A síndrome do segundo sistema, síndroma do segundo sistema ou efeito do segundo sistema é a tendência de sistemas pequenos, elegantes, e bem-sucedidos serem sucedidos por sistemas sobre-engenhados e inchados, devido a expectativas infladas e excesso de confiança.
Introdução
O que você precisa saber de cara
Síndrome de Fowler é uma doença autossômica recessiva rara associada ao gene FLVCR2, caracterizada por prematuridade, acinesia, hipoplasia muscular e cerebral (incluindo agenesia do corpo caloso e hipoplasia cerebelar), convulsões e polidrâmnio. Geralmente resulta em microcefalia e deficiências neurológicas graves.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Entender a doença
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 9 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 24 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. Padrão de herança: Autosomal recessive.
Choline uniporter that specifically mediates choline uptake at the blood-brain-barrier (PubMed:38302740, PubMed:38778100). Responsible for the majority of choline uptake across the blood-brain-barrier from the circulation into the brain (By similarity). Choline, a nutrient critical for brain development, is a precursor of phosphatidylcholine, as well as betaine (By similarity). Also mediates transport of ethanolamine (PubMed:38778100). Choline and ethanolamine transport is not coupled with proto
Cell membraneMitochondrion membraneEndoplasmic reticulum membrane
Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome
A rare prenatally lethal disorder characterized by hydranencephaly, a distinctive glomerular vasculopathy in the central nervous system and retina, and diffuse ischemic lesions of the brain stem, basal ganglia, and spinal cord with calcifications. Hydranencephaly is a condition where the greater portions of the cerebral hemispheres and corpus striatum are replaced by cerebrospinal fluid and glial tissue.
Variantes genéticas (ClinVar)
47 variantes patogênicas registradas no ClinVar.
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 Fowler
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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
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Accounting for non-adherence to assigned antibiotic treatment duration for bloodstream infection (BALANCE): a post-hoc analysis of a randomised clinical trial.
The BALANCE trial (NCT03005145) showed non-inferiority of 7-day versus 14-day antibiotic duration for treatment of patients with non-Staphylococcus aureus uncomplicated bloodstream infection (BSI). Non-adherence to assigned duration occurred in 728 (20·3%) of 3581 patients. This post-hoc analysis aimed to identify factors associated with this non-adherence, and evaluate its effect on validity of trial results. We identified factors associated with non-adherence using generalised linear mixed models. Adherence was defined as receiving antibiotic duration up to 2 days longer or shorter than assigned duration, measured using a trial-specific adherence variable (assessed daily by research staff) and a separate variable capturing total antibiotic duration. We estimated the effect of antibiotic duration on the primary outcome of 90-day all-cause mortality, accounting for confounding introduced by non-adherence, in adjusted per-protocol and as-treated populations (using two different adherence definitions: first, using an adherence variable as assessed daily by site research staff, and second, using a total antibiotic duration variable recording the total cumulative antibiotic duration received), using inverse probability of treatment weighting (IPTW) and instrumental variable methods. We compared these adjusted estimates to the primary effect estimates in BALANCE and used the same 4% non-inferiority margin to determine non-inferiority of 7-day duration. 3581 patients with complete outcome data were included. Non-adherence was higher in the 7-day group (432 [24·0%] of 1802 patients) versus 14-day group (296 [16·6%] of 1779). Disease severity, intra-abdominal and skin or soft tissue source of infection, persistent fever, and persistent bacteraemia were associated with treatment prolongation, whereas vascular catheter source and antimicrobial resistance were associated with treatment shortening. Adjusted risk differences for the primary outcome of 90-day all-cause mortality were similar to the primary results in BALANCE: (1) IPTW per-protocol analysis (definition one): -1·61% (95% CI -4·13 to 0·87); IPTW per-protocol analysis (definition two): -1·91% (95% CI -4·61 to 0·93); and IPTW as-treated analysis: -0·75% (95% CI -3·36 to 1·86); and (2) instrumental variable analysis (definition one): -2·68% (95% CI -6·65 to 1·29) and instrumental variable analysis (definition two): -2·80% (95% CI -5·98 to 0·37). Non-adherence in BALANCE was significantly associated with a range of important prognostic factors, which might have introduced bias. Causal inference methods addressing this bias showed a consistent conclusion of non-inferiority, strengthening the validity of this finding. 7-day antibiotic duration should be the standard of care for patients with uncomplicated BSI. The BALANCE trial was funded by the Canadian Institutes of Health Research, Health Research Council of New Zealand, Australian National Medical Research Council, Physicians Services Incorporated Ontario, and Ontario Ministry of Health and Long-term Care Innovation Fund.
A hypomorphic FLVCR2 variant resulting in moderate transport deficiency causes hydranencephaly syndrome with brain calcifications.
