / Pathophysiology

Molecular pathways and cellular processes (current model)

Genomic duplication/triplication at Xq28 → increased MECP2 transcript and protein (supported by RNA/protein correlation in patient-derived lines). (pehlivan2024structuralvariantallelic pages 1-2)
MeCP2 overabundance (a methylated-DNA binding transcriptional regulator) perturbs neuronal transcription programs and synaptic function/plasticity. (pehlivan2024structuralvariantallelic pages 1-2, maino2024anirak1mecp2tandem pages 23-26)
System-level outcomes: neurodevelopmental impairment, epilepsy, progressive motor dysfunction/spasticity; additionally, immune dysregulation and infection susceptibility may be modified by co-duplication of IRAK1 and MeCP2’s roles in T cell biology. (maino2024anirak1mecp2tandem pages 1-5, maino2024anirak1mecp2tandem pages 23-26)

Key mechanistic data (2023–2024 emphasis)

Dose–biomolecule link: MECP2 RNA correlates with MeCP2 protein (Pearson R=0.6) in lymphoblastoid lines; triplications show distinct transcript quantities vs duplications. (pehlivan2024structuralvariantallelic pages 1-2)
Genotype–phenotype gradient: Severity (including survival) worsens across rearrangement classes; visual summary available in Pehlivan 2024 figures/tables. (pehlivan2024structuralvariantallelic media 2a375656, pehlivan2024structuralvariantallelic media 1eb0878d)
iPSC-derived neurons (human) and ASO response: MDS neurons show “global transcriptional dysregulation,” and MECP2-targeting ASO partially modulates a disease gene signature and partially rescues abnormal neuronal morphology. (bajikar2024modelingantisenseoligonucleotide pages 1-2)
Mouse tandem-duplication model including Irak1: Demonstrates neurobehavioral MDS-like phenotype plus an abnormal pro-inflammatory/Th1-skewed response to influenza, with quantified increases in BALF cytokines/chemokines (e.g., IFNγ 6.26-fold; TNFα 2.19-fold). (maino2024anirak1mecp2tandem pages 23-26)

Suggested ontology mappings

GO Biological Process (examples):
Regulation of transcription, DNA-templated (GO:0006355)
Synaptic plasticity (GO:0048167)
Long-term synaptic potentiation (GO:0060291)
T helper 1 type immune response (GO:0042088)
Cell Ontology (CL) (examples):
Cortical neuron (CL:0000540) / pyramidal neuron (context dependent)
Hippocampal neuron (subclassing varies)
CD4-positive, alpha-beta T cell (CL:0000624)
UBERON (examples): brain (UBERON:0000955), hippocampus (UBERON:0001954), lung (UBERON:0002048)

7. Anatomical Structures Affected

Primary system: Central nervous system (brain; cortical/hippocampal circuits implicated by transcriptional and plasticity phenotypes). (maino2024anirak1mecp2tandem pages 23-26, pehlivan2024structuralvariantallelic pages 1-2)
Respiratory system: recurrent LRTIs/aspiration; pulmonary hypertension risk. (giudice‐nairn2019theincidenceprevalence pages 1-2, ta2022medicalcomorbiditiesin pages 6-7)
Gastrointestinal tract: constipation/dysmotility, reflux. (percy2023currentstatusof pages 11-15, lim2017expandingtheclinical pages 10-13)

8. Temporal Development

Onset: often infancy (developmental delay in first 6 months, hypotonia early). (percy2023currentstatusof pages 11-15)
Epilepsy onset: median ~8–10 years in registry cohort, with severe seizures often linked to regression. (ta2022medicalcomorbiditiesin pages 6-7, percy2023currentstatusof pages 11-15)
Progression: progressive spasticity and later complications (respiratory morbidity, severe epilepsy) contribute to long-term burden and mortality risk. (ta2022abriefhistory pages 2-4, lim2017expandingtheclinical pages 10-13)

9. Inheritance and Population

Inheritance

X-linked inheritance, predominantly maternal transmission; review suggests ~20% de novo. (ta2022abriefhistory pages 2-4)
Australian series: most males inherited from carrier mothers (13/15). (giudice‐nairn2019theincidenceprevalence pages 1-2)

