Genetics

Achondroplasia: new consensus statement on management

ACHONDROPLASIA, caused by a mutation in a gene critical for normal skeleton growth, is the most common form of human restricted growth and 360,000 people worldwide are estimated to have the condition. In four out of five cases when a child is born with achondroplasia, there is no family history of the condition, as the genetic variant has arisen from germline changes involved in the formation of parental sperm or egg cells. In the other cases, it is inherited from an affected parent as a dominant trait.

Achondroplasia can be diagnosed readily at birth with short-limbed short stature, characteristic radiographic appearance of the pelvis and spine, and confirmed by genetic testing of the fibroblast growth factor receptor 3 (FGFR3) gene.

People with achondroplasia can experience a variety of medical complications, psychosocial challenges, and functional limitations consequent to an environment not geared towards recognizing or supporting their needs throughout their lifespan. These include cranio-cervical junction compression, obstructive sleep apnea, challenges with access to their environment due to disproportionate short stature, and issues with discrimination and pain.

To date, there has been no consensus regarding the optimal management of individuals with achondroplasia worldwide. This has led to several diagnostic, surveillance, and management practices being used in different regions with varied outcomes. No evidence-based “standards of care” have been established to optimize outcomes and provide a baseline against which new treatments can be judged.

This unmet need provided the impetus for the formation of the International Achondroplasia Consensus Group, tasked with developing consensus guidelines for the diagnosis and management of people with achondroplasia over their lifespan and across 15 medical specialties. This group of 55 participants included health care professionals and patient advocates from 16 countries and five continents, who came together in Oslo in late 2019 to develop this consensus statement. They used a modified Delphi process to develop these statements, based on evidence where available and combined experience of managing this condition where not. This was followed by two rounds of voting, with the final 136 consensus statements being those that received 80% or more agreement.

These statements include management guidelines of achondroplasia in pregnancy, infancy, childhood, adolescence and adulthood and subspecialty management, allied health management and family-centered support and care.

The consensus statement was published recently in the journal Nature Reviews Endocrinology and has been translated into 14 languages ​​to facilitate dissemination to the widest possible audience. It is hoped that it will provide a valuable resource for clinicians, patients and families, as well as providing a platform for further research.

Recently, several new drug therapies for the treatment of children with achondroplasia have emerged, and it will be important to see how the natural history and management of people with achondroplasia will evolve and change as these treatments become established in clinical care.

For GPs who might see people who have achondroplasia, it is important that they are able to recognize the medical and other needs of these patients, be able to engage in preliminary genetic counseling regarding the risks of the condition being passed to children, and refer to specialist skeletal centers for ongoing multidisciplinary management.

It is hoped that this new consensus statement will facilitate these goals.

Professor Ravi Savarirayan is a clinical geneticist at Victorian Clinical Genetics Services and Group Leader of Skeletal Therapies at Murdoch Children’s Research Institute.

The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight + unless so stated.

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