Olmsted Syndrome 2

1. Disease Information

Overview. Olmsted syndrome (OS) is a rare genodermatosis classically defined by the combination of bilateral mutilating transgredient palmoplantar keratoderma (PPK) and periorificial keratotic plaques, with considerable clinical heterogeneity. PERP-related disease (OLMS2) is the specific molecular subtype caused by PERP mutations, first delineated by Duchatelet et al. in 2019 (PMID: 30321533).

"Olmsted syndrome (OS) is a rare genodermatosis classically characterized by the combination of bilateral mutilating transgredient palmoplantar keratoderma (PPK) and periorificial keratotic plaques, but which shows considerable clinical heterogeneity." — PMID: 25886873

Key identifiers.

Synonyms / alternative names. OLMS2; PERP-related Olmsted syndrome; autosomal dominant PERP-related keratoderma.

Information source. The knowledge base entry is derived from aggregated, disease-level resources (OMIM, Orphanet, Mondo) and primary literature (case series and functional studies), not individual EHR patient records. Given the ultra-rarity of the disease, the evidence is drawn from a small number of kindreds and functional/model-organism studies.

2. Etiology

Disease causal factors. OLMS2 is a monogenic (Mendelian) genetic disorder caused by germline mutations in PERP. There is no environmental, infectious, or acquired cause of the core disease. PERP encodes a desmosomal component, and its disruption is both necessary and sufficient to produce the keratoderma phenotype.

"...mutations in PERP, encoding a crucial component of desmosomes, cause both dominant and recessive human keratoderma" — PMID: 30321533

Genetic risk factors. The causal variants are the PERP truncating/missense mutations themselves (detailed in Section 4). There are no known common susceptibility loci — the disease is fully penetrant Mendelian, not multifactorial.

Environmental risk factors. None established as causal. Mechanical stress is relevant as a modifier/trigger of manifestation at the cellular level (impaired adhesion manifests "upon mechanical stress," PMID: 30321533), consistent with the acral (palmoplantar) distribution of the most severe lesions, which are the body sites under greatest frictional load. In recessive biallelic cases, cutaneous fungal infection has been reported to coincide with psoriasiform plaque flares (PMID: 34863005), suggesting infection may act as a secondary trigger/aggravator rather than a cause.

Protective factors. No genetic or environmental protective factors have been identified. This is expected for a rare Mendelian disorder with high penetrance.

Gene–environment interactions. Not formally studied. The acral/periorificial and friction-prone distribution of lesions is consistent with mechanical load interacting with the underlying adhesion defect, but this is inferred, not demonstrated.

3. Phenotypes

The core clinical phenotype of Olmsted syndrome, and specifically PERP-related disease, comprises:

"Suggestive features: PPK with pseudoainhum and periorificial keratotic plaques. Frequently associated features include hair and nail abnormalities, leukokeratosis, corneal default and recurrent infections. Pain and itching are variable but can be severe." — PMID: 25886873

Genotype–phenotype gradient of severity. Dominant C-terminal truncations produce the most severe, mutilating periorificial + palmoplantar keratoderma (OLMS2 proper); homozygous N-terminal truncation produces widespread erythrokeratoderma; biallelic missense variants produce the mildest ichthyosis/erythrokeratoderma with psoriasiform plaques (PMID: 30321533; PMID: 34863005).

Quality of life impact. The mutilating PPK with pseudoainhum, severe pain, and pruritus produces profound functional disability affecting ambulation, manual dexterity, and daily living; QoL in treatment studies has been assessed with pain/pruritus visual analog scales (VAS) and the Children's Dermatology Life Quality Index (CDLQI) (PMID: 31895414). No disease-specific EQ-5D/SF-36 data exist given rarity.

4. Genetic / Molecular Information

Causal gene. PERP (HGNC:17637; NCBI Gene 64065; UniProt Q96FX8; chromosome 6q23.3; transcript NM_022121.5; OMIM *609301). PERP is a tetraspan membrane glycoprotein of the PMP22/EMP/MP20/claudin family localized to epidermal desmosomes and is a direct transcriptional target of p63.

Pathogenic variants and genotype–phenotype correlation.

