Spondyloepimetaphyseal Dysplasia, Sponastrime Type — Comprehensive Disease Report

MONDO: MONDO:0010068 · OMIM: #271510 · Orphanet: ORPHA:93357 · Category: Mendelian (autosomal recessive skeletal dysplasia)

Evidence base: This report is derived from aggregated disease-level literature and case series/reports (there is no population EHR dataset for this ultra-rare disorder). Primary sources are cited by PMID. Evidence source types are flagged: human clinical, in vitro, model organism, computational.

Summary

Spondyloepimetaphyseal dysplasia, Sponastrime type ("SPONASTRIME dysplasia") is an ultra-rare autosomal-recessive skeletal dysplasia caused by biallelic hypomorphic (loss-of-function) variants in TONSL (8q24.3), which encodes the Tonsoku-like DNA-repair protein. The disease name is an acronym derived from its cardinal radiographic features: SPOndylar abnormalities, NAsal changes (midface hypoplasia/depressed nasal bridge), and STRIations of the MEtaphyses. First delineated by Fanconi et al. in 1983, it remained a purely descriptive radiological entity for 36 years until two independent 2019 studies (PMID: 30773278; PMID: 30773277) identified TONSL as the causal gene.

Mechanistically, SPONASTRIME dysplasia is a genome-instability disorder. TONSL is the H4K20me0-reading subunit of the TONSL–MMS22L complex, which is recruited to newly replicated ("post-replicative") chromatin to promote homologous-recombination (HR) repair of stalled and collapsed replication forks. Hypomorphic TONSL variants impair this function, producing replication stress, spontaneous chromosome breakage, defective cell proliferation, and increased apoptosis in dividing cells. The prevailing (partly inferred) model holds that loss of proliferating growth-plate chondrocytes underlies the endochondral-ossification defects that manifest as disproportionate short stature, age-dependent vertebral abnormalities, and metaphyseal striations, with branch effects in hematopoietic and other rapidly dividing tissues (neutropenia, hypogammaglobulinemia).

Clinically, patients present with severe disproportionate short-limb short stature (adult heights ~91–135 cm), platyspondyly with characteristic age-dependent "pear-shaped" vertebral bodies, metaphyseal striations (distal femur/proximal tibia), midface hypoplasia, frontal bossing, joint laxity, and variable childhood cataracts, short dental roots, and immunologic/hematologic abnormalities. Intelligence is normal in most classic cases, though a historically delineated variant subgroup features severe intellectual disability. Diagnosis rests on radiological criteria confirmed by molecular testing (WES/WGS or targeted TONSL/skeletal-dysplasia panels). Only supportive management exists; growth hormone therapy has shown little benefit. Fewer than ~30–40 cases have been reported worldwide.

1. Disease Information

• Overview: An ultra-rare, congenital, autosomal-recessive spondyloepimetaphyseal dysplasia (SEMD) characterized by disproportionate short stature, distinctive age-dependent vertebral abnormalities, metaphyseal striations, and midface hypoplasia. It is caused by biallelic hypomorphic TONSL variants and is mechanistically a DNA-repair/genome-instability disorder.
• Key identifiers: MONDO:0010068; OMIM #271510; Orphanet ORPHA:93357; MeSH — indexed under skeletal dysplasias/osteochondrodysplasias; ICD-10 Q77.8 (other osteochondrodysplasia with defects of growth of tubular bones and spine) / ICD-11 LD24 range for osteochondrodysplasias (no unique code).
• Synonyms / alternative names: SPONASTRIME dysplasia; Sponastrime dysplasia; SPONASTRIME (SPOndylar and NAsal changes with STRIations of the MEtaphyses).
• Data source: Aggregated disease-level resources (OMIM, Orphanet) and primary case series/reports — not individual EHR data. This reflects the disorder's extreme rarity.

