{ "@context": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/context/doc", "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134", "id": "CG-AC:AC134", "type": "ClinicalActionabilityReport", "metadata": { "schemaLabel": "AC-Sepio.Beta-1 (Unofficial)", "contentVersionId": "28014", "producedAtUTC": "Thu, 10 Sep 2026 19:38:52 -0000", "note": "DISCLAIMER: The SEPIO-inspired schema presented here is an initial prototype for Clinical Actionability curation summaries and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema." }, "description": "JSON-LD representation of ClinGen Actionability Stage 2 report modeled with SEPIO. The hierarchically structured document will include:\n1. Contextual & topic information, such as the **conditions/diseases** and the **genes**.\n2. Categorized **evidence narratives**, with references.\n\t* This content corresponds to the texts within the *Actionability Summary Report*\n4. **Outcome & Intervention** pairs, with **consensus scoring** in 5 dimensions:\n\t1. Outcome Severity\n\t2. Outcome Likelihood\n\t3. Intervention Effectiveness\n\t4. Nature of the Intervention\n\t5. Total (Overall) Score\n\n*( Note: The summary report does not include the **Screening Survey** which led to preparation of the actionability report. )", "condition": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/co", "id": "CG-AC:AC134/co", "type": "GeneticCondition", "label": "Familial thoracic aortic aneurysms and dissections (FTAAD)" }, "outcome": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ou/Clinically%20significant%20aortic%20aneurysm", "id": "CG-AC:AC134/ou/Clinically significant aortic aneurysm", "type": "Outcome", "label": "Clinically significant aortic aneurysm" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ou/Aortic%20dilation%20progression", "id": "CG-AC:AC134/ou/Aortic dilation progression", "type": "Outcome", "label": "Aortic dilation progression" } ], "intervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/intv/Aortic%20surveillance", "id": "CG-AC:AC134/intv/Aortic surveillance", "type": "Intervention", "label": "Aortic surveillance" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/intv/Pharmacotherapy", "id": "CG-AC:AC134/intv/Pharmacotherapy", "type": "Intervention", "label": "Pharmacotherapy" } ], "clinicalActionabilityProfile": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/cap", "id": "CG-AC:AC134/cap", "type": "Assertion", "assertionMethod": "The ClinGen AWG developed a standardized protocol to generate evidence-based profiles of clinical actionability of genes and associated disorders in the form of summary reports and semiquantitative metric (SQM) scores.", "releaseDate": "Mon, 16 Aug 2021 00:00:00 -0000", "releaseNum": "1.1.4" }, "evidenceStatements": { "evidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/en/ACMI2683", "id": "CG-AC:AC134/en/ACMI2683", "type": "EvidenceNarrative", "narrative": "Autosomal Dominant", "evidenceDomainTag": "Threat Materialization Chances.Modes of Inheritance" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/en/cf", "id": "CG-AC:AC134/en/cf", "type": "EvidenceNarrative", "narrative": "FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta). While in the past, FTAAD of known genetic cause may have been considered to be either syndromic (part of a set of clinical findings such as in Marfan syndrome, Loeys-Dietz syndrome, or Ehlers-Danlos syndrome) or non-syndromic (occurring as an isolated finding), the distinction between syndromic and non-syndromic FTAAD has become increasingly blurred as it is common for pathogenic variants in a gene to result in a phenotypic spectrum that ranges from syndromic to non-syndromic. This report focuses on non-syndromic FTAAD; syndromic forms of FTAAD have been summarized in other reports. Depending on the size, location, and progression rate of dilatation/dissection, patients may be asymptomatic or may present with dyspnea, cough, jaw, neck, chest or back pain, head, neck or upper limb edema, difficulty swallowing, voice hoarseness, pale skin, faint pulse, and/or numbness/tingling in limbs.", "evidenceDomainTag": "Nature of the Threat.Clinical Features", "publication": [ "CG-AC:RF000596", "CG-AC:RF002543", "CG-AC:RF002544" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/en/potgd", "id": "CG-AC:AC134/en/potgd", "type": "EvidenceNarrative", "narrative": "The estimated population prevalence of familial thoracic aortic aneurysms and dissections (FTAAD) ranges between 1:5,000 and 1:4,000,000 in adults depending on the occurrence of an isolated thoracic aortic aneurysm or as a symptom of a syndromic disorder, excluding non-genetic causes.", "evidenceDomainTag": "Nature of the Threat.Prevalence of the Genetic Disorder", "publication": [ "CG-AC:RF002542" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/en/nh", "id": "CG-AC:AC134/en/nh", "type": "EvidenceNarrative", "narrative": "In the absence of surgical repair, affected individuals typically have progressive enlargement of the aorta leading to a life-threatening acute dissection or rupture. The age of onset and presentation of aortic disease are highly variable across genes, as are other vascular diseases and features. Pregnant women are at an increased risk for complications such as rapid aortic root enlargement and aortic dissection or rupture during pregnancy, delivery, and the post-partum period. Onset can range from childhood to adulthood.", "evidenceDomainTag": "Nature of the Threat.Natural History", "publication": [ "CG-AC:RF000596", "CG-AC:RF002544" ] } ], "tieredEvidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/CDEC2833", "id": "CG-AC:AC134/ten/CDEC2833", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Thoracic aortic aneurysms are usually asymptomatic and enlarge over time. Undiagnosed or untreated thoracic aortic aneurysms can lead to life-threatening acute ascending aortic dissections.