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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2019

Open Access 01-12-2019 | Obesity | Review

Obesity in achondroplasia patients: from evidence to medical monitoring

Authors: Celine Saint-Laurent, Laura Garde-Etayo, Elvire Gouze

Published in: Orphanet Journal of Rare Diseases | Issue 1/2019

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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.
Literature
1.
2.
Rousseau F, Bonaventure J, Legeai-Mallet L, Pelet A, Rozet JM, Maroteaux P, et al. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature. 1994;371(6494):252–4.PubMedCrossRef
3.
Wilkin DJ, Szabo JK, Cameron R, Henderson S, Bellus GA, Mack ML, et al. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. Am J Hum Genet. 1998;63(3):711–6.PubMedPubMedCentralCrossRef
4.
Bellus GA, Hefferon TW, Ortiz de Luna RI, Hecht JT, Horton WA, Machado M, et al. Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am J Hum Genet. 1995;56(2):368–73.PubMedPubMedCentral
5.
Xue Y, Sun A, Mekikian PB, Martin J, Rimoin DL, Lachman RS, et al. FGFR3 mutation frequency in 324 cases from the international skeletal dysplasia registry. Mol Genet Genomic Med. 2014;2(6):497–503.PubMedPubMedCentralCrossRef
6.
L’Hote CG, Knowles MA. Cell responses to FGFR3 signalling: growth, differentiation and apoptosis. Exp Cell Res. 2005;304(2):417–31.PubMedCrossRef
7.
Webster MK, Donoghue DJ. Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia. EMBO J. 1996;15(3):520–7.PubMedPubMedCentralCrossRef
8.
9.
Richette P, Bardin T, Stheneur C. Achondroplasia: from genotype to phenotype. Joint Bone Spine. 2008;75(2):125–30.PubMedCrossRef
10.
Hecht JT, Hood OJ, Schwartz RJ, Hennessey JC, Bernhardt BA, Horton WA. Obesity in achondroplasia. Am J Med Genet. 1988;31(3):597–602.PubMedCrossRef
11.
Saint-Laurent C, Garcia S, Sarrazy V, Dumas K, Authier F, Sore S, et al. Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia. PLoS One. 2018;13(4):e0195876.PubMedPubMedCentralCrossRef
12.
13.
Owen OE, Smalley KJ, D'Alessio DA, Mozzoli MA, Knerr AN, Kendrick ZV, et al. Resting metabolic rate and body composition of achondroplastic dwarfs. Medicine (Baltimore). 1990;69(1):56–67.CrossRef
14.
Alatzoglou KS, Hindmarsh PC, Brain C, Torpiano J, Dattani MT. Acanthosis nigricans and insulin sensitivity in patients with achondroplasia and hypochodroplasia due to FGFR3 mutations. J Clin Endocrinol Metab. 2009;94(10):3959–63.PubMedCrossRef
15.
Hoover-Fong J, McGready J, Schulze K, Alade AY, Scott CI. A height-for-age growth reference for children with achondroplasia: expanded applications and comparison with original reference data. Am J Med Genet A. 2017;173(5):1226–30.PubMedCrossRef
16.
Del Pino M, Ramos Mejia R, Fano V. Leg length, sitting height, and body proportions references for achondroplasia: new tools for monitoring growth. Am J Med Genet A. 2018;176(4):896–906.PubMedCrossRef
17.
Merker A, Neumeyer L, Hertel NT, Grigelioniene G, Makitie O, Mohnike K, et al. Growth in achondroplasia: development of height, weight, head circumference, and body mass index in a European cohort. Am J Med Genet A. 2018;176(8):1723–34.PubMedCrossRef
18.
19.
Shepard TH, Bass GL. Organ-culture studies of achondroplastic rabbit cartilage: evidence for a metabolic defect in glucose utilization. J Embryol Exp Morpholog. 1971;25(3):347–63.
20.
Collipp PJ, Sharma RK, Thomas J, Maddaiah VT, Chen SY. Abnormal glucose tolerance in children with achondroplasia. Am J Dis Child. 1972;124(5):682–5.PubMed