2. Etiology

• Primary cause (genetic): Biallelic (homozygous or compound-heterozygous) hypomorphic loss-of-function variants in TONSL (8q24.3). This is a monogenic Mendelian disorder (PMID: 30773278; PMID: 30773277). See Finding F001.
• Genetic risk factors: The causal variants themselves are the risk factor; no separate susceptibility loci or GWAS signals apply (Mendelian disease). Recurrent variants include R934W and G973R. Complete loss of function is embryonic-lethal, so viable disease requires residual (hypomorphic) function.
• Environmental risk factors: None known. No toxin, radiation, infectious, occupational, dietary, age, or sex association exists — the disorder is fully explained by germline genetics.
• Protective factors: None identified (genetic or environmental).
• Gene–environment interactions: None established. Phenotypic variability (F004) is more likely attributable to allelic heterogeneity and putative genetic modifiers than to environmental interactions.

3. Phenotypes

Cardinal and associated features with suggested HPO terms (Burrage 2019 PMID: 30773277; Cooper 2000 PMID: 10797420; Langer 1997 PMID: 9133352; Arponen 2025 PMID: 40122363; see Finding F003).

• Progression: Skeletal features are chronic and progressive relative to peers; vertebral radiographic changes evolve with age. Short stature is fixed.
• Quality of life: Not formally measured (no EQ-5D/SF-36/PROMIS data). Impact derives chiefly from short stature, orthopedic complications (scoliosis, coxa vara), and, where present, visual impairment (cataracts) or immune susceptibility. Intelligence and life expectancy are typically normal in classic disease.

Direct quote (Burrage 2019): "characterized by spine (spondylar) abnormalities, midface hypoplasia with a depressed nasal bridge, metaphyseal striations, and disproportionate short stature. Scoliosis, coxa vara, childhood cataracts, short dental roots, and hypogammaglobulinemia have also been reported."

4. Genetic / Molecular Information

• Causal gene: TONSL (Tonsoku-like DNA repair protein), chromosome 8q24.3; NCBI Gene ID 4796; HGNC:11989; UniProt Q96HA7; OMIM gene 604546. Disease OMIM #271510.
• Pathogenic variants: Biallelic; a mix of missense, frameshift, and nonsense hypomorphic (partial loss-of-function) alleles spanning multiple domains. Recurrent variants R934W and G973R. Novel variants continue to be reported (Yao 2025 PMID: 40794898; Zhu 2024 PMID: 38684304; Micale 2020 PMID: 32959051).
• Variant classification: Pathogenic/likely pathogenic per ACMG; functional assays (fibroblast complementation, HEK293T expression, dimerization studies) provide PS3-level functional evidence.
• Allele frequency: Very low/absent in gnomAD (consistent with a rare recessive disorder); no common founder allele established.
• Origin: Germline; no somatic/mosaic mechanism. Inherited from unaffected heterozygous carrier parents.
• Functional consequence: Loss of function / hypomorphic. Complete null is embryonic-lethal (mouse), so only residual-function alleles produce viable disease. R934W and G973R abolish UBL-domain dimerization (PMID: 42525765).
• Modifier genes: None specifically identified, though phenotypic variability implies their existence.
• Epigenetic information: No disease-specific DNA-methylation/histone-modification signature reported. (Note: TONSL's function is to read the H4K20me0 chromatin mark, but this is its normal biology, not a disease epigenetic lesion.)
• Chromosomal abnormalities: None as a cause. The cellular consequence, however, is spontaneous chromosome breakage from defective DNA repair (PMID: 32959051).

5. Environmental Information

Not applicable. No environmental factors (toxins, radiation, pollution, occupational exposure), lifestyle factors (smoking, diet, exercise, alcohol), or infectious agents are known to cause or trigger SPONASTRIME dysplasia. It is a purely genetic monogenic disorder.

