{ "@context": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/context/doc", "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061", "id": "CG-AC:AC1061", "type": "ClinicalActionabilityReport", "metadata": { "schemaLabel": "AC-Sepio.Beta-1 (Unofficial)", "contentVersionId": "29903", "producedAtUTC": "Thu, 10 Sep 2026 19:40:55 -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/AC1061/co", "id": "CG-AC:AC1061/co", "type": "GeneticCondition", "label": "Multiple endocrine neoplasia type 4", "description": "Multiple endocrine neoplasia type 4 (MEN4) is a very rare form of MEN, an inherited cancer syndrome, characterized by parathyroid and anterior pituitary tumors, possibly associated with adrenal, renal, and reproductive organ tumors." }, "outcome": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/ou/Morbidity%20from%20parathyroid%20adenoma", "id": "CG-AC:AC1061/ou/Morbidity from parathyroid adenoma", "type": "Outcome", "label": "Morbidity from parathyroid adenoma" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/ou/Morbidity%20and%20mortality%20from%20MEN4-related%20tumors%20other%20than%20parathyroid%20adenoma", "id": "CG-AC:AC1061/ou/Morbidity and mortality from MEN4-related tumors other than parathyroid adenoma", "type": "Outcome", "label": "Morbidity and mortality from MEN4-related tumors other than parathyroid adenoma" } ], "intervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/intv/Evaluation%20and%20management%20by%20specialists%2C%20including%20biochemical%20surveillance%20to%20guide%20imaging%20and%20parathyroidectomy", "id": "CG-AC:AC1061/intv/Evaluation and management by specialists, including biochemical surveillance to guide imaging and parathyroidectomy", "type": "Intervention", "label": "Evaluation and management by specialists, including biochemical surveillance to guide imaging and parathyroidectomy" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/intv/Evaluation%20and%20management%20by%20specialists%2C%20including%20biochemical%20and%20imaging%20surveillance%20to%20guide%20treatment", "id": "CG-AC:AC1061/intv/Evaluation and management by specialists, including biochemical and imaging surveillance to guide treatment", "type": "Intervention", "label": "Evaluation and management by specialists, including biochemical and imaging surveillance to guide treatment" } ], "clinicalActionabilityProfile": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/cap", "id": "CG-AC:AC1061/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": "Tue, 13 Feb 2024 00:00:00 -0000", "releaseNum": "1.0.0", "media": "call" }, "evidenceStatements": { "evidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/en/ACMI2813", "id": "CG-AC:AC1061/en/ACMI2813", "type": "EvidenceNarrative", "narrative": "Autosomal Dominant", "evidenceDomainTag": "Threat Materialization Chances.Modes of Inheritance", "publication": [ "CG-AC:RF003652", "CG-AC:RF003653", "CG-AC:RF000548", "CG-AC:RF003654", "CG-AC:RF002502", "CG-AC:RF003658" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/en/cf", "id": "CG-AC:AC1061/en/cf", "type": "EvidenceNarrative", "narrative": "MEN4 is a very rare hereditary cancer syndrome characterized by parathyroid adenoma/hyperplasia and pituitary adenomas (Cushing disease, prolactinoma, somatotroph, corticotroph, and nonfunctioning adenomas). Primary hyperparathyroidism (pHPT) as a uniglandular disease is the leading pathology. Less frequently, additional endocrine/neuroendocrine neoplasias have been reported, including gastroenteropancreatic neuroendocrine tumors (NETs) and Zollinger-Ellison syndrome, NETs of the cervix and lungs, papillary thyroid carcinoma, thymic tumors, and adrenal masses. Other reported rare manifestations include meningiomas, and cancers of the uterus, testes, breast, colon, and kidneys. Due to the small number of individuals with MEN4 reported in the medical literature, the precise tumor spectrum is still poorly defined.", "evidenceDomainTag": "Nature of the Threat.Clinical Features", "publication": [ "CG-AC:RF003652", "CG-AC:RF003653", "CG-AC:RF000548", "CG-AC:RF003654", "CG-AC:RF003655", "CG-AC:RF003657", "CG-AC:RF002502", "CG-AC:RF003658" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/en/potgd", "id": "CG-AC:AC1061/en/potgd", "type": "EvidenceNarrative", "narrative": "The prevalence of multiple endocrine neoplasia type 4 (MEN4) is unknown, but the condition is very rare. To date, about 50 individuals worldwide have been reported. Prevalence is thought to be less than 1:1,000,000. Due to very few cases of MEN4 being reported and many being undiagnosed, there are uncertainties regarding the exact incidence and penetrance of MEN4.", "evidenceDomainTag": "Nature of the Threat.Prevalence