21.
Vukovic R, Milenkovic T, Mitrovic K, Todorovic S, Plavsic L, Vukovic A, et al. Preserved insulin sensitivity predicts metabolically healthy obese phenotype in children and adolescents. Eur J Pediatr. 2015;174(12):1649–55.PubMedCrossRef
22.
Nuttall ME, Gimble JM. Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications. Curr Opin Pharmacol. 2004;4(3):290–4.PubMedCrossRef
23.
24.
Mackler B, Grace R, Davis KA, Shepard TH, Hall JG. Studies of human achondroplasia: oxidative metabolism in tissue culture cells. Teratology. 1986;33(1):9–13.PubMedCrossRef
25.
Mackler B, Davis KA, Grace R. Cytochrome a3 deficiency in human achondroplasia. Biochim Biophys Acta. 1987;891(2):145–9.PubMedCrossRef
26.
Sims DT, Onambele-Pearson GL, Burden A, Payton C, Morse CI. The oxygen consumption and metabolic cost of walking and running in adults with Achondroplasia. Front Physiol. 2018;9:410.PubMedPubMedCentralCrossRef
27.
Takken T, van Bergen MW, Sakkers RJ, Helders PJ, Engelbert RH. Cardiopulmonary exercise capacity, muscle strength, and physical activity in children and adolescents with achondroplasia. J Pediatr. 2007;150(1):26–30.PubMedCrossRef
28.
Madsen A, Fredwall SO, Maanum G, Henriksen C, Slettahjell HB. Anthropometrics, diet, and resting energy expenditure in Norwegian adults with achondroplasia. Am J Med Genet A. 2019;179(9):1745–55.PubMedCrossRef
29.
Park JR, Lee H, Kim CH, Hong SH, Ha KS, Yang SR. Functional characteristics of mesenchymal stem cells derived from the adipose tissue of a patient with achondroplasia. In Vitro Cell Dev Biol Anim. 2016;52(5):545–54.PubMedCrossRef
30.
Elabd C, Basillais A, Beaupied H, Breuil V, Wagner N, Scheideler M, et al. Oxytocin controls differentiation of human mesenchymal stem cells and reverses osteoporosis. Stem Cells. 2008;26(9):2399–407.PubMedCrossRef
31.
Ahdjoudj S, Fromigue O, Marie PJ. Plasticity and regulation of human bone marrow stromal osteoprogenitor cells: potential implication in the treatment of age-related bone loss. Histol Histopathol. 2004;19(1):151–7.PubMed
32.
Wu CL, Diekman BO, Jain D, Guilak F. Diet-induced obesity alters the differentiation potential of stem cells isolated from bone marrow, adipose tissue and infrapatellar fat pad: the effects of free fatty acids. Int J Obes. 2013;37(8):1079–87.CrossRef
33.
Murakami S, Balmes G, McKinney S, Zhang Z, Givol D, de Crombrugghe B. Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype. Genes Dev. 2004;18(3):290–305.PubMedPubMedCentralCrossRef
34.
Mustafa M, Moghrabi N, Boin-Abbas B. Hypochondroplasia, Acanthosis Nigricans, and insulin resistance in a child with FGFR3 mutation: is it just an association? Case Rep Endocrinol. 2014;2014:840492.PubMedPubMedCentral
35.
Pauli RM, Scott CI, Wassman ER Jr, Gilbert EF, Leavitt LA, Ver Hoeve J, et al. Apnea and sudden unexpected death in infants with achondroplasia. J Pediatr. 1984;104(3):342–8.PubMedCrossRef
36.
Hoover-Fong JE, McGready J, Schulze KJ, Barnes H, Scott CI. Weight for age charts for children with achondroplasia. Am J Med Genet A. 2007;143A(19):2227–35.PubMedCrossRef
37.
Tenconi R, Khirani S, Amaddeo A, Michot C, Baujat G, Couloigner V, et al. Sleep-disordered breathing and its management in children with achondroplasia. Am J Med Genet A. 2017;173(4):868–78.PubMedCrossRef
38.
Afsharpaiman S, Saburi A, Waters KA. Respiratory difficulties and breathing disorders in achondroplasia. Paediatr Respir Rev. 2013;14(4):250–5.PubMed
39.
