| Domain | Finding | Suggested ontology/identifier | Evidence/notes |
|---|---|---|---|
| Disease | Weill-Marchesani syndrome (rare hereditary connective-tissue / acromelic dysplasia syndrome with ocular, skeletal, and sometimes cardiac involvement) | ORPHA:3447; MONDO:0018097 *(verification recommended)*; Mendelian disease | Estimated prevalence about 1 in 100,000; phenotype and gene evidence are disease-level aggregated from published case reports/reviews, not EHR-derived (pqac-00000001, pqac-00000003) |
| Disease subtypes | Historically subdivided by gene/inheritance into AD and AR forms; “WMS4” used for ADAMTS17-related disease in recent literature | OMIM subtype labels *verification needed* | Recent sources explicitly distinguish AD FBN1-associated disease from AR ADAMTS10/ADAMTS17/LTBP2-associated disease; exact OMIM subtype mapping should be checked directly in OMIM before database load (pqac-00000001, pqac-00000006) |
| Synonym/related label | Weill-Marchesani-like syndrome | Disease synonym/related concept *(verification needed)* | Used especially for some LTBP2-associated families and overlapping phenotypes; may not always be nosologically identical to classic WMS (pqac-00000008) |
| Gene / inheritance | FBN1: autosomal dominant WMS | HGNC: FBN1 | Dominant WMS linked to heterozygous FBN1 variants; often associated with ectopia lentis/joint stiffness and acromelic dysplasia overlap (pqac-00000001, pqac-00000003, pqac-00000015) |
| Gene / inheritance | ADAMTS10: autosomal recessive WMS | HGNC: ADAMTS10 | Established AR cause; recent quantitative review of 19 ADAMTS10 cases found universal microspherophakia, high myopia, short stature, brachydactyly, and joint stiffness (pqac-00000001, pqac-00000004, pqac-00000012) |
| Gene / inheritance | ADAMTS17: autosomal recessive WMS / WMS4 | HGNC: ADAMTS17 | ADAMTS17-related disease shows ocular-predominant presentation and may lack heart defects/joint stiffness compared with other forms (pqac-00000006) |
| Gene / inheritance | LTBP2: autosomal recessive WMS; atypical dominant WMS-like families also reported | HGNC: LTBP2 | Classic teaching supports AR disease; a 2024 Chinese family report proposed dominant WMS-like inheritance from haplotypic LTBP2 variants, requiring cautious interpretation (pqac-00000001, pqac-00000008) |
| Variant class | Germline pathogenic variants include missense, nonsense, frameshift, splice-site, exon deletions, and in-frame/deletion events depending on gene | ACMG/AMP classification framework | Somatic origin is not implicated; reported disease variants are germline. ADAMTS10 frameshift c.1560_1575dup p.Ile526Valfs*51 classified pathogenic in 2026 report (pqac-00000001, pqac-00000012) |
| Phenotype | Microspherophakia / spherophakia | HPO term suggestion: Microspherophakia | Core ocular trait; 100% in ADAMTS10 literature synthesis cited in recent report (19/19) (pqac-00000004, pqac-00000012) |
| Phenotype | High myopia / lenticular myopia | HPO term suggestion: High myopia; Lenticular myopia | Universal in ADAMTS10 synthesis (19/19); in WMS4 child, progressive myopia tracked with lens thickening despite normal axial length (pqac-00000004, pqac-00000006) |
| Phenotype | Ectopia lentis / lens subluxation | HPO term suggestion: Ectopia lentis | Frequently reported across genetic subtypes; especially emphasized in dominant FBN1 disease and WMS-like families (pqac-00000003, pqac-00000008) |
| Phenotype | Glaucoma, often secondary angle closure / phacomorphic mechanism | HPO term suggestion: Glaucoma; Angle-closure glaucoma | Glaucoma in 47.4% (9/19) in ADAMTS10 synthesis; literature range 44.4%–51%; mean onset in one cited series ~20 ± 13 years, but childhood acute attacks can occur (pqac-00000012, pqac-00000014, pqac-00000016) |
| Phenotype | Short stature | HPO term suggestion: Short stature | Universal in recent ADAMTS10 synthesis; common across WMS spectrum (pqac-00000003, pqac-00000012) |
| Phenotype | Brachydactyly | HPO term suggestion: Brachydactyly | Universal in recent ADAMTS10 synthesis; useful for syndromic recognition in ophthalmology settings (pqac-00000004, pqac-00000006, pqac-00000012) |
| Phenotype | Joint stiffness / contractures | HPO term suggestion: Joint stiffness | Universal in ADAMTS10 synthesis; may be absent or less conspicuous in ADAMTS17-related WMS4 (pqac-00000004, pqac-00000006) |
| Phenotype | Thick skin / muscular habitus | HPO term suggestion: Thickened skin; Muscular hypertrophy/pseudomuscular build | Recurrently described in reviews and classic WMS descriptions; frequency not well quantified in retrieved recent primary evidence (pqac-00000001, pqac-00000003) |
