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Growth Topics in FGFR3-Related Skeletal Dysplasias

  • Pediatrics in South America (L Landry and WB de Carvalho, Section Editors)
  • Published:
Current Treatment Options in Pediatrics Aims and scope Submit manuscript

Abstract

Purpose of Review

Describe growth at different periods of life to understand the effects of genetic impairment in FGFR3-related conditions. We hope this data will be used to compare different populations and the effects of future treatments towards growth improvement.

Recent Findings

The FGFR3 plays a critical role in early mammalian skeletal development, especially in postembryonic linear bone growth; however, little is known about its role during all of the growth process stages. In the achondroplasia growth curve, infancy, childhood, and puberty periods can be well recognized, coexisting with fast changes in body proportions.

Summary

FGFR3 gain-of-function mutations are responsible for autosomal dominant chondrodysplasias characterized by a severe disproportionate short stature, as thanatophoric dysplasia, severe achondroplasia with developmental delay and acanthosis nigricans, achondroplasia, and hypochondroplasia. While achondroplasia is homogeneous with low variability, hypochondroplasia findings are less constant due to genotypic heterogeneity. In both conditions, birth size is slightly reduced, followed by a period of fast growth deceleration during infancy and a low magnitude pubertal growth spurt, most evident in sitting height. Some phenomena as shifting centile lines during infancy and parent-child height correlation are well described. A slight variability is shown between achondroplasia and hypochondroplasia populations within different ethnic backgrounds.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Falkner, Tanner. Human growth: a comprehensive treatise. 2nd ed. New York: Plenum Press; 1986.

    Book  Google Scholar 

  2. Karlberg J. A biologically-oriented mathematical model (ICP) for human growth. Acta Paediatr Scand Suppl. 1989;350:70–94. https://doi.org/10.1111/j.1651-2227.1989.tb11199.x.

    Article  CAS  PubMed  Google Scholar 

  3. Mei Z, Grummer-Strawn LM, Thompson D, Dietz WH. Shifts in percentiles of growth during early childhood: analysis of longitudinal data from the California Child Health and Development Study. Pediatrics. 2004;113(6):e617–27. https://doi.org/10.1542/peds.113.6.e617.

    Article  PubMed  Google Scholar 

  4. Smith DW, Truog W, Rogers JE, Greitzer LJ, Skinner AL, McCann JJ, et al. Shifting linear growth during infancy: illustration of genetic factors in growth from fetal life through infancy. J Pediatr. 1976;89(2):225–30. https://doi.org/10.1016/s0022-3476(76)80453-2.

    Article  CAS  PubMed  Google Scholar 

  5. del Pino M, Orden AB, Arenas MA, Fano V. Argentine references for the assessment of body proportions from birth to 17 years of age. Arch Argent Pediatr. 2017;115(3):234–40. https://doi.org/10.5546/aap.2017.eng.234.

    Article  PubMed  Google Scholar 

  6. del Pino M, Orden AB, Arenas MA, Caíno S, Fano V. Referencias Argentinas de estatura sentada y longitud de miembros inferiores de 0 a 18 años. Med Inf. 2016;XXXIII(4):279–86.

    Google Scholar 

  7. Foldynova-Trantirkova S, Wilcox WR, Krejci P. Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias. Hum Mutat. 2012;33(1):29–41. https://doi.org/10.1002/humu.21636.

    Article  CAS  PubMed  Google Scholar 

  8. Qi H, Jin M, Duan Y, Du X, Zhang Y, Ren F, et al. FGFR3 induces degradation of BMP type I receptor to regulate skeletal development. Biochim Biophys Acta. 2014;1843(7):1237–47. https://doi.org/10.1016/j.bbamcr.2014.03.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mugniery E, Dacquin R, Marty C, Benoist-Lasselin C, de Vernejoul MC, Jurdic P, et al. An activating Fgfr3 mutation affects trabecular bone formation via a paracrine mechanism during growth. Hum Mol Genet. 2012;21(11):2503–13. https://doi.org/10.1093/hmg/dds065.