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF000596" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/NOI2843", "id": "CG-AC:AC134/ten/NOI2843", "type": "TieredEvidenceNarrative", "narrative": "The identified interventions involve invasive prophylactic surgery, which is likely associated with some risk of mortality and morbidity.", "evidenceDomainTag": "Acceptability of Intervention.Natures of Intervention" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/RR2621", "id": "CG-AC:AC134/ten/RR2621", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "Information regarding relative risk was unavailable.", "evidenceDomainTag": "Threat Materialization Chances.Relative Risks" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/ACPE4069", "id": "CG-AC:AC134/ten/ACPE4069", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "A study of 965 patients with FBN1 pathogenic variants indicated that 29% had an aortic event defined as either aortic dissection or prophylactic aortic aneurysm repair (estimated cumulative risk by age 60 was 74%, 95% CI: 67-81%). Specifically, 19% had an aortic dissection (estimated cumulative risk by age 60 was 51%, 95% CI: 42-60%) and 10% underwent prophylactic surgery (estimated cumulative risk by age 60 was 40%, 95% CI: 33-49%).", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000596" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/PGM2794", "id": "CG-AC:AC134/ten/PGM2794", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "Information regarding the prevalence of genetic mutations associated with FTAAD was unavailable.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/ACPE4075", "id": "CG-AC:AC134/ten/ACPE4075", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF002547" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/ACPE4072", "id": "CG-AC:AC134/ten/ACPE4072", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "A study of 12 individuals with MYH11 pathogenic variants indicated that 34% had an aortic dissection and one individual (8%) underwent prophylactic aortic aneurysm repair.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000596" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/ACPE4071", "id": "CG-AC:AC134/ten/ACPE4071", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "A study of 23 individuals with TGFB2 pathogenic variants indicated that 74% had an aortic root aneurysm, 3% had an aortic dissection, and 9% underwent aortic aneurysm repair. (Tier 3)", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000596" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/ACPE4076", "id": "CG-AC:AC134/ten/ACPE4076", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "A study of 44 individuals with SMAD3 pathogenic variants indicated that 71% had an aortic root aneurysm, 29% had an aortic dissection, and 34% underwent prophylactic aortic aneurysm repair.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000596" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/ACPE4070", "id": "CG-AC:AC134/ten/ACPE4070", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%).", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000596" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/ACPE4077", "id": "CG-AC:AC134/ten/ACPE4077", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "A study of 176 individuals with TGFBR1 pathogenic variants and 265 with TGFBR2 pathogenic variants indicated that the first aortic event was aortic dissection in 20% for TGFBR1 and 21% for TGFBR2 and aortic aneurysm repair in 20% for TGFBR1 and 24% for TGFBR2. Survival estimates indicated that 100% of individuals with TGFBR1 variants would have a vascular or aortic event (including surgery or dissection) by age 80 and 100% of individuals with TGFBR2 variants would have a vascular or aortic event by age 90.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000596" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/ACPE4074", "id": "CG-AC:AC134/ten/ACPE4074", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "A study of 277 individuals with ACTA2 pathogenic variants indicated that 48% had an aortic event defined as either an aortic dissection (42%) or surgical repair of aortic aneurysms (6%). An additional 9% had an aneurysm that did not require repair. The overall cumulative risk of an aortic event by age 86 was estimated as 76% (95% CI: 64-86%).", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000596" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/ACPE4073", "id": "CG-AC:AC134/ten/ACPE4073", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "FTAAD displays incomplete penetrance, primarily in women.