{ "@context": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/context/doc", "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081", "id": "CG-AC:AC081", "type": "ClinicalActionabilityReport", "metadata": { "schemaLabel": "AC-Sepio.Beta-1 (Unofficial)", "contentVersionId": "26997", "producedAtUTC": "Thu, 10 Sep 2026 19:40:06 -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/Pediatric/api/sepio/doc/AC081/co", "id": "CG-AC:AC081/co", "type": "GeneticCondition", "label": "Multiple Endocrine Neoplasia Type IIB", "description": "There are 3 subtypes: MEN2A accounts for 70-80% for cases, familial medullary thyroid carcinoma (FMTC - not in this report), accounts for 10-20% of cases and MEN2B accounts for 5% of cases. \n\nMEN2B disease symptoms appear in early childhood. It characterized by aggressive medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, and thickened corneal nerves but no hyperparathyroidism. Most affected individuals have characteristic physical features, including full lips, thickened eyelids, high-arched palate, and marfanoid habitus. Other more variable features include skeletal anomalies and gastrointestinal problems." }, "outcome": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/ou/Medullary%20thyroid%20carcinoma", "id": "CG-AC:AC081/ou/Medullary thyroid carcinoma", "type": "Outcome", "label": "Medullary thyroid carcinoma" }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/ou/Pheochromocytoma", "id": "CG-AC:AC081/ou/Pheochromocytoma", "type": "Outcome", "label": "Pheochromocytoma" } ], "intervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/intv/Prophylactic%20thyroidectomy", "id": "CG-AC:AC081/intv/Prophylactic thyroidectomy", "type": "Intervention", "label": "Prophylactic thyroidectomy" }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/intv/Biochemical%20Surveillance", "id": "CG-AC:AC081/intv/Biochemical Surveillance", "type": "Intervention", "label": "Biochemical Surveillance" } ], "clinicalActionabilityProfile": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/cap", "id": "CG-AC:AC081/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, 13 Sep 2021 00:00:00 -0000", "releaseNum": "1.1.3", "media": "call" }, "evidenceStatements": { "evidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/en/potgd", "id": "CG-AC:AC081/en/potgd", "type": "EvidenceNarrative", "narrative": "Multiple endocrine neoplasia type 2 (MEN2) has two main subtypes, MEN2A and MEN2B. The exact prevalence of MEN2B is unknown but it accounts for 5 to 10% of all cases of MEN2, providing an estimated prevalence of 1/700,000 to 1/350,000. This report includes MEN2B; MEN2A is covered separately.", "evidenceDomainTag": "Nature of the Threat.Prevalence of the Genetic Disorder", "publication": [ "CG-AC:RF002501", "CG-AC:RF002509", "CG-AC:RF000342", "CG-AC:RF002510" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/en/cf", "id": "CG-AC:AC081/en/cf", "type": "EvidenceNarrative", "narrative": "MEN2B is a rare, aggressive form of MEN2. characterized by medullary thyroid carcinoma (MTC) with or without pheochromocytoma (PHEO). In contrast to MEN2A, MEN2B is not associated with an increased risk for hyperparathyroidism. MEN2B is associated with developmental features including mucosal neuromas of the lips, eyelids, and tongue, distinctive facies with enlarged lips, ganglioneuromatosis of the gastrointestinal tract, ophthalmological abnormalities (e.g., inability to make tears in infancy and medullated corneal nerve fibers), and marfanoid body habitus (with joint laxity and skeletal abnormalities). Chronic constipation, abdominal distension, diarrhea, or megacolon at birth can be the initial manifestations of the disease due to ganglioneuromatosis of the gastrointestinal tract, and some patients require surgery for bowel obstruction. Patients with PHEOs can have associated symptoms of headache, palpitations, nervousness, hypertension and tachycardia. Though possible, primary hyperparathyroidism (PHPT) is rare.", "evidenceDomainTag": "Nature of the Threat.Clinical Features", "publication": [ "CG-AC:RF002501", "CG-AC:RF002509", "CG-AC:RF000342", "CG-AC:RF002510", "CG-AC:RF000127", "CG-AC:RF002502", "CG-AC:RF002520", "CG-AC:RF002521", "CG-AC:RF002522" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/en/nh", "id": "CG-AC:AC081/en/nh", "type": "EvidenceNarrative", "narrative": "MTC is usually the first manifestation of disease in individuals with MEN2. MTC in individuals with MEN2 typically presents at a younger age than sporadic MTC and is more often associated with C-cell hyperplasia as well as multifocality or bilaterality. In patients with MEN2B, the MTC presents in infancy or early childhood and is highly aggressive, metastasizing early to regional lymph nodes and beyond. A rare group of patients have atypical MEN2B that develops around 20 