Achondroplasia Natural History Study (CLARITY): a multicenter retrospective cohort study of achondroplasia in the United States

Genet Med. 2021 Aug;23(8):1498-1505. doi: 10.1038/s41436-021-01165-2. Epub 2021 May 18.

Abstract

Purpose: Achondroplasia is the most common short stature skeletal dysplasia (1:20,000-30,000), but the risk of adverse health outcomes from cardiovascular diseases, pain, poor function, excess weight, and sleep apnea is unclear. A multicenter retrospective natural history study was conducted to understand medical and surgical practices in achondroplasia.

Methods: Data from patients with achondroplasia evaluated by clinical geneticists at Johns Hopkins University, A.I. duPont Hospital for Children, McGovern Medical School UTHealth, and University of Wisconsin were populated into a REDCap database. All available retrospective medical records of anthropometry (length/height, weight, occipitofrontal circumference), surgery, polysomnography (PSG), and imaging (e.g., X-ray, magnetic resonance imaging) were included.

Results: Data from 1,374 patients (48.8% female; mean age 15.4 ± 13.9 years) constitute the primary achondroplasia cohort (PAC) with 496 subjects remaining clinically active and eligible for prospective studies. Within the PAC, 76.0% had a de novo FGFR3 pathologic variant and 1,094 (79.6%) had one or more achondroplasia-related surgeries. There are ≥37,000 anthropometry values, 1,631 PSGs and 10,727 imaging studies.

Conclusion: This is the largest multicenter achondroplasia natural history study, providing a vast array of medical information for use in caring for these patients. This well-phenotyped cohort is a reference population against which future medical and surgical interventions can be compared.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achondroplasia* / diagnostic imaging
  • Achondroplasia* / epidemiology
  • Achondroplasia* / genetics
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Male
  • Osteochondrodysplasias*
  • Polysomnography
  • Prospective Studies
  • Retrospective Studies
  • United States / epidemiology
  • Young Adult