A Síndrome de Fraser é uma doença rara que tem como principais características olhos que não se formam completamente e ficam cobertos pela pele, e dedos grudados.
Introdução
O que você precisa saber de cara
A Síndrome de Fraser é uma doença rara que tem como principais características olhos que não se formam completamente e ficam cobertos pela pele, e dedos grudados.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Entender a doença
Do básico ao detalhe, leia no seu ritmo
Preparando trilha educativa...
Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 46 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 128 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
3 genes identificados com associação a esta condição. Padrão de herança: Autosomal recessive.
Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia (PubMed:15838507). Required for epidermal adhesion (PubMed:15838507). Involved in the development of eyelids and the anterior segment of the eyeballs (PubMed:29688405, PubMed:30802441)
Cell membrane
Fraser syndrome 2
A form of Fraser syndrome, an autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, and urogenital abnormalities including renal agenesis or hypoplasia. Additional features include abnormalities of the larynx, ear malformations, and facial abnormalities.
May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons (PubMed:10197531). Through complex formation with NSG1, GRIA2 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity)
Cytoplasmic vesiclePerikaryonCell projection, dendriteCytoplasmEndomembrane systemPostsynaptic cell membranePostsynaptic densityEndoplasmic reticulum membrane
Fraser syndrome 3
A form of Fraser syndrome, an autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, and urogenital abnormalities including renal agenesis or hypoplasia. Additional features include abnormalities of the larynx, ear malformations, and facial abnormalities.
Involved in extracellular matrix organization (By similarity). Required for the regulation of epidermal-basement membrane adhesion responsible for proper organogenesis during embryonic development (By similarity). Involved in brain organization and function (By similarity)
Cell membrane
Fraser syndrome 1
A form of Fraser syndrome, an autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, and urogenital abnormalities including renal agenesis or hypoplasia. Additional features include abnormalities of the larynx, ear malformations, and facial abnormalities.
Variantes genéticas (ClinVar)
798 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 2,243 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
1 via biológica associada 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 Fraser
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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
Ensaios em destaque
Pesquisa e ensaios clínicos
1 ensaios clínicos encontrados.
Publicações mais relevantes
Genetic insights into syndromic anophthalmia/microphthalmia: novel molecular findings in a prenatal context.
Anophthalmia and microphthalmia (A/M) are among the most severe developmental eye defects. The aim of this study is to describe the genetic landscape of fetal syndromic phenotypes that include A/M. We recruited 31 fetuses who underwent prenatal ultrasound examination, postnatal assessment, quantitative fluorescent PCR (QF-PCR) and prenatal exome sequencing (pES). All cases displayed A/M associated with at least one extra-ocular malformation and of these, cerebellar hypoplasia was the most common ultrasound finding, detected in 14 (45.2%) cases. Chromosomal aneuploidies were identified in seven cases. Among the other fetuses (n=24), pES identified single nucleotide variants (SNVs) in 21 and copy number variations (CNVs) in three. Recurrent genetic diagnoses within our cohort included muscular dystrophy-dystroglycanopathy type A-3 (MDDGA3; n=3), MDDGA1 (n=2), cerebro-oculo-facio-skeletal syndrome 3 (n=2), syndromic microphthalmia type 9 (n=2), and Fraser syndrome (n=2). We report on seven novel variants. This study broadens the molecular spectrum of syndromic A/M with 19 distinct variants identified across 16 different genes. Furthermore, some variants were detected in genes that have been rarely, or not previously, linked to human A/M, thereby highlighting atypical clinical findings and suggesting a possible expansion of the phenotypic spectrum associated with these genes.
MOTA syndrome diagnosis following unexpected neonatal death.