    Article  CAS  PubMed  Google Scholar 

  10. Spranger JW. Achondroplasia. In: Spranger JW, Brill PW, Poznanski A, editors. Bone dysplasia: an atlas of genetic disorders of skeletal development. 2e ed. New York: Oxford University Press; 2012. p. 83–9.

    Chapter  Google Scholar 

  11. • Mortier GR, Cohn DH, Cormier-Daire V, Hall C, Krakow D, Mundlos S, et al. Nosology and classification of genetic skeletal disorders: 2019 revision. Am J Med Genet A. 2019;179(12):2393–419. https://doi.org/10.1002/ajmg.a.61366. This study provides an update in the skeletal dysplasias nosology, comprising 461 different diseases classified into 42 groups based on their clinical, radiographic, and/or molecular phenotypes. By providing a reference list of recognized entities and their causal genes, this nosology helps clinicians to achieve accurate diagnoses for their patients.

    Article  PubMed  Google Scholar 

  12. Horton WA, Hall JG, Hecht JT. Achondroplasia. Lancet. 2007;370(9582):162–72. https://doi.org/10.1016/S0140-6736(07)61090-3.

    Article  CAS  PubMed  Google Scholar 

  13. Wang Y, Liu Z, Liu Z, Zhao H, Zhou X, Cui Y, et al. Advances in research on and diagnosis and treatment of achondroplasia in China. Intractable Rare Dis Res. 2013;2(2):45–50. https://doi.org/10.5582/irdr.2013.v2.2.45.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Krakow D. Skeletal dysplasias. Clin Perinatol. 2015;42(2):301–19, viii. https://doi.org/10.1016/j.clp.2015.03.003.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Aterman K, Welch JP, Taylor PG. Presumed homozygous achondroplasia. A review and report of a further case. Pathol Res Pract. 1983;178(1):27–39. https://doi.org/10.1016/S0344-0338(83)80082-X.

    Article  CAS  PubMed  Google Scholar 

  16. Pauli RM, Conroy MM, Langer LO Jr, McLone DG, Naidich T, Franciosi R, et al. Homozygous achondroplasia with survival beyond infancy. Am J Med Genet. 1983;16(4):459–73. https://doi.org/10.1002/ajmg.1320160404.

  17. Bober MB, Bellus GA, Nikkel SM, Tiller GE. Hypochondroplasia. 1999 Jul 15 [updated 2020 May 7]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle: University of Washington, Seattle; 1993–2020.

  18. Saito T, Nagasaki K, Nishimura G, Takagi M, Hasegawa T, Uchiyama M. Radiological clues to the early diagnosis of hypochondroplasia in the neonatal period: report of two patients. Am J Med Genet. 2012;158A(3):630–4. https://doi.org/10.1002/ajmg.a.34424.

    Article  PubMed  Google Scholar 

  19. • Saito T, Nagasaki K, Nishimura G, Wada M, Nyuzuki H, Takagi M, et al. Criteria for radiologic diagnosis of hypochondroplasia in neonates. Pediatr Radiol. 2016;46(4):513–8. https://doi.org/10.1007/s00247-015-3518-2. This study highlights the importance of radiological findings in the diagnosis of FGFR3-related disorders. This publication helps in the differential diagnosis focusing on the neonatal period of life.

    Article  PubMed  Google Scholar 

  20. Bellus GA, McIntosh I, Smith EA, Aylsworth AS, Kaitila I, Horton WA, et al. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nat Genet. 1995;10(3):357–9. https://doi.org/10.1038/ng0795-357.

    Article  CAS  PubMed  Google Scholar 

  21. Bellus GA, McIntosh I, Szabo J, Aylsworth A, Kaitila I, Francomano CA. Hypochondroplasia: molecular analysis of the fibroblast growth factor receptor 3 gene. Ann N Y Acad Sci. 1996;785:182–7. https://doi.org/10.1111/j.1749-6632.1996.tb56257.x.