of the Genetic Disorder", "publication": [ "CG-AC:RF003652", "CG-AC:RF003653", "CG-AC:RF000548", "CG-AC:RF003654", "CG-AC:RF000121", "CG-AC:RF003655" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/en/nh", "id": "CG-AC:AC1061/en/nh", "type": "EvidenceNarrative", "narrative": "In general for MEN4, age of onset of tumors and the organs affected are variable, lesions can be multiglandular or multifocal, and there is a female preponderance. pHPT due to parathyroid tumor is the predominant feature of MEN4, affecting over 75% and being the presenting feature in over half the affected individuals. pHPT presents at a median age of 51 years (range from 15–79 years). Pituitary pathologies are the second most common feature, affecting about half and being the presenting feature in about a quarter of individuals with MEN4. Pituitary tumors present at a median age of 39 years (range 5–79) and are usually non-functioning.\\n\\nA recent review of 48 symptomatic individuals with genetically confirmed MEN4 reported the youngest individual to date, presenting at 5 years of age with a GH-secreting pituitary adenoma. Overall, 15% presented between 5-15 years of age, 5 of which presented with ACTH-secreting pituitary microadenomas. The majority of symptomatic individuals were female (75%). The median age for the presentation of the first endocrinopathy was 43.5 years (range 5–76). Males became symptomatic at a median age of 32.5 years (range 10–68), whereas the same event was recorded for females at a median age of 49.5 years (range 5–76). The presenting first endocrine pathology concerned the parathyroid (56%) and the pituitary gland (23%). Just under half of the individuals had multiple syn- or metachronously affected endocrine organs.", "evidenceDomainTag": "Nature of the Threat.Natural History", "publication": [ "CG-AC:RF003652", "CG-AC:RF003653", "CG-AC:RF000548", "CG-AC:RF003654", "CG-AC:RF003655", "CG-AC:RF002502", "CG-AC:RF003658" ] } ], "tieredEvidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/ten/CDEC3027", "id": "CG-AC:AC1061/ten/CDEC3027", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "Prior to the identification of the underlying CDKN1B pathogenic variants in MEN4 in 2006, most individuals were probably misclassified as MEN1 based on clinical features.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF003655" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/ten/CDEC3026", "id": "CG-AC:AC1061/ten/CDEC3026", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Since MEN4 is a new newly described neoplastic condition and shares phenotypical characteristics of MEN1, very few cases have been reported and many are undiagnosed.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF003652" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/ten/NOI3004", "id": "CG-AC:AC1061/ten/NOI3004", "type": "TieredEvidenceNarrative", "narrative": "Medical management of manifestations is dependent on tumor type and extent of disease. Radiotherapy, chemotherapeutic agents, and certain biopsy techniques may be needed, which could be burdensome. Most individuals will require parathyroidectomy. In this procedure, postoperative bleeding or hoarseness due to injury to the recurrent laryngeal nerve may occur in about 1% of individuals. An RCT including 32 individuals with MEN1 comparing surgical approaches for pHPT reported postoperative hypocalcemia (40-58%), which was transient in most, permanent hypoparathyroidism (7-12%), even when performed by experienced surgeons.\\n\\nRoutine surveillance recommendations are primarily biochemical (phlebotomy), clinical, and imaging. With preferred imaging modalities there is concern over the exposure to repeated doses of ionizing radiation, particularly in the pediatric population.", "evidenceDomainTag": "Acceptability of Intervention.Natures of Intervention", "publication": [ "CG-AC:RF000548", "CG-AC:RF000121", "CG-AC:RF003657", "CG-AC:RF002502" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/ten/RR2742", "id": "CG-AC:AC1061/ten/RR2742", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "Information on relative risk was not identified.", "evidenceDomainTag": "Threat Materialization Chances.Relative Risks" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/ten/EN3055", "id": "CG-AC:AC1061/ten/EN3055", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "In general, pituitary tumors in MEN4 are present with reduced aggressiveness compared to MEN1 but may exert a variable degree of morbidity depending on the hormonal functional status, size, and presence of invasion or mitotic index. The age of diagnosis for these lesions also varies widely.