The Manitoba Oculo-Tricho-Anal (MOTA) syndrome was first described in 1992. MOTA syndrome is a rare syndrome. MOTA syndrome has a clear genetic autosomal recessive inheritance pattern. The MOTA syndrome is related to FRAS1 (Fraser extracellular matrix complex subunit 1) related extracellular matrix 1 (FREM1) gene mutation, which can also cause genitourinary defects (including renal agenesis), nasal abnormalities and anorectal abnormalities. In our case, a pregnant woman whose fetus had been diagnosed during a routine mid-trimester ultrasound scan with unilateral renal agenesis and no other structural abnormalities delivered at 39 weeks by elective caesarean section. Unfortunately, the baby died shortly after delivery due to failed intubation. On post-mortem genetic analysis using whole genome sequencing, MOTA syndrome was diagnosed. Previous reports suggested that FREM1 mutations may contribute to upper airway malformations. This case highlights the need for genetic analysis to diagnose MOTA syndrome.
Case Report: A case of Fraser syndrome 2 in a Chinese fetus caused by novel compound heterozygous variants in the FREM2 gene.
Fraser syndrome (FS) is an autosomal recessive inherited malformation disorder characterized by cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tracts. Variants in the FRAS1-related extracellular matrix 2 (FREM2) gene are the major genetic cause. However, clinical diagnosis remains challenging due to phenotypic heterogeneity. A 24-week pregnant woman came to our hospital for genetic diagnosis. Ultrasound examination showed bilateral renal agenesis or dysplasia, absence of the bladder, and almost oligohydramnios. Trio whole-exome sequencing (Trio-WES) identified two novel compound heterozygous variants in the fetal FREM2 gene: a maternal, frameshift variant, c.5908_5909del, p.Leu1970ValfsTer33, and a paternal, nonsense variant, c.7881C>G,p.Tyr2627Ter. We report a rare case of Fraser syndrome 2 caused by compound heterozygous mutations in the FREM2 gene. Our findings expanded the FREM2 genotypic spectrum and demonstrated the significance of Trio-WES in the prenatal diagnosis of recessive disorders.
Prenatal Diagnosis of Fraser Syndrome at 20 Weeks' Gestation: A Case Report and Review of Literature.
Fraser syndrome is a rare congenital multisystem disorder, characterised by cryptophthalmos, syndactyly, and urogenital/renal anomalies, with high perinatal mortality. We report a pregnancy in which multiple severe fetal anomalies were identified at the routine anomaly scan (20 + 4 weeks' gestation), including central nervous system, craniofacial, renal, and limb findings highly suggestive of Fraser syndrome. The mother declined invasive testing and postmortem examination. Following multidisciplinary counselling regarding prognosis and options, the patient opted for medical termination of pregnancy. She experienced an allergic reaction to mifepristone and was managed with a misoprostol-based regimen. A stillborn female infant was delivered; the mother required a transfusion for postpartum haemorrhage due to retained placenta. Suspicion of Fraser syndrome on prenatal ultrasound should prompt multidisciplinary input and offer of genetic counselling. Where molecular or postmortem confirmation is not available, diagnosis may remain presumptive, but anticipatory counselling regarding poor prognosis and recurrence risk is essential.
Buffering of genetic defects in animal development by regeneration programs.
Regeneration programs enable animals to restore damaged or lost tissues, and the range of stimuli for these programs is incompletely understood. Here, we used zebrafish, a vertebrate species with exceptional regenerative capacity, to identify chemically induced mutations that alter regeneration-associated gene activation. Transgenic zebrafish with a permissive promoter and EGFP cassette inserted in the vicinity of the pro-regenerative factor gene fgf20a were mutagenized, and larvae homozygous for ENU-induced mutations were assessed for disruptions in fgf20a-directed reporter gene expression following fin fold amputation. One line was identified with heritable, elevated fgf20a:EGFP presence in the absence of experimental injury, localized to regions of fin fold tissue undergoing degeneration. Whole-genome sequencing (WGS) identified a mutation within exon 72 of the fraser syndrome 1 (fras1) gene, mutated in patients with inherited skin disease. fras1 mutant larvae spontaneously displayed elevated expression of other known injury/regeneration-responsive reporter lines in fin fold, and zebrafish crispants for homologs of other genes mutated in human developmental diseases also displayed regeneration-associated gene expression in regions of dysmorphology. Tempering Fgf signaling by transgenic expression of a dominant-negative Fgf receptor in fras1 mutants exacerbated the disease phenotype. Our findings provide evidence that regeneration programs are harnessed in response to developmental defects caused by genetic mutations, potentially buffering deleterious phenotypes.