"Monoallelic nonsense mutations cause Olmsted syndrome with severe periorificial keratoderma and palmoplantar keratoderma (PPK). Biallelic recessive frameshift and missense mutations are associated with milder forms of the disease, including generalised erythrokeratoderma and PPK." — PMID: 34863005

"Homozygosity for an N-terminal truncation ablates expression and causes widespread erythrokeratoderma, with expansion of epidermal differentiation markers." — PMID: 30321533

Exact variant nomenclature (recessive, milder cases).

"two novel biallelic PERP variants, NM_022121.5, c.89T > C, p.Leu30Pro and c.466G > C, p.Gly156Arg" — PMID: 34863005

Variant classification (ACMG/AMP). Truncating variants in a gene with an established loss-of-function/dominant-negative mechanism are classified pathogenic/likely pathogenic; the recessive missense variants were reported as novel disease-associated (likely pathogenic in the context of biallelic inheritance and phenotype segregation).

Allele frequency. Pathogenic PERP variants are private/rare and largely absent from gnomAD at appreciable frequency. No founder allele or recurrent hotspot has been established.

Somatic vs germline. All disease-causing PERP variants are germline. No somatic PERP disease association exists for OLMS2. (Of note, PERP loss is relevant to somatic skin carcinogenesis in model systems — see Sections 6 and 15 — but that is a tumor-suppressor context, not OLMS2 itself.)

Functional consequences. Dominant C-terminal truncation = dominant-negative (unstable protein incorporated into desmosomes, destabilizing them); N-terminal truncation = loss of function (no expression); recessive missense = partial/complete loss of function.

Modifier genes. None established.

Epigenetic information. PERP is transcriptionally controlled by the master epithelial regulator p63 (and p53); SATB2 can attenuate p63-driven perp expression (PMID: 21965674). No disease-specific DNA-methylation or histone-modification data for OLMS2 exist.

Chromosomal abnormalities. None — OLMS2 is a single-gene point-mutation disorder, not a copy-number/structural disorder.

5. Environmental Information

• Environmental factors: None causal. Mechanical friction plausibly aggravates acral lesions given the adhesion defect (inferred).
• Lifestyle factors: None established.
• Infectious agents: Not causal. Cutaneous fungal infection was reported to coincide with psoriasiform plaque flares in biallelic PERP disease (PMID: 34863005) — a secondary trigger/aggravator — and recurrent infections are a frequently associated feature of OS generally (PMID: 25886873), likely secondary to barrier compromise.

6. Mechanism / Pathophysiology

Ordered causal chain

1. A heterozygous C-terminal truncating PERP mutation produces an unstable PERP protein that is poorly incorporated into desmosomes (dominant-negative). [Human; PMID: 30321533]
2. This leads to immature desmosomes lacking a dense midline (electron microscopy), while other desmosomal components localize normally. [Human; PMID: 30321533]
3. This results in impaired keratinocyte intercellular adhesion upon mechanical stress [Human/in vitro; PMID: 30321533], mirrored by blistering in Perp-null mouse stratified epithelia [Mouse; PMID: 15797384, PMID: 16417219].
4. Loss of desmosomal adhesion / PERP function results in epidermal hyperproliferation and altered differentiation. [Human + mouse]
5. Inferred: downstream over-activation of EGFR and mTOR/RPS6 signaling in the epidermis drives hyperkeratosis. [Human IHC; PMID: 31895414]
6. This produces the clinical palmoplantar and periorificial keratoderma with pain and pruritus.

Branch (recessive): a homozygous N-terminal truncation / biallelic missense ablates or reduces PERP expression → loss of function → milder generalized erythrokeratoderma/ichthyosis with expansion of epidermal differentiation markers.

 PERP mutation
    │
    ├── Heterozygous C-term truncation ──► unstable protein, poorly incorporated
    │        │   (DOMINANT-NEGATIVE)
    │        ▼
    │   immature desmosomes (no dense midline)
    │        ▼
    │   impaired keratinocyte adhesion (mechanical stress)
    │        ▼
    │   epidermal hyperproliferation + altered differentiation
    │        ▼
    │   [inferred] ↑EGFR + ↑mTOR/RPS6 signaling ──► HYPERKERATOSIS
    │        ▼
    │   severe mutilating PPK + periorificial plaques (OLMS2)
    │
    └── Homozygous N-term truncation / biallelic missense ──► loss of expression
     │   (LOSS OF FUNCTION)
     ▼
 widespread erythrokeratoderma / milder ichthyosis