6. Mechanism / Pathophysiology

Ordered causal chain (initiating lesion → clinical manifestation)

1. Biallelic hypomorphic TONSL variants reduce protein function by disrupting the ankyrin-repeat domain (ARD; H4K20me0 reading) or the ubiquitin-like (UBL) domain (dimerization) — demonstrated (PMID: 30773278; PMID: 42525765). Leads to →
2. Impaired recruitment of the TONSL–MMS22L complex to post-replicative chromatin marked by H4K20me0 — demonstrated (PMID: 27338793). Results in →
3. Compromised homologous-recombination repair of replication-associated double-strand breaks at stalled/collapsed forks — demonstrated (PMID: 30773277; PMID: 27338793). Leads to →
4. Replication stress and spontaneous chromosome breakage in patient cells — demonstrated (PMID: 32959051). Results in →
5. Defective cell proliferation and increased apoptosis of dividing cells — demonstrated (PMID: 32959051). Then branches:
6. 6a (skeletal branch — INFERRED): Loss of proliferating growth-plate chondrocytes → impaired endochondral ossification → disproportionate short stature, metaphyseal striations, age-dependent vertebral dysplasia.
7. 6b (hematopoietic/immune branch — observed): Depletion/dysfunction of rapidly dividing progenitors → neutropenia and hypogammaglobulinemia.
8. 6c (other proliferative tissues — observed): lens epithelium (cataracts), odontoblasts (short dental roots/dentin anomalies).
9. Complete loss of TONSL is embryonic-lethal in mouse, defining the requirement for residual function in viable disease — demonstrated (PMID: 30773278).

 TONSL biallelic hypomorphic variants (ARD or UBL domain)
      │  (loss of H4K20me0 reading / dimerization)
      ▼
 Failure to recruit TONSL–MMS22L to post-replicative chromatin
      │
      ▼
 Defective HR repair of replication-associated DSBs
      │
      ▼
 Replication stress → spontaneous chromosome breaks
      │
      ▼
 Impaired proliferation + increased apoptosis of dividing cells
┌─────────────┼──────────────────┬───────────────┐
▼             ▼                  ▼               ▼
 Growth-plate    Hematopoietic     Lens epithelium   Odontoblasts
 chondrocytes    progenitors       (cataracts)       (short roots)
 (INFERRED)      (neutropenia,
│         hypogammaglob.)
▼
 Impaired endochondral ossification
 → short stature, metaphyseal striations, vertebral dysplasia

Detail by category

• Molecular pathways: DNA double-strand-break repair via homologous recombination; replication-fork protection/restart. The TONSL–MMS22L complex is the effector. Not a classical signaling cascade (Wnt/MAPK/mTOR) disease.
• Cellular processes: DNA replication, DNA-damage response, cell-cycle progression, apoptosis (increased), proliferation (decreased) — all demonstrated in patient fibroblasts.
• Protein dysfunction: Loss/reduction of TONSL function via impaired H4K20me0 reading (ARD variants) or loss of homodimerization (UBL-domain variants R934W/G973R). Hypomorphic, not gain-of-function or dominant-negative.
• Metabolic changes: None specific reported.
• Immune involvement: Secondary — hypogammaglobulinemia and neutropenia in a subset, consistent with impaired proliferation of immune/hematopoietic progenitors.
• Tissue damage mechanism: Genome instability (chromosome breaks) → apoptosis and proliferation failure in dividing cell populations.
• Molecular profiling / advanced technologies: No transcriptomic, proteomic, metabolomic, single-cell, or CRISPR-screen dataset specific to this disease is available.

Ontology annotations

• GO biological process: double-strand break repair via homologous recombination (GO:0000724); DNA replication (GO:0006260); chromatin binding (GO:0003682); replication fork processing (GO:0031297); endochondral ossification (GO:0001958, downstream); apoptotic process (GO:0006915).
• GO cellular component: nucleus (GO:0005634); chromatin (GO:0000785); replication fork (GO:0005657).
• CL cell types: chondrocyte (CL:0000138), growth-plate chondrocyte, neutrophil (CL:0000775), B cell/plasma cell (CL:0000236 / CL:0000786), lens fiber cell (CL:0011004), odontoblast (CL:0000060).