to 30 years of age; these patients have dual tandem RET pathogenic variants. Individuals with MEN2B who do not undergo thyroidectomy prior to age 1 will develop metastatic MTC at an early age; even distant metastases can develop within the first year. Without thyroidectomy, the average age of death for those with MEN2B is age 21. PHEOs occur in only 50% of individuals and may develop as early as 12 years of age; 50% of those are multiple and often bilateral. Even without malignant progression, PHEOs can be lethal from intractable hypertension or anesthesia-induced hypertensive-crises. MEN2B individuals may be identified in infancy or early childhood by the presence of mucosal neuromas, a distinctive facial appearance, and lack of tear production.", "evidenceDomainTag": "Nature of the Threat.Natural History", "publication": [ "CG-AC:RF002501", "CG-AC:RF002509", "CG-AC:RF000342", "CG-AC:RF002510", "CG-AC:RF000127", "CG-AC:RF002502", "CG-AC:RF002520", "CG-AC:RF002521", "CG-AC:RF002522" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/en/ACMI2597", "id": "CG-AC:AC081/en/ACMI2597", "type": "EvidenceNarrative", "narrative": "Autosomal Dominant", "evidenceDomainTag": "Threat Materialization Chances.Modes of Inheritance", "publication": [ "CG-AC:RF002501", "CG-AC:RF002509", "CG-AC:RF000342", "CG-AC:RF002510", "CG-AC:RF000127", "CG-AC:RF002502", "CG-AC:RF002520", "CG-AC:RF002521", "CG-AC:RF002522" ] } ], "tieredEvidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/ten/NOI2733", "id": "CG-AC:AC081/ten/NOI2733", "type": "TieredEvidenceNarrative", "narrative": "Compared to adults, children, and especially infants, have higher complication rates associated with thyroidectomy and node dissection, the most significant being hypoparathyroidism. There is some concern about potential detrimental effects of insufficient thyroid hormone replacement in young children, such as impaired brain development and slowed growth. The surveillance interventions identified herein are biochemical monitoring and imaging by ultrasound. Patients who have had adrenalectomy secondary to PHEO are at risk of adrenal crisis, which can cause death, during stressors and may require corticosteroid replacement therapy for adrenal insufficiency, depending on extent of resection. Following adrenalectomy, alpha blockade is necessary to treat hypotension. All patients undergoing thyroidectomy require thyroid hormone replacement therapy, and patients at risk for hypoparathyroidism must be monitored. Additionally, following thyroidectomy, patients must continue to be surveilled: calcitonin and CEA levels every six months for one year and then annually.", "evidenceDomainTag": "Acceptability of Intervention.Natures of Intervention", "publication": [ "CG-AC:RF002501", "CG-AC:RF002510", "CG-AC:RF000127", "CG-AC:RF002502", "CG-AC:RF002520", "CG-AC:RF002521", "CG-AC:RF000126" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/ten/PGM2676", "id": "CG-AC:AC081/ten/PGM2676", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "RET pathogenic variants are identified in more than 98% of MEN2B cases. \n\nInformation on the population frequency of RET pathogenic variants associated with MEN2B was not available.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF002510", "CG-AC:RF002520" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/ten/EN2729", "id": "CG-AC:AC081/ten/EN2729", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Patients carrying the same pathogenic variant may show a heterogeneous progression of disease. Even within the same family, the natural course of disease may vary.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF002509", "CG-AC:RF002502" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/ten/ACPE3794", "id": "CG-AC:AC081/ten/ACPE3794", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Without intervention, nearly all (98-100%) patients with MEN2B will develop MTC; about 50% of patients develop PHEO. PHPT is rare (<1%).", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF002510", "CG-AC:RF000127", "CG-AC:RF002502", "CG-AC:RF002520", "CG-AC:RF002521" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/ten/RR2567", "id": "CG-AC:AC081/ten/RR2567", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "Information regarding relative risk was not available.", "evidenceDomainTag": "Threat Materialization Chances.Relative Risks" }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/ten/CDEC2725", "id": "CG-AC:AC081/ten/CDEC2725", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Individuals with undiagnosed PHEO may die from a cardiovascular hypertensive crisis perioperatively.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF002510" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/ten/CDEC2724", "id": "CG-AC:AC081/ten/CDEC2724", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Most patients with MEN2B are diagnosed when the MTC is clinically evident and too advanced to be cured.