Duplicações distais de Xq referem-se a distúrbios cromossômicos resultantes do envolvimento do braço longo do cromossomo X (Xq). As manifestações clínicas variam amplamente dependendo do sexo do paciente e do conteúdo genético do segmento duplicado. A prevalência de duplicações Xq permanece desconhecida.
Introdução
O que você precisa saber de cara
Duplicações distais de Xq referem-se a distúrbios cromossômicos resultantes do envolvimento do braço longo do cromossomo X (Xq). As manifestações clínicas variam amplamente dependendo do sexo do paciente e do conteúdo genético do segmento duplicado. A prevalência de duplicações Xq permanece desconhecida.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 45 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 112 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
1 gene identificado com associação a esta condição.
Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC)
Nucleus
Angelman syndrome
A neurodevelopmental disorder characterized by severe motor and intellectual retardation, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, open-mouthed expression revealing the tongue.
Variantes genéticas (ClinVar)
1,419 variantes patogênicas registradas no ClinVar.
Vias biológicas (Reactome)
11 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Síndrome de duplicação proximal Xq28
Selecione um estado ou use sua localização para ver resultados.
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Functional skills in MECP2 duplication syndrome: developmental dynamics and regression.
MECP2 duplication syndrome (MDS) is an ultrarare, X-linked neurodevelopmental disorder that is poorly understood in terms of its natural history and phenotypic variability. There is limited information on how individuals with MDS acquire, retain or lose fundamental functional skills (gross motor, purposeful hand function and communication) - that of which this study aimed to better characterise in the largest case series to date.For 160 individuals with MDS (median age 9.06 y, range: 0.57-51.63 y; 84% male), we report that phenotypic penetrance in females can, in some, result in a similar functional skill deficits to males. However, a higher proportion of females acquired gross motor and fine motor skills compared to males. Use of words was the most common parent-reported skill regression (34/90 [38%]) followed by fine motor/hand function (26/90 [29%]), independent walking (25/90 [28%]) and feeding (25/90 [28%]). Additionally, lower proportions of functional ability were present in those with seizures compared to those without. A general trend was also observed for decreasing functional skills with increasing age. Additionally, those with a larger duplication length (1 + Mb) were less likely to be able to acquire independent walking compared with those with less than a 1 + Mb duplication (p < 0.001).This is the first study to comprehensively map the developmental trajectory of functional skills in MDS and provides a seminal baseline for better characterising the natural history of this disorder. Further investigations are required to understand the importance of interventional therapy on the retainment of functional skills.
MECP2 duplication syndrome: Recent advances in pathophysiology and therapeutic perspectives.
MECP2 duplication syndrome (MDS) is an X-linked neurodevelopmental disorder caused by duplication or extra copies of MECP2 gene. It primarily affects males and is characterized by intellectual disability, hypotonia, epilepsy, recurrent infections, and autistic features. Methyl-CpG binding protein 2 (MeCP2) encoded by MECP2 is a crucial epigenetic regulator of brain function. Expression levels are strictly regulated during brain development and maturation, and altered levels lead to severe neurodevelopmental disorders; excessive levels are associated with MDS, while insufficient levels cause Rett syndrome. This review provides a comprehensive overview of the recent advances in the pathophysiology and therapeutic perspectives of MDS, focusing on its pathophysiology, clinical features, disease models, and therapeutic strategies. Advances in studies using animal and patient-derived induced pluripotent stem cells (iPSCs)-derived neuronal models have provided insights into the molecular and cellular abnormalities associated with MDS and have facilitated therapeutic development. Among the emerging treatments, antisense oligonucleotide (ASO) therapy has gained significant attention as a promising approach for selectively suppressing MeCP2 overexpression. Preclinical studies using MDS mouse models and iPSCs-derived neurons have demonstrated that ASO treatment can partially restore neuronal abnormalities and clinical trials are currently underway.
A novel approach to metabolic profiling in case models of MECP2-related disorders.