7. Anatomical Structures Affected

• Primary organ/system — skeletal: vertebral column (platyspondyly, pear-shaped bodies; UBERON:0001130), metaphyses of long bones (striations; UBERON:0002515), growth plate (UBERON:0006332), hips (coxa vara), carpal bones (delayed ossification), craniofacial skeleton (midface hypoplasia, frontal bossing).
• Secondary/associated: eye — lens (childhood cataracts; UBERON:0000965); teeth (short roots, dentin dysplasia I-like; UBERON:0001091); immune/hematopoietic system (hypogammaglobulinemia, neutropenia); nervous system (Arnold–Chiari I in a subset; intellectual disability in variant form).
• Tissue level: cartilage/connective tissue (growth-plate chondrocytes) primarily.
• Subcellular level: nucleus / chromatin / replication fork (site of TONSL function; GO:0005634, GO:0005657).
• Lateralization: bilateral / symmetric skeletal involvement.

8. Temporal Development

• Onset: congenital / early childhood; short stature and radiographic changes evident in infancy/childhood. Onset pattern is chronic/insidious rather than acute.
• Progression: chronic, lifelong, non-remitting. Vertebral radiographic features are age-dependent and evolve through childhood into adulthood (Cooper 2000 PMID: 10797420). Short stature is fixed/progressive relative to peers.
• Course: stable-to-progressive; not episodic or relapsing-remitting. Disease duration is lifelong.
• Critical periods: the childhood window of active growth-plate function is when skeletal manifestations develop; no established intervention alters the trajectory.
• Remission: none (no spontaneous or treatment-induced remission).

9. Inheritance and Population

• Epidemiology: Ultra-rare. Orphanet prevalence <1/1,000,000 (ORPHA:93357). By 2000, only ~12–16 patients from 6 families had been reported (Cooper 2000 PMID: 10797420: "To date, 12 patients from 6 families have been reported."); total reported cases remain ~30–40 worldwide. No formal incidence figure.
• Inheritance: Autosomal recessive; biallelic TONSL variants; both parents are obligate unaffected carriers (Zhu 2024 PMID: 38684304: variants "were inherited from her phenotypically normal parents."). Sibling recurrence risk 25%.
• Penetrance: Complete for the biallelic genotype (all reported biallelic individuals are affected).
• Expressivity: Variable — severity of short stature and presence of cataracts, dental, immune, and (in the variant form) neurodevelopmental features differ between patients (F004).
• Genetic anticipation: Not applicable (not a repeat-expansion disorder).
• Germline mosaicism / founder effects: None established.
• Carrier frequency: Not estimated; expected very low given rarity.
• Population demographics: No ethnic predilection; cases reported across European, Asian, and other populations. Sex ratio approximately equal (recessive). Age distribution: diagnosed in childhood; affected across the lifespan.

10. Diagnostics

• Clinical/radiological (mainstay): Diagnostic radiological criteria (Langer 1997 PMID: 9133352: "The radiological features are more specific than the clinical ones. We have developed diagnostic radiological criteria based on information from our five cases and from six previously published ones.") — age-dependent vertebral changes (pear-shaped bodies, platyspondyly, narrow lumbar interpedicular distances), metaphyseal striations (distal femur/proximal tibia), delayed carpal ossification. Imaging: skeletal survey / X-ray.
• Genetic testing (definitive): WES/WGS or targeted TONSL sequencing / skeletal-dysplasia gene panels identifying biallelic TONSL variants. WES has been the diagnostic modality in most recent reports (Chang 2019; Burrage 2019; Zhu 2024 PMID: 38684304). Single-gene TONSL testing/segregation confirms carrier parents. CMA/karyotyping/FISH/mtDNA/repeat-expansion testing are not indicated for diagnosis (the causal lesion is a small variant).
• Supportive laboratory tests: serum immunoglobulins (hypogammaglobulinemia), CBC (neutropenia); cytogenetic analysis of cultured fibroblasts may reveal spontaneous chromosome breaks (Micale 2020 PMID: 32959051).
• Biomarkers / omics: No validated circulating biomarker; no metabolomic/proteomic/lipidomic diagnostic signature.
• Differential diagnosis: spondyloepimetaphyseal dysplasia with joint laxity (leptodactylic/Hall type; Sulko 2008 PMID: 18841068), spondyloepiphyseal dysplasia (SED — a documented initial misdiagnosis in Cooper 2000), other dysplasias with metaphyseal striations (e.g., osteopathia striata), and other short-stature SEMDs.
• Screening: Not part of newborn screening. Cascade/carrier testing of relatives is possible once familial variants are known.