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF003658" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/ten/EN3054", "id": "CG-AC:AC1061/ten/EN3054", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "MEN4 has heterogeneous phenotypic expression leading to different manifestations of the condition in the same family.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF003652" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/ten/ACPE4489", "id": "CG-AC:AC1061/ten/ACPE4489", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "A recent review of 48 symptomatic individuals with genetically confirmed MEN4 reported the frequencies of endocrine disorders as:\n•pHPT (75% overall, 14% multiglandular, 81% female)\n•pituitary adenomas (44% overall, 76% hormone-secreting, 48% presented with microadenoma, 76% female)\n•pancreatic NETs (15% overall, 43% presented with metastatic disease)\n•papillary thyroid carcinoma (8%)\n•adrenal gland tumors (6%)\n•thymic tumors (4%)\n•gastrointestinal NETs (4%)\n•kidney angiolipomas (4%)\nForty-four percent of individuals had 2 or more syn- or metachronously affected endocrine organs.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF003655" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/ten/PGM2977", "id": "CG-AC:AC1061/ten/PGM2977", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Population prevalence of CDKN1B pathogenic variants has not been reported. However, the incidence of CDKN1B pathogenic variants in individuals with MEN-related phenotypes without MEN1 gene pathogenic variants is likely to be in the range of 1.5-3.7%.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF003652", "CG-AC:RF003653", "CG-AC:RF000548", "CG-AC:RF003655", "CG-AC:RF003658" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/ten/ACPE4490", "id": "CG-AC:AC1061/ten/ACPE4490", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "Due to the small number of individuals with MEN4 reported in the medical literature, the clinical penetrance is still poorly defined.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF003655", "CG-AC:RF003658" ] } ], "tieredRecommendations": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/ACPM6499", "id": "CG-AC:AC1061/tr/ACPM6499", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "The management approach for gastropancreatic NETs in MEN4 is similar to MEN1. Surgical resection may be curative if the tumor is fully excised and nonmetastatic. Medical treatment includes proton-pump inhibitors and somatostatin analogs.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003652" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/ACPM6496", "id": "CG-AC:AC1061/tr/ACPM6496", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Management of pituitary adenomas in MEN4 is similar to that of non-MEN4 pituitary tumors. Medical treatment can include somatostatin receptor analogs for acromegaly and dopamine agonists for prolactinomas. Transsphenoidal surgery should be performed if the tumor is functional or causing a visual field defect. Radiotherapy can be considered if the tumor has aggressive features on radiological or histological examination.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003652" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/ACPM6497", "id": "CG-AC:AC1061/tr/ACPM6497", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In a similar condition, multiple endocrine neoplasia type 1 (MEN1), there is some indirect evidence of the effectiveness of parathyroidectomy. A randomized controlled trial comparing surgical outcomes in 32 individuals with MEN1 using various surgical approaches found no differences in recurrent (13-24%) or persistent HPT (2-5%) between procedures. The mean time to recurrence was 6.2 ± 5.0 years, and 5 of the 6 individuals with recurrent HPT underwent reoperation. A retrospective study of 73 individuals with MEN1 found that the risk of persistent or recurrent pHPT was between 17-53%, depending on the type of resection (removal of <3 parathyroid glands, SP, or TP). Persistent pHPT occurred in 24-66%, and time to recurrence was between 9 months and 3 years (range: 1.5 months to 6.75 years, depending on type of resection).", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000548", "CG-AC:RF003657" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/ACPM6495", "id": "CG-AC:AC1061/tr/ACPM6495", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "A tailored case-specific surgical approach is recommended for the treatment of pHPT. Surgical strategies should include either subtotal parathyroidectomy (SP) or total parathyroidectomy (TP) with autologous reimplantation and transcervical thymectomy. No definitive conclusion can be drawn concerning optimal surgical management or surgical outcomes due to the small number of individuals with MEN4-associated pHPT reported to have undergone parathyroid surgery.