Genetic abnormalities of the MECP2 gene cause several conditions grouped under the umbrella term of MECP2-related disorders and characterized by a variety of phenotypes. We applied a functional approach to identify metabolic profiles in two patients with Rett syndrome (RTT) and one patient with MECP2 duplication syndrome (MRXSL). Such an approach is based on the Phenotype Mammalian Microarray (PM-M) technology, which is designed to assess the cellular production of energy in the presence of different compounds generating distinct metabolic environments. The findings in the three case models were compared versus 50 controls. Although the small number of samples prevented most results from reaching significant p-values when adjusted with the Benjamini-Hochberg correction, some interesting trends emerged. Some compounds indicated metabolic trends shared by the two conditions, like increased energy production in the presence of energy sources such as pectin, adenosine, and pyruvic acid, or decreased metabolic response to certain hormones. Other compounds showed opposite trends for the two disorders, like interleukin-1 beta (IL-1 beta), which caused decreased energy production in the RTT group but increased energy production in the patient with MRXSL. The response to IL-1 beta also offers valuable insights into the pathogenic mechanism and potential therapeutic approaches. The metabolic profiling of MECP2-related disorders bears a remarkable translational potential since it may be helpful to investigate the molecular abnormalities underlying the phenotypical variety in this spectrum of conditions, develop biomarkers for the identification of ideal candidates for treatments like the recently approved trofenatide, and identify potential targets for the development of novel therapeutic approaches.
Comprehensive assessment reveals numerous clinical and neurophysiological differences between MECP2-allelic disorders.
Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) result from under- and overexpression of MECP2, respectively. Preclinical studies using genetic-based treatment showed robust phenotype recovery for both MDS and RTT. However, there is a risk of converting MDS to RTT, or vice versa, if accurate MeCP2 levels are not achieved. The aim of this study was to identify biomarkers distinguishing RTT from MDS. We prospectively enrolled 11 MDS and 6 male RTT like (MRL) individuals for a panel of clinical and neurophysiological assessments over two visits, 8-10 months apart. We identified numerous clinical and physiological features as promising biomarkers. MRL individuals exhibited large amplitude whole body tremor, midline stereotypies (vs. hand flapping at sides in MDS), earlier neuromotor regression, and earlier onset but less commonly refractory epilepsy. In the neurophysiological domain, we observed several marked differences in sleep physiology between MDS/MRL and typically developing (TD) individuals including reduced sleeping time, increased delta power during rapid eye movement (REM) sleep, decreased occipital alpha and increased brain-wide delta power during wakefulness, and reduced spindle density and duration. MRL individuals also had much lower delta power during NREM 2 and 3 stages than the TD group. We found differences in spindle duration in the temporal lobes and spindle amplitude in the frontal lobes between MDS and MRL. Our study revealed distinct clinical features of MDS and MRL that can be monitored during a clinical trial and may serve as target engagement, disease progression, or safety biomarkers for interventional studies.
An RNA editing strategy rescues gene duplication in a mouse model of MECP2 duplication syndrome and nonhuman primates.
Duplication of methyl-CpG-binding protein 2 (MECP2) gene causes MECP2 duplication syndrome (MDS). To normalize the duplicated MECP2 in MDS, we developed a high-fidelity Cas13Y (hfCas13Y) system capable of targeting the MECP2 (hfCas13Y-gMECP2) messenger RNA for degradation and reducing protein levels in the brain of humanized MECP2 transgenic mice. Moreover, the intracerebroventricular adeno-associated virus (AAV) delivery of hfCas13Y-gMECP2 in newborn or adult MDS mice restored dysregulated gene expression and improved behavior deficits. Notably, treatment with AAV9-hfCas13Y-gMECP2 extended the median survival of MECP2 transgenic mice from 156.5 to 226 d. Furthermore, studies with monkeys showed a single injection of AAV9-hfCas13Y-gMECP2 was sufficient to drive robust expression of hfCas13Y in widespread brain regions, with MECP2 knockdown efficiency reaching 52.19 ± 0.03% and significantly decreased expression of biomarker gene GDF11. Our results demonstrate that the RNA-targeting hfCas13Y-gMECP2 system is an effective intervention for MDS, providing a potential strategy for treating other dosage-sensitive diseases.