11. Outcome / Prognosis

• Survival/mortality: No disease-specific mortality data; life expectancy appears essentially normal with supportive care in classic disease. (Complete TONSL loss is embryonic-lethal, but affected individuals have residual-function alleles.)
• Morbidity/function: Driven by short stature, orthopedic complications (scoliosis, coxa vara), visual impairment (cataracts) where present, and immune susceptibility (hypogammaglobulinemia/neutropenia) in a subset. In the variant form, intellectual disability is a major morbidity.
• QoL measures: Not formally quantified (no EQ-5D/SF-36/PROMIS data).
• Complications: scoliosis, coxa vara, cataract-related visual loss, recurrent infections (if immunodeficient), Chiari I malformation (rare), dental problems.
• Prognostic factors: genotype (residual function level), presence/absence of the neurodevelopmental variant phenotype, and immune/hematologic involvement. No validated prognostic biomarker.

12. Treatment

No disease-modifying or curative therapy exists. Management is entirely supportive/symptomatic. Suggested NCIT clinical-intervention concepts in brackets.

• Pharmacotherapy: None disease-specific. Immunoglobulin replacement if clinically significant hypogammaglobulinemia [NCIT: Immunoglobulin Therapy]. Pharmacogenomics: not applicable.
• Growth hormone: Trialed but largely ineffective (Yao 2025 PMID: 40794898: "Six-month growth hormone therapy was administered to the patient after confirmed diagnosis, with limited improvement.") [NCIT: Recombinant Human Growth Hormone Therapy].
• Advanced therapeutics (gene/cell/RNA/targeted/immuno): None available or in trials.
• Surgical/interventional: Orthopedic correction of scoliosis/coxa vara [NCIT: Orthopedic Surgery]; cataract surgery [NCIT: Cataract Extraction]; neurosurgical foramen-magnum decompression for Chiari I (Jeong 2016 PMID: 27149441: "The malformation was successfully treated by decompression of the foramen magnum and elevation of the cerebellum, with complete resolution of pain.") [NCIT: Decompression Surgery].
• Supportive/rehabilitative: physical/occupational therapy, dental care, ophthalmologic monitoring, audiology as needed.
• Experimental treatments / trials: None registered.
• Treatment strategy: multidisciplinary supportive care coordinated by clinical genetics, orthopedics, ophthalmology, immunology, and dentistry.

13. Prevention

• Primary prevention: Not possible (genetic disorder). The only preventive avenue is genetic counseling — 25% sibling recurrence risk, carrier testing of at-risk relatives, and reproductive options (prenatal diagnosis or preimplantation genetic testing, PGT-M) once the familial TONSL variants are known [NCIT: Genetic Counseling].
• Secondary prevention: Early ophthalmologic screening for cataracts, immune evaluation, and orthopedic surveillance in diagnosed individuals to detect and treat complications early.
• Tertiary prevention: Management of complications as above.
• Immunization / behavioral / public-health / environmental interventions: Not applicable.

14. Other Species / Natural Disease

• Taxonomy / orthologs: TONSL is evolutionarily conserved. Human TONSL (NCBI Gene 4796); mouse Tonsl (Mus musculus, NCBI Taxon 10090); zebrafish tonsl (Danio rerio, NCBI Taxon 7955).
• Natural disease in other species: No naturally occurring SPONASTRIME-equivalent disease has been reported in companion animals or wildlife (no OMIA entry). Existing animal models are engineered, not natural.
• Comparative biology: The DNA-repair function of TONSL is conserved across vertebrates, supporting the mechanistic model; complete loss is lethal in mouse.
• Transmission / zoonosis: Not applicable (non-communicable genetic disorder).

