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Thanatophoric Dysplasia Type 1 phenotype curation 2026 04 18

Scope

Focused phenotype curation for kb/disorders/Thanatophoric_Dysplasia_Type_1.yaml for issue #1457.

Goals: - strengthen phenotype assertions with exact PMID-backed abstract evidence - add clinically important TD1 phenotypes missing from the phenotype block - remove unsupported frequency claims - remove or soften phenotype claims that were not directly supportable from abstracts

PMIDs Used

  • PMID:11241532 TD1 prenatal cases with polyhydramnios, macrocephaly, narrow thoracic cage, and curved short femora; also supports redundant skin folds on 3D ultrasound.
  • PMID:11270184 TD1 summary stating respiratory failure is due to narrow thorax with pulmonary hypoplasia.
  • PMID:17048442 Molecularly confirmed TD1 case with severe limb shortening, redundant skin folds, frontal bossing, depressed nasal bridge, narrow thoracic cage, respiratory insufficiency, short ribs, platyspondyly, and bowed femora.
  • PMID:18504386 Prenatal ultrasound case showing short limbs at 12 weeks and short bowed long bones by 16 weeks.
  • PMID:23408600 Larger prenatal TD cohort supporting short fingers as a recurring sonographic feature.
  • PMID:23551494 Molecularly confirmed TD1 neuropathology with enlarged hyperconvoluted temporal lobe and cortical disorganization.
  • PMID:25328339 TD1 fetal autopsy report listing short neck and protuberant abdomen.
  • PMID:26043509 TD1-specific case report supporting cloverleaf skull as a rare variant rather than a typical TD1 finding.
  • PMID:9481650 TD1 postmortem series describing H-, U-, and reversed U-shaped vertebrae.

Phenotype Decisions

Added or materially strengthened: - Micromelia - Curved femurs - Short ribs - Narrow thorax - Platyspondyly - Macrocephaly - Frontal bossing - Depressed nasal bridge - Short neck - Protuberant abdomen - Pulmonary hypoplasia - Respiratory insufficiency - Redundant skin folds - Polyhydramnios - Cloverleaf skull retained only as a rare TD1 variant - Abnormal temporal lobe morphology

Kept but sourced cautiously: - Brachydactyly Supported by short fingers language from a larger prenatal thanatophoric dysplasia cohort, but the abstract does not break down frequency by subtype.

Removed or softened: - all phenotype frequency: assignments The available abstracts support association but generally do not justify a TD1 subtype-specific frequency band. - Midface retrusion Removed because I did not find a clean abstract-backed TD1-specific statement supporting this exact phenotype. - Hypotonia Removed because the available abstract support was tertiary/general TD wording rather than direct TD1 abstract evidence.

Curation Notes

  • I favored TD1-specific case reports and prenatal series over generalized review language whenever possible.
  • When only mixed TD evidence was available, I kept the phenotype only if the abstract statement was still clinically useful and I made the limitation explicit in the explanation.