Publicações recentes
Recurrent abdominal pain as a leading symptom for branchio-oto-renal syndrome: a case report.
Genetic insights into syndromic anophthalmia/microphthalmia: novel molecular findings in a prenatal context.
Case Report: A case of Fraser syndrome 2 in a Chinese fetus caused by novel compound heterozygous variants in the FREM2 gene.
Prenatal Diagnosis of Fraser Syndrome at 20 Weeks' Gestation: A Case Report and Review of Literature.
Buffering of genetic defects in animal development by regeneration programs.
📚 EuropePMC157 artigos no totalmostrando 79
Genetic insights into syndromic anophthalmia/microphthalmia: novel molecular findings in a prenatal context.
Ophthalmic geneticsCase Report: A case of Fraser syndrome 2 in a Chinese fetus caused by novel compound heterozygous variants in the FREM2 gene.
Frontiers in medicinePrenatal Diagnosis of Fraser Syndrome at 20 Weeks' Gestation: A Case Report and Review of Literature.
CureusBuffering of genetic defects in animal development by regeneration programs.
bioRxiv : the preprint server for biologyMOTA syndrome diagnosis following unexpected neonatal death.
BMJ case reportsFrem2 knockout mice exhibit Fraser syndrome phenotypes and neonatal lethality due to bilateral renal agenesis.
Scientific reportsFraser Syndrome: A Narrative Review Based on a Case from Vietnam and the Past 20 Years of Research.
Diagnostics (Basel, Switzerland)[Effect of acupuncture on early embryos in poor ovarian response mice based on transcriptome sequencing].
Zhongguo zhen jiu = Chinese acupuncture & moxibustionExome Sequencing in Fetuses With Bilateral Renal Agenesis Identified on Second Trimester Ultrasound: A Single Referral Center Experience.
Prenatal diagnosisFraser syndrome with limb reduction defect: a rare and unique anatomic variation.
Surgical and radiologic anatomy : SRA[About a case of Fraser syndrome. Autopsy of a 37 weeks gestation fetus with multiple malformations].
Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de CitologiaCryptophthalmos: associated syndromes and genetic disorders.
Ophthalmic geneticsThe Fraser complex interconnects tissue layers to support basal epidermis and osteoblast integrated morphogenesis underlying fin skeletal patterning.
bioRxiv : the preprint server for biologyBilateral cryptophthalmos with overlapping features of Manitoba oculo-tricho-anal (MOTA) syndrome and Fraser syndrome 2.
BMJ case reportsThe Fraser Complex Proteins (Frem1, Frem2, and Fras1) Can Form Anchoring Cords in the Absence of AMACO at the Dermal-Epidermal Junction of Mouse Skin.
International journal of molecular sciencesHeterozygous Variants in FREM2 Are Associated with Mesiodens, Supernumerary Teeth, Oral Exostoses, and Odontomas.
Diagnostics (Basel, Switzerland)Oral and Craniofacial Anomalies of Fraser Syndrome:Prosthetic Management.
Kathmandu University medical journal (KUMJ)Prenatal hydrometrocolpos as an unusual finding in Fraser syndrome. Case report.
Case reports in perinatal medicineFraser Syndrome: A Stumbling Block for the Anaesthesiologist.
Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of IndiaFREM2-related Fraser syndrome with popliteal pterygium and structural central nervous system anomalies.
European journal of medical geneticsComprehensive analysis of FRAS1/FREM family as potential biomarkers and therapeutic targets in renal clear cell carcinoma.
Frontiers in pharmacology"Hypothesis: Patient with possible disturbance in programmed cell death": further insights in pathogenicity and clinical features of Fraser syndrome.
European journal of human genetics : EJHGBilateral Cryptophthalmus: First Case Report from Nepal.
Nepalese journal of ophthalmology : a biannual peer-reviewed academic journal of the Nepal Ophthalmic Society : NEPJOPHA Rare Case of Fraser Syndrome with Partial Vaginal Agenesis and Its Successful Reconstructive Cosmetic Management: A Case Report.
Journal of obstetrics and gynaecology of IndiaClinical features and orbital anomalies in Fraser syndrome and a review of management options.
Indian journal of ophthalmologyTessier cranio-facial clefts presenting to a tertiary eye care center in Northern India: Ophthalmic features and a review of management.
Indian journal of ophthalmologyAnchoring Cords: A Distinct Suprastructure in the Developing Skin.
The Journal of investigative dermatologyWhole exome sequencing identifies a novel FRAS1 mutation and aids in vitro fertilization with preimplantation genetic diagnosis in Fraser syndrome.
Taiwanese journal of obstetrics & gynecology[Bilateral anophthalmia in Fraser syndrome: A case report].
Journal francais d'ophtalmologieA multidisciplinary approach for prenatal diagnosis of FRASER SYNDROME-report of a novel variant in FRAS1.
Taiwanese journal of obstetrics & gynecologyExcluding embryos with two novel mutations in FREM2 gene by the next-generation sequencing-based single nucleotide polymorphism haplotyping.
AgingPathogenesis of Anorectal Malformations in Retinoic Acid Receptor Knockout Mice Studied by HREM.
BiomedicinesHuman disease-associated extracellular matrix orthologs ECM3 and QBRICK regulate primary mesenchymal cell migration in sea urchin embryos.
Experimental animalsCo-occurrence of orofacial clefts and clubfoot phenotypes in a sub-Saharan African cohort: Whole-exome sequencing implicates multiple syndromes and genes.
Molecular genetics & genomic medicineThe first adolescent case of Fraser syndrome 3, with a novel nonsense variant in GRIP1.
American journal of medical genetics. Part A[Congenital high airway obstruction syndrome (CHAOS): a case report].
The Pan African medical journalPrenatal diagnosis of Fraser syndrome caused by novel variants of FREM2.
Human genome variationHeterozygous intragenic deletions of FREM1 are not associated with trigonocephaly.
Clinical dysmorphologyNovel loss of function variants in FRAS1 AND FREM2 underlie renal agenesis in consanguineous families.
Journal of nephrologyBilateral anophthalmia and intrahepatic biliary atresia, two unusual components of Fraser syndrome: a case report.
BMC pregnancy and childbirthCharacteristic dental pattern with hypodontia and short roots in Fraser syndrome.
American journal of medical genetics. Part ABehavioural effects of extracellular matrix protein Fras1 depletion in the mouse.
The European journal of neuroscienceNoninvasive prenatal diagnosis in a family at risk for Fraser syndrome.
Prenatal diagnosisTransgene-mediated skeletal phenotypic variation in zebrafish.
Journal of fish biologyAnesthetic management of Fraser syndrome-Check laryngoscopy can help!
Paediatric anaesthesiaTwo unrelated families with variable expression of Fraser syndrome due to the same pathogenic variant in the FRAS1 gene.
American journal of medical genetics. Part AFraser syndrome: review of the literature illustrated by a historical adult case.
International journal of oral and maxillofacial surgeryFraser syndrome without cryptophthalmos: Two cases.
European journal of medical geneticsThe monster of Ascheraden: A description of syndromic cryptophthalmos by poet Daniel Hermann in "De monstroso partu…" published in Riga, 1596.
Birth defects researchGenetic mutation of Frem3 does not causeFraser syndrome in mice.
Experimental animalsDiagnosis of Fraser syndrome missed out until the age of six months old in a low-resource setting: a case report.
BMC pediatricsAn atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics.
Nature communicationsLoss-of-function mutations in FREM2 disrupt eye morphogenesis.
Experimental eye research[Fraser syndrome: Case report].
Journal francais d'ophtalmologieEndoscopic Management of Lacrimal System Dysgenesis and Dacryocystoceles in Fraser Syndrome: A Case Report and Literature Review.