Epidemiology (recent best-available numbers from retrieved sources)

Australia birth prevalence: 0.65/100,000 all live births and 1/100,000 males. (giudice‐nairn2019theincidenceprevalence pages 1-2)
Estimated live birth prevalence in males: 1/150,000 (review estimate). (ta2022abriefhistory pages 1-2)
Diagnostic incidence in Australia: 0.07/100,000 person-years overall, 0.12/100,000 in males. (giudice‐nairn2019theincidenceprevalence pages 1-2)

10. Diagnostics

Recommended/used genetic tests

Chromosomal microarray / array-CGH: recommended for children with undiagnosed intellectual disability/global developmental delay in the Australian cohort. (giudice‐nairn2019theincidenceprevalence pages 1-2)
qPCR: used historically to detect duplications missed by earlier methods. (ta2022abriefhistory pages 2-4)
Karyotyping + WES + CNV-seq: applied in a 2024 pedigree; CNV-seq confirmed a 14.45 Mb Xq27.1–q28 duplication. (zeng2024geneticanalysisof pages 1-2)
Advanced structural characterization + omics: 2024 Genome Medicine study combined genomics with RNA-seq and deep HPO phenotyping. (pehlivan2024structuralvariantallelic pages 1-2)

Clinical evaluations/monitoring highlighted

Cardiac assessment/monitoring recommended due to pulmonary hypertension/CHD concerns in MDS cohorts. (giudice‐nairn2019theincidenceprevalence pages 1-2, ta2022medicalcomorbiditiesin pages 9-10)
Respiratory aspiration risk assessment and airway clearance support frequently needed (aspiration and secretion clearance deficits common). (ta2022medicalcomorbiditiesin pages 6-7)

Differential diagnosis

No formal differential diagnosis list was extracted from the retrieved sources; closely related disorders discussed in comparative reviews include Rett syndrome (MECP2 loss-of-function) and other developmental encephalopathies (CDKL5 deficiency, FOXG1 disorder). (percy2023currentstatusof pages 11-15)

11. Outcome / Prognosis

Historical minimal-region cohort summarized in Ta 2022 review: 6/11 individuals died before age 25 in one series (indicative of elevated early mortality risk). (ta2022abriefhistory pages 2-4)
2024 genotype–phenotype analyses support that survival and severity worsen with increasing MECP2 dosage and certain rearrangement classes (triplication most severe). (pehlivan2024structuralvariantallelic pages 1-2, pehlivan2024structuralvariantallelic media 2a375656)

12. Treatment

Current standard of care (real-world implementation)

Symptomatic/supportive, multidisciplinary care is standard: management of epilepsy, feeding/GI dysmotility (constipation, reflux), and proactive infection prevention/treatment. Supportive respiratory approaches include airway clearance devices and noninvasive ventilation in a subset. Vaccination and prompt antibiotics are emphasized, and immunoglobulin or prophylactic antibiotics may be used for recurrent infections in some patients. (allison2024mecp2relateddisorderswhile pages 7-8, ta2022medicalcomorbiditiesin pages 6-7)

Suggested MAXO terms (examples): - Antiseizure therapy (MAXO:0000465) (term may vary) - Airway clearance therapy (MAXO:0000747; check exact MAXO) - Noninvasive ventilation (MAXO:0000506; check exact MAXO) - Physical therapy (MAXO:0000011)

Emerging disease-modifying therapies (2023–2024 focus)

Antisense oligonucleotide (ASO) MECP2-lowering strategies

Preclinical rationale: Normalizing MECP2 dosage with ASOs rescues neurological phenotypes in MECP2 overexpression mouse models. (bajikar2024modelingantisenseoligonucleotide pages 1-2)
Human translational evidence (2024): In MDS patient iPSC-derived neurons, ASO treatment partially rescues gene-expression programs and neuronal morphology. (bajikar2024modelingantisenseoligonucleotide pages 1-2)
Key safety concern (expert analysis): MeCP2 is dose-sensitive—oversuppression risks inducing Rett-like insufficiency; ASOs’ repeat dosing enables titration. (allison2024mecp2relateddisorderswhile pages 7-8, percy2023currentstatusof pages 11-15)