| Phenotype | Cardiac abnormalities (valves/other cardiovascular findings) | HPO term suggestion: Abnormality of the cardiovascular system; Heart valve abnormality | Cardiac abnormalities in 55.6% (10/18) of literature cases in one ADAMTS10 review; ADAMTS17-related WMS4 may have fewer/no heart defects (pqac-00000004, pqac-00000006, pqac-00000012) |
| Onset/course | Usually congenital or childhood-onset, chronic lifelong condition | Temporal descriptor: congenital/childhood onset | Ocular findings often first recognized in childhood; WMS4 can present insidiously as “high myopia” before glaucoma or overt ectopia lentis (pqac-00000001, pqac-00000006) |
| Anatomy affected | Crystalline lens, zonule/ciliary zonule, anterior chamber angle | UBERON term suggestions: lens of eye; suspensory ligament of lens / ciliary zonule; anterior chamber angle of eye | Ocular biometry/imaging shows thick, small-diameter lenses, shallow anterior chambers, and zonular pathology driving glaucoma risk (pqac-00000005, pqac-00000006, pqac-00000011) |
| Anatomy affected | Cornea / anterior segment | UBERON term suggestions: cornea; anterior segment of eyeball | Increased corneal thickness reported in WMS; anterior segment crowding is clinically important for angle-closure risk (pqac-00000005, pqac-00000016) |
| Anatomy affected | Growth plate, long bone skeleton, digits, joints | UBERON term suggestions: epiphyseal growth plate; long bone; digit; synovial joint | Short stature/brachydactyly implicate disturbed skeletogenesis and endochondral growth (pqac-00000009) |
| Anatomy affected | Heart valves / cardiovascular connective tissue | UBERON term suggestions: heart valve; cardiovascular system | Cardiovascular manifestations are less consistent than ocular/skeletal features but important for surveillance (pqac-00000003, pqac-00000012) |
| Cell/tissue context | Connective tissue fibroblasts, chondrocytes, ocular microfibril-rich tissues | CL term suggestions: fibroblast; chondrocyte | Mechanistic studies and models implicate ECM-producing stromal cells and growth-plate chondrocytes; exact cell ontology IDs should be verified during curation (pqac-00000009, pqac-00000011) |
| Mechanism | Extracellular matrix and fibrillin microfibril assembly disorder | GO term suggestion: extracellular matrix organization; microfibril assembly | Strong convergence across FBN1, ADAMTS10, ADAMTS17, and LTBP2 supports a shared microfibril/ECM pathway (pqac-00000003, pqac-00000009, pqac-00000010) |
| Mechanism | ADAMTS10 proteolytic regulation of fibrillin-2 in ocular tissues | GO term suggestion: proteolysis; extracellular matrix disassembly | Mouse/in vitro work showed reduced fibrillin-2 cleavage and persistence of ocular microfibrils after Adamts10 inactivation (pqac-00000011) |
| Mechanism | Local tissue-microenvironment dysregulation rather than classic Marfan-like generalized TGF-β activation | GO term suggestion: regulation of signaling receptor activity; extracellular structure organization | FBN1 WMS models suggest altered local microenvironments and collagen regulation; mechanism diverges from canonical Marfan pathogenesis (pqac-00000009) |
| Mechanism | BMP-Smad pathway involvement in skeletogenesis (especially ADAMTS17 biology) | GO term suggestion: BMP signaling pathway; endochondral bone morphogenesis | Experimental data in Adamts17 biology support BMP-Smad1/5/8 modulation during skeletogenesis; relevance to human WMS is plausible but still mechanistically incomplete (pqac-00000009) |
| Mechanism | LTBP2-related zonule/microfibril and elastic-fiber biology | GO term suggestion: elastic fiber assembly; ciliary zonule development | LTBP2 is implicated in microfibril formation and ocular connective tissue integrity; precise causal chain to all WMS manifestations remains incompletely resolved (pqac-00000008, pqac-00000010) |
| Diagnostics | Clinical recognition based on syndromic combination of microspherophakia/high myopia/ectopia lentis plus short stature and brachydactyly | Clinical feature set *(no single universal formal criteria retrieved)* | No universally adopted formal diagnostic criteria were retrieved; diagnosis is phenotype-led and then molecularly confirmed (pqac-00000003, pqac-00000006) |
| Diagnostics | Ophthalmic biometry and imaging | Test suggestions: slit-lamp exam; ocular biometry; Pentacam; ultrasound biomicroscopy; IOLMaster | 2023 WMS4 case used multiple imaging modalities to document lens thickening and reduced equatorial diameter over 3 years (pqac-00000006) |