    Article  CAS  PubMed  Google Scholar 

  22. The Human Gene Database. Genecards®. Weizmann Institute of Science, rehovot, Israel. World Wide Web URL: https://www.genecards.org/cgi-bin/carddisp.pl?gene=FGFR3&keywords=Hypochondroplasia&prefilter=publications#publications. Assessed 30 august, 2020.

  23. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {134934}: {Date last edited}: 6/11/2019 . World Wide Web URL: https://www.omim.org/entry/134934#0001. Assessed 30 august, 2020.

  24. Barbosa-Buck CO, Orioli IM, da Graça DM, Lopez-Camelo J, Castilla EE, Cavalcanti DP. Clinical epidemiology of skeletal dysplasias in South America. Am J Med Genet A. 2012;158A(5):1038–45. https://doi.org/10.1002/ajmg.a.35246.

    Article  PubMed  Google Scholar 

  25. Tavormina PL, Shiang R, Thompson LM, Zhu YZ, Wilkin DJ, Lachman RS, et al. Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. Nat Genet. 1995;9(3):321–8. https://doi.org/10.1038/ng0395-321.

    Article  CAS  PubMed  Google Scholar 

  26. Tavormina PL, Rimoin DL, Cohn DH, Zhu YZ, Shiang R, Wasmuth JJ. Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I. Hum Mol Genet. 1995;4(11):2175–7. https://doi.org/10.1093/hmg/4.11.2175.

    Article  CAS  PubMed  Google Scholar 

  27. Wilcox WR, Tavormina PL, Krakow D, Kitoh H, Lachman RS, Wasmuth JJ, et al. Molecular, radiologic, and histopathologic correlations in thanatophoric dysplasia. Am J Med Genet. 1998;78(3):274–81. https://doi.org/10.1002/(sici)1096-8628(19980707)78:3<274::aid-ajmg14>3.0.co;2-c.

    Article  CAS  PubMed  Google Scholar 

  28. Wainwright H. Thanatophoric dysplasia: a review. S Afr Med J. 2016;106(6 Suppl 1):S50–3. https://doi.org/10.7196/SAMJ.2016.v106i6.10993.

    Article  CAS  PubMed  Google Scholar 

  29. Tavormina PL, Bellus GA, Webster MK, Bamshad MJ, Fraley AE, McIntosh I, et al. A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene. Am J Hum Genet. 1999;64(3):722–31. https://doi.org/10.1086/302275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bellus GA, Bamshad MJ, Przylepa KA, Dorst J, Lee RR, Hurko O, et al. Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN): phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3. Am J Med Genet. 1999;85(1):53–65.

    Article  CAS  Google Scholar 

  31. Horton WA, Rotter JI, Rimoin DL, Scott CI, Hall JG. Standard growth curves for achondroplasia. J Pediatr. 1978;93(3):435–8. https://doi.org/10.1016/s0022-3476(78)81152-4.

    Article  CAS  PubMed  Google Scholar 

  32. •• 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. https://doi.org/10.1007/s00431-010-1302-8. This study provides the first growth references for height, weight, and head circumference for South American children and adults with achondroplasia.

    Article  PubMed  Google Scholar 

  33. del Pino M, Ramos Mejía 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. https://doi.org/10.1002/ajmg.a.38633.

    Article  CAS  PubMed  Google Scholar 

  34. •• del Pino M, Fano V, Adamo P. Growth velocity and biological variables during puberty in achondroplasia. J Pediatr Endocrinol Metab. 2018;31(4):421–8. https://doi.org/10.1515/jpem-2017-0471. This longitudinal study assesses biological parameters and growth during puberty in achondroplasia. Of particular interest, this paper reports that approximately 80% of the growth spurt in this period is due to the trunk growth, increasing body disproportion in puberty.