FLVCR2 is a highly conserved member of the major facilitator superfamily (MFS), the largest superfamily of solute carriers that are involved in the transport of small molecules across lipid bilayers. The loss of the murine ortholog Mfsd7c, an endothelial transporter in brain blood vessels, causes brain angiogenic growth deficiency and lethality. Recessive FLVCR2 variants cause proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), also known as Fowler syndrome. This often-lethal condition features microcephaly, skeletal deformities, and severe cerebrovascular defects. Although a number of cases have been reported, very limited evidence of the pathogenicity of FLVCR2 variants is available. In this study, we thoroughly investigated a new fetal case of Fowler syndrome. Through exome sequencing, we identified two compound heterozygous FLVCR2 variants: the maternal c.1124+3_1124+6del and the paternal p.(Arg492Trp). The effects of the c.1124+3_1124+6del variant were investigated through a minigene assay, which showed impaired splicing of the exon 5 of FLVCR2. To characterize the impact of the p.(Arg492Trp) substitution, we performed protein modeling using Rosetta and DynaMut2, that showed a highly destabilizing effect. Then, based on the very recent evidence that choline is a major FLVCR2 ligand, we performed a radiolabeled-choline or ethanolamine transport assays in HEK 293 cells and found that the p.(Arg492Trp) variant causes a 50-60% reduction of FLVCR2 transport activity, resulting in a net activity of 25-30%. Our findings suggest that FLVCR2 deficiency may be sufficient to cause PVHH even in the absence of a complete loss of transport activity, possibly involving extragenetic factors in the pathophysiology of this complex condition.
Ultrasonographic Diagnosis of Bilateral Spontaneous Ovarian Hemorrhage in a 7-Year-Old Female Black-and-White Ruffed Lemur (Varecia variegata).
A 7-year-old female intact, black-and-white ruffed lemur (Varecia variegata) presented for acute anorexia, lethargy, and abnormal behavior. Initial radiographs were concerning for gastrointestinal ileus. Abdominal ultrasonography identified bilateral periovarian masses and a moderate volume of echogenic peritoneal effusion; no definitive blood flow was seen within the masses on Color Doppler. Bilateral ovariectomy was performed, and histopathology confirmed bilateral ovarian hematomata and hemoabdomen due to an idiopathic arteriopathy. The patient recovered with no significant postoperative complications. This is the first reported case of spontaneous bilateral ovarian hemorrhage in a black-and-white ruffed lemur, secondary to idiopathic arteriopathy, reported within the veterinary literature.
Experiences with real-world teclistamab administration in community and outpatient settings: a mixed-methods study of hematology providers.
To describe real-world care models for teclistamab step-up dosing (SUD) and considerations for successful implementation among community-based practices and/or practices employing outpatient SUD. This mixed-methods study involved a survey, interviews, and roundtable discussion with US providers with real-world teclistamab experience. Survey topics included their practice's SUD model, adverse event management, and transition of care processes. Select survey respondents were interviewed to describe their practices' SUD models in-depth and barriers/facilitators to these models. A subsequent roundtable was held to provide additional context on current models. A total of 38 clinicians from unique practices completed the survey between March-August 2024; 76% worked at community-based practices and 66% had treated ≥5 multiple myeloma patients with teclistamab. Among survey participants, eight completed an interview and seven joined the roundtable. Among the 38 practices, 53% employed outpatient SUD, 26% inpatient SUD, and 21% referred out for SUD. Patient-level requirements for outpatient SUD (n = 20) included caregiver support (90%), proximity to administering site (70%), good performance status (65%), and low disease burden (30%). The top factors which triggered inpatient admissions were any grade immune effector cell-associated neurotoxicity syndrome (85%), grade ≥2 cytokine release syndrome (70%), and abnormal vital signs (60%). Over a quarter of practices (29%) used tocilizumab prophylactically. Outpatient teclistamab SUD has been successfully implemented in real-world practice for appropriately selected patients. This study provides insights into real-world outpatient SUD, including in community practices, to inform providers seeking to implement similar models to improve patient access while reducing cost and resource burden. Multiple myeloma is a blood cancer that develops in plasma cells. Teclistamab is a new treatment for patients whose multiple myeloma has returned or no longer responds to other therapies. Teclistamab can cause certain side effects and hence needs to be given in a special way called step-up dosing to lower the risk of these side effects. The risk of side effects and step-up dosing may cause some healthcare providers to feel unsure about how to use teclistamab safely. In this study, we asked doctors and other healthcare providers who have experience with using teclistamab about how they give this drug, manage the side effects, and handle patient care before and after the dosing. About half of the providers said that they give teclistamab in outpatient clinics to select patients (e.g. with caregivers or living close to the clinic). To help prevent side effects, preventive treatments are recommended but may be challenging to get coverage for these preventive treatments. However, recent changes in national guidelines supporting the use of preventive treatments have helped to reduce this challenge. More real-world information is needed to help community clinics to safely use teclistamab for their patients.