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000047" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/ten/EN2843", "id": "CG-AC:AC134/ten/EN2843", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "No information on variable expressivity was available.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes" } ], "tieredRecommendations": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACSU3656", "id": "CG-AC:AC134/tr/ACSU3656", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Patients with a confirmed genetic variant known to predispose to aortic aneurysms and aortic dissections should undergo complete aortic imaging at initial diagnosis and 6 months later to determine the rate of aortic enlargement followed by imaging annually or every 6 months for those with a >4.5 cm diameter, a significant rate of growth, or aortic regurgitation.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF000050", "CG-AC:RF000047", "CG-AC:RF000049", "CG-AC:RF000045", "CG-AC:RF002527" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACPM5576", "id": "CG-AC:AC134/tr/ACPM5576", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Individuals with a pathogenic variant in TGFBR1/2 should be taught the signs and symptoms of aortic dissection and should consider wearing a medical alert bracelet.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000049" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACPM5579", "id": "CG-AC:AC134/tr/ACPM5579", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Other cardiovascular risk factors, including hyperlipidemia, should be addressed", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000596" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACPM5575", "id": "CG-AC:AC134/tr/ACPM5575", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Hypertension should be promptly identified and treated.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002543" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACPM5577", "id": "CG-AC:AC134/tr/ACPM5577", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Beta adrenergic-blocking agents are recommended to reduce aortic dilation.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000049" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACPM5574", "id": "CG-AC:AC134/tr/ACPM5574", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "For female patients considering pregnancy, a prophylactic repair may be considered when the aortic root exceeds 4.0 cm.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000050" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACPM5578", "id": "CG-AC:AC134/tr/ACPM5578", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2. Earlier repair can be considered in patients with a family history of aortic dissection, growth of the aorta approaches 1 cm/year, or aortic regurgitation. In patients with Marfan syndrome (MFS), timely repair of aortic aneurysms prolongs survival and approaches that of age-matched controls; however, evidence on effectiveness was not provided for patients with FTAAD.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000050", "CG-AC:RF000047", "CG-AC:RF000049", "CG-AC:RF002535", "CG-AC:RF000045" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/REC2927", "id": "CG-AC:AC134/tr/REC2927", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "A meta-analysis of six randomized clinical trials among children and adults with MFS indicated that losartan, an angiotensin II receptor antagonist, significantly decreased the rate of aortic dilation compared to no losartan treatment (standardized mean difference: -0.13; 95% CI: -0.25 to 0.00; p=0.04). However, improvements in mortality, cardiovascular surgery, or aortic dissection or rupture were assessed but not observed. Follow-up time in these studies ranged from 35 months to 3.5 years, which may have limited the ability to assess these outcomes.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002531" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/REC2926", "id": "CG-AC:AC134/tr/REC2926", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "Though no evidence for effectiveness of these medications is available for FTAAD, a meta-analysis of five cohort studies among children and adolescents with MFS indicated that beta-blocker treatment decreased the rate of aortic dilation compared to no treatment (standardized mean difference: -1.30; 95% CI: -2.11 to -0.49; p=0.002). A randomized trial of 70 patients with MFS aged 12-50 years showed that beta-blocker vs. no treatment slowed the rate of aortic dissection as measured by the slope of the aortic ratio, calculated by dividing the measured aortic diameter by the diameter predicted by the participant’s height, weight, and age (mean slope of the aortic ratio plotted against time: 0.084 vs. 0.023, respectively). However, none of the studies demonstrated an impact on mortality, occurrence of aortic dissection, or the need for elective repair of the aorta and/or aortic valve, though these studies were likely underpowered.