Interventional clinical trials

ATTUNE — ION440 (Ionis): Phase 1–2, randomized, double-blind, sham-controlled, multiple-ascending dose trial using intrathecal bolus administration; recruiting; start date 2024-10-21 (NCT06430385). (NCT06430385 chunk 1)

Biomarker/disease progression characterization (trial readiness)

Ionis observational biomarker study: Terminated after meeting objectives; included CSF and blood collection (lumbar puncture), EEG/evoked potentials/pupillometry, and multiple clinical scales; primary endpoints included change in MeCP2 in CSF (NCT06014541). (NCT06014541 chunk 1)

Gene therapy and gene-based approaches (expert perspective)

Gene-based therapies must address MECP2’s narrow therapeutic window; experts caution that over-treatment could “convert” toward the opposite dosage disorder, and one-time gene replacement carries irreversibility risk compared with titratable approaches. (allison2024mecp2relateddisorderswhile pages 7-8)

13. Prevention

No primary prevention is available for a germline CNV disorder beyond genetic counseling, carrier testing, and prenatal/preimplantation options where legally/ethically appropriate. Maternal carrier transmission is common, supporting cascade testing in families. (giudice‐nairn2019theincidenceprevalence pages 1-2, ta2022abriefhistory pages 2-4)

14. Other Species / Natural Disease

No naturally occurring non-human veterinary syndrome was identified in the retrieved sources.

15. Model Organisms

Mouse models

CRISPR Irak1–Mecp2 tandem duplication mouse (2024): Designed to mimic patient-like tandem duplication including Irak1; shows neurobehavioral phenotypes and abnormal immune response to infection, enabling mechanistic and therapeutic studies. (maino2024anirak1mecp2tandem pages 1-5, maino2024anirak1mecp2tandem pages 23-26)

Human cellular models

Patient iPSC-derived neurons (2024): Used to evaluate MECP2-targeting ASO effects on transcriptional signatures and neuronal morphology. (bajikar2024modelingantisenseoligonucleotide pages 1-2)

Recent developments and “latest research” highlights (2023–2024)

Large 2024 cohort (n=137) integrating genomics + transcriptomics + deep HPO phenotyping demonstrates graded severity across rearrangement classes and MECP2 RNA–protein correlation, improving genotype–phenotype resolution and informing trial stratification. (pehlivan2024structuralvariantallelic pages 1-2, pehlivan2024structuralvariantallelic media 1eb0878d)
2024 human iPSC-neuron ASO modeling study provides a translational bridge between mouse rescue data and human neuronal biology, identifying MeCP2-level-responsive gene programs. (bajikar2024modelingantisenseoligonucleotide pages 1-2)
2024 CRISPR tandem-duplication mouse including Irak1 adds immune dysregulation biology absent from MECP2-only transgenic models, supporting multi-gene contributions to MDS. (maino2024anirak1mecp2tandem pages 1-5, maino2024anirak1mecp2tandem pages 23-26)
Clinical translation (2024 onward): an intrathecal ASO trial (ION440) has entered Phase 1–2 testing in MDS (NCT06430385), and a terminated observational biomarker study (NCT06014541) indicates active biomarker/trajectory definition by industry sponsors. (NCT06430385 chunk 1, NCT06014541 chunk 1)

Visual evidence (genotype–phenotype)

Pehlivan et al. (Genome Medicine 2024) provide figure/table visual summaries of structural rearrangement classes and phenotype severity ordering across classes (tandem duplications through triplications). (pehlivan2024structuralvariantallelic media 2e1d3f3a, pehlivan2024structuralvariantallelic media 1eb0878d, pehlivan2024structuralvariantallelic media 2a375656)

Notes on gaps / limitations of this tool run

Ontology identifiers (MONDO, Orphanet, MeSH, ICD-10/11) were not present in the retrieved full text chunks and therefore are not asserted here.
Some phenotype frequencies (e.g., pneumonia/bronchitis/GERD/scoliosis exact prevalence) were described qualitatively in the MDBase abstract, but complete numeric tables were not fully captured in retrieved excerpts; a direct full-text table extraction would improve completeness. (ta2022medicalcomorbiditiesin pages 1-2)
The CRISPR RNA-editing interventional trial record (NCT06615206) was retrieved earlier but not present in the evidence chunks extracted here; therefore, it is not detailed in this report.