ACR Appropriateness Criteria® Imaging After Liver Transplant.
Liver transplantation is currently the treatment of choice for patients with acute or advanced chronic liver failure. Complications that can lead to liver allograft failure or patient mortality include vascular abnormalities, biliary complications, infection, rejection, and recurrent or posttransplant malignancy. Imaging plays a vital role in detecting these complications. This document summarizes the relevant literature for the selection of imaging after liver transplant for the following clinical scenarios: immediate postoperative period, postoperative complications of suspected vascular etiology, postoperative complications of suspected biliary etiology, and postoperative surveillance. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
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Lancet (London, England)Lack of Flvcr2 impairs brain angiogenesis without affecting the blood-brain barrier.
The Journal of clinical investigationDeficiency of MFSD7c results in microcephaly-associated vasculopathy in Fowler syndrome.
The Journal of clinical investigationExpanding the clinical spectrum of Fowler syndrome: Three siblings with survival into adulthood and systematic review of the literature.
Clinical geneticsA Glioma Presenting as a Posterior Circulation Stroke.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiquesUK consensus on pre-clinical vascular cognitive impairment functional outcomes assessment: Questionnaire and workshop proceedings.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and MetabolismEarly elevation in plasma high-sensitivity troponin T and morbidity after elective noncardiac surgery: prospective multicentre observational cohort study.
British journal of anaesthesiaPrevalence and predictors of elevated central venous pressure and obstructive sleep apnea in patients with lower extremity chronic venous disease.
Journal of vascular surgery. Venous and lymphatic disordersIncidence and predictors of adherence to sleep apnea treatment in rehabilitation inpatients with acquired brain injury.
Sleep medicineFive-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement.
The New England journal of medicineA pilot randomized controlled trial of 7 versus 14 days of antibiotic treatment for bloodstream infection on non-intensive care versus intensive care wards.
TrialsInfluence of Comorbidity of Cerebrovascular Disease and Amyloid-β on Alzheimer's Disease.
Journal of Alzheimer's disease : JADHow to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma.
Clinical cancer research : an official journal of the American Association for Cancer ResearchMutations in MTHFR and POLG impaired activity of the mitochondrial respiratory chain in 46-year-old twins with spastic paraparesis.
Journal of human geneticsInteraction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors.
DiabetesHealthcare resource utilization and costs in patients with multiple myeloma with and without skeletal-related events.
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy PractitionersA 'stroke' of genius: celebrating the 20-year anniversary of the Bernard Sanberg Memorial Award for Brain Repair.
Regenerative medicineEffects of acellular equine amniotic allografts on the healing of experimentally induced full-thickness distal limb wounds in horses.
Veterinary surgery : VSInsights From Dynamic Neuro-Immune Imaging on Murine Immune Responses to CNS Damage.
Frontiers in neuroscienceRegression From Prediabetes to Normal Glucose Regulation and Prevalence of Microvascular Disease in the Diabetes Prevention Program Outcomes Study (DPPOS).
Diabetes careDulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.
Lancet (London, England)Images in Vascular Medicine. Rat bite fever: A rare case of critical limb ischemia.
Vascular medicine (London, England)Energy Metabolism in the Failing Right Ventricle: Limitations of Oxygen Delivery and the Creatine Kinase System.
International journal of molecular sciencesImpact of lenalidomide on collected hematopoietic myeloid and erythroid progenitors: peripheral stem cell collection may not be affected.
Leukemia & lymphomaAdjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis.
The New England journal of medicinePredictive models of surgical site infections after coronary surgery: insights from a validation study on 7090 consecutive patients.
The Journal of hospital infectionReducing Door-to-Needle Times for Ischaemic Stroke to a Median of 30 Minutes at a Community Hospital.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiquesFeasibility and safety of delivering full-dose anticoagulation therapy in children treated according to Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium therapy protocols.
Pediatric blood & cancerBlood Pressure Measurement in Severely Obese Patients: Validation of the Forearm Approach in Different Arm Positions.
American journal of hypertensionEffect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly.
The New England journal of medicineNovel Use of a Nurse-Led Telemedicine Team in Acute Stroke: A Retrospective Review of the Impact on a Regional Health Care System.
Journal of emergency nursingMedical Comorbidities and Functional Dependent Living Are Independent Risk Factors for Short-Term Complications Following Osteotomy Procedures about the Knee.
CartilageCoronary CT Angiography and 5-Year Risk of Myocardial Infarction.