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002532", "CG-AC:RF002529" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACPM5580", "id": "CG-AC:AC134/tr/ACPM5580", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Pregnancy and the post-partum period confer a higher risk for aortic complications. Among women with aortopathy with aortic dissection and/or rupture during this period, about 50% of events occur in the third trimester and 33% in the peripartum period. Women should be managed closely throughout the pregnancy, ideally in a high-risk obstetric clinic with a multidisciplinary team. Pregnant women should have strict blood pressure control to prevent stage II hypertension. 4.4% of carefully monitored patients with MFS developed aortic dissection and in unmonitored patients, the risk is likely higher.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002543", "CG-AC:RF000047" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACPM5582", "id": "CG-AC:AC134/tr/ACPM5582", "type": "TieredRecommendation", "evidenceSourceTier": "3", "recommendation": "Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000596" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACPM5581", "id": "CG-AC:AC134/tr/ACPM5581", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Management of thoracic aortic aneurysm and/or dissection requires coordinated input from a multidisciplinary team of specialists familiar with FTAAD, including a clinical geneticist, cardiologist, and cardiothoracic and vascular surgeons.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000596" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACCA3372", "id": "CG-AC:AC134/tr/ACCA3372", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Athletes with FTAAD should not participate in any competitive sports that involve intense physical exertion or the potential for bodily collision.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002527" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/tr/ACCA3371", "id": "CG-AC:AC134/tr/ACCA3371", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Athletes with a pathogenic variant in a gene associated with FTAAD should not participate in low and moderate static/low dynamic competitive sports if they have more than one of the following:\\n• Aortic root dilation\\n• Moderate to severe mitral regurgitation\\n• Family history of aortic dissection\\n• Cerebrovascular disease\\n• Branch vessel aneurysm or dissection.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002527" ] } ] }, "evidenceCategory": { "outcomeEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei", "id": "CG-AC:AC134/oei", "type": "EvidenceItem", "natureOfTheThreat": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/nott", "id": "CG-AC:AC134/oei/nott", "type": "EvidenceLine", "prevalenceOfTheGeneticDisorder": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/pgd", "id": "CG-AC:AC134/oei/pgd", "type": "EvidenceItem", "keyText": "1-2 in 5000", "sourceOfPopulation": "General population", "evidenceNarrative": { "@id": "CG-AC:AC134/en/potgd" } }, "clinicalFeatures": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/cf", "id": "CG-AC:AC134/oei/cf", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC134/en/cf" } }, "naturalHistory": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/nh", "id": "CG-AC:AC134/oei/nh", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC134/en/nh" } } }, "threatMaterializationChances": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/tmc", "id": "CG-AC:AC134/oei/tmc", "type": "EvidenceLine", "modeOfInheritance": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/moi", "id": "CG-AC:AC134/oei/moi", "type": "EvidenceItem", "keyText": "Autosomal Dominant", "evidenceNarrative": { "@id": "CG-AC:AC134/en/ACMI2683" } }, "prevalenceOfTheGeneticMutation": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/pgm", "id": "CG-AC:AC134/oei/pgm", "type": "EvidenceItem", "keyText": "Unknown", "sourceOfPopulation": "General population", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/PGM2794" } }, "penetrance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/pe/ACPE4073", "id": "CG-AC:AC134/oei/pe/ACPE4073", "type": "EvidenceItem", "keyText": "Unknown", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/ACPE4073" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/pe/ACPE4069", "id": "CG-AC:AC134/oei/pe/ACPE4069", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/ACPE4069" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/pe/ACPE4074", "id": "CG-AC:AC134/oei/pe/ACPE4074", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/ACPE4074" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/pe/ACPE4077", "id": "CG-AC:AC134/oei/pe/ACPE4077", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/ACPE4077" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/pe/ACPE4070", "id": "CG-AC:AC134/oei/pe/ACPE4070", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/ACPE4070" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/pe/ACPE4076", "id": "CG-AC:AC134/oei/pe/ACPE4076", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/ACPE4076" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/pe/ACPE4071", "id": "CG-AC:AC134/oei/pe/ACPE4071", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/ACPE4071" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/pe/ACPE4072", "id": "CG-AC:AC134/oei/pe/ACPE4072", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