| Section | Item | Details | Ontology suggestions | Evidence |
|---|---|---|---|---|
| Disease identifiers & synonyms | Primary disease name | Achondrogenesis type II; lethal congenital/perinatal skeletal dysplasia within the type II collagenopathy spectrum | MONDO: Not found in retrieved sources | (pqac-00000000, pqac-00000001, pqac-00000006) |
| Disease identifiers & synonyms | Named subtype / synonyms | Langer-Saldino achondrogenesis; ACG2; achondrogenesis type II/hypochondrogenesis spectrum | MONDO: Not found in retrieved sources | (pqac-00000001, pqac-00000003) |
| Disease identifiers & synonyms | Database identifiers available in retrieved evidence | OMIM #200610 for achondrogenesis type II; COL2A1 MIM #108300 | MeSH: Not found in retrieved sources; Orphanet: Not found in retrieved sources; ICD-10: Not found in retrieved sources; ICD-11: Not found in retrieved sources | (pqac-00000000, pqac-00000006) |
| Disease identifiers & synonyms | Evidence provenance | Retrieved information is aggregated from disease-level and mutation review resources plus individual prenatal/newborn case reports, radiology reports, and molecular case series; not from EHR datasets | — | (pqac-00000000, pqac-00000001, pqac-00000003, pqac-00000006) |
| Genetic / molecular | Causal gene | COL2A1 (collagen type II alpha 1 chain), encoding the alpha-1 chain of type II procollagen, the major collagen of cartilage | HGNC gene symbol: COL2A1 | (pqac-00000000, pqac-00000006, pqac-00000012) |
| Genetic / molecular | Inheritance | Typically autosomal dominant; many cases are de novo; recurrence can occur due to parental germline/somatic mosaicism | — | (pqac-00000001, pqac-00000005, pqac-00000009) |
| Genetic / molecular | Typical pathogenic variant classes | Predominantly heterozygous glycine substitutions in the triple-helical Gly-X-Y repeat; also splice-site variants and in-frame deletions reported | Sequence ontology suggestions: missense_variant, splice_acceptor_variant, inframe_deletion | (pqac-00000003, pqac-00000006, pqac-00000011) |
| Genetic / molecular | Example variants (HGVS) | c.2987G>A (p.Gly996Asp), likely pathogenic; c.2546G>A (p.Gly849Asp), novel; c.1267-2_1269del causing exon 21 skipping/in-frame deletion; familial recurrence reported with G316D | — | (pqac-00000000, pqac-00000002, pqac-00000005) |
| Genetic / molecular | Mechanistic notes | Glycine substitutions disrupt collagen triple-helix folding/assembly (dominant-negative effect), impair cartilage matrix formation, and underlie severe/lethal phenotypes; ACG2/hypochondrogenesis are among the most severe COL2A1 phenotypes, associated with neonatal death | GO: collagen trimer assembly; extracellular matrix organization; CL: chondrocyte | (pqac-00000006, pqac-00000012, pqac-00000013) |
| Phenotype / anatomy | Core prenatal findings | Severe micromelia/short limbs, short humerus/femur, thoracic hypoplasia or small/narrow chest, cystic hygroma, hydrops/polyhydramnios, increased nuchal fold; may be detectable from first/second trimester | HPO: Short limb, Micromelia, Narrow thorax, Cystic hygroma, Hydrops fetalis, Polyhydramnios; UBERON: limb, thoracic cage | (pqac-00000000, pqac-00000003, pqac-00000009) |
| Phenotype / anatomy | Core neonatal/physical findings | Short trunk, prominent/distended abdomen, relatively large head/prominent forehead, small chin/midface hypoplasia, severe respiratory distress due to pulmonary hypoplasia | HPO: Short trunk, Abnormal abdomen morphology, Frontal bossing, Micrognathia, Midface retrusion, Respiratory distress, Pulmonary hypoplasia; UBERON: abdomen, lung, skull | (pqac-00000001, pqac-00000002, pqac-00000010) |
| Phenotype / anatomy | Hallmark radiographic findings | Very short long bones with widened/flared metaphyses; non-ossification or markedly reduced ossification of vertebral bodies (including cervical/sacral), lack of pelvic ossification, short unfractured ribs, narrow bell-shaped thorax, cupped ribs, iliac “paraglider” appearance; skull ossification usually relatively preserved compared with type I achondrogenesis | HPO: Platyspondyly/abnormal vertebral ossification, Short rib, Bell-shaped thorax, Short long bone, Flared metaphysis, Abnormal iliac bone morphology; UBERON: vertebral body, rib, ilium, pelvis | (pqac-00000001, pqac-00000002, pqac-00000008, pqac-00000010) |