Supporting detail

"Both exhibit epidermal hyperproliferation, immature desmosomes lacking a dense midline observed via electron microscopy, and impaired intercellular adhesion upon mechanical stress." — PMID: 30321533

"Localization of other desmosomal components appears normal, which is in contrast to other conditions caused by mutations in genes encoding desmosomal proteins." — PMID: 30321533

"increased phosphorylated ribosomal protein S6 (RPS6) and phosphorylated EGFR staining in the epidermis, indicating enhanced mTOR and EGFR signaling activation" — PMID: 31895414

• Molecular pathways: p63 → PERP transcriptional axis (upstream); desmosomal adhesion; downstream EGFR and mTOR/PI3K–AKT–RPS6 signaling (therapeutically targetable). Suggested GO: GO:0002934 (desmosome organization), GO:0007155 (cell adhesion), GO:0008544 (epidermis development), GO:0030216 (keratinocyte differentiation).
• Cellular processes: keratinocyte adhesion failure, epidermal hyperproliferation, abnormal keratinocyte differentiation. PERP is also p53/p63-linked to apoptosis.
• Protein dysfunction: dominant-negative (unstable truncated protein destabilizing desmosomes) vs loss of function (no expression).
• Cell types: keratinocytes of stratified squamous epithelium (CL:0000312 keratinocyte; CL:0000362 epidermal cell).
• Upstream vs downstream: the PERP desmosomal structural lesion is upstream; EGFR/mTOR activation and hyperkeratosis are downstream and druggable.

Molecular profiling is limited: lesional immunohistochemistry (p-RPS6, p-EGFR up) is the principal profiling data; no large transcriptomic/proteomic/metabolomic datasets specific to OLMS2 exist.

7. Anatomical Structures Affected

• Primary organ: skin (UBERON:0002097), specifically palms and soles (palmoplantar epidermis) and periorificial skin (around mouth, eyes, nose, anus).
• Secondary involvement: hair (alopecia), nails, oral mucosa (leukokeratosis), cornea/eye (corneal defects). Body system: integumentary system.
• Tissue/cell level: stratified squamous epithelium; keratinocytes (CL:0000312) are the targeted cell population; desmosomes (cell–cell junctions) are the affected structure.
• Subcellular level: desmosome (GO:0030057, cellular component); plasma membrane. PERP is a tetraspan plasma-membrane/desmosomal protein.
• Localization: acral (palms/soles) and periorificial; bilateral and symmetric; transgredient (extending beyond palms/soles onto dorsal surfaces).

"Perp localizes specifically to desmosomes, adhesion junctions important for tissue integrity" — PMID: 15797384

Suggested UBERON: UBERON:0002097 (skin of body), UBERON:0002389 (skin of manus/palm), UBERON:0001513 (skin of pes/sole), UBERON:0001456 (face skin / periorificial region).

8. Temporal Development

• Onset: congenital / early childhood — PPK and periorificial plaques typically begin at birth or early childhood. Onset pattern is chronic/insidious.
• Progression: progressive — keratoderma worsens over time; pseudoainhum constricting bands can develop and progress toward a risk of autoamputation. Course is chronic, lifelong.
• Disease duration: lifelong; not self-limited.
• Remission: no spontaneous remission; partial, treatment-induced improvement reported with targeted therapy (erlotinib/sirolimus) and retinoids.
• Critical periods: early intervention may limit mutilating complications (pseudoainhum), but no formal natural-history window is defined.

"...usually starting at birth or early childhood..." — PMID: 25886873

9. Inheritance and Population

Epidemiology. Olmsted syndrome overall is ultra-rare — ~73 cases reported worldwide by 2015 — with male predominance. PERP-related cases are a small subset first delineated in 2019. No validated prevalence/incidence rate exists.

"About 73 cases have been reported worldwide. OS is observed in both sexes, although male cases are more frequent." — PMID: 25886873

Inheritance — dual pattern:

• Autosomal dominant OLMS2 from heterozygous C-terminal truncating variants, across multiple unrelated kindreds (de novo occurrence consistent with sporadic presentation).
• Autosomal recessive milder keratoderma/erythrokeratoderma from biallelic N-terminal truncating or missense variants, reported in consanguineous families (e.g., within a cohort of 180 extended Iranian families).

