Skip to content

Hypochondroplasia phenotype curation notes

Date: 2026-04-19 Target file: kb/disorders/Hypochondroplasia.yaml Issue: #1450

Scope

Focused phenotype-only curation pass for hypochondroplasia. The goal was to make the phenotype section more complete while tightening every retained statement to exact PMID-backed evidence.

Core sources used

  • PMID:20301650. GeneReviews summary with the broadest clinically relevant phenotype overview and radiographic pattern.
  • PMID:41762373. 2026 diagnostic pathway review with age-specific phenotype recognition clues.
  • PMID:36442838. Korean FGFR3 N540K cohort with directly quotable frequencies for genu varum, macrocephaly, and developmental delay.
  • PMID:23165795. Finnish FGFR3 N540K cohort defining seizure burden and MRI abnormalities.
  • PMID:41040055. 2026 cohort analysis quantifying head-height disproportion.
  • PMID:26867606. Neonatal radiology study supporting specific skeletal findings.
  • PMID:14755409. Prenatal/neonatal case confirming early rhizomelic limb shortening.
  • PMID:11475794. Radiology-focused review confirming classic vertebral and metaphyseal findings.

Added or strengthened

  • Short stature
  • Rhizomelic limb shortening
  • Relative macrocephaly
  • Mild joint laxity
  • Neurodevelopmental delay
  • Hydrocephalus
  • Spinal canal stenosis
  • Narrow vertebral interpedicular distance
  • Posterior scalloping of vertebral bodies
  • Metaphyseal widening
  • Short iliac bones
  • Short femur

Kept but softened

  • Seizure: kept as an association, but frequency removed because the strongest quantitative evidence comes from a neurologically selected cohort.
  • Temporal lobe dysplasia: retained with ascertainment caveat and without a whole-disease frequency claim.
  • Ventriculomegaly: retained without frequency because available counts come from MRI-selected patients.

Removed as unsupported or overclaimed

  • Lumbar hyperlordosis
  • Brachydactyly
  • Frontal bossing
  • The old combined entry Spinal stenosis with reduced interpedicular distance was replaced by separate clinical and radiographic findings.

Frequency decisions

  • Kept HP_0040282 for relative macrocephaly based on 9/20 (45%) in PMID:36442838.
  • Kept HP_0040282 for genu varum based on 11/20 (55%) in PMID:36442838.
  • Kept HP_0040283 for neurodevelopmental delay based on 5/20 (25%) in PMID:36442838.
  • Removed unsupported frequencies from short stature, seizures, temporal lobe dysplasia, ventriculomegaly, and radiographic findings.