Allergy & rhinology (Providence, R.I.)Oral manifestations and rehabilitation in Fraser syndrome: A case report.
Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric DentistryA homozygous mutation p.Arg2167Trp in FREM2 causes isolated cryptophthalmos.
Human molecular geneticsThe role of FREM2 and FRAS1 in the development of congenital diaphragmatic hernia.
Human molecular geneticsA homozygous missense variant in VWA2, encoding an interactor of the Fraser-complex, in a patient with vesicoureteral reflux.
PloS oneLacrimal Drainage Anomalies in Fraser Syndrome.
Ophthalmic plastic and reconstructive surgeryInvolvement of the bone morphogenic protein/SMAD signaling pathway in the etiology of congenital anomalies of the kidney and urinary tract accompanied by cryptorchidism.
BMC urologyOral healthcare in Fraser syndrome.
Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric DentistryLocating the Level and Extent of Congenital High Airway Obstruction: Fluid in the Airway Tract as Reference Points.
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in MedicineIsolated Bilateral Complete Cryptophthalmos.
Nepalese journal of ophthalmology : a biannual peer-reviewed academic journal of the Nepal Ophthalmic Society : NEPJOPHFraser syndrome: features suggestive of prenatal diagnosis in a review of 38 cases.
Prenatal diagnosisVariable presentation of Fraser syndrome in two fetuses and a novel mutation in FRAS1.
Congenital anomaliesPrenatal diagnosis of Fraser syndrome using routine ultrasound examination, confirmed by exome sequencing: Report of a novel homozygous missense FRAS1 mutation.
Congenital anomaliesFraser Syndrome - a Case Report and Review of Literature.
MaedicaSyndactyly in a novel Fras1(rdf) mutant results from interruption of signals for interdigital apoptosis.
Developmental dynamics : an official publication of the American Association of AnatomistsPrenatal diagnosis of Fraser syndrome: a matter of life or death?
Italian journal of pediatricsMesenchymal expression of the FRAS1/FREM2 gene unit is decreased in the developing fetal diaphragm of nitrofen-induced congenital diaphragmatic hernia.
Pediatric surgery internationalEstablishment of proprotein convertase, furinA knocked-out lines in medaka, Oryzias latipes, and unique form of medaka furin-like prorprotein convertase (mflPC).
Comparative biochemistry and physiology. Toxicology & pharmacology : CBPFraser syndrome with laryngeal webs: Report of two cases and a review of the literature.
International journal of pediatric otorhinolaryngologyFrontal Encephalocele Associated With a Bilateral Tessier Number Three Cleft and Fraser Syndrome.
The Journal of craniofacial surgeryA novel mutation in the FRAS1 gene in a patient with Fraser syndrome.
Genetic counseling (Geneva, Switzerland)[Bilateral cryptophthalmos in Fraser syndrome: Case report and review of the literature].
Journal francais d'ophtalmologieReconstruction of Unilateral Incomplete Cryptophthalmos in Fraser Syndrome.
Ophthalmic plastic and reconstructive surgeryThe incidence, embryology, and oculofacial abnormalities associated with eyelid colobomas.
Eye (London, England)Fraser syndrome-oral manifestations and a dental care protocol.
Case reports in dentistryAssociações
Organizações que acompanham esta doença — pra ter apoio e orientação
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Comunidades
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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.
- Genetic insights into syndromic anophthalmia/microphthalmia: novel molecular findings in a prenatal context.
- MOTA syndrome diagnosis following unexpected neonatal death.
- Case Report: A case of Fraser syndrome 2 in a Chinese fetus caused by novel compound heterozygous variants in the FREM2 gene.
- Prenatal Diagnosis of Fraser Syndrome at 20 Weeks' Gestation: A Case Report and Review of Literature.
- Buffering of genetic defects in animal development by regeneration programs.
- Recurrent abdominal pain as a leading symptom for branchio-oto-renal syndrome: a case report.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:2052(Orphanet)
- MONDO:0009046(MONDO)
- GARD:6465(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q1425572(Wikidata)
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
