| Domain | Recommended identifier/ontology term | Annotation/use | Evidence caveat |
|---|---|---|---|
| Disease | Familial non-medullary thyroid carcinoma (FNMTC) | Core disease label for hereditary thyroid carcinoma arising from follicular-cell–derived, non-medullary histologies; typically used for disease-level KB entry | Commonly defined clinically as NMTC in ≥2 first-degree relatives, but many experts note families with only 2 cases may include sporadic clustering; stricter research enrichment often uses ≥3 affected relatives (pqac-00000000, pqac-00000003, pqac-00000017) |
| Disease identifier | MONDO: unverified | MONDO ID should be added only after curation against current MONDO release | A stable MONDO term was not established from available evidence; do not invent ID (pqac-00000017) |
| Disease identifier | OMIM: heterogeneous trait / unverified disease-level OMIM | OMIM may be better represented through susceptibility loci/genes and syndromic conditions rather than a single definitive nonsyndromic disease entry | Available evidence emphasizes marked genetic heterogeneity and lack of one confirmed driver gene (pqac-00000001, pqac-00000022) |
| Disease identifier | MeSH / ICD-10 / ICD-11: use broader thyroid carcinoma terms if needed; FNMTC-specific code unverified | For coding, map to broader non-medullary/differentiated thyroid carcinoma terms with a familial modifier in local schema | FNMTC is mainly a clinical/familial aggregation construct rather than a uniquely coded nosologic entity in available sources (pqac-00000000, pqac-00000004) |
| Synonym | Familial nonmedullary thyroid carcinoma | Exact synonym/label normalization | Hyphenation varies by source (pqac-00000004) |
| Synonym | Familial non-medullary thyroid cancer | Common literature synonym | Often used interchangeably with carcinoma in reviews (pqac-00000000, pqac-00000002) |
| Synonym | Familial nonmedullary thyroid cancer | Common synonym for search expansion | Includes papillary-predominant familial disease (pqac-00000002, pqac-00000017) |
| Synonym | Familial papillary thyroid carcinoma (subset term) | Use when kindred/pathology is specifically papillary thyroid carcinoma | Not synonymous with all FNMTC because follicular and rarer histologies also occur (pqac-00000002, pqac-00000017) |
| HPO phenotype | Thyroid carcinoma (HPO term recommended; stable ID not asserted here) | Parent malignant phenotype for affected individuals | Most familial tumors are papillary histology; exact HPO ID not asserted to avoid miscoding (pqac-00000002, pqac-00000017) |
| HPO phenotype | Thyroid nodule (HPO term recommended; stable ID not asserted here) | Captures benign or suspicious nodules found in affected relatives and screening | Benign nodules frequently accompany NS-FNMTC; exact HPO ID not asserted here (pqac-00000016, pqac-00000017) |
| HPO phenotype | Multifocal thyroid carcinoma / multifocal neoplasm (HPO term recommended; stable ID not asserted here) | Important clinicopathologic feature often reported in familial cases | Familial series reported multifocality around 56%; exact HPO wording may require curator choice (pqac-00000012) |
| HPO phenotype | Lymph node metastasis (HPO term recommended; stable ID not asserted here) | Use for nodal spread, especially cervical lymph nodes | Familial cases often present with more nodal disease/aggressive features, but outcome may remain similar with treatment (pqac-00000002, pqac-00000010, pqac-00000020) |
| HPO phenotype | Lung metastasis (HPO term recommended; stable ID not asserted here) | Use for distant metastatic spread to lung | Present in a minority of reported familial cases (~7% in one monocentric series) (pqac-00000012) |
| HPO phenotype | Goiter / multinodular goiter (HPO term recommended; stable ID not asserted here) | Useful for syndromic or non-syndromic familial thyroid disease annotation | Multinodular goiter can co-occur and may be part of some familial definitions in older/pathology literature (pqac-00000017) |
| Anatomy | UBERON:0002046 thyroid gland | Primary affected organ for FNMTC | Robust stable anatomy term; disease arises from follicular epithelium (pqac-00000017, pqac-00000020) |
| Anatomy | UBERON cervical lymph node term recommended; stable ID unverified here | Secondary site for regional metastasis annotation | Cervical nodal spread is clinically important, but exact UBERON descendant term not asserted without ontology lookup (pqac-00000012, pqac-00000020) |
| Cell type | CL:0000501 thyroid follicular cell | Principal cell of origin for non-medullary thyroid carcinoma | Appropriate for papillary/follicular lineage annotation (pqac-00000017, pqac-00000020) |
| Biological process | GO:0000165 MAPK cascade | Mechanistic pathway annotation for signaling dysregulation | Supported by WGS/pathway analyses implicating MAPK/ERK signaling, though specific causal germline alterations vary by family (pqac-00000011, pqac-00000015) |
| Biological process | PI3K-AKT signaling pathway (GO/Reactome term recommended; stable GO ID not asserted here) | Complementary pathway annotation for predisposition/mechanism | Central pathway implicated in WGS/network analyses; exact ontology ID not asserted here (pqac-00000011, pqac-00000015) |
| Biological process | GO:0008283 cell population proliferation | Generic downstream cancer process annotation | Broad downstream consequence rather than FNMTC-specific mechanism (pqac-00000011, pqac-00000015) |
| Gene | APC | Syndromic FNMTC gene; annotate when thyroid carcinoma occurs with familial adenomatous polyposis/Gardner syndrome | High-confidence syndromic association, not a confirmed common cause of isolated non-syndromic FNMTC (pqac-00000001, pqac-00000005, pqac-00000017) |
| Gene | PTEN | Syndromic FNMTC gene; annotate for Cowden/PTEN hamartoma tumor syndrome | Strong syndromic evidence; actionable in appropriate phenotype context (pqac-00000005, pqac-00000017) |
| Gene | DICER1 | Syndromic predisposition gene for familial thyroid neoplasia | Relevant especially when other DICER1-spectrum manifestations are present (pqac-00000001, pqac-00000017) |
| Gene | PRKAR1A | Syndromic gene for Carney complex-associated thyroid carcinoma | Use when phenotype supports Carney complex rather than isolated FNMTC (pqac-00000001, pqac-00000017) |
| Gene | WRN | Syndromic gene for Werner syndrome-associated thyroid carcinoma | Rare syndromic association; not typical isolated FNMTC driver (pqac-00000001, pqac-00000017) |
| Gene/locus evidence caveat | FOXE1, HABP2, SRGAP1, TITF1/NKX2.1, MAP2K5, DUOX2, POT1, CHEK2 and others as candidate susceptibility genes/loci | Consider as research/candidate annotations, not definitive disease-gene assertions for routine KB causal field unless separately curated | Reviews emphasize heterogeneity, low-to-moderate penetrance, inconsistent replication, and no single confirmed nonsyndromic driver gene (pqac-00000001, pqac-00000009, pqac-00000010, pqac-00000022) |
| Intervention | NCIT term recommended: Thyroidectomy | Primary definitive local treatment annotation | Total thyroidectomy frequently used in reported familial series; current guidelines generally do not mandate different surgery solely for family history (pqac-00000007, pqac-00000012) |
| Intervention | NCIT term recommended: Radioactive Iodine Therapy | Adjuvant treatment annotation for selected differentiated thyroid cancers | Applied according to standard differentiated thyroid cancer risk stratification rather than FNMTC-specific evidence (pqac-00000017) |
| Intervention | NCIT term recommended: Thyroid-Stimulating Hormone Suppression Therapy | Postoperative endocrine management annotation | Use as standard differentiated thyroid cancer management; FNMTC-specific modification not established (pqac-00000007, pqac-00000017) |
| Intervention | NCIT term recommended: Kinase Inhibitor Therapy | Targeted systemic treatment annotation for advanced/refractory disease | Because familial and sporadic NMTC share morphology and somatic drivers, similar targeted therapies are currently used when indicated (pqac-00000017) |
| Screening/implementation | Neck ultrasound surveillance in at-risk relatives | Real-world screening annotation for high-risk families/research cohorts | Evidence is mixed: one prospective cohort found thyroid cancer in 4.6% of screened relatives from families with 2 affected members, and major guidelines do not currently recommend universal genetic screening of at-risk relatives (pqac-00000001, pqac-00000016, pqac-00000019) |


*Table: This compact table lists practical knowledge-base annotations for familial nonmedullary thyroid carcinoma, including disease labels, suggested ontology terms, syndromic genes, mechanisms, and interventions. It also flags where the evidence is strong versus where identifiers or causal claims remain unverified or heterogeneous.*