References

(ta2022abriefhistory pages 1-2): Daniel Ta, Jenny Downs, Gareth Baynam, Andrew Wilson, Peter Richmond, and Helen Leonard. A brief history of mecp2 duplication syndrome: 20-years of clinical understanding. Orphanet Journal of Rare Diseases, Mar 2022. URL: https://doi.org/10.1186/s13023-022-02278-w, doi:10.1186/s13023-022-02278-w. This article has 64 citations and is from a peer-reviewed journal.
(pehlivan2024structuralvariantallelic pages 1-2): Davut Pehlivan, Jesse D. Bengtsson, Sameer S. Bajikar, Christopher M. Grochowski, Ming Yin Lun, Mira Gandhi, Angad Jolly, Alexander J. Trostle, Holly K. Harris, Bernhard Suter, Sukru Aras, Melissa B. Ramocki, Haowei Du, Michele G. Mehaffey, KyungHee Park, Ellen Wilkey, Cemal Karakas, Jesper J. Eisfeldt, Maria Pettersson, Lynn Liu, Marwan S. Shinawi, Virginia E. Kimonis, Wojciech Wiszniewski, Kyle Mckenzie, Timo Roser, Angela M. Vianna-Morgante, Alberto S. Cornier, Ahmed Abdelmoity, James P. Hwang, Shalini N. Jhangiani, Donna M. Muzny, Tadahiro Mitani, Kazuhiro Muramatsu, Shin Nabatame, Daniel G. Glaze, Jawid M. Fatih, Richard A. Gibbs, Zhandong Liu, Anna Lindstrand, Fritz J. Sedlazeck, James R. Lupski, Huda Y. Zoghbi, and Claudia M. B. Carvalho. Structural variant allelic heterogeneity in mecp2 duplication syndrome provides insight into clinical severity and variability of disease expression. Genome Medicine, Dec 2024. URL: https://doi.org/10.1186/s13073-024-01411-7, doi:10.1186/s13073-024-01411-7. This article has 14 citations and is from a highest quality peer-reviewed journal.
(percy2023currentstatusof pages 11-15): Alan K. Percy, Jeffrey L. Neul, Sarika Peters, Knut Brockmann, Eric Marsh, and Tim Benke. Current status of developmental encephalopathies: rett syndrome, mecp2 duplication disorder, cdkl5 deficiency disorder and foxg1 disorder. Translational Science of Rare Diseases, 6:73-100, Jul 2023. URL: https://doi.org/10.3233/trd-220055, doi:10.3233/trd-220055. This article has 2 citations.
(ta2022medicalcomorbiditiesin pages 6-7): Daniel Ta, Jenny Downs, Gareth Baynam, Andrew Wilson, Peter Richmond, and Helen Leonard. Medical comorbidities in mecp2 duplication syndrome: results from the international mecp2 duplication database. Children, 9:633, Apr 2022. URL: https://doi.org/10.3390/children9050633, doi:10.3390/children9050633. This article has 14 citations.
(pehlivan2024structuralvariantallelic media 2e1d3f3a): Davut Pehlivan, Jesse D. Bengtsson, Sameer S. Bajikar, Christopher M. Grochowski, Ming Yin Lun, Mira Gandhi, Angad Jolly, Alexander J. Trostle, Holly K. Harris, Bernhard Suter, Sukru Aras, Melissa B. Ramocki, Haowei Du, Michele G. Mehaffey, KyungHee Park, Ellen Wilkey, Cemal Karakas, Jesper J. Eisfeldt, Maria Pettersson, Lynn Liu, Marwan S. Shinawi, Virginia E. Kimonis, Wojciech Wiszniewski, Kyle Mckenzie, Timo Roser, Angela M. Vianna-Morgante, Alberto S. Cornier, Ahmed Abdelmoity, James P. Hwang, Shalini N. Jhangiani, Donna M. Muzny, Tadahiro Mitani, Kazuhiro Muramatsu, Shin Nabatame, Daniel G. Glaze, Jawid M. Fatih, Richard A. Gibbs, Zhandong Liu, Anna Lindstrand, Fritz J. Sedlazeck, James R. Lupski, Huda Y. Zoghbi, and Claudia M. B. Carvalho. Structural variant allelic heterogeneity in mecp2 duplication syndrome provides insight into clinical severity and variability of disease expression. Genome Medicine, Dec 2024. URL: https://doi.org/10.1186/s13073-024-01411-7, doi:10.1186/s13073-024-01411-7. This article has 14 citations and is from a highest quality peer-reviewed journal.
