Lifetime impact of achondroplasia: Current evidence and perspectives on the natural history

Julie Hoover-Fong; Moira S Cheung; Virginia Fano; Lars Hagenas; Jacqueline T Hecht; Penny Ireland; Melita Irving; Klaus Mohnike; Amaka C Offiah; Ericka Okenfuss; Keiichi Ozono; Cathleen Raggio; Louise Tofts; Dominique Kelly; Renée Shediac; Wayne Pan; Ravi Savarirayan

doi:10.1016/j.bone.2021.115872

Lifetime impact of achondroplasia: Current evidence and perspectives on the natural history

Bone. 2021 May:146:115872. doi: 10.1016/j.bone.2021.115872. Epub 2021 Feb 3.

Authors

Julie Hoover-Fong¹, Moira S Cheung², Virginia Fano³, Lars Hagenas⁴, Jacqueline T Hecht⁵, Penny Ireland⁶, Melita Irving², Klaus Mohnike⁷, Amaka C Offiah⁸, Ericka Okenfuss⁹, Keiichi Ozono¹⁰, Cathleen Raggio¹¹, Louise Tofts¹², Dominique Kelly¹³, Renée Shediac¹³, Wayne Pan¹³, Ravi Savarirayan¹⁴

Affiliations

¹ McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: jhoover2@jhmi.edu.
² Guy's and St. Thomas' NHS Foundation Trust, Evelina Children's Hospital, London, UK.
³ Department of Growth and Development, Hospital Garrahan, Buenos Aires, Argentina.
⁴ Karolinska Institute, Division of Pediatric Endocrinology, Department of Women's and Children's Health, Stockholm, Sweden.
⁵ University of Texas, Houston, McGovern Medical School, Department of Pediatrics, Houston, TX, USA.
⁶ Queensland Paediatric Rehabilitation Service, Queensland Children's Hospital, Brisbane, Queensland, Australia.
⁷ Otto-von-Guericke-University Magdeburg, Department of Pediatrics, Magdeburg, Germany.
⁸ Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK.
⁹ Kaiser Permanente - Sacramento Medical Center, Department of Genetics, Sacramento, CA, USA.
¹⁰ Osaka University Graduate School of Medicine, Department of Pediatrics, Osaka, Japan.
¹¹ Hospital for Special Surgery, Pediatric Orthopedic Surgery Service, New York, NY, USA.
¹² Kids Rehab, The Children's Hospital at Westmead, Westmead, NSW, Australia.
¹³ BioMarin Pharmaceutical Inc., Global Medical Affairs, Novato, CA, USA.
¹⁴ Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Parkville, Victoria, Australia.

PMID: 33545406
DOI: 10.1016/j.bone.2021.115872

Abstract

Achondroplasia, the most common form of disproportionate short stature, is caused by a variant in the fibroblast growth factor receptor 3 (FGFR3) gene. Advances in drug treatment for achondroplasia have underscored the need to better understand the natural history of this condition. This article provides a critical review and discussion of the natural history of achondroplasia based on current literature evidence and the perspectives of clinicians with extensive knowledge and practical experience in managing individuals with this diagnosis. This review draws evidence from recent and ongoing longitudinal natural history studies, supplemented with relevant cross-sectional studies where longitudinal research is lacking, to summarize the current knowledge on the nature, incidence, chronology, and interrelationships of achondroplasia-related comorbidities across the lifespan. When possible, data related to adults are presented separately from data specific to children and adolescents. Gaps in knowledge regarding clinical care are identified and areas for future research are recommended and discussed.

Keywords: Achondroplasia; Cervicomedullary decompression; Fibroblast growth factor receptor 3 (FGFR3); Foramen magnum stenosis; Genu varum; Natural history; Skeletal dysplasia.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Achondroplasia* / genetics
Adolescent
Adult
Child
Cross-Sectional Studies
Foramen Magnum*
Humans
Longitudinal Studies