"Heterozygosity for a C-terminal truncation...causes Olmsted syndrome with severe periorificial and palmoplantar keratoderma in multiple unrelated kindreds." — PMID: 30321533

"Among 26 previously unresolved families within a cohort of 180 extended Iranian families with syndromic or non-syndromic ichthyosis" — PMID: 34863005

• Penetrance: high/complete for the dominant truncating variants (based on segregation in kindreds); expressivity varies with variant class (dominant-negative vs loss of function).
• Genetic anticipation: not applicable (not a repeat-expansion disorder).
• Germline mosaicism: not specifically documented.
• Founder effects: none established; variants are private/rare.
• Consanguinity: relevant to the recessive biallelic form (consanguineous Iranian families).
• Carrier frequency: not established; pathogenic alleles largely absent from gnomAD.
• Sex ratio: male predominance at the OS level.

Identifiers recap: MONDO:0030961 (OLMS2); ORPHA:659; PERP OMIM *609301; distinct from TRPV3-OS OMIM #614594.

10. Diagnostics

Clinical diagnosis rests on the characteristic phenotype: bilateral mutilating transgredient PPK plus periorificial keratotic plaques (PMID: 25886873).

Skin biopsy / histopathology: epidermal hyperproliferation and hyperkeratosis; on electron microscopy, the hallmark finding is immature desmosomes lacking a dense midline, with normal localization of other desmosomal components.

"immature desmosomes lacking a dense midline observed via electron microscopy" — PMID: 30321533

Immunohistochemistry (research/mechanistic): increased p-RPS6 and p-EGFR in lesional epidermis (PMID: 31895414).

Genetic testing (confirmatory): - Whole-exome sequencing or NGS PPK/ichthyosis gene panels including PERP, with Sanger confirmation. - Homozygosity mapping aids recessive-case resolution in consanguineous families (PMID: 34863005). - Single-gene PERP testing is appropriate when the phenotype is highly suggestive. WGS is useful but generally unnecessary. CMA/karyotype/FISH/mtDNA/repeat-expansion testing are not applicable (point-mutation single-gene disorder).

Differential diagnosis:

"Keratosis Follicularis Spinulosa Decalvans (KFSD), Olmsted syndrome, and Osteogenesis Imperfecta type XIX" — PMID: 33743732 (supporting MBTPS2 as a differential)

Screening: no newborn/population screening exists; cascade genetic testing of at-risk relatives and genetic counseling are appropriate once a familial variant is identified.

11. Outcome / Prognosis

• Survival / mortality: OLMS2 is non-lethal in humans; life expectancy is not reduced by the skin disease itself. (By contrast, constitutive Perp-null mice die postnatally — a species difference reflecting gene dosage / complete loss.)
• Morbidity / function: high — mutilating PPK, pseudoainhum with autoamputation risk, severe pain and pruritus produce major, lifelong disability affecting mobility and manual function.
• Quality of life: substantially impaired; monitored via pain/pruritus VAS and CDLQI in therapy studies (PMID: 31895414).
• Disease course: chronic, progressive; complications include secondary infection of fissured keratotic skin, constricting bands, and functional loss.
• Recovery potential: no cure; partial improvement with targeted therapy and supportive care.
• Prognostic factors: variant class (dominant-negative C-terminal truncation = most severe), extent of pseudoainhum, and response to EGFR/mTOR-targeted therapy.

12. Treatment

There is no approved disease-specific therapy. Management is multimodal.

Targeted pharmacotherapy (emerging, mechanism-based):

"Lesional skin immunostaining showed increased phosphorylated ribosomal protein S6 (RPS6) and phosphorylated EGFR staining in the epidermis, indicating enhanced mTOR and EGFR signaling activation." — PMID: 31895414

"A review of the literature indicates that erlotinib has shown efficacy in other cases of OS, making it a promising therapeutic option." — PMID: 39910762

Note: the strongest published erlotinib data are in TRPV3-associated OS (PMID: 39926429, PMID: 39910762); extrapolation to PERP-OLMS2 is rational given shared downstream EGFR/mTOR activation but remains to be demonstrated specifically for PERP cases.