Publicações recentes
Zebrafish models for congenital disorders of glycosylation (CDG): a systematic review.
Syndromic male subfertility: A network view of genome-phenome associations.
📚 EuropePMCmostrando 93
Functional skills in MECP2 duplication syndrome: developmental dynamics and regression.
Orphanet journal of rare diseasesMECP2 duplication syndrome: Recent advances in pathophysiology and therapeutic perspectives.
Brain & development[Duplication of the X-chromosomal Xq28 region containing the MECP2 gene in X-linked intellectual disability syndrome Lubs-type].
Orvosi hetilapA novel approach to metabolic profiling in case models of MECP2-related disorders.
Metabolic brain diseaseRapid Whole Genome Sequencing Uncovers a Triple Diagnosis: X-Linked Chondrodysplasia Punctata, MECP2-Related Disorder, and Mosaic Jacobs Syndrome.
Molecular genetics & genomic medicineComprehensive assessment reveals numerous clinical and neurophysiological differences between MECP2-allelic disorders.
Annals of clinical and translational neurologyStructural variant allelic heterogeneity in MECP2 duplication syndrome provides insight into clinical severity and variability of disease expression.
Genome medicineAn RNA editing strategy rescues gene duplication in a mouse model of MECP2 duplication syndrome and nonhuman primates.
Nature neuroscienceModeling antisense oligonucleotide therapy in MECP2 duplication syndrome human iPSC-derived neurons reveals gene expression programs responsive to MeCP2 levels.
Human molecular geneticsAn Irak1-Mecp2 tandem duplication mouse model for the study of MECP2 duplication syndrome.
Disease models & mechanismsImbalance between hippocampal projection cell and parvalbumin interneuron architecture increases epileptic susceptibility in mouse model of methyl CpG binding protein 2 duplication syndrome.
EpilepsiaMulti-omics in MECP2 duplication syndrome patients and carriers.
The European journal of neuroscience[Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with co-morbid Ornithine carbamoyl transferase deficiency and MECP2 duplication syndrome].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsGenetic analysis of a pedigree with MECP2 duplication syndrome in China.
BMC medical genomicsDevelopment and validation of parent-reported gastrointestinal health scale in MECP2 duplication syndrome.
Orphanet journal of rare diseases[Diagnosis of MECP2 duplication in a child and prenatally].
Orvosi hetilapGeneration of five induced pluripotent stem cell lines from patients with MECP2 Duplication Syndrome.
Stem cell researchGut microbiome and metabolic profiles of mouse model for MeCP2 duplication syndrome.
Brain research bulletinTug-of-Peace: Visual Rivalry and Atypical Visual Motion Processing in MECP2 Duplication Syndrome of Autism.
eNeuroMoya moya vasculopathy and MECP2 duplication syndrome.
Child's nervous system : ChNS : official journal of the International Society for Pediatric NeurosurgeryIdentification of molecular signatures and pathways involved in Rett syndrome using a multi-omics approach.
Human genomicsExploring gastrointestinal health in MECP2 duplication syndrome.
Neurogastroenterology and motilityMECP2 duplication syndrome initially misdiagnosed as cerebral palsy: a case report.
The Journal of international medical researchDuplication within two regions distal to MECP2: clinical similarity with MECP2 duplication syndrome.
BMC medical genomicsComparison of evoked potentials across four related developmental encephalopathies.
Journal of neurodevelopmental disordersMeCP2 regulates Gdf11, a dosage-sensitive gene critical for neurological function.
eLifeClinical application of long-read nanopore sequencing in a preimplantation genetic testing pre-clinical workup to identify the junction for complex Xq chromosome rearrangement-related disease.
Prenatal diagnosisAbnormal Prefrontal Neural Oscillations are Associated with Social Deficits in MECP2 Duplication Syndrome.
Neuroscience bulletinIRAK1 Duplication in MECP2 Duplication Syndrome Does Not Increase Canonical NF-κB-Induced Inflammation.
Journal of clinical immunologyAberrant brain functional and structural developments in MECP2 duplication rats.
