Obesity in achondroplasia patients: from evidence to medical monitoring

Abstract

Achondroplasia is a rare genetic disease representing the most common form of short-limb dwarfism. It is characterized by bone growth abnormalities that are well characterized and by a strong predisposition to abdominal obesity for which causes are unknown. Despite having aroused interest at the end of the 20 h century, there are still only very little data available on this aspect of the pathology. Today, interest is rising again, and some studies are now proposing mechanistic hypotheses and guidance for patient management. These data confirm that obesity is a major health problem in achondroplasia necessitating an early yet complex clinical management. Anticipatory care should be directed at identifying children who are at high risk to develop obesity and intervening to prevent the metabolic complications in adults. In this review, we are regrouping available data characterizing obesity in achondroplasia and we are identifying the current tools used to monitor obesity in these patients.

Cardiovascular risk factors and body composition in adults with achondroplasia

“…[1][2][3] Obesity is a concern in achondroplasia, as individuals with this condition commonly have a body mass index (BMI) in the obesity range, with a predisposition to abdominal obesity. [4][5][6][7] Some previous studies have reported an increased cardiovascular mortality in this condition. 8 However, the correlation between BMI, cardiovascular risks, and body composition has not been investigated in detail in adults with achondroplasia.…”

“…5 Center for Medical Image Science and Visualization, University of Linköping, Linköping, Sweden. 6 Oslo University Hospital, Division of Radiology and Nuclear Medicine, Oslo, Norway. 7 Oslo Centre for Biostatistics and Epidemiology, Research Support Service, Oslo University Hospital, Oslo, Norway.…”

“…8 However, the correlation between BMI, cardiovascular risks, and body composition has not been investigated in detail in adults with achondroplasia. 6,7,9 Achondroplasia is the most common cause of disproportionate short stature, and is caused by a gain-of-function pathogenic variant in the fibroblast growth factor receptor 3 (FGFR3) gene. 10 The appendicular skeleton (arms and legs) is short, while the trunk is of almost average size.…”

“…1,2,12 Moreover, assessment of obesity in achondroplasia remains challenging, due to the different body shape, and no established reference standards are available for adults with this condition. 6,7 Magnetic resonance imaging (MRI) is currently regarded as the reference standard for body composition analysis. 12,13,15 Recent developments of standardized acquisition protocols and automated image analysis for anatomical segmentations have enabled direct assessment and quantification of visceral, subcutaneous, and liver fat, fat-free muscle volume, and muscle fat infiltration.…”

New developments in the management of achondroplasia

“…Obesity is certainly an issue in individuals with achondroplasia and tends to emerge early in life. Obesity is predominantly of abdominal origin and its causes are currently not understood [21]. Approximately 50% of children are affected [22].…”