Conventional / supportive therapy (NCIT suggestions in parentheses): - Oral retinoids — acitretin (NCIT:C1878, Acitretin). - Topical keratolytics and emollients (NCIT:C1507, Keratolytic Agent). - Pain and pruritus management. - Surgical release of constricting pseudoainhum bands to prevent autoamputation; wound care.

Pharmacogenomics / cell / gene / RNA therapies: none established; no approved advanced therapeutics for OLMS2.

13. Prevention

• Primary prevention: not possible (Mendelian germline disorder). Genetic counseling is the mainstay — risk assessment and family-planning guidance for affected families.
• Secondary prevention: early diagnosis and early targeted/supportive therapy to limit mutilating complications.
• Tertiary prevention: managing pseudoainhum, treating secondary infections, preserving function.
• Genetic screening: cascade testing of relatives; prenatal testing / preimplantation genetic diagnosis are feasible once the familial PERP variant is known.
• Immunization / public health / environmental interventions: not applicable.

14. Other Species / Natural Disease

• Orthologous gene: mouse Perp (well characterized; see Section 15). Human PERP NCBI Gene 64065.
• Natural disease in other species: no naturally occurring PERP-related Olmsted-like disease documented in companion animals or wildlife (OMIA); the animal evidence is from engineered models.
• Comparative biology: Perp function in desmosomal adhesion and epithelial integrity is evolutionarily conserved between mouse and human; the human dominant disease arises via a dominant-negative truncation, whereas complete murine loss is postnatally lethal — a dosage/species difference.
• Transmission / zoonosis: not applicable (non-infectious genetic disease).

15. Model Organisms

Mouse (Mus musculus) is the principal model.

"Perp-/- mice die postnatally, with dramatic blistering in stratified epithelia symptomatic of compromised adhesion." — PMID: 15797384

"the majority of mice lacking Perp in stratified epithelia die within 10 days after birth, accompanied by blistering and hyperproliferation in the epithelia" — PMID: 16417219

"Perp ablation promotes both tumor initiation and progression" — PMID: 20975948

Model characteristics. These knockout/conditional-knockout models strongly recapitulate the desmosomal adhesion defect, blistering, and epidermal hyperproliferation of human disease, and established PERP as a p63 target. Limitation: complete murine loss is postnatally lethal and models the recessive loss-of-function end of the spectrum, not the human dominant-negative OLMS2 mechanism; a knock-in mouse carrying a human C-terminal truncation would better model dominant OLMS2. Resources: MGI (mouse Perp). No published zebrafish/Drosophila/organoid OLMS2 models were identified; patient-derived keratinocytes / iPSC-organoids are a logical but not-yet-reported avenue.

An incidental PERP missense variant (p.Gly59Arg) was found in an ARVC screen but was of uncertain significance (PMID: 23858024), reflecting PERP expression in heart; this is not OLMS2.

Mechanistic Model / Interpretation

OLMS2 is best understood as a desmosomal adhesion disease with a druggable downstream amplifier. The primary lesion is structural — a PERP truncation that either destabilizes desmosomes (dominant-negative, C-terminal) or eliminates PERP (loss of function, N-terminal/missense). Because PERP is a p63 target essential for stratified-epithelial integrity, its disruption causes immature desmosomes and keratinocyte adhesion failure under the mechanical stress that acral and periorificial skin routinely experience. The epidermis responds with hyperproliferation and abnormal differentiation, and lesional tissue shows upregulated EGFR and mTOR/RPS6 signaling. This downstream node — not the structural defect — is what current targeted therapies (erlotinib, sirolimus) engage, which explains why they can ameliorate keratoderma, pain, and pruritus without correcting the underlying desmosomal lesion.

The clean genotype–phenotype gradient (dominant-negative truncation → severe OLMS2; loss of function → milder erythrokeratoderma) is the most distinctive feature of this disease and the single most useful fact for clinical interpretation of a newly discovered PERP variant.

Evidence Base

Evidence source types: human clinical/genetic (30321533, 34863005, 25886873, 31895414); model organism (15797384, 16417219, 20975948); in vitro/IHC (30321533, 31895414).

