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Brachyolmia phenotype curation notes

Date: 2026-04-18 Target file: kb/disorders/Brachyolmia.yaml Scope: phenotype section only

Primary phenotype papers used

  • PMID:22791835 "PAPSS2 mutations cause autosomal recessive brachyolmia." Key phenotype statements used: short-trunk short stature becoming conspicuous during childhood; irregular endplates and narrow intervertebral discs; precocious rib cartilage calcification; short femoral neck; mildly shortened metacarpals.

  • PMID:23824674 "Clinical and radiographic features of the autosomal recessive form of brachyolmia caused by PAPSS2 mutations." Key phenotype statements used: spinal deformity; platyspondyly with rectangular vertebral bodies and irregular end plates; proximal femoral metaphyseal change with short femoral neck and striation.

  • PMID:31313512 "PAPSS2-related brachyolmia: Clinical and radiological phenotype in 18 new cases." Key phenotype statements used: prenatal short femora in 8 patients; platyspondyly with elongated vertebral bodies, irregular end plates, narrow disc spaces and short over-faced pedicles; pain, stiffness and spinal deformity; low DHEAS.

  • PMID:18587396 "Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia." Key phenotype statements used: short trunk, scoliosis and mild short stature.

  • PMID:24677493 "Autosomal dominant brachyolmia in a large Swedish family: phenotypic spectrum and natural course." Key phenotype statements used: scoliosis and platyspondyly in TRPV4-related disease; pain by school age; paresthesias; progressive growth deterioration with spinal involvement.

  • PMID:25669657 "Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta." Key phenotype statements used: significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta with almost absent enamel.

  • PMID:35352826 "Expanding genotypic and phenotypic spectrums of LTBP3 variants in dental anomalies and short stature syndrome." Key phenotype statements used: hypodontia; underdeveloped maxilla; thoracic aortic aneurysm and dissection as part of LTBP3-related DASS.

  • PMID:38192829 "Brachyolmia, dental anomalies and short stature (DASS): Phenotype and genotype analyses of Egyptian and Pakistani patients." Key phenotype statements used: short trunk, short stature, scoliosis and generalized platyspondyly as defining brachyolmia features; osteopenic bone texture and pes planus as additional LTBP3-associated findings.

Curation decisions

  • Added high-confidence PAPSS2 skeletal phenotypes: prenatal short femora and short metacarpals.
  • Added high-confidence LTBP3 phenotypes not previously represented: hypodontia, maxillary hypoplasia, thoracic aortic aneurysm, aortic dissection, osteopenia and pes planus.
  • Softened wording that implied unsupported frequency, especially around scoliosis and generalized "all subtype" claims.
  • Simplified the amelogenesis imperfecta description to stay within exact published support.

Considered but not added

  • CABP2-related hearing impairment from PMID:38192829 was excluded because the paper states it had a separate transmission mechanism independent of LTBP3.
  • One-family LTBP3 findings such as interatrial septal aneurysm, secundum atrial septal defect, tricuspid valve prolapse and recurrent glenohumeral dislocation were noted but not added in this pass because the evidence in the abstract presents them as newly observed family-level findings rather than established core brachyolmia manifestations.
  • Broad proximal interphalangeal joints, broad ilia and short distal phalanges were not added because the exact HPO term mapping needed more time than was justified for this phenotype-only issue.