  35. del Pino M, Fano V, Adamo P. Height growth velocity during infancy and childhood in achondroplasia. Am J Med Genet A. 2019;179(6):1001–9. https://doi.org/10.1002/ajmg.a.61120.

    Article  PubMed  Google Scholar 

  36. •• 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. https://doi.org/10.1002/ajmg.a.38150. This study adds new information regarding growth references for children with achondroplasia for the North American population.

    Article  PubMed  Google Scholar 

  37. •• Tofts L, Das S, Collins F, Burton KLO. Growth charts for Australian children with achondroplasia. Am J Med Genet A. 2017;173(8):2189–200. https://doi.org/10.1002/ajmg.a.38312. Data from this study provides growth charts for Australian children with achondroplasia.

    Article  CAS  PubMed  Google Scholar 

  38. •• Merker A, Neumeyer L, Hertel NT, Grigelioniene G, Mäkitie 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. https://doi.org/10.1002/ajmg.a.38853. This research summarizes growth information for the achondroplasia European population. The authors reinforce the fact that there is a positive association between parental and adult height in de novo ACH cases.

    Article  PubMed  Google Scholar 

  39. •• Del Pino M, Fano V, Adamo P. Growth in achondroplasia, from birth to adulthood, analysed by the JPA-2 model. J Pediatr Endocrinol Metab. 2020. https://doi.org/10.1515/jpem-2020-0298. This research describes the human growth curve in achondroplasia. We can recognize the three periods, infancy, childhood, and puberty.

  40. •• Arenas MA, Del Pino M, Fano V. FGFR3-related hypochondroplasia: longitudinal growth in 57 children with the p.Asn540Lys mutation. J Pediatr Endocrinol Metab. 2018;31(11):1279–84. https://doi.org/10.1515/jpem-2018-0046This study describes and characterizes growth in an Argentinian hypochondroplasia cohort due to N540K mutation. One of the findings reported is the early compromise of body disproportion.

    Article  CAS  PubMed  Google Scholar 

  41. Fano V, Gravina LP, Pino MD, Chertkoff L, Barreiro C, Lejarraga H. High specificity of head circumference to recognize N540K mutation in hypochondroplasia. Ann Hum Biol. 2005;32(6):782–8. https://doi.org/10.1080/03014460500268481.

    Article  PubMed  Google Scholar 

  42. Stensvold K, Ek J, Hovland AR. An infant with thanatophoric dwarfism surviving 169 days. Clin Genet. 1986;29(2):157–9. https://doi.org/10.1111/j.1399-0004.1986.tb01241.x.

    Article  CAS  PubMed  Google Scholar 

  43. Tonoki H. A boy with thanatophoric dysplasia surviving 212 days. Clin Genet. 1987;32(6):415–6. https://doi.org/10.1111/j.1399-0004.1987.tb03161.x.

    Article  CAS  PubMed  Google Scholar 

  44. MacDonald IM, Hunter AGW, MacLeod PM, MacMurray SB. Growth and development in thanatophoric dysplasia. Am J Med Genet. 1989;33(4):508–12. https://doi.org/10.1002/ajmg.1320330420.

    Article  CAS  PubMed  Google Scholar 

  45. Baker KM, Olson DS, Harding CO, Pauli RM. Long-term survival in typical thanatophoric dysplasia type 1. Am J Med Genet. 1997;70(4):427–36.

    Article  CAS  Google Scholar 

  46. • Nikkel SM, Major N, King WJ. Growth and development in thanatophoric dysplasia - an update 25 years later. Clin Case Rep. 2013;1(2):75–8. https://doi.org/10.1002/ccr3.29. This description shows unique data regarding late survival in a patient with thanatophoric dysplasia.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Zankl A, Elakis G, Susman RD, Inglis G, Gardener G, Buckley MF, et al. Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 Lys650Met mutation. Am J Med Genet