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF000127" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/ten/CDEC2726", "id": "CG-AC:AC081/ten/CDEC2726", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "50-75% of MEN2B cases are associated with a de novo pathogenic variant.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF002510", "CG-AC:RF000127" ] } ], "tieredRecommendations": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/tr/ACSU3482", "id": "CG-AC:AC081/tr/ACSU3482", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Biochemical screening for PHEO should begin at age 11 for patients with MEN2B. Older guidelines have suggested PHEO surveillance should begin as early at the time of thyroidectomy or by 5-8 years of age.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF000127", "CG-AC:RF002502", "CG-AC:RF002521", "CG-AC:RF000126" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/tr/ACCA3169", "id": "CG-AC:AC081/tr/ACCA3169", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "All glucagon-like peptide 1 (GLP-1) receptor agonists except twice-daily exenatide are contraindicated in patients with MEN2B.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002517", "CG-AC:RF002523" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/tr/ACPM5096", "id": "CG-AC:AC081/tr/ACPM5096", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Biochemical screening for PHEO should be performed prior to any planned surgery or pregnancy regardless of age. PHEOs should be removed prior to thyroidectomy. Preoperative alpha-adrenergic blockade is essential for patients with catecholamine-secreting PHEOs to mitigate risk of intraoperative hypertensive crisis. Undiagnosed PHEO can result in substantial morbidity and even death as a result of hypertensive crisis during surgery.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000127", "CG-AC:RF002502", "CG-AC:RF002520", "CG-AC:RF002521" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/tr/ACPM5097", "id": "CG-AC:AC081/tr/ACPM5097", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "The cornerstone of MTC management for patients with MEN2B is prophylactic thyroidectomy within the first six-months to year of life due to the early development of MTC and metastases in these children. The exact timing depends on surgical expert recommendations and taking into consideration preferences of the patient’s parents. Preserving the parathyroid glands should be a priority and should guide extent of central neck dissection. In a study of 44 children with MEN2B, three patients had a thyroidectomy during the first year of life and were cured. Further, all nine children having thyroidectomy prior to age 4 years were cured biochemically, compared to only 1 of 35 children having thyroidectomy after age 5 years.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000127", "CG-AC:RF002502", "CG-AC:RF002520", "CG-AC:RF002521", "CG-AC:RF000126", "CG-AC:RF002515" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/tr/ACPM5098", "id": "CG-AC:AC081/tr/ACPM5098", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Experienced physicians and surgeons with experience in pediatric thyroid surgery in tertiary care centers should be responsible for the management of children with MEN2B, especially in view of the risks of thyroidectomy in very young children.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000127", "CG-AC:RF002521" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/tr/ACPM5095", "id": "CG-AC:AC081/tr/ACPM5095", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Additionally, the following evaluations are recommended at diagnosis: Referral to an endocrinologist, consultation with a clinical geneticist and/or genetic counselor, plasma catecholamines and metanephrines, serum calcium and parathyroid hormone, and workup to evaluate for metastases when MTC is present.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002510" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/tr/ACPM5099", "id": "CG-AC:AC081/tr/ACPM5099", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Upon diagnosis, initial evaluation should include physical exam and ultrasound of the neck, basal carcinoembryonic antigen (CEA) and calcitonin levels, and PHEO screening.