Wynn J, King TM, Gambello MJ, Waller DK, Hecht JT. Mortality in achondroplasia study: a 42-year follow-up. Am J Med Genet A. 2007;143A(21):2502–11.PubMedCrossRef
40.
41.
Martinez JA, Parra MD, Santos JL, Moreno-Aliaga MJ, Marti A, Martinez-Gonzalez MA. Genotype-dependent response to energy-restricted diets in obese subjects: towards personalized nutrition. Asia Pac J Clin Nutr. 2008;17(Suppl 1):119–22.PubMed
42.
Koliaki C, Spinos T, Spinou M, Brinia Mu E, Mitsopoulou D, Katsilambros N. Defining the Optimal Dietary Approach for Safe, Effective and Sustainable Weight Loss in Overweight and Obese Adults. Healthcare (Basel). 2018;6(3):73.CrossRef
43.
Hartley L, May MD, Loveman E, Colquitt JL, Rees K. Dietary fibre for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2016;1(1):Cd011472.
44.
Trumbo P, Schlicker S, Yates AA, Poos M. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc. 2002;102(11):1621–30.PubMedCrossRef
45.
WHO Guidelines Approved by the Guidelines Review Committee. Guideline: Sugars Intake for Adults and Children, vol. 2015. Geneva: World Health Organization Copyright (c) World Health Organization; 2015.
46.
Styne DM, Arslanian SA, Connor EL, Farooqi IS, Murad MH, Silverstein JH, et al. Pediatric obesity-assessment, treatment, and prevention: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(3):709–57.PubMedPubMedCentral
47.
Posey KL, Coustry F, Veerisetty AC, Hossain M, Alcorn JL, Hecht JT. Antioxidant and anti-inflammatory agents mitigate pathology in a mouse model of pseudoachondroplasia. Hum Mol Genet. 2015;24(14):3918–28.PubMedPubMedCentralCrossRef
48.
Goni L, Cuervo M, Milagro FI, Martinez JA. Future Perspectives of Personalized Weight Loss Interventions Based on Nutrigenetic, Epigenetic, and Metagenomic Data. J Nutr. 2016;146(4):905S.CrossRef
49.
Jacobs N, Clays E, De Bacquer D, De Backer G, Dendale P, Thijs H, et al. Effect of a tailored behavior change program on a composite lifestyle change score: a randomized controlled trial. Health Educ Res. 2011;26(5):886–95.PubMedCrossRef
50.
Wolever RQ, Webber DM, Meunier JP, Greeson JM, Lausier ER, Gaudet TW. Modifiable disease risk, readiness to change, and psychosocial functioning improve with integrative medicine immersion model. Altern Ther Health Med. 2011;17(4):38–47.PubMedPubMedCentral
51.
Abrao MA, da Silveira VG, de Almeida Barcellos CF, Cosenza RC, Carneiro JR. Anesthesia for bariatric surgery in an achondroplastic dwarf with morbid obesity. Rev Bras Anestesiol. 2009;59(1):79–86.PubMedCrossRef
52.
Carneiro JR, da Silveira VG, Vasconcelos AC, de Souza LL, Xerez D, da Cruz GG, et al. Bariatric surgery in a morbidly obese achondroplasic patient--use of the 6-minute walk test to assess mobility and quality of life. Obes Surg. 2007;17(2):255–7.PubMedCrossRef
53.
Sims D, Onambele-Pearson G, Burden A, Payton C, Morse C. Whole-body and segmental analysis of body composition in adult males with achondroplasia using dual X-ray absorptiometry. PLoS One. 2019;14(3):e0213806.PubMedPubMedCentralCrossRef
54.
del Pino M, Fano V, Lejarraga H. Growth references for height, weight, and head circumference for argentine children with achondroplasia. Eur J Pediatr. 2011;170(4):453–9.PubMedCrossRef
Metadata
Title
Obesity in achondroplasia patients: from evidence to medical monitoring
Authors
Celine Saint-Laurent
Laura Garde-Etayo
Elvire Gouze
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2019
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-019-1247-6

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