Neurobiology of diseaseIncreased Reliability of Visually-Evoked Activity in Area V1 of the MECP2-Duplication Mouse Model of Autism.
The Journal of neuroscience : the official journal of the Society for NeuroscienceAssessing the Burden on Caregivers of MECP2 Duplication Syndrome.
Pediatric neurologyExploring the characteristics and most bothersome symptoms in MECP2 duplication syndrome to pave the path toward developing parent-oriented outcome measures.
Molecular genetics & genomic medicineRecurrent pneumonia in three patients with MECP2 duplication syndrome with aspiration as the possible cause.
Brain & developmentA brief history of MECP2 duplication syndrome: 20-years of clinical understanding.
Orphanet journal of rare diseasesExploration of group II metabotropic glutamate receptor modulation in mouse models of Rett syndrome and MECP2 Duplication syndrome.
NeuropharmacologyAstrocytic Gap Junctions Contribute to Aberrant Neuronal Synchronization in a Mouse Model of MeCP2 Duplication Syndrome.
Neuroscience bulletin[Clinical phenotype and genetic analysis of MECP2 duplication syndrome].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsMolecular and clinical insights into complex genomic rearrangements related to MECP2 duplication syndrome.
European journal of medical geneticsMECP2-Related Disorders in Males.
International journal of molecular sciencesElectroclinical Features in MECP2 Duplication Syndrome: Pediatric Case Series.
Journal of child neurologyThe int22h1/int22h2-Mediated Xq28 Duplication Syndrome: An Intersection between Neurodevelopment, Immunology, and Cancer.
GenesAbdominal compartment syndrome secondary to chronic constipation in MECP2 duplication syndrome.
BMJ case reportsStereotyped Upper Limb Movement in MECP2 Duplication Syndrome.
NeurologyIdentification and characterization of conserved noncoding cis-regulatory elements that impact Mecp2 expression and neurological functions.
Genes & developmentAntisense oligonucleotide therapy in a humanized mouse model of MECP2 duplication syndrome.
Science translational medicineMECP2 and the biology of MECP2 duplication syndrome.
Journal of neurochemistryEarly diagnosis of MECP2 duplication syndrome: Insights from a nationwide survey in Japan.
Journal of the neurological sciencesPhenotypic features in MECP2 duplication syndrome: Effects of age.
American journal of medical genetics. Part ASleep-disordered breathing and nocturnal hypoventilation in children with the MECP2 duplication syndrome: A case series and review of the literature.
American journal of medical genetics. Part AAnesthetic Management for a Patient With MECP2 Duplication Syndrome: A Case Report.
A&A practiceAdvances in understanding of Rett syndrome and MECP2 duplication syndrome: prospects for future therapies.
The Lancet. NeurologyCortisol profiles and clinical severity in MECP2 duplication syndrome.
Journal of neurodevelopmental disordersComparison of Core Features in Four Developmental Encephalopathies in the Rett Natural History Study.
Annals of neurology[Familial MECP2 duplication syndrome].
Revista de neurologiaMECP2 duplication syndrome in a patient from Cameroon.
American journal of medical genetics. Part AMolecular characterization of Spanish patients with MECP2 duplication syndrome.
Clinical geneticsDelineation of MidXq28-duplication syndrome distal to MECP2 and proximal to RAB39B genes.
Clinical genetics[Molecular diagnosis and functional study of a pedigree affected with Lubs X-linked mental retardation syndrome].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsCharacterizing the phenotypic effect of Xq28 duplication size in MECP2 duplication syndrome.
Clinical geneticsElectroencephalographic and epilepsy findings in mecp2 duplication syndrome. A family study.
Brain & developmentSpectrum and time course of epilepsy and the associated cognitive decline in MECP2 duplication syndrome.
NeurologyToxicity of overexpressed MeCP2 is independent of HDAC3 activity.
Genes & developmentSuccessful corpus callosotomy for post-encephalopathic refractory epilepsy in a patient with MECP2 duplication syndrome.
Brain & developmentIncreased Axonal Bouton Stability during Learning in the Mouse Model of MECP2 Duplication Syndrome.
eNeuroMouse models as a tool for discovering new neurological diseases.