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000548" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/ACPM6498", "id": "CG-AC:AC1061/tr/ACPM6498", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "The management of individuals with MEN4 should be undertaken by an expert multidisciplinary team in a tertiary care center and any necessary surgeries should be carried out by an experienced endocrine surgeon.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003652" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/REC3118", "id": "CG-AC:AC1061/tr/REC3118", "type": "TieredRecommendation", "evidenceSourceTier": "5", "recommendation": "In a recent review of symptomatic individuals with genetically confirmed MEN4, of the 36 individuals who underwent parathyroidectomy, only two cases (6%) of recurrent hyperparathyroidism (HPT) were reported after resection.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003655" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/ACPM6500", "id": "CG-AC:AC1061/tr/ACPM6500", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "The management approach for other clinical manifestations (such as adrenal tumor, thyroid, testicular cancer, carcinoid, meningioma, colon cancer) is based on the organ affected. There is no specific guidance due to the paucity of literature.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003652" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/ACSU3977", "id": "CG-AC:AC1061/tr/ACSU3977", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Similar to MEN1, prognosis for individuals with MEN4 may be improved by presymptomatic tumor detection as earlier diagnosis and treatment of these tumors may help reduce morbidity and mortality. In the last 20 years there has been a trend toward decreasing mortality in MEN1, presumably due to enhanced surveillance and early intervention. In a multicenter study of 258 individuals with heterozygous for pathogenic variants in MEN1, individuals born during the second half of the 20th century tended to have their tumors diagnosed earlier than carriers of the same age born in the first half. Surgical morbidity has been shown to be reduced in other hereditary cancer syndromes when presymptomatic early surgical intervention is performed.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF000121", "CG-AC:RF002502" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/ACSU3975", "id": "CG-AC:AC1061/tr/ACSU3975", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Surveillance recommendations for other affected organ systems differ by guideline. One guideline states that gastroenteropancreatic NETs, uterine neoplasms, thyroid tumors, and others are not at high enough frequency in affected individuals with MEN4 to mandate surveillance, and that a role for baseline or serial presymptomatic central nervous system imaging has not been established. However, a second guideline states that since surveillance guidelines are not available for MEN4 for most tumor types, given the clinical overlap with MEN1, consideration can be given to following MEN1-related surveillance recommendations.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF003657", "CG-AC:RF002502" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/ACSU3978", "id": "CG-AC:AC1061/tr/ACSU3978", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Apart from the MEN4-specific recommendations above, supplementary laboratory and radiological investigations used for the similar condition of MEN1, may be considered for the parathyroid, pituitary, and adrenal glands.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF003652" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/ACSU3976", "id": "CG-AC:AC1061/tr/ACSU3976", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Presymptomatic surveillance recommendations for MEN4 have been suggested and are as follows:\n•Annual bloodwork is recommended for pHPT (calcium) and biochemical surveillance for secretory pituitary somatotroph adenomas (annual IGF-1), beginning in adolescence. \n•In children, routine anthropometric assessment with review of growth charts is relevant, as pituitary NETs may present with growth acceleration or growth delay with weight gain.\n•Endocrine surveillance is primarily clinical and should concentrate on evidence of growth hormone excess (gigantism/acromegaly) and glucocorticoid excess (Cushing syndrome), with concern for either prompting endocrine consultation.