/ACPE4072" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/pe/ACPE4075", "id": "CG-AC:AC134/oei/pe/ACPE4075", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/ACPE4075" } } ], "relativeRisk": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/rr/RR2621", "id": "CG-AC:AC134/oei/rr/RR2621", "type": "EvidenceItem", "keyText": "Unknown", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/RR2621" } } ], "expressivity": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/oei/ex/EN2843", "id": "CG-AC:AC134/oei/ex/EN2843", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/EN2843" } } ] } }, "interventionEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei", "id": "CG-AC:AC134/iei", "type": "EvidenceItem", "acceptabilityOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/aoi", "id": "CG-AC:AC134/iei/aoi", "type": "EvidenceLine", "natureOfIntervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/noi/NOI2843", "id": "CG-AC:AC134/iei/noi/NOI2843", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/NOI2843" } } ] }, "effectivenessOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/eoi", "id": "CG-AC:AC134/iei/eoi", "type": "EvidenceLine", "patientManagement": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/pm/ACPM5581", "id": "CG-AC:AC134/iei/pm/ACPM5581", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACPM5581" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/pm/ACPM5578", "id": "CG-AC:AC134/iei/pm/ACPM5578", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACPM5578" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/pm/ACPM5574", "id": "CG-AC:AC134/iei/pm/ACPM5574", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACPM5574" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/pm/ACPM5577", "id": "CG-AC:AC134/iei/pm/ACPM5577", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACPM5577" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/pm/REC2926", "id": "CG-AC:AC134/iei/pm/REC2926", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/REC2926" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/pm/ACPM5582", "id": "CG-AC:AC134/iei/pm/ACPM5582", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACPM5582" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/pm/REC2927", "id": "CG-AC:AC134/iei/pm/REC2927", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/REC2927" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/pm/ACPM5575", "id": "CG-AC:AC134/iei/pm/ACPM5575", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACPM5575" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/pm/ACPM5579", "id": "CG-AC:AC134/iei/pm/ACPM5579", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACPM5579" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/pm/ACPM5576", "id": "CG-AC:AC134/iei/pm/ACPM5576", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACPM5576" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/pm/ACPM5580", "id": "CG-AC:AC134/iei/pm/ACPM5580", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACPM5580" } } ], "circumstanceToAvoid": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/cta/ACCA3371", "id": "CG-AC:AC134/iei/cta/ACCA3371", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACCA3371" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/cta/ACCA3372", "id": "CG-AC:AC134/iei/cta/ACCA3372", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACCA3372" } } ], "surveillance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/su/ACSU3656", "id": "CG-AC:AC134/iei/su/ACSU3656", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC134/tr/ACSU3656" } } ] }, "conditionEscapeDetection": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/ced", "id": "CG-AC:AC134/iei/ced", "type": "EvidenceLine", "chanceToEscapeDetection": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC134/iei/cted/CDEC2833", "id": "CG-AC:AC134/iei/cted/CDEC2833", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC134/ten/CDEC2833" } } ] } } }, "references": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000045", "id": "CG-AC:RF000045", "type": "Publication", "publicationType": "PMID", "citation": "Boodhwani M, Andelfinger G, Leipsic J, Lindsay T, McMurtry MS, Therrien J, Siu SC. Canadian Cardiovascular Society position statement on the management of thoracic aortic disease. Can J Cardiol. (2014) 30(6):577-89.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=24882528", "xdbref": [ "PMID:24882528" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000047", "id": "CG-AC:RF000047", "type": "Publication", "publicationType": "PMID", "citation": "Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE Jr, Eagle KA, Hermann LK, Isselbacher EM, Kazerooni EA, Kouchoukos NT, Lytle BW, Milewicz DM, Reich DL, Sen S, Shinn JA, Svensson LG, Williams DM. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology,American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons,and Society for Vascular Medicine. J Am Coll Cardiol. (2010) 55(14):e27-e129.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=20359588", "xdbref": [ "PMID:20359588" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000049", "id": "CG-AC:RF000049", "type": "Publication", "publicationType": "PMID", "citation": "Pyeritz RE. Evaluation of the adolescent or adult with some features of Marfan syndrome. Genet Med. (2012) 14(1):171-7.