Neurobiology of learning and memoryFurther delineation of the MECP2 duplication syndrome phenotype in 59 French male patients, with a particular focus on morphological and neurological features.
Journal of medical geneticsFirst report of an unusual novel double mutation affecting the transcription repression domain of MeCP2 and causing a severe phenotype of Rett syndrome: Molecular analyses and computational investigation.
Biochemical and biophysical research communicationsIntellectual disability and epilepsy due to the K/L-mediated Xq28 duplication: Further evidence of a distinct, dosage-dependent phenotype.
American journal of medical genetics. Part AGenetic Reduction or Negative Modulation of mGlu7 Does Not Impact Anxiety and Fear Learning Phenotypes in a Mouse Model of MECP2 Duplication Syndrome.
ACS chemical neuroscienceClinical and molecular genetic characterization of familial MECP2 duplication syndrome in a Chinese family.
BMC medical geneticsAntibiotic Prophylaxis, Immunoglobulin Substitution and Supportive Measures Prevent Infections in MECP2 Duplication Syndrome.
The Pediatric infectious disease journalDistinguishing response to names in Rett and MECP2 Duplication syndrome: An ERP study of auditory social information processing.
Brain researchAltered visual cortical processing in a mouse model of MECP2 duplication syndrome.
Scientific reports[MECP2 gene and MECP2-related diseases].
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics[MECP2 duplication syndrome: a clinical analysis of three cases and literature review].
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatricsExpansion of the phenotypic spectrum in three families of methyl CpG-binding protein 2 duplication syndrome.
Clinical dysmorphologyAccumulated quiescent neural stem cells in adult hippocampus of the mouse model for the MECP2 duplication syndrome.
Scientific reportsInfluenza A induces dysfunctional immunity and death in MeCP2-overexpressing mice.
JCI insightA Case of MECP2 Duplication Syndrome with Gonadotropin-Dependent Precocious Puberty.
Hormone research in paediatricsExpanding the clinical picture of the MECP2 Duplication syndrome.
Clinical geneticsMonkey model of MECP2 duplication syndrome aids autism research: Monkeys genetically altered with extra copies of MECP2 are being used as a model for research into autism and MECP2 duplication syndrome.
American journal of medical genetics. Part AMECP2 Duplication Syndrome: Evidence of Enhanced Oxidative Stress. A Comparison with Rett Syndrome.
PloS one[Progress of MECP2 duplication syndrome].
Zhonghua er ke za zhi = Chinese journal of pediatricsMECP2 DUPLICATION SYNDROME WITH ADDITIONAL FINDINGS.
Genetic counseling (Geneva, Switzerland)MECP2 duplication syndrome in a Chinese family.
BMC medical geneticsReversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides.
NatureHepatoblastoma in a male with MECP2 duplication syndrome.
American journal of medical genetics. Part AMECP2 disorders: from the clinic to mice and back.
The Journal of clinical investigation[Advance in research on MECP2 [corrected] duplication syndrome].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsDiurnal Salivary Cortisol and Regression Status in MECP2 Duplication Syndrome.
Journal of child neurologyInfectious and immunologic phenotype of MECP2 duplication syndrome.
Journal of clinical immunology[Diagnosis of MECP2 duplication syndrome with molecular genetic techniques].
Zhonghua er ke za zhi = Chinese journal of pediatricsAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Functional skills in MECP2 duplication syndrome: developmental dynamics and regression.
- MECP2 duplication syndrome: Recent advances in pathophysiology and therapeutic perspectives.
- A novel approach to metabolic profiling in case models of MECP2-related disorders.
- Comprehensive assessment reveals numerous clinical and neurophysiological differences between MECP2-allelic disorders.
- An RNA editing strategy rescues gene duplication in a mouse model of MECP2 duplication syndrome and nonhuman primates.
- Zebrafish models for congenital disorders of glycosylation (CDG): a systematic review.
- Syndromic male subfertility: A network view of genome-phenome associations.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:1762(Orphanet)
- OMIM OMIM:300260(OMIM)
- MONDO:0010283(MONDO)
- GARD:9781(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar