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

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

Julie E Hoover-Fong  1 , Adekemi Y Alade  2   3 , S Shahrukh Hashmi  4 , Jacqueline T Hecht  4   5 , Janet M Legare  6 , Mary Ellen Little  7 , Chengxin Liu  2 , John McGready  2   8 , Peggy Modaff  6 , Richard M Pauli  6 , David F Rodriguez-Buritica  4 , Kerry J Schulze  2   8 , Maria Elena Serna  4 , Cory J Smid  6   9 , Michael B Bober  7
Affiliations
Multicenter Study

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

Julie E Hoover-Fong et al. Genet Med. 2021 Aug.

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.

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Conflict of interest statement

This is an investigator-initiated independent research study supported, in part, by BioMarin, Inc. The data presented in this paper do not pertain to the investigational pharmaceuticals under development by BioMarin, Ascendis, Therachon, or QED. Data from this natural history of patients with achondroplasia have not been published previously. These activities were reviewed and approved by our respective institutions. J.E.H.-F. has participated in Advisory Boards sponsored by BioMarin pertaining to achondroplasia. J.E.H.-F. has been consulted by BioMarin, Alexion, and Therachon for clinical issues related to achondroplasia and other genetic skeletal conditions as well as acting as a site principal investigator (PI) for clinical trials for BioMarin and Therachon. M.B.B. has participated in Advisory Boards sponsored by BioMarin, consulted with BioMarin, Ascendis, Therachon and QED for clinical issues related achondroplasia as well as acting as a site PI in their clinical trials in achondroplasia. He is a member of Alexion’s Speaker’s Bureau (HPP). M.B.B. is a site PI and consultant for MedLife Discoveries (RCDP), and a site PI for Shire (Hunter) and SOBI (Sanfilliopo). J.T.H. has participated in Advisory Boards pertaining to achondroplasia sponsored by BioMarin. D.R.-B. has participated in Advisory Boards pertaining to achondroplasia sponsored by BioMarin. J.L. is acting as a site PI for Ascendis and has lectured for BioMarin. The other authors declare no competing interests.

Comment in

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