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=22237449", "xdbref": [ "PMID:22237449" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000050", "id": "CG-AC:RF000050", "type": "Publication", "publicationType": "PMID", "citation": "Svensson LG, Adams DH, Bonow RO, Kouchoukos NT, Miller DC, O'Gara PT, Shahian DM, Schaff HV, Akins CW, Bavaria JE, Blackstone EH, David TE, Desai ND, Dewey TM, D'Agostino RS, Gleason TG, Harrington KB, Kodali S, Kapadia S, Leon MB, Lima B, Lytle BW, Mack MJ, Reardon M, Reece TB, Reiss GR, Roselli EE, Smith CR, Thourani VH, Tuzcu EM, Webb J, Williams MR. Aortic valve and ascending aorta guidelines for management and quality measures. Ann Thorac Surg. (2013) 95(6 Suppl):S1-66.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=23688839", "xdbref": [ "PMID:23688839" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000596", "id": "CG-AC:RF000596", "type": "Publication", "publicationType": "GeneReview", "citation": "DM Milewicz, E Regalado. Heritable thoracic aortic disease overview. 2003 Feb 13[Updated 2016 Dec 29]. In: RA Pagon, MP Adam, HH Ardinger, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washingtom, Seattle; 1993-2026. ", "webUrl": "https://www.ncbi.nlm.nih.gov/books/NBK1120/", "xdbref": [ "GeneReview:NBK1120", "PMID:20301299" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF002527", "id": "CG-AC:RF002527", "type": "Publication", "publicationType": "PMID", "citation": "Braverman AC, Harris KM, Kovacs RJ, Maron BJ. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 7: Aortic Diseases, Including Marfan Syndrome: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol. (2015) 66(21):2398-2405.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=26542664", "xdbref": [ "PMID:26542664" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF002529", "id": "CG-AC:RF002529", "type": "Publication", "publicationType": "PMID", "citation": "Koo HK, Lawrence KA, Musini VM. Beta-blockers for preventing aortic dissection in Marfan syndrome. Cochrane Database Syst Rev. (2017) 11:CD011103.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=29110304", "xdbref": [ "PMID:29110304" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF002531", "id": "CG-AC:RF002531", "type": "Publication", "publicationType": "PMID", "citation": "Gao L, Chen L, Fan L, Gao D, Liang Z, Wang R, Lu W. The effect of losartan on progressive aortic dilatation in patients with Marfan's syndrome: a meta-analysis of prospective randomized clinical trials. Int J Cardiol. (2016) 217:190-4.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=27187761", "xdbref": [ "PMID:27187761" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF002532", "id": "CG-AC:RF002532", "type": "Publication", "publicationType": "PMID", "citation": "Gao L, Mao Q, Wen D, Zhang L, Zhou X, Hui R. The effect of beta-blocker therapy on progressive aortic dilatation in children and adolescents with Marfan's syndrome: a meta-analysis. Acta Paediatr. (2011) 100(9):e101-5.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=21443687", "xdbref": [ "PMID:21443687" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF002535", "id": "CG-AC:RF002535", "type": "Publication", "publicationType": "PMID", "citation": "Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, Iung B, Lancellotti P, Lansac E, Rodriguez Munoz D, Rosenhek R, Sjogren J, Tornos Mas P, Vahanian A, Walther T, Wendler O, Windecker S, Zamorano JL. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. (2017) 38(36):2739-2791.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=28886619", "xdbref": [ "PMID:28886619" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF002542", "id": "CG-AC:RF002542", "type": "Publication", "publicationType": "PMID", "citation": "Arslan-Kirchner M, Arbustini E, Boileau C, Charron P, Child AH, Collod-Beroud G, De Backer J, De Paepe A, Dierking A, Faivre L, Hoffjan S, Jondeau G, Keyser B, Loeys B, Mayer K, Robinson PN, Schmidtke J. Clinical utility gene card for: Hereditary thoracic aortic aneurysm and dissection including next-generation sequencing-based approaches. Eur J Hum Genet. (2016) 24(1):e1-5.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=26508578", "xdbref": [ "PMID:26508578" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF002543", "id": "CG-AC:RF002543", "type": "Publication", "publicationType": "Other", "citation": "true. Updated on the diagnosis and management of inherited aortopathies, including marfan syndrome. (2016) ", "webUrl": "https://www.csanz.edu.au/" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF002544", "id": "CG-AC:RF002544", "type": "Publication", "publicationType": "Orphanet", "citation": "Familial thoracic aortic aneurysm and aortic dissection. Orphanet encyclopedia [Internet]", "xdbref": [ "Orphanet:91387" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF002547", "id": "CG-AC:RF002547", "type": "Publication", "publicationType": "OMIM", "citation": "Online Medelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. Aortic aneurysm, familial thoracic 10; aat10. MIM: 6171682016 Oct 24. ", "webUrl": "https://www.omim.org/entry/617168", "xdbref": [ "OMIM:617168" ] } ] }