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000127", "CG-AC:RF002502", "CG-AC:RF002520", "CG-AC:RF002521" ] } ] }, "evidenceCategory": { "outcomeEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/oei", "id": "CG-AC:AC081/oei", "type": "EvidenceItem", "natureOfTheThreat": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/oei/nott", "id": "CG-AC:AC081/oei/nott", "type": "EvidenceLine", "prevalenceOfTheGeneticDisorder": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/oei/pgd", "id": "CG-AC:AC081/oei/pgd", "type": "EvidenceItem", "keyText": "< 1-2 in 100000", "sourceOfPopulation": "General population", "evidenceNarrative": { "@id": "CG-AC:AC081/en/potgd" } }, "clinicalFeatures": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/oei/cf", "id": "CG-AC:AC081/oei/cf", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC081/en/cf" } }, "naturalHistory": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/oei/nh", "id": "CG-AC:AC081/oei/nh", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC081/en/nh" } } }, "threatMaterializationChances": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/oei/tmc", "id": "CG-AC:AC081/oei/tmc", "type": "EvidenceLine", "modeOfInheritance": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/oei/moi", "id": "CG-AC:AC081/oei/moi", "type": "EvidenceItem", "keyText": "Autosomal Dominant", "evidenceNarrative": { "@id": "CG-AC:AC081/en/ACMI2597" } }, "prevalenceOfTheGeneticMutation": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/oei/pgm", "id": "CG-AC:AC081/oei/pgm", "type": "EvidenceItem", "keyText": "Unknown", "sourceOfPopulation": "Other", "tieredEvidenceNarrative": { "@id": "CG-AC:AC081/ten/PGM2676" } }, "penetrance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/oei/pe/ACPE3794", "id": "CG-AC:AC081/oei/pe/ACPE3794", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC081/ten/ACPE3794" } } ], "relativeRisk": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/oei/rr/RR2567", "id": "CG-AC:AC081/oei/rr/RR2567", "type": "EvidenceItem", "keyText": "Unknown", "tieredEvidenceNarrative": { "@id": "CG-AC:AC081/ten/RR2567" } } ], "expressivity": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/oei/ex/EN2729", "id": "CG-AC:AC081/oei/ex/EN2729", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC081/ten/EN2729" } } ] } }, "interventionEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei", "id": "CG-AC:AC081/iei", "type": "EvidenceItem", "acceptabilityOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/aoi", "id": "CG-AC:AC081/iei/aoi", "type": "EvidenceLine", "natureOfIntervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/noi/NOI2733", "id": "CG-AC:AC081/iei/noi/NOI2733", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC081/ten/NOI2733" } } ] }, "effectivenessOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/eoi", "id": "CG-AC:AC081/iei/eoi", "type": "EvidenceLine", "patientManagement": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/pm/ACPM5099", "id": "CG-AC:AC081/iei/pm/ACPM5099", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC081/tr/ACPM5099" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/pm/ACPM5095", "id": "CG-AC:AC081/iei/pm/ACPM5095", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC081/tr/ACPM5095" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/pm/ACPM5098", "id": "CG-AC:AC081/iei/pm/ACPM5098", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC081/tr/ACPM5098" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/pm/ACPM5097", "id": "CG-AC:AC081/iei/pm/ACPM5097", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC081/tr/ACPM5097" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/pm/ACPM5096", "id": "CG-AC:AC081/iei/pm/ACPM5096", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC081/tr/ACPM5096" } } ], "circumstanceToAvoid": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/cta/ACCA3169", "id": "CG-AC:AC081/iei/cta/ACCA3169", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC081/tr/ACCA3169" } } ], "surveillance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/su/ACSU3482", "id": "CG-AC:AC081/iei/su/ACSU3482", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC081/tr/ACSU3482" } } ] }, "conditionEscapeDetection": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/ced", "id": "CG-AC:AC081/iei/ced", "type": "EvidenceLine", "chanceToEscapeDetection": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/cted/CDEC2726", "id": "CG-AC:AC081/iei/cted/CDEC2726", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC081/ten/CDEC2726" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/cted/CDEC2724", "id": "CG-AC:AC081/iei/cted/CDEC2724", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC081/ten/CDEC2724" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC081/iei/cted/CDEC2725", "id": "CG-AC:AC081/iei/cted/CDEC2725", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC081/ten/CDEC2725" } } ] } } }, "references": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF000126", "id": "CG-AC:RF000126", "type": "Publication", "publicationType": "PMID", "citation": "Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJ, Lombardi G, Mannelli M, Pacini F, Ponder BA, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA Jr, Marx SJ. 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