The New England journal of medicineAstrocyte-specific overexpression of Nrf2 protects against optic tract damage and behavioural alterations in a mouse model of cerebral hypoperfusion.
Scientific reportsAssociation between age, deprivation and specific comorbid conditions and the receipt of major surgery in patients with non-small cell lung cancer in England: A population-based study.
ThoraxOver- and underestimation of motor ability after a stroke: Implications for anosognosia.
NeuropsychologiaCardiogenic Shock in the Septic Patient: Early Identification and Evidence-Based Management.
Critical care nursing clinics of North AmericaAryl Hydrocarbon Receptor Nuclear Translocator in Vascular Smooth Muscle Cells Is Required for Optimal Peripheral Perfusion Recovery.
Journal of the American Heart AssociationQuantitative measurement of lipid rich plaque by coronary computed tomography angiography: A correlation of histology in sudden cardiac death.
AtherosclerosisBeta1-adrenoceptor antagonist, metoprolol attenuates cardiac myocyte Ca2+ handling dysfunction in rats with pulmonary artery hypertension.
Journal of molecular and cellular cardiologyGender-based outcome differences for emergency department presentation ofnon-STEMI acute coronary syndrome.
The American journal of emergency medicinePathological mechanisms of left main stent failure.
International journal of cardiologySmall vessels, dementia and chronic diseases - molecular mechanisms and pathophysiology.
Clinical science (London, England : 1979)Testicular torsion in a patient with Ehlers-Danlos syndrome.
BMJ case reportsFowler syndrome and fetal MRI findings: a genetic disorder mimicking hydranencephaly/hydrocephalus.
Pediatric radiologyProliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism.
Molecular genetics & genomic medicineThe economic burden of overactive bladder (OAB) and its effects on the costs associated with other chronic, age-related comorbidities in the United States.
Neurourology and urodynamics7 versus 14 days of antibiotic treatment for critically ill patients with bloodstream infection: a pilot randomized clinical trial.
TrialsIs there a learning effect when the 6-minute walk test is repeated in people with suspected pulmonary hypertension?
Chronic respiratory diseaseSex-Based Differences in Discharge Disposition and Outcomes for ST-Segment Elevation Myocardial Infarction Patients Within a Regional Network.
Journal of women's health (2002)Amifostine reduces gastro-intestinal toxicity after autologous transplantation for multiple myeloma.
Leukemia & lymphomaSequence data and association statistics from 12,940 type 2 diabetes cases and controls.
Scientific dataManifestations of neurological symptoms and thromboembolism in adults with MTHFR-deficiency.
Journal of the neurological sciencesDiastolic dysfunction in pulmonary artery hypertension: Creatine kinase and the potential therapeutic benefit of beta-blockers.
Clinical and experimental pharmacology & physiologyVery Late Pathological Responses to Cobalt-Chromium Everolimus-Eluting, Stainless Steel Sirolimus-Eluting, and Cobalt-Chromium Bare Metal Stents in Humans.
Journal of the American Heart AssociationIgM Myeloma with Plasma Cell Leukemia: Case Report and Literature Review.
Annals of clinical and laboratory scienceRisk of Infective Endocarditis in Patients with End Stage Renal Disease.
Clinical journal of the American Society of Nephrology : CJASNAssociações
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.
- Accounting for non-adherence to assigned antibiotic treatment duration for bloodstream infection (BALANCE): a post-hoc analysis of a randomised clinical trial.
- A hypomorphic FLVCR2 variant resulting in moderate transport deficiency causes hydranencephaly syndrome with brain calcifications.
- Ultrasonographic Diagnosis of Bilateral Spontaneous Ovarian Hemorrhage in a 7-Year-Old Female Black-and-White Ruffed Lemur (Varecia variegata).Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association· 2026· PMID 41787645mais citado
- Experiences with real-world teclistamab administration in community and outpatient settings: a mixed-methods study of hematology providers.
- ACR Appropriateness Criteria® Imaging After Liver Transplant.
- Higher-order neuromorphic Ising machines-autoencoders and Fowler-Nordheim annealers are all you need for scalability.
- Respiratory Responses during Therapeutic Positioning in Adults with and without Abdominal Obesity.
- Characterization of a Core Fungal Community and Captivity-Induced Gut "Mycobiome" Change in Fowler's Toad (Anaxyrus fowleri).
- Testicular atrophy rate in single-stage versus two-stage fowler-stephens orchidopexy: a systematic review and meta-analysis.
- Ramped Position Improves Oxygenation During Mechanical Ventilation for Patients With Severe Obesity.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:221126(Orphanet)
- OMIM OMIM:225790(OMIM)
- MONDO:0009168(MONDO)
- GARD:17138(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q22965443(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