Limitations and Knowledge Gaps

1. Ultra-rarity. The entire PERP-OLMS2 literature rests on a small number of kindreds; no prevalence/incidence, formal penetrance estimates, or natural-history cohorts exist.
2. Downstream mechanism is inferred. EGFR/mTOR activation is demonstrated by lesional IHC in Olmsted syndrome, but the causal link from desmosomal failure to EGFR/mTOR activation is not mechanistically proven, and the IHC evidence is not exclusively from PERP cases.
3. Therapy evidence is indirect for PERP. The best erlotinib/sirolimus data come from TRPV3-OS; direct PERP-OLMS2 treatment-response data are minimal.
4. No dominant-negative animal model. Mouse models reproduce loss of function (lethal), not the human dominant-negative OLMS2 mechanism.
5. No omics depth. No transcriptomic/proteomic/metabolomic/single-cell datasets specific to OLMS2; molecular profiling is limited to IHC.
6. Variant classification. Few variants, no ClinVar-scale curation, and no functional assays for most missense variants.

Proposed Follow-up Experiments / Actions

1. Knock-in dominant-negative mouse or human keratinocyte/organoid model expressing a C-terminal truncated PERP to directly test the dominant-negative desmosome-destabilization mechanism and recapitulate OLMS2 (rather than lethal loss of function).
2. Mechanistic linkage study: test whether restoring desmosomal adhesion or depleting mutant PERP normalizes EGFR/mTOR–RPS6 signaling in patient-derived keratinocytes — to prove the inferred downstream step.
3. Prospective, PERP-specific therapeutic registry/trial of erlotinib and/or sirolimus with standardized VAS/CDLQI endpoints and lesional p-EGFR/p-RPS6 as pharmacodynamic biomarkers.
4. Functional classification of PERP VUS (e.g., recessive missense p.Leu30Pro, p.Gly156Arg) via desmosome-incorporation and adhesion assays to support ACMG curation.
5. International OLMS2 registry to estimate prevalence, penetrance, expressivity, and natural history, and to collect ultrastructural EM data as a diagnostic standard.
6. Single-cell/spatial transcriptomics of lesional skin to map keratinocyte-state changes and signaling activation in situ.

Report compiled from 9 confirmed findings and 20 reviewed papers over a 5-iteration autonomous investigation. Evidence quotes are verbatim from the cited abstracts.

Artifacts

• OpenScientist final report
• OpenScientist final report

Reference Validation

Checked with linkml-reference-validator 0.3.0.

Quotes not found in the cited source

Searched the abstract, any retrieved full text, and the title. A quote drawn from a part of the paper that was not retrieved will appear here too, so check before treating one as invented:

• PMID:25886873: "Suggestive features: PPK with pseudoainhum and periorificial keratotic plaques. Frequently associated features include hair and nail abnormalities, leukokeratosis, corneal default and recurrent infections. Pain and itching are variable but can be severe."
• closest text in source: "Frequently associated features include hair and nail abnormalities, leukokeratosis, corneal default and recurrent infections"
• PMID:25886873: "...usually starting at birth or early childhood..."
• closest text in source: "The disease starts usually at birth or in early childhood"

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:0011220 (1 mention) - the report calls it "periorificial hyperkeratosis type"; HP calls it Prominent forehead
• HP:0011817 (1 mention) - the report calls it "oral leukoplakia type"; HP calls it Basal encephalocele
• HP:0001055 (1 mention) - the report calls it "Erythrokeratoderma"; HP calls it Erysipelas
• UBERON:0001456 (1 mention) - the report calls it "face skin / periorificial region"; UBERON calls it face

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:

• MONDO:0030961 (4 mentions) - the report calls it "Olmsted syndrome 2 / OLMS2", "OLMS2"; MONDO calls it Olmsted syndrome 2
• HP:0000481 (1 mention) - the report calls it "Abnormality of the cornea"; HP calls it Abnormal cornea morphology, and lists "Abnormality of the cornea" among its other names
• UBERON:0002097 (2 mentions) - the report calls it "Primary organ: skin", "skin of body"; UBERON calls it skin of body**, and lists "skin organ" among its other names
• UBERON:0002389 (1 mention) - the report calls it "skin of manus/palm"; UBERON calls it manual digit, and lists "digit of manus" among its other names
• UBERON:0001513 (1 mention) - the report calls it "skin of pes/sole"; UBERON calls it skin of pes

Terms named inconsistently

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

• MONDO:0030961 - called "Olmsted syndrome 2 / OLMS2", "OLMS2"
• UBERON:0002097 - called "Primary organ:** skin", "skin of body"

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.