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF002502" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/tr/ACCA3688", "id": "CG-AC:AC1061/tr/ACCA3688", "type": "TieredRecommendation", "evidenceSourceTier": "Not provided", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid" } ] }, "evidenceCategory": { "outcomeEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei", "id": "CG-AC:AC1061/oei", "type": "EvidenceItem", "natureOfTheThreat": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/nott", "id": "CG-AC:AC1061/oei/nott", "type": "EvidenceLine", "prevalenceOfTheGeneticDisorder": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/pgd", "id": "CG-AC:AC1061/oei/pgd", "type": "EvidenceItem", "keyText": "Unknown", "sourceOfPopulation": "General population", "evidenceNarrative": { "@id": "CG-AC:AC1061/en/potgd" } }, "clinicalFeatures": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/cf", "id": "CG-AC:AC1061/oei/cf", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC1061/en/cf" } }, "naturalHistory": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/nh", "id": "CG-AC:AC1061/oei/nh", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC1061/en/nh" } } }, "threatMaterializationChances": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/tmc", "id": "CG-AC:AC1061/oei/tmc", "type": "EvidenceLine", "modeOfInheritance": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/moi", "id": "CG-AC:AC1061/oei/moi", "type": "EvidenceItem", "keyText": "Autosomal Dominant", "evidenceNarrative": { "@id": "CG-AC:AC1061/en/ACMI2813" } }, "prevalenceOfTheGeneticMutation": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/pgm", "id": "CG-AC:AC1061/oei/pgm", "type": "EvidenceItem", "keyText": "Unknown", "sourceOfPopulation": "Other", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1061/ten/PGM2977" } }, "penetrance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/pe/ACPE4490", "id": "CG-AC:AC1061/oei/pe/ACPE4490", "type": "EvidenceItem", "keyText": "Unknown", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1061/ten/ACPE4490" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/pe/ACPE4489", "id": "CG-AC:AC1061/oei/pe/ACPE4489", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1061/ten/ACPE4489" } } ], "relativeRisk": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/rr/RR2742", "id": "CG-AC:AC1061/oei/rr/RR2742", "type": "EvidenceItem", "keyText": "Unknown", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1061/ten/RR2742" } } ], "expressivity": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/ex/EN3054", "id": "CG-AC:AC1061/oei/ex/EN3054", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1061/ten/EN3054" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/oei/ex/EN3055", "id": "CG-AC:AC1061/oei/ex/EN3055", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1061/ten/EN3055" } } ] } }, "interventionEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei", "id": "CG-AC:AC1061/iei", "type": "EvidenceItem", "acceptabilityOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/aoi", "id": "CG-AC:AC1061/iei/aoi", "type": "EvidenceLine", "natureOfIntervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/noi/NOI3004", "id": "CG-AC:AC1061/iei/noi/NOI3004", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1061/ten/NOI3004" } } ] }, "effectivenessOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/eoi", "id": "CG-AC:AC1061/iei/eoi", "type": "EvidenceLine", "patientManagement": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/pm/ACPM6498", "id": "CG-AC:AC1061/iei/pm/ACPM6498", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/ACPM6498" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/pm/ACPM6495", "id": "CG-AC:AC1061/iei/pm/ACPM6495", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/ACPM6495" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/pm/REC3118", "id": "CG-AC:AC1061/iei/pm/REC3118", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/REC3118" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/pm/ACPM6497", "id": "CG-AC:AC1061/iei/pm/ACPM6497", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/ACPM6497" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/pm/ACPM6496", "id": "CG-AC:AC1061/iei/pm/ACPM6496", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/ACPM6496" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/pm/ACPM6499", "id": "CG-AC:AC1061/iei/pm/ACPM6499", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/ACPM6499" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/pm/ACPM6500", "id": "CG-AC:AC1061/iei/pm/ACPM6500", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/ACPM6500" } } ], "circumstanceToAvoid": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/cta/ACCA3688", "id": "CG-AC:AC1061/iei/cta/ACCA3688", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/ACCA3688" } } ], "surveillance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/su/ACSU3976", "id": "CG-AC:AC1061/iei/su/ACSU3976", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/ACSU3976" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/su/ACSU3978", "id": "CG-AC:AC1061/iei/su/ACSU3978", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/ACSU3978" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/su/ACSU3975", "id": "CG-AC:AC1061/iei/su/ACSU3975", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/ACSU3975" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/su/ACSU3977", "id": "CG-AC:AC1061/iei/su/ACSU3977", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC1061/tr/ACSU3977" } } ] }, "conditionEscapeDetection": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/ced", "id": "CG-AC:AC1061/iei/ced", "type": "EvidenceLine", "chanceToEscapeDetection": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/cted/CDEC3026", "id": "CG-AC:AC1061/iei/cted/CDEC3026", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1061/ten/CDEC3026" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1061/iei/cted/CDEC3027", "id": "CG-AC:AC1061/iei/cted/CDEC3027", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC1061/ten/CDEC3027" } } ] } } }, "references": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000121", "id": "CG-AC:RF000121", "type": "Publication", "publicationType": "PMID", "citation": "Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. (2012) 97(9):2990-3011.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=22723327", "xdbref": [ "PMID:22723327" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000548", "id": "CG-AC:RF000548", "type": "Publication", "publicationType": "PMID", "citation": "Iacobone M, Carnaille B, Palazzo FF, Vriens M. Hereditary hyperparathyroidism--a consensus report of the European Society of Endocrine Surgeons (ESES). Langenbecks Arch Surg. (2015) 400(8):867-86.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=26450137", "xdbref": [ "PMID:26450137" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF002502", "id": "CG-AC:RF002502", "type": "Publication", "publicationType": "PMID", "citation": "Wasserman JD, Tomlinson GE, Druker H, Kamihara J, Kohlmann WK, Kratz CP, Nathanson KL, Pajtler KW, Parareda A, Rednam SP, States LJ, Villani A, Walsh MF, Zelley K, Schiffman JD. Multiple Endocrine Neoplasia and Hyperparathyroid-Jaw Tumor Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood. Clin Cancer Res. (2017) 23(13):e123-e132.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=28674121", "xdbref": [ "PMID:28674121" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003652", "id": "CG-AC:RF003652", "type": "Publication", "publicationType": "PMID", "citation": "Ahmed FW, Majeed MS, Kirresh O. Multiple Endocrine Neoplasias Type 4. (2023)", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=33760487", "xdbref": [ "PMID:33760487" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003653", "id": "CG-AC:RF003653", "type": "Publication", "publicationType": "PMID", "citation": "PDQ Cancer Genetics Editorial Board. Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®): Health Professional Version. (2002)", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=26389271", "xdbref": [ "PMID:26389271" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003654", "id": "CG-AC:RF003654", "type": "Publication", "publicationType": "Orphanet", "citation": "Multiple endocrine neoplasia type 4. Orphanet encyclopedia [Internet]", "xdbref": [ "Orphanet:276152" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003655", "id": "CG-AC:RF003655", "type": "Publication", "publicationType": "PMID", "citation": "Singeisen H, Renzulli MM, Pavlicek V, Probst P, Hauswirth F, Muller MK, Adamczyk M, Weber A, Kaderli RM, Renzulli P. Multiple endocrine neoplasia type 4: a new member of the MEN family. Endocr Connect. (2023) 12(2049-3614).", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=36520683", "xdbref": [ "PMID:36520683" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003657", "id": "CG-AC:RF003657", "type": "Publication", "publicationType": "Other", "citation": "true. Neuroendocrine and adrenal tumors version 1.2023. (2023) ", "webUrl": "https://arupconsult.com/reference/nccn-neuroendocrine-and-adrenal-tumors-version-12023" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003658", "id": "CG-AC:RF003658", "type": "Publication", "publicationType": "PMID", "citation": "Alrezk R, Hannah-Shmouni F, Stratakis CA. MEN4 and CDKN1B mutations: the latest of the MEN syndromes. Endocr Relat Cancer. (2017) 24(1479-6821):T195-T208.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=28824003", "xdbref": [ "PMID:28824003" ] } ] }