| Phenotype / anatomy | Tissue/cell focus | Primary pathology localizes to cartilage/growth plate; histology shows hypercellular, hypervascular cartilage with enlarged chondrocytes and disorganized growth plate maturation | CL: chondrocyte; UBERON: cartilage tissue, growth plate; GO: endochondral ossification | (pqac-00000005, pqac-00000006) |
| Diagnostics | Prenatal imaging | Detailed obstetric ultrasound is first-line; fetal CT and sometimes MRI may assist characterization of skeletal dysplasia and thoracic/rib/ossification abnormalities | MAXO: prenatal imaging evaluation; fetal ultrasonography; computed tomography | (pqac-00000000, pqac-00000004, pqac-00000009) |
| Diagnostics | Postnatal / postmortem confirmation | Skeletal survey/radiography confirms classic ossification and limb/rib/pelvic abnormalities; pathology/histology may support classification | MAXO: radiographic skeletal survey; pathologic examination | (pqac-00000001, pqac-00000005, pqac-00000008) |
| Diagnostics | Molecular testing strategy | Molecular confirmation by NGS-based testing (single-gene COL2A1, targeted skeletal dysplasia panels, clinical exome/WES); variants commonly confirmed by Sanger sequencing; exome sequencing increases diagnostic yield in fetuses with short long bones after negative karyotype/CMA | MAXO: sequence analysis of COL2A1; exome sequencing; confirmatory Sanger sequencing | (pqac-00000000, pqac-00000002, pqac-00000009) |
| Diagnostics | Differential diagnosis clues | Distinguish from achondrogenesis type I, thanatophoric dysplasia, osteogenesis imperfecta type II, and hypophosphatasia congenita; preserved skull ossification with poor vertebral/pelvic ossification favors ACG2 over some type I forms | MAXO: differential diagnostic assessment | (pqac-00000001, pqac-00000007, pqac-00000010) |
| Management / prognosis / prevention | Prognosis | Usually lethal: many affected fetuses are stillborn or die in utero, immediately after birth, or in the early neonatal period; death is driven largely by pulmonary hypoplasia/respiratory failure | HPO: Perinatal lethality; Pulmonary hypoplasia | (pqac-00000001, pqac-00000002, pqac-00000006, pqac-00000009) |
| Management / prognosis / prevention | Supportive care | No disease-modifying therapy identified in retrieved evidence; neonatal management is supportive/palliative, including respiratory support when liveborn, but survival is generally poor | MAXO: respiratory support; palliative care; neonatal intensive care | (pqac-00000002, pqac-00000009) |
| Management / prognosis / prevention | Prevention / reproductive options | Genetic counseling is recommended; prenatal diagnosis in future pregnancies via targeted molecular testing and fetal imaging; recurrence counseling should include possibility of germline mosaicism; pregnancy termination may be considered where legally/ethically appropriate after definitive diagnosis | MAXO: genetic counseling; prenatal molecular diagnosis; prenatal ultrasound monitoring; reproductive counseling | (pqac-00000001, pqac-00000005, pqac-00000006) |
| Research / real-world implementation | Current implementations / studies | A natural history study in children with type II collagen disorders and short stature is recruiting (NCT05408715), but retrieved evidence does not indicate an interventional trial specific to lethal ACG2 | MAXO: natural history study enrollment | (pqac-00000004) |


*Table: This table condenses the retrieved evidence on Achondrogenesis type II into knowledge-base-ready fields covering identifiers, genetics, phenotype, diagnostics, and management. It is useful as a structured source map with ontology suggestions and per-row citation IDs.*