15. Model Organisms

• Mouse: A knock-in Tonsl model is embryonic-lethal (Chang 2019 PMID: 30773278: "a knock-in (KI) Tonsl mouse model leads to embryonic lethality, implying the physiological importance of TONSL."). Establishes essentiality; limitation: complete-null models cannot recapitulate the postnatal skeletal phenotype, so hypomorphic/conditional models are needed.
• Zebrafish: tonsl used alongside complementation assays to support variant pathogenicity (Burrage 2019 PMID: 30773277).
• In vitro human models: Patient dermal fibroblasts show cellular defects complemented by wild-type TONSL (Chang 2019 PMID: 30773278: "cellular defects in dermal fibroblasts from affected individuals are complemented by the expression of wild-type TONSL") — direct causal proof. Patient fibroblasts show spontaneous chromosome breaks, reduced proliferation, and increased apoptosis (Micale 2020 PMID: 32959051). HEK293T transfection assays confirmed pathogenicity of novel variants (Yao 2025 PMID: 40794898).
• Phenotype recapitulation: Cellular models faithfully reproduce the genome-instability phenotype; no whole-animal model reproduces the skeletal dysplasia (a key gap).
• Resources: MGI (mouse Tonsl), ZFIN (zebrafish tonsl).

Mechanistic Model / Interpretation (Synthesis)

SPONASTRIME dysplasia unifies a molecular defect in replication-coupled DNA repair with a tissue-level phenotype of failed skeletal growth. The upstream mechanism is firmly established: TONSL reads the H4K20me0 mark on newly deposited histones to recruit the TONSL–MMS22L HR complex to post-replicative chromatin (PMID: 27338793); hypomorphic variants disrupt either the reader (ARD) or dimerization (UBL) function (PMID: 42525765), impairing repair and causing chromosome breakage, proliferation failure, and apoptosis in patient cells (PMID: 32959051). The downstream tissue specificity — why a general DNA-repair defect produces a predominantly skeletal phenotype — is the central inferential step: growth-plate chondrocytes are among the most proliferative postnatal cell populations, so they may be selectively vulnerable to a proliferation/apoptosis defect, explaining short stature, metaphyseal striations, and vertebral dysplasia, with parallel effects in other high-turnover tissues (marrow, lens, odontoblasts). The requirement for residual function (null is embryonic-lethal) explains why the disease is compatible with life and why severity tracks with allelic residual activity.

Evidence Base

Limitations and Knowledge Gaps

1. Chondrocyte mechanism is inferred, not proven. The link from genome instability to the specific skeletal phenotype (growth-plate chondrocyte depletion → endochondral ossification defect) has not been directly demonstrated in a bone/chondrocyte model.
2. No viable whole-animal disease model. Complete Tonsl knockout is embryonic-lethal; tissue-specific or patient-variant knock-in models are required to study skeletal pathogenesis in vivo.
3. Weak genotype–phenotype correlation. Why some patients have severe intellectual disability/microcephaly and others normal cognition (with overlapping skeletal features) is unresolved; residual-function level and modifier genes are candidate explanations.
4. Small N (~30–40 cases). Phenotype frequencies (cataracts, immunodeficiency, neutropenia, Chiari I) are qualitative rather than precise percentages.
5. No natural-history study or registry, so progression rates, adult outcomes, and QoL are not systematically documented.
6. No therapeutic pipeline. Management is supportive; growth hormone is largely ineffective; no disease-modifying strategy exists.

Proposed Follow-up Experiments / Actions

1. Conditional / knock-in mouse models carrying patient hypomorphic alleles (e.g., R934W, G973R) or chondrocyte-specific Tonsl deletion to directly test the growth-plate-chondrocyte hypothesis (measure chondrocyte proliferation, apoptosis, endochondral ossification).
2. Patient-iPSC-derived chondrocytes / cartilage organoids to assay replication stress, γH2AX foci, chromosome breakage, and proliferation/apoptosis in the disease-relevant cell type, with wild-type TONSL rescue.
3. Structure–function dissection across all reported variants (ARD vs. UBL vs. other domains), correlating residual H4K20me0-reading, dimerization, and HR-repair activity with clinical severity — building a validated functional assay for ACMG PS3 variant classification.
4. International registry / natural-history study to quantify phenotype frequencies, age-dependent radiographic evolution, immune/hematologic penetrance, and long-term outcomes.
5. Systematic immunophenotyping and marrow evaluation to characterize the hematologic/immunologic branch and guide surveillance.
6. Modifier discovery via combined WGS + transcriptomics across the cohort to explain the ID/microcephaly variant subgroup.
7. gnomAD/large-cohort carrier-frequency estimation for recurrent and predicted-LOF TONSL alleles to inform recurrence risk and possible under-diagnosis.

Report compiled from 8 confirmed findings and 15 reviewed papers across 5 investigation iterations. Evidence types span human clinical, in-vitro human, and model-organism sources. Key mechanistic steps (molecular reader function, HR-repair defect, chromosome breakage, proliferation/apoptosis defect, embryonic lethality of null) are experimentally demonstrated; the chondrocyte-to-skeletal-phenotype link is the principal inferred step.

Artifacts

• OpenScientist final report
• OpenScientist final report

Reference Validation

Checked with linkml-reference-validator 0.2.1.

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

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:

• HP:0000944 (1 mention) - the report calls it "Platyspondyly / vertebral abnormalities"; HP calls it Abnormal metaphysis morphology
• HP:0002650 (2 mentions) - the report calls it "Narrow lumbar interpedicular distances", "Scoliosis"; HP calls it Scoliosis
• HP:0005789 (1 mention) - the report calls it "Metaphyseal striations"; HP calls it Generalized osteosclerosis
• HP:0001541 (1 mention) - the report calls it "Delayed carpal ossification"; HP calls it Ascites
• HP:0004315 (1 mention) - the report calls it "Hypogammaglobulinemia"; HP calls it Decreased circulating IgG concentration

Obsolete terms

These terms are real but deprecated. Citing one is not a fabrication; it does mean the report is naming something the ontology has retired:

• HP:0001388 (obsolete Joint laxity) (1 mention) - replaced by HP:0001382

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

• HP:0004322 (1 mention) - the report calls it "Disproportionate short-limb short stature"; HP calls it Short stature
• HP:0005280 (1 mention) - the report calls it "Depressed nasal bridge / short upturned nose"; HP calls it Depressed nasal bridge, and lists "Depressed bridge of nose" among its other names
• HP:0002938 (1 mention) - the report calls it "Lumbar lordosis"; HP calls it Lumbar hyperlordosis, and lists "Lumbar lordosis" among its other names
• HP:0001388 (1 mention) - the report calls it "Joint laxity / hypermobility"; HP calls it obsolete Joint laxity
• HP:0000519 (1 mention) - the report calls it "Childhood cataracts"; HP calls it Developmental cataract, and lists "Congenital cataracts" among its other names
• HP:0001875 (1 mention) - the report calls it "Neutropenia"; HP calls it Decreased total neutrophil count, and lists "Neutropenia" among its other names
• HP:0007099 (1 mention) - the report calls it "Arnold–Chiari I malformation"; HP calls it Chiari type I malformation, and lists "Arnold Chiari type I malformation" among its other names
• GO:0005634 (2 mentions) - the report calls it "GO cellular component: nucleus"; GO calls it nucleus**, and lists "cell nucleus" among its other names
• CL:0000138 (1 mention) - the report calls it "CL cell types: chondrocyte"; CL calls it chondrocyte**

Terms named inconsistently

The report gives these identifiers more than one name of its own:

• HP:0002650 - called "Narrow lumbar interpedicular distances", "Scoliosis"

Prefixes with no resolver

Terms carrying these prefixes were not checked either way, because no configured ontology covers them. An unrecognised prefix may name an ontology this run could not reach as easily as one that does not exist, so nothing here is evidence of fabrication: ORPHA.