Skip to content

Thanatophoric Dysplasia Type 2 phenotype curation notes for issue #1458

Date: 2026-04-19 Curator: Codex Scope: Phenotype section only for kb/disorders/Thanatophoric_Dysplasia_Type_2.yaml

Curation approach

  • Prefer primary human clinical sources with subtype-specific TD2 wording when available.
  • Keep frequency only when the cited abstract directly supports it.
  • Remove mechanistic or prevalence claims from phenotype descriptions when the phenotype evidence was only associative.
  • Avoid adding isolated anomalies from single case reports unless they are clinically important or already central to TD2 recognition.

Phenotype evidence added or strengthened

  • PMID:3130852
  • Supports Cloverleaf skull as very frequent in TD2: "Almost all type 2 cases have severe CS."
  • PMID:11241532
  • Supports TD2 prenatal findings: narrow thoracic cage, hydrocephalus, cloverleaf skull, straight short femora, and polyhydramnios.
  • Supports Redundant skin folds from 3D ultrasound wording in the same TD series.
  • PMID:23323754
  • Supports Pulmonary hypoplasia as a constant morphologic finding in thanatophoric dysplasia.
  • Supports Temporal lobe dysplasia as a recurring neuropathologic finding in a 25-case autopsy series.
  • PMID:24075385
  • Supports subtype-specific TD2 facial and limb findings: macrocephaly, frontal bossing/prominent forehead, brachydactyly, narrow chest, straight femora, cloverleaf skull.
  • PMID:11965423
  • Confirms that the CNS malformation pattern also occurs in TD2, including temporal lobe polymicrogyria and hippocampal abnormalities.
  • PMID:33520059
  • Supports Respiratory insufficiency and its relationship to reduced thoracic capacity and hypoplastic lungs.
  • PMID:23573386
  • Used cautiously for Short ribs because the abstract explicitly lists short ribs among core TD features while also distinguishing TD2 by straight femurs and severe cloverleaf deformity.

Unsupported or softened points

  • Removed unsupported frequency qualifiers from most phenotypes; retained a frequency only for Cloverleaf skull.
  • Softened Hydrocephalus from a generalized/common claim to a documented prenatal finding in some TD2 fetuses.
  • Softened Small foramen magnum to avoid overstating TD2-specific evidence from broader FGFR3 chondrodysplasia literature.
  • Simplified survivor phenotypes (Global developmental delay, Short stature, Acanthosis nigricans) to stay close to the cohort data without extra mechanistic inference.
  • Left out one-off anomalies such as pseudoencephalocele, encephalocele, cleft palate, holoprosencephaly, and vascular anomalies because they appear too case-specific for the core phenotype section.