(pehlivan2024structuralvariantallelic media 2a375656): Davut Pehlivan, Jesse D. Bengtsson, Sameer S. Bajikar, Christopher M. Grochowski, Ming Yin Lun, Mira Gandhi, Angad Jolly, Alexander J. Trostle, Holly K. Harris, Bernhard Suter, Sukru Aras, Melissa B. Ramocki, Haowei Du, Michele G. Mehaffey, KyungHee Park, Ellen Wilkey, Cemal Karakas, Jesper J. Eisfeldt, Maria Pettersson, Lynn Liu, Marwan S. Shinawi, Virginia E. Kimonis, Wojciech Wiszniewski, Kyle Mckenzie, Timo Roser, Angela M. Vianna-Morgante, Alberto S. Cornier, Ahmed Abdelmoity, James P. Hwang, Shalini N. Jhangiani, Donna M. Muzny, Tadahiro Mitani, Kazuhiro Muramatsu, Shin Nabatame, Daniel G. Glaze, Jawid M. Fatih, Richard A. Gibbs, Zhandong Liu, Anna Lindstrand, Fritz J. Sedlazeck, James R. Lupski, Huda Y. Zoghbi, and Claudia M. B. Carvalho. Structural variant allelic heterogeneity in mecp2 duplication syndrome provides insight into clinical severity and variability of disease expression. Genome Medicine, Dec 2024. URL: https://doi.org/10.1186/s13073-024-01411-7, doi:10.1186/s13073-024-01411-7. This article has 14 citations and is from a highest quality peer-reviewed journal.
(giudice‐nairn2019theincidenceprevalence pages 1-2): Peter Giudice‐Nairn, Jenny Downs, Kingsley Wong, Dylan Wilson, Daniel Ta, Michael Gattas, David Amor, Elizabeth Thompson, Cathy Kirrali‐Borri, Carolyn Ellaway, and Helen Leonard. The incidence, prevalence and clinical features of mecp2 duplication syndrome in australian children. Journal of Paediatrics and Child Health, 55:1315-1322, Nov 2019. URL: https://doi.org/10.1111/jpc.14399, doi:10.1111/jpc.14399. This article has 47 citations and is from a peer-reviewed journal.
(ak2022exploringthecharacteristics pages 1-2): Muharrem Ak, Bernhard Suter, Zekeriya Akturk, Holly Harris, Kristina Bowyer, Laurence Mignon, Sasidhar Pasupuleti, Daniel G. Glaze, and Davut Pehlivan. Exploring the characteristics and most bothersome symptoms in mecp2 duplication syndrome to pave the path toward developing parent‐oriented outcome measures. Molecular Genetics & Genomic Medicine, Jun 2022. URL: https://doi.org/10.1002/mgg3.1989, doi:10.1002/mgg3.1989. This article has 10 citations and is from a peer-reviewed journal.
(maino2024anirak1mecp2tandem pages 23-26): Eleonora Maino, Ori Scott, Samar Z. Rizvi, Shagana Visuvanathan, Youssif Ben Zablah, Hongbin Li, Ameet S. Sengar, Michael W. Salter, Zhengping Jia, Janet Rossant, Ronald D. Cohn, Bin Gu, and Evgueni A. Ivakine. An irak1-mecp2 tandem duplication mouse model for the study of mecp2 duplication syndrome. Disease Models & Mechanisms, Feb 2024. URL: https://doi.org/10.1101/2023.02.07.527511, doi:10.1101/2023.02.07.527511. This article has 1 citations and is from a domain leading peer-reviewed journal.
(bajikar2024modelingantisenseoligonucleotide pages 1-2): Sameer S Bajikar, Yehezkel Sztainberg, Alexander J Trostle, Harini P Tirumala, Ying-Wooi Wan, Caroline L Harrop, Jesse D Bengtsson, Claudia M B Carvalho, Davut Pehlivan, Bernhard Suter, Jeffrey L Neul, Zhandong Liu, Paymaan Jafar-Nejad, Frank Rigo, and Huda Y Zoghbi. Modeling antisense oligonucleotide therapy in mecp2 duplication syndrome human ipsc-derived neurons reveals gene expression programs responsive to mecp2 levels. Human Molecular Genetics, 33:1986-2001, Sep 2024. URL: https://doi.org/10.1093/hmg/ddae135, doi:10.1093/hmg/ddae135. This article has 11 citations and is from a domain leading peer-reviewed journal.
(ta2022abriefhistory pages 2-4): Daniel Ta, Jenny Downs, Gareth Baynam, Andrew Wilson, Peter Richmond, and Helen Leonard. A brief history of mecp2 duplication syndrome: 20-years of clinical understanding. Orphanet Journal of Rare Diseases, Mar 2022. URL: https://doi.org/10.1186/s13023-022-02278-w, doi:10.1186/s13023-022-02278-w. This article has 64 citations and is from a peer-reviewed journal.
(lim2017expandingtheclinical pages 10-13): Zhan Lim, Jenny Downs, Jenny Downs, Kingsley Wong, C. Ellaway, C. Ellaway, and Helen Leonard. Expanding the clinical picture of the mecp2 duplication syndrome. Clinical Genetics, 91:557-563, Apr 2017. URL: https://doi.org/10.1111/cge.12814, doi:10.1111/cge.12814. This article has 67 citations and is from a peer-reviewed journal.
