Growth parameters in children with achondroplasia: A 7-year, prospective, multinational, observational study

Ravi Savarirayan¹, Melita Irving², Paul Harmatz³, Borja Delgado⁴, William R Wilcox⁵, John Philips⁶, Natalie Owen⁶, Carlos A Bacino⁷, Louise Tofts⁸, Joel Charrow⁹, Lynda E Polgreen¹⁰, Julie Hoover-Fong¹¹, Paul Arundel¹², Ignacio Ginebreda¹³, Howard M Saal¹⁴, Donald Basel¹⁵, Rosendo Ullot Font¹⁶, Keiichi Ozono¹⁷, Michael B Bober¹⁸, Valerie Cormier-Daire¹⁹, Kim-Hanh Le Quan Sang¹⁹, Genevieve Baujat¹⁹, Yasemin Alanay²⁰, Frank Rutsch²¹, Daniel Hoernschemeyer²², Klaus Mohnike²³, Hiroshi Mochizuki²⁴, Asako Tajima²⁴, Yumiko Kotani²⁵, David D Weaver²⁶, Klane K White²⁷, Clare Army²⁸, Kevin Larrimore²⁸, Keith Gregg²⁸, George Jeha²⁸, Claire Milligan²⁹, Elena Fisheleva²⁹, Alice Huntsman-Labed²⁹, Jonathan Day²⁹

Affiliations

¹ Murdoch Children's Research Institute, Royal Children's Hospital and University of Melbourne, Parkville, Victoria, Australia. Electronic address: ravi.savarirayan@vcgs.org.au.
² Evelina London Children's Hospital, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
³ UCSF Benioff Children's Hospital Oakland, Oakland, CA.
⁴ Hospital Universitario Virgen de la Victoria, Málaga, Spain.
⁵ Department of Human Genetics, Emory University School of Medicine, Emory University, Atlanta, GA.
⁶ Vanderbilt University Medical Center, Nashville, TN.
⁷ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
⁸ Kids Rehab, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
⁹ Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
¹⁰ Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
¹¹ McKusick-Nathans Institute of Genetic Medicine and Department of Genetic Medicine, Johns Hopkins University, Baltimore, MD.
¹² Sheffield Children's NHS Foundation Trust, Sheffield Children's Hospital, Sheffield, United Kingdom.
¹³ Hospiat Universitari Quiron Dexeus, ICATME Foundation, Barcelona, Spain.
¹⁴ Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH.
¹⁵ Medical College of Wisconsin, Milwaukee, WI.
¹⁶ Hospital Sant Joan de Déu, Barcelona, Spain.
¹⁷ Osaka University Hospital, Osaka, Japan.
¹⁸ Nemours Children's Hospital, Delaware, Wilmington, DE.
¹⁹ Clinical Genetics, Université Paris Cité, INSERM UMR 1163, Institut Imagine, Hôpital Necker Enfants Maladies, Paris, France.
²⁰ School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.
²¹ Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.
²² University of Missouri Columbia, Columbia, MO.
²³ Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany.
²⁴ Saitama Children's Medical Center, Saitama, Japan.
²⁵ Tokushima University Hospital, Tokushima, Japan.
²⁶ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University, Indianapolis, IN.
²⁷ Seattle Children's Hospital, Seattle, WA.
²⁸ BioMarin Pharmaceutical Inc, Novato, CA.
²⁹ BioMarin (UK) Limited, London, United Kingdom.

PMID: 36107167
DOI: 10.1016/j.gim.2022.08.015

Free article

Observational Study

Growth parameters in children with achondroplasia: A 7-year, prospective, multinational, observational study

Ravi Savarirayan et al. Genet Med. 2022 Dec.

Free article

. 2022 Dec;24(12):2444-2452.

doi: 10.1016/j.gim.2022.08.015. Epub 2022 Sep 16.

Authors

Affiliations

¹ Murdoch Children's Research Institute, Royal Children's Hospital and University of Melbourne, Parkville, Victoria, Australia. Electronic address: ravi.savarirayan@vcgs.org.au.
² Evelina London Children's Hospital, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
³ UCSF Benioff Children's Hospital Oakland, Oakland, CA.
⁴ Hospital Universitario Virgen de la Victoria, Málaga, Spain.
⁵ Department of Human Genetics, Emory University School of Medicine, Emory University, Atlanta, GA.
⁶ Vanderbilt University Medical Center, Nashville, TN.
⁷ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
⁸ Kids Rehab, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
⁹ Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
¹⁰ Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
¹¹ McKusick-Nathans Institute of Genetic Medicine and Department of Genetic Medicine, Johns Hopkins University, Baltimore, MD.
¹² Sheffield Children's NHS Foundation Trust, Sheffield Children's Hospital, Sheffield, United Kingdom.
¹³ Hospiat Universitari Quiron Dexeus, ICATME Foundation, Barcelona, Spain.
¹⁴ Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH.
¹⁵ Medical College of Wisconsin, Milwaukee, WI.
¹⁶ Hospital Sant Joan de Déu, Barcelona, Spain.
¹⁷ Osaka University Hospital, Osaka, Japan.
¹⁸ Nemours Children's Hospital, Delaware, Wilmington, DE.
¹⁹ Clinical Genetics, Université Paris Cité, INSERM UMR 1163, Institut Imagine, Hôpital Necker Enfants Maladies, Paris, France.
²⁰ School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.
²¹ Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.
²² University of Missouri Columbia, Columbia, MO.
²³ Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany.
²⁴ Saitama Children's Medical Center, Saitama, Japan.
²⁵ Tokushima University Hospital, Tokushima, Japan.
²⁶ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University, Indianapolis, IN.
²⁷ Seattle Children's Hospital, Seattle, WA.
²⁸ BioMarin Pharmaceutical Inc, Novato, CA.
²⁹ BioMarin (UK) Limited, London, United Kingdom.

PMID: 36107167
DOI: 10.1016/j.gim.2022.08.015

Abstract

Purpose: This study was undertaken to collect baseline growth parameters in children with achondroplasia who might enroll in interventional trials of vosoritide, and to establish a historical control.

Methods: In this prospective, observational study, participants (≤17 years) underwent a detailed medical history and physical examination and were followed every 3 months until they finished participating in the study by enrolling in an interventional trial or withdrawing.

Results: A total of 363 children were enrolled (28 centers, 8 countries). Mean (SD) follow up was 20.4 (15.0) months. In participants <1 year, mean annualized growth velocity (AGV) was 11.6 cm/year for girls and 14.6 cm/year for boys. By age 1 year, mean AGV decreased to 7.4 cm/year in girls and 7.1 cm/year in boys. By age 10 years, mean AGV decreased to 3.6 cm/year for both sexes. Mean height z-score in participants <1 year was -2.5 for girls and -3.2 for boys and decreased up to the age 5 years (-5.3 for girls; -4.6 for boys). Girls and boys had a disproportionate upper-to-lower body segment ratio. Mean ratio was highest in participants aged <1 year (2.9 for girls; 2.8 for boys) and decreased gradually to approximately 2 in both sexes from 4 years of age onward.

Conclusion: This study represents one of the largest datasets of prospectively collected medical and longitudinal growth data in children with achondroplasia. It serves as a robust historical control to measure therapeutic interventions against and to further delineate the natural history of this condition.

Trial registration: ClinicalTrials.gov NCT01603095.

Keywords: Achondroplasia; Annualized growth velocity; Anthropometrics; Observational; Pediatrics.

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Conflict of interest statement

Conflict of Interest All authors were investigators in this clinical trial except for C.A., K.L., K.G., G.J., C.M., E.F., A.H.-L., and J.D., who are employees of the funder (BioMarin). R.S. L.T., F.R., K.M., have received consulting fees and grants from BioMarin. M.I. and W.R.W. have received consulting fees from BioMarin. D.B. has received grants from BioMarin. J.C. has received honoraria from Genzyme, Applied Therapeutics, and CHIESI Farmaceutici S.p.A. P.A. has received honoraria from BioMarin. P.H. and C.B. have received consulting fees, honoraria and grants from BioMarin. J.H.F. has received consulting fees from BioMarin,Therachon AG and Ascendis, and grants from BioMarin. M.B. has received consulting fees and grants from BioMarin, Ascendis, Therachon, QED, Tyra Biosciences, and Alexion Pharmaceuticals, Inc, and grants from BioMarin, Ascendis, Therachon, QED, Medlife, SOBI, and Shire. K.K.W. has received consulting fees from BioMarin, grants from BioMarin, Ultragenyx, Pfizer, and Theracon, and royalties from UptoDate.com. L.P. has received consulting fees from BioMarin, Sanofi/Genzyme, and Therachon, and grants from Sanofi/Genzyme, Takeda/Shire, Pfizer, and SOBI. The other authors declare no conflict of interests.

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Growth parameters in children with achondroplasia: A 7-year, prospective, multinational, observational study

Affiliations

Growth parameters in children with achondroplasia: A 7-year, prospective, multinational, observational study

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Associated data

LinkOut - more resources

Full Text Sources

Medical