| Diagnostics | Intraocular pressure assessment / gonioscopy for glaucoma surveillance | Test suggestions: tonometry; gonioscopy | Essential because glaucoma is common and may arise acutely in anatomically crowded eyes (pqac-00000005, pqac-00000014) |
| Diagnostics | Echocardiography / cardiovascular evaluation | Test suggestion: echocardiography | Recommended because cardiac involvement occurs in a substantial subset, especially some AR forms (pqac-00000003, pqac-00000012) |
| Diagnostics | Molecular testing | WES/WGS/gene panel; confirmatory Sanger sequencing | WES plus Sanger was used in recent ADAMTS10 and ADAMTS17 cases; gene panels for ectopia lentis/anterior segment dysgenesis/connective-tissue disease are reasonable (pqac-00000001, pqac-00000006) |
| Differential diagnosis | Marfan syndrome, isolated ectopia lentis, acromicric dysplasia, geleophysic dysplasia, other microspherophakia syndromes | Related disease term suggestions | Distinguishing clues include short stature/brachydactyly/joint stiffness rather than tall stature; acromelic dysplasia spectrum overlaps at FBN1 TB5 domain (pqac-00000003, pqac-00000015) |
| Intervention | Peripheral iridotomy / laser iridotomy | NCIT-style term suggestion: Peripheral Iridotomy | Used prophylactically or therapeutically for pupillary block/angle closure risk in WMS (pqac-00000002, pqac-00000003) |
| Intervention | Lensectomy / lens extraction | NCIT-style term suggestion: Lensectomy | Key intervention for microspherophakia-related glaucoma or lens-induced crowding; recent pediatric case used staged bilateral lens extraction (pqac-00000002, pqac-00000016) |
| Intervention | Anterior vitrectomy | NCIT-style term suggestion: Anterior Vitrectomy | Used in advanced ocular surgical management alongside lensectomy in reviews/case-based practice (pqac-00000002) |
| Intervention | Intraocular lens implantation | NCIT-style term suggestion: Intraocular Lens Implantation | May be deferred initially in high-risk eyes; individualized surgical planning is emphasized (pqac-00000002, pqac-00000016) |
| Intervention | Glaucoma drainage or filtering procedures | NCIT-style term suggestions: Glaucoma Surgery; Molteno Implantation; ExPRESS Shunt Placement | Described for refractory glaucoma in review literature (pqac-00000002) |
| Intervention | Multidisciplinary supportive care | NCIT-style term suggestions: Ophthalmologic Monitoring; Cardiology Follow-Up; Orthopedic Care; Physical Therapy | No disease-modifying pharmacotherapy identified; management is complication-directed and longitudinal (pqac-00000002, pqac-00000003) |
| Prevention | Genetic counseling, cascade testing, reproductive counseling | Clinical service term suggestion: Genetic Counseling | Most actionable prevention relates to family-risk assessment for AD or AR inheritance and early ophthalmic surveillance of at-risk relatives (pqac-00000001, pqac-00000003) |
| Prognosis | Morbidity driven mainly by progressive refractive error, ectopia lentis, and glaucoma; vision can be preserved with early detection/intervention | Outcome descriptor *(no validated prognostic biomarker retrieved)* | Acute glaucoma can occur in childhood, but mean glaucoma onset in one cited literature set was ~20 years; survival/life-expectancy data were not retrieved (pqac-00000014, pqac-00000016) |
| Model organisms | Adamts10-null mouse | Model suggestion: Mus musculus Adamts10 loss-of-function | Recapitulates ocular microfibril persistence and supports ADAMTS10-mediated fibrillin-2 cleavage mechanism; limited for full human multisystem spectrum (pqac-00000011) |
| Model organisms | Fbn1 WMS mouse model | Model suggestion: Mus musculus Fbn1 WMS-associated deletion model | Replicates thick skin, short stature, and brachydactyly, supporting tissue-microenvironment mechanism distinct from Marfan syndrome (pqac-00000009) |
| Evidence limitations | Most evidence comes from small case reports/series and mechanistic mouse studies; phenotype frequencies differ by gene and publication bias is likely | Evidence-quality note | No randomized trials retrieved; no disease-specific interventional ClinicalTrials.gov evidence found in the search set; several detailed 2024 papers were cited in references but not fully available in retrieved text (pqac-00000003, pqac-00000013, pqac-00000016) |


*Table: This table summarizes key disease, gene, phenotype, anatomy, mechanism, diagnostic, and management mappings for Weill-Marchesani syndrome. It is designed as a compact curation aid and flags ontology identifiers or claims that should be verified before formal database ingestion.*