(allison2024mecp2relateddisorderswhile pages 4-5): Katherine Allison, Mirjana Maletic-Savatic, and Davut Pehlivan. Mecp2-related disorders while gene-based therapies are on the horizon. Frontiers in Genetics, Feb 2024. URL: https://doi.org/10.3389/fgene.2024.1332469, doi:10.3389/fgene.2024.1332469. This article has 14 citations and is from a peer-reviewed journal.
(allison2024mecp2relateddisorderswhile pages 7-8): Katherine Allison, Mirjana Maletic-Savatic, and Davut Pehlivan. Mecp2-related disorders while gene-based therapies are on the horizon. Frontiers in Genetics, Feb 2024. URL: https://doi.org/10.3389/fgene.2024.1332469, doi:10.3389/fgene.2024.1332469. This article has 14 citations and is from a peer-reviewed journal.
(ta2022medicalcomorbiditiesin pages 9-10): Daniel Ta, Jenny Downs, Gareth Baynam, Andrew Wilson, Peter Richmond, and Helen Leonard. Medical comorbidities in mecp2 duplication syndrome: results from the international mecp2 duplication database. Children, 9:633, Apr 2022. URL: https://doi.org/10.3390/children9050633, doi:10.3390/children9050633. This article has 14 citations.
(maino2024anirak1mecp2tandem pages 1-5): Eleonora Maino, Ori Scott, Samar Z. Rizvi, Shagana Visuvanathan, Youssif Ben Zablah, Hongbin Li, Ameet S. Sengar, Michael W. Salter, Zhengping Jia, Janet Rossant, Ronald D. Cohn, Bin Gu, and Evgueni A. Ivakine. An irak1-mecp2 tandem duplication mouse model for the study of mecp2 duplication syndrome. Disease Models & Mechanisms, Feb 2024. URL: https://doi.org/10.1101/2023.02.07.527511, doi:10.1101/2023.02.07.527511. This article has 1 citations and is from a domain leading peer-reviewed journal.
(pehlivan2024structuralvariantallelic media 1eb0878d): Davut Pehlivan, Jesse D. Bengtsson, Sameer S. Bajikar, Christopher M. Grochowski, Ming Yin Lun, Mira Gandhi, Angad Jolly, Alexander J. Trostle, Holly K. Harris, Bernhard Suter, Sukru Aras, Melissa B. Ramocki, Haowei Du, Michele G. Mehaffey, KyungHee Park, Ellen Wilkey, Cemal Karakas, Jesper J. Eisfeldt, Maria Pettersson, Lynn Liu, Marwan S. Shinawi, Virginia E. Kimonis, Wojciech Wiszniewski, Kyle Mckenzie, Timo Roser, Angela M. Vianna-Morgante, Alberto S. Cornier, Ahmed Abdelmoity, James P. Hwang, Shalini N. Jhangiani, Donna M. Muzny, Tadahiro Mitani, Kazuhiro Muramatsu, Shin Nabatame, Daniel G. Glaze, Jawid M. Fatih, Richard A. Gibbs, Zhandong Liu, Anna Lindstrand, Fritz J. Sedlazeck, James R. Lupski, Huda Y. Zoghbi, and Claudia M. B. Carvalho. Structural variant allelic heterogeneity in mecp2 duplication syndrome provides insight into clinical severity and variability of disease expression. Genome Medicine, Dec 2024. URL: https://doi.org/10.1186/s13073-024-01411-7, doi:10.1186/s13073-024-01411-7. This article has 14 citations and is from a highest quality peer-reviewed journal.
(zeng2024geneticanalysisof pages 1-2): Lan Zeng, Hui Zhu, Jin Wang, Qiyan Wang, Ying Pang, Zemin Luo, Ai Chen, Shengfang Qin, and Shuyao Zhu. Genetic analysis of a pedigree with mecp2 duplication syndrome in china. BMC Medical Genomics, Feb 2024. URL: https://doi.org/10.1186/s12920-024-01831-9, doi:10.1186/s12920-024-01831-9. This article has 0 citations and is from a peer-reviewed journal.
(NCT06430385 chunk 1): ATTUNE: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION440 in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome (MDS). Ionis Pharmaceuticals, Inc.. 2024. ClinicalTrials.gov Identifier: NCT06430385
(NCT06014541 chunk 1): Observational Study to Characterize Biomarkers and Disease Progression in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome. Ionis Pharmaceuticals, Inc.. 2023. ClinicalTrials.gov Identifier: NCT06014541
(ta2022medicalcomorbiditiesin pages 1-2): Daniel Ta, Jenny Downs, Gareth Baynam, Andrew Wilson, Peter Richmond, and Helen Leonard. Medical comorbidities in mecp2 duplication syndrome: results from the international mecp2 duplication database. Children, 9:633, Apr 2022. URL: https://doi.org/10.3390/children9050633, doi:10.3390/children9050633. This article has 14 citations.

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Genetic Associations

Treatments

Source YAML

References & Deep Research

References

Deep Research

1. Disease Information

What is the disease?

Key identifiers (from retrieved literature)

Synonyms / alternative names

Evidence type note

2. Etiology

Disease causal factors

Risk factors

Protective factors

Gene–environment interactions

3. Phenotypes (with quantitative data where available)

Core neurodevelopmental phenotype

Epilepsy

Respiratory infections / aspiration and pulmonary complications

Gastrointestinal and feeding phenotype

Autonomic/vasomotor and related features

Sleep-disordered breathing and pain sensitivity

Musculoskeletal/bone health

Quality of life impact

4. Genetic / Molecular Information

Causal gene(s)

Variant class / chromosomal abnormality

Functional consequence

Modifier genes

5. Environmental Information

6. Mechanism / Pathophysiology

Molecular pathways and cellular processes (current model)

Key mechanistic data (2023–2024 emphasis)

Suggested ontology mappings

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

Inheritance

Epidemiology (recent best-available numbers from retrieved sources)

10. Diagnostics

Recommended/used genetic tests

Clinical evaluations/monitoring highlighted

Differential diagnosis

11. Outcome / Prognosis

12. Treatment

Current standard of care (real-world implementation)

Emerging disease-modifying therapies (2023–2024 focus)

Antisense oligonucleotide (ASO) MECP2-lowering strategies

Interventional clinical trials

Biomarker/disease progression characterization (trial readiness)

Gene therapy and gene-based approaches (expert perspective)

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Mouse models

Human cellular models

Recent developments and “latest research” highlights (2023–2024)

Visual evidence (genotype–phenotype)

Notes on gaps / limitations of this tool run