BMP2-Related Short Stature-Facial Dysmorphism-Skeletal Anomalies Syndrome

1. Disease Information

Overview. SSFSC1 is a Mendelian multiple-congenital-anomaly / dysmorphism syndrome caused by BMP2 haploinsufficiency. It was formally delineated as a single nosological entity by Tan et al. in 2017, who reported 12 individuals from 8 unrelated families carrying monoallelic truncating/frameshift/splice BMP2 variants or 20p12.3 deletions and sharing "features of short stature, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease" (PMID: 29198724).

Key identifiers.

Synonyms / alternative names: SSFSC syndrome; SSFSC1; BMP2-related skeletal dysplasia spectrum; BMP2 haploinsufficiency; 20p12.3 microdeletion syndrome (BMP2-related, when deletion is the mechanism).

Source of information. The knowledge base for this disease is derived from aggregated disease-level resources (OMIM, Orphanet, MONDO) and from individual-patient case series published in the primary literature (Tan 2017; Priestley 2023; Stavrén-Eriksson 2025; plus single/small case reports). There is no EHR-scale or population-registry dataset for this ultra-rare condition.

2. Etiology

Primary cause — genetic. SSFSC1 is a monogenic disorder caused by reduced BMP2 dosage. Two mechanistic classes converge on the same haploinsufficient state:

• Intragenic loss-of-function variants — truncating (nonsense), frameshift, splice-altering, and (functionally validated) missense variants. Example ClinVar/literature variants: NM_001200.4:c.460C>T (p.Arg154Ter); c.231dup (p.Tyr78Leufs*38).
• Contiguous gene deletions — 1.3–5.5 Mb 20p12 deletions encompassing BMP2 (PMID: 29198724; PMID: 39970956).

Tan et al. concluded that "haploinsufficiency of BMP2 could be the primary phenotypic determinant in individuals with predicted truncating variants and deletions encompassing BMP2" (PMID: 29198724). Missense variants were later shown to be LOF by modeling in zebrafish (PMID: 37125634).

Genetic risk factors. The causal variant is the risk factor; there are no established susceptibility loci or modifier genes with proven effect on SSFSC1 expression. The wide inter- and intrafamilial variability suggests as-yet-unidentified genetic and/or stochastic modifiers.

Environmental risk factors. None identified. There is no evidence for toxin, teratogen, infection, or lifestyle contribution to disease occurrence. (Note: BMP2/SMAD1-5-8 biology is modulated by estrogen and hyperglycemia in unrelated disease models — e.g., vascular calcification [PMID: 32089109] and diabetic-pregnancy growth-plate effects [PMID: 34934622] — but these are not implicated in SSFSC1.)

Protective factors / gene-environment interactions. No genetic protective alleles or gene-environment interactions are documented for this disorder. This is expected for a highly penetrant dominant developmental syndrome.

3. Phenotypes

The phenotype spans four core domains plus an expanded spectrum. Frequencies below are qualitative or drawn from the small published cohorts (Tan 2017, n=12; Priestley 2023, n=18; Stavrén-Eriksson 2025, n=7).

Craniofacial (physical manifestations / clinical signs)

Recognizable gestalt: broad forehead with bitemporal narrowing, flat/retruded midface, short nose with anteverted nares, long philtrum, thin upper lip, crowded dentition, high-arched or cleft palate, micrognathia; Pierre-Robin sequence in some. Onset congenital; highly penetrant with variable severity. - Suggested HPO: HP:0000337 (broad forehead), HP:0011800 (midface retrusion), HP:0000463 (anteverted nares), HP:0000343 (long philtrum), HP:0000219 (thin upper lip vermilion), HP:0000175 (cleft palate), HP:0000347 (micrognathia), HP:0000201 (Pierre-Robin sequence).

Growth (physical manifestation)

Proportionate short stature, non-endocrine in most, congenital/early-childhood onset. Growth-hormone evaluation is recommended in some cases. - Suggested HPO: HP:0004322 (short stature), HP:0003508 (proportionate short stature).

Skeletal (clinical signs / imaging)

Fifth-ray brachydactyly (short fifth-digit proximal phalanges) and clinodactyly; 11 pairs of ribs (axial patterning defect); sandal gap; scoliosis, hip dysplasia/coxa vara, and osteopenia reported in expanded cohorts. - Suggested HPO: HP:0009237 (short 5th finger), HP:0004209 (clinodactyly of 5th finger), HP:0000921 (rib abnormality / 11 pairs of ribs), HP:0001177 (sandal gap), HP:0002650 (scoliosis), HP:0001385 (hip dysplasia), HP:0000938 (osteopenia).

Cardiac (physical manifestations / clinical signs)

Congenital heart disease in ~4/12 in the delineating series, predominantly outflow-tract lesions: transposition of the great arteries, pulmonary valve stenosis, Ebstein anomaly, ventricular septal defect; expanded reports add bicuspid aortic valve with aortic root/ascending aortic aneurysm (PMID: 33247540) and isolated dextrocardia (situs solitus) (PMID: 37572998). Arrhythmias (Wolff-Parkinson-White, paroxysmal SVT, palpitations) in 3/12. - Suggested HPO: HP:0001631 (VSD), HP:0001642 (pulmonary valve stenosis), HP:0001680 (coarctation/great-artery anomaly), HP:0010316 (Ebstein anomaly), HP:0001647 (bicuspid aortic valve), HP:0002616 (aortic root aneurysm), HP:0001696 (dextrocardia), HP:0011675 (arrhythmia).

Expanded spectrum (later cohorts)

Neural tube defects, structural brain anomalies, endocrinopathies (including a patient with hypercalcemia, hypercalciuria, nephrolithiasis, hypophosphatemia, suppressed PTH); secretory otitis media (4/5) with conductive hearing loss; delayed language development (4/5). Global/intellectual developmental delay is not a core feature (PMID: 37125634; PMID: 39970956). - Suggested HPO: HP:0012443 (structural brain anomaly), HP:0045005 (neural tube defect), HP:0000405 (conductive hearing impairment), HP:0000388 (otitis media), HP:0000750 (delayed speech and language development).

Quality-of-life impact. No formal EQ-5D/SF-36/PROMIS data exist. Functional impact is driven mainly by feeding/airway compromise from cleft palate/Pierre-Robin in infancy, hearing loss affecting language, cardiac morbidity, and orthopedic issues; overall cognition and independence are typically preserved.

4. Genetic / Molecular Information

Causal gene. BMP2 (Bone Morphogenetic Protein 2), the sole causal gene. HGNC:1069; NCBI Gene 650; UniProt P12643; OMIM *112261; 20p12.3.

Pathogenic variants.

Missense pathogenicity was validated functionally: "Missense variants modeled in zebrafish resulted in loss of protein function" (impaired bmp2b-driven embryonic ventralization) (PMID: 37125634).

Modifier genes / epigenetics. None established. Variable expressivity implies modifiers exist but they are uncharacterized. No disease-specific DNA-methylation or histone-modification signature is described.

Chromosomal abnormalities. 20p12 microdeletions (1.3–5.5 Mb) encompassing BMP2 are a recognized cause; detected by chromosomal microarray/karyotype (PMID: 21671386; PMID: 22965927; PMID: 39970956).

Dosage sensitivity (key concept). OMIM links two reciprocal, allelic BMP2 entities: haploinsufficiency → SSFSC1 (#617877) and duplication of a downstream cis-regulatory element (~110 kb 3′ of BMP2) → BDA2 (#112600). The gene tolerates reduced but not absent dosage in humans (heterozygotes viable; complete loss embryonic-lethal in mouse) (PMID: 37125634; PMID: 29198724).

5. Environmental Information

No environmental, lifestyle, or infectious factors contribute to SSFSC1. It is a purely genetic developmental disorder. This section is not applicable except to note the negative: no toxin, radiation, occupational exposure, diet, or pathogen has been implicated in causation or triggering.

6. Mechanism / Pathophysiology

Causal chain (initiating lesion → clinical manifestation)

1. A heterozygous LOF BMP2 variant (truncating/frameshift/splice/missense) or a 20p12 deletion removes one functional BMP2 allele → leads to ~50% reduction in secreted BMP2 ligand (haploinsufficiency).
2. Reduced BMP2 ligand results in attenuated binding to BMP type I/II receptors → leads to reduced phosphorylation of the canonical effectors SMAD1/5/8 (with reduced non-canonical MAPK/p38 signaling as an inferred parallel branch).
3. Attenuated SMAD1/5/8 output reduces transcription of BMP2 target genes in multiple developing tissues simultaneously (the mechanism then branches by tissue):

Branch A — Skeleton/growth plate: Reduced BMP2 signaling impairs growth-plate chondrocyte maturation/hypertrophy (cross-talk with EGFR, Wnt/β-catenin, IHH, and IGF-I) → results in disordered endochondral ossification → proportionate short stature and skeletal anomalies (fifth-ray brachydactyly, 11 rib pairs; the last also reflecting an axial patterning defect).

Branch B — Craniofacial: Reduced BMP2 during palatogenesis and midface development → leads to cleft/high-arched palate, midface retrusion, and the recognizable facial gestalt (Pierre-Robin sequence in some).

Branch C — Heart: Reduced BMP2 in myocardium overlying the AV canal/outflow tract impairs endocardial-cushion EMT and valvuloseptal morphogenesis, and (via BMP-2/4) impairs neural-crest migration into the outflow tract to form the aortopulmonary septum → results in outflow-tract/septal defects, valve anomalies (including BAV → aortic aneurysm), Ebstein anomaly, and, via disturbed left-right/axis cues, dextrocardia; arrhythmia (WPW/SVT) is a downstream consequence of abnormal conduction-tissue/AV-junction development.

1. Wide inter-individual variability (same variant, different severity) is inferred to reflect stochastic developmental noise plus unidentified genetic modifiers, since no genotype-phenotype correlation has been demonstrated.

Supporting molecular detail

Molecular pathway. BMP2 is a TGF-β superfamily ligand signaling through BMP type I/II serine-threonine kinase receptors to SMAD1/5/8. Chen, Zhao & Mundy: "Smad1, 5 and 8 are the immediate downstream molecules of BMP receptors and play a central role in BMP signal transduction," and "BMP signaling plays critical roles in heart, neural and cartilage development" (PMID: 15621726). Suggested pathway/GO terms: GO:0030509 (BMP signaling pathway), GO:0071773 (cellular response to BMP stimulus).

Cardiac cushion / neural-crest mechanism. BMP2 is expressed in myocardium overlying the AV canal and OFT cushions and is required for endothelial-to-mesenchymal transformation (EMT). Yamagishi et al.: antisense BMP2 inhibited AV mesenchyme formation (rescued by recombinant BMP2), and "BMP2 … plays an important role in the formation of endocardial cushion tissue and … acts synergistically with TGFbeta3 in the regulation of this developmental event" (PMID: 10362015). Abdelwahid et al. localized Bmp-2 to AV canal/junctional myocardium and maturing valves (PMID: 11512673). Allen et al.: "BMP-2/4 function is required for the migration of neural crest cells into the developing OFT to form the aortopulmonary septum" (PMID: 11412030). Dyer et al. confirmed BMP2 canonical SMAD/Sox9 regulation fine-tunes cushion EMT (PMID: 26418455). Suggested terms: GO:0003198 (epithelial-to-mesenchymal transition involved in endocardial cushion formation), GO:0003203 (endocardial cushion morphogenesis), CL:0002350 (endocardial cell), CL:0000333 (migratory neural crest cell), UBERON:0002062 (endocardial cushion), UBERON:0004145 (cardiac outflow tract).

Growth-plate mechanism. Lees-Shepard et al.: "Signals from the epidermal growth factor receptor (EGFR), and from bone morphogenetic protein-2 (BMP2), are required for normal chondrocyte maturation" (PMID: 34773433). BMP2 promotes chondrocyte hypertrophy with Wnt/β-catenin ("chondrocyte maturation, possibly involving a bone morphogenic protein 2 (BMP2)-mediated mechanism," PMID: 22508079) and IHH, and augments IGF-I anabolic action: "both BMP-2 and BMP-9 augmented the mitogenic action of IGF-I" (PMID: 17549388). COX-2 cross-talk fine-tunes hypertrophy (PMID: 22183916). Suggested terms: GO:0001958 (endochondral ossification), GO:0003413 (chondrocyte differentiation involved in endochondral bone morphogenesis), CL:0000138 (chondrocyte), CL:0000743 (hypertrophic chondrocyte), UBERON:0002515 (growth plate of bone).

Cell types / compartments. Chondrocytes (reserve/prehypertrophic/hypertrophic), endocardial/endothelial cells undergoing EMT, cardiac neural crest cells, palatal mesenchyme. Signaling is transmembrane-receptor → cytoplasmic SMAD → nucleus (GO:0005634) for transcriptional output; ligand is secreted (GO:0005576, extracellular region).

7. Anatomical Structures Affected

Organ level. - Primary: skeleton (long bones/growth plates, ribs, digits, spine, hips), craniofacial complex (palate, midface, mandible), heart (outflow tract, valves, septa, conduction system). - Secondary: middle ear (secretory otitis media → conductive hearing loss); brain/neural tube (structural anomalies in a subset); kidney (nephrolithiasis in an endocrinopathy case); endocrine axes. - Body systems: musculoskeletal, cardiovascular, craniofacial/orofacial, auditory, nervous, endocrine.

Suggested UBERON: UBERON:0002481 (bone tissue), UBERON:0002515 (growth plate), UBERON:0002228 (rib), UBERON:0002389 (manual digit), UBERON:0001716 (secondary palate), UBERON:0000948 (heart), UBERON:0004145 (cardiac outflow tract), UBERON:0002062 (endocardial cushion), UBERON:0001756 (middle ear).

Tissue/cell level. Connective/skeletal (cartilage, bone), cardiac (myocardium, endocardium, valve mesenchyme), neural crest–derived tissues. Cell Ontology: CL:0000138 (chondrocyte), CL:0000746 (cardiac muscle cell), CL:0000333 (neural crest cell).

Subcellular level. Signaling nodes at plasma membrane receptor (GO:0005886), cytoplasm/nucleus for SMAD shuttling (GO:0005634), and the extracellular region for the secreted ligand (GO:0005576).

Localization / lateralization. Skeletal and cardiac defects are typically bilateral/midline (palate, septa) though laterality defects (dextrocardia, situs) reflect disturbed left-right axis determination; digit anomalies are usually bilateral.

8. Temporal Development

• Onset: Congenital / prenatal (structural anomalies form during embryogenesis); recognized at birth or early childhood. Onset pattern is developmental/insidious rather than acute.
• Progression: The malformations are largely static/structural (fixed at birth), but several features are age-progressive or age-emergent: short stature manifests over the growth years; scoliosis/hip issues and osteopenia can progress; aortic root dilatation associated with BAV can progress and requires monitoring; arrhythmias may present later; hearing loss and language delay emerge in early childhood.
• Disease course: Chronic/lifelong but non-degenerative for most core features; no relapsing-remitting pattern.
• Critical periods / windows for intervention: Infancy for airway/feeding (cleft palate/Pierre-Robin), early childhood for hearing and language surveillance, and lifelong cardiac/orthopedic monitoring.

9. Inheritance and Population

Inheritance. Autosomal dominant. Tan et al. observed "De novo occurrence and autosomal-dominant inheritance of variants, including paternal mosaicism in two affected sisters who inherited a BMP2 splice-altering variant … across all reported families" (PMID: 29198724) — documenting de novo events, vertical transmission, and germline (paternal) mosaicism relevant to recurrence-risk counseling.

Penetrance / expressivity. High penetrance with variable expressivity: "suggesting high penetrance, yet variable expressivity for haploinsufficiency of BMP2" (PMID: 22965927). No genotype-phenotype correlation established. No genetic anticipation (not a repeat-expansion disorder).

Epidemiology. Ultra-rare. Approximately 40+ patients reported cumulatively (Tan 2017 n=12; single/small reports ~4; Priestley 2023 n=18; Stavrén-Eriksson 2025 n=7). No established prevalence or incidence figures. No strong sex bias, founder effect, or geographic clustering reported. Consanguinity is not relevant (dominant disorder). Carrier frequency is not applicable in the recessive sense; affected parents transmit at 50% risk.

10. Diagnostics

Molecular diagnosis is definitive and requires two complementary approaches, because both small variants and CNVs cause disease:

1. Sequence analysis of BMP2 (NM_001200.4) via exome/genome or targeted testing → detects truncating/frameshift/splice/missense variants (e.g., c.460C>T p.Arg154Ter; c.231dup p.Tyr78Leufs*38).
2. Copy-number analysis — chromosomal microarray (CMA) or karyotype → detects 1.3–5.5 Mb 20p12 deletions.

(PMID: 29198724; PMID: 39970956)

Supporting clinical evaluations (phenotype-driven): echocardiography + ECG (outflow-tract defects, BAV/aortic root, WPW/arrhythmia); skeletal and spine radiographs (rib count, brachydactyly, scoliosis, hip dysplasia/coxa vara); bone densitometry (osteopenia); growth charting ± GH-axis evaluation; audiology and tympanometry (secretory otitis media, conductive loss); language/developmental assessment; brain/spine imaging and metabolic/endocrine work-up where indicated (a patient had hypercalcemia, hypercalciuria, nephrolithiasis, hypophosphatemia, suppressed PTH).

Clinical criteria / differential diagnosis. No formal consensus diagnostic criteria; diagnosis rests on the recognizable gestalt plus molecular confirmation. Differential diagnoses include other short-stature/dysmorphism/brachydactyly syndromes such as autosomal-dominant Robinow syndrome (PMID: 32256301) and BDA2 caused by BMPR1B/GDF5/BMP2-regulatory duplication (PMID: 33486847); distinguishing features are the specific BMP2 variant/deletion and the combination of 11 rib pairs, fifth-ray brachydactyly, and outflow-tract cardiac disease.

Screening. Cascade genetic testing of at-risk relatives once a familial variant is identified. Prenatal/preimplantation testing feasible when the familial variant is known. No population newborn screening exists.

11. Outcome / Prognosis

Survival / life expectancy. Generally normal life expectancy with appropriate management; no disease-specific mortality rate is established. The main mortality risk driver is severe congenital heart disease/aortic complications in the subset with cardiac involvement.

Morbidity / function. Morbidity is driven by cleft palate/airway issues in infancy, cardiac disease and arrhythmia, orthopedic problems (scoliosis, hip dysplasia), hearing loss, and short stature. Cognition is typically normal; global developmental delay is not a core feature (PMID: 39970956). No standardized QoL data.

Complications. Feeding/airway compromise (Pierre-Robin), progressive aortic root dilatation with BAV, arrhythmias (WPW/SVT), conductive hearing loss and its effect on language, nephrolithiasis in endocrinopathy cases.

Prognostic factors. Severity of cardiac malformation and presence of aortic aneurysm are the principal determinants of serious outcomes. No molecular prognostic biomarker exists, and absence of genotype-phenotype correlation limits prediction.

12. Treatment

There is no disease-specific or curative therapy; management is symptomatic, anticipatory, and multidisciplinary. Priestley et al. explicitly recommended this framework: "We use this expansion of reported phenotypes to suggest multidisciplinary medical monitoring and management of patients with BMP2-related skeletal dysplasia spectrum" (PMID: 37125634).

Stavrén-Eriksson et al. specifically recommended surveillance additions: "we propose that evaluation of language development and regular controls of the middle ear should be included in the surveillance of these individuals" (PMID: 39970956).

Advanced/experimental therapeutics, pharmacogenomics. None specific to SSFSC1; no gene/cell/RNA therapy trials. No pharmacogenomic considerations beyond standard care of individual complications.

13. Prevention

• Primary prevention: Not applicable to disease occurrence (genetic, largely de novo). Preventive value lies in reproductive counseling: for affected parents, 50% transmission risk; for families with an affected child and apparently unaffected parents, recurrence risk is low but non-zero due to demonstrated germline mosaicism (PMID: 29198724).
• Secondary prevention: Cascade testing of relatives; prenatal/PGT when the familial variant is known; early echocardiography/audiology/growth surveillance to enable early intervention.
• Tertiary prevention: Anticipatory organ-system surveillance to prevent complications (aortic monitoring, arrhythmia detection, hearing/language support, orthopedic care).
• Genetic counseling is the central preventive intervention. Immunization, public-health/environmental measures, and prophylactic medication are not applicable.

14. Other Species / Natural Disease

• Taxonomy / orthologs: BMP2 is deeply conserved. Mouse Bmp2 (NCBI Gene 12156), zebrafish bmp2b (used to validate human missense LOF), chick Bmp2 (developmental studies). NCBI Taxon: Mus musculus (10090), Danio rerio (7955), Gallus gallus (9031).
• Natural disease / veterinary relevance: No naturally occurring companion-animal or wildlife equivalent of SSFSC1 is catalogued (no specific OMIA entry mirroring this syndrome identified in this investigation).
• Comparative biology / conservation: BMP2's roles in endocardial cushion EMT, outflow-tract septation, and chondrocyte maturation are conserved across chick, mouse, and zebrafish, providing strong cross-species mechanistic validation (PMID: 10362015; PMID: 11512673; PMID: 11412030).
• Transmission / zoonosis: Not applicable (non-infectious genetic disorder).

15. Model Organisms

Model limitations. The heterozygous mouse captures growth/skeletal phenotypes but the full human craniofacial gestalt and the variable cardiac/laterality spectrum are incompletely modeled; homozygous lethality prevents study of complete loss postnatally. Resources: MGI (mouse Bmp2), ZFIN (bmp2b).

Mechanistic Model / Interpretation

 Heterozygous BMP2 LOF variant  OR  20p12 deletion (encompassing BMP2)
          │
          ▼
~50% reduction in secreted BMP2 ligand  (HAPLOINSUFFICIENCY)
          │
          ▼
Reduced BMP receptor engagement → ↓ SMAD1/5/8 phosphorylation
     (± ↓ non-canonical MAPK/p38 — inferred)
          │
  ┌───────────────┼───────────────────────────┐
  ▼               ▼                           ▼
   GROWTH PLATE      CRANIOFACIAL                    HEART
 ↓ chondrocyte      ↓ palatogenesis /         ↓ endocardial cushion EMT
 maturation &        midface growth            ↓ OFT neural-crest septation
 hypertrophy         (Pierre-Robin)            ↓ valve/septum morphogenesis
 (EGFR, Wnt/β-cat,        │                    ↓ L-R axis cues
  IHH, IGF-I, COX-2)      │                          │
  ▼               ▼                          ▼
 Proportionate short   Cleft/high-arched    Outflow-tract CHD, BAV→aortic
 stature; brachydactyly palate; facial      aneurysm, Ebstein, VSD, TGA,
 (5th ray); 11 ribs     gestalt; micrognathia dextrocardia; WPW/arrhythmia
  └───────────────┴───────────────────────────┘
          │
          ▼
   Variable expressivity (unidentified modifiers + stochastic noise)

Dosage axis: Loss (haploinsufficiency) → SSFSC1. Gain (downstream regulatory duplication) → BDA2. BMP2 is thus a two-sided dosage-sensitive locus.

Evidence Base

Limitations and Knowledge Gaps

• Small evidence base: ~40+ total patients; no prevalence/incidence, survival, or formal QoL data. All frequencies are from small case series and may be biased by ascertainment.
• No genotype-phenotype correlation: The basis of the wide variable expressivity (modifier genes, stochastic effects) is unknown, limiting prognostic prediction.
• Mechanism partly inferred in humans: The causal chain is anchored in model-organism developmental biology (chick/mouse/zebrafish); the precise human tissue-level steps (e.g., non-canonical MAPK contribution) are inferred, not directly demonstrated in patient tissue.
• No SSFSC1-specific molecular profiling: No patient transcriptomic, proteomic, metabolomic, or methylation signature exists.
• No natural animal disease equivalent catalogued; no dedicated therapeutic development.

Proposed Follow-up Experiments / Actions

1. International registry & natural-history study to establish penetrance-by-feature frequencies, prevalence, cardiac/aortic progression rates, and QoL using standardized instruments.
2. Modifier-gene search via combined WGS + phenotyping across the growing cohort to explain variable expressivity.
3. Patient-derived iPSC models (chondrocyte and cardiac-neural-crest differentiation) to directly quantify SMAD1/5/8 dosage effects in human cells and test whether pathway-augmenting agents rescue phenotypes.
4. Aortic surveillance protocol for BAV-positive patients, given the demonstrated aneurysm risk, to standardize imaging intervals.
5. Systematic audiology/language screening implementation, per Stavrén-Eriksson recommendations, to test whether early intervention improves outcomes.
6. Functional assays for VUS using the validated zebrafish bmp2b ventralization readout to reclassify uncertain missense variants.

Report compiled from 10 confirmed findings and ~24 primary papers across the delineating human cohorts, developmental-biology mechanistic studies, and model-organism work. Evidence types are indicated throughout as human clinical, model organism, or in vitro.

Artifacts

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Quotes not found in the cited source

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• PMID:10362015 (abstract only): "BMP2 … plays an important role in the formation of endocardial cushion tissue and … acts synergistically with TGFbeta3 in the regulation of this developmental event"
• closest text in source: "These results suggest that BMP2 1) plays an important role in the formation of endocardial cushion tissue and 2) acts synergistically with TGFbeta3 in the regulation of this developmental event."
• PMID:29198724 (abstract only): "De novo occurrence and autosomal-dominant inheritance of variants, including paternal mosaicism in two affected sisters who inherited a BMP2 splice-altering variant … across all reported families"
• closest text in source: "De novo occurrence and autosomal-dominant inheritance of variants, including paternal mosaicism in two affected sisters who inherited a BMP2 splice-altering variant, were observed across all reported families"

Term Validation

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Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

• MONDO:0100297 (2 mentions) - the report calls it "MONDO"; MONDO calls it short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1
• NCIT:C15192 (1 mention) - the report calls it "Speech Therapy"; NCIT calls it Blood Transfusion
• NCIT:C15266 (1 mention) - the report calls it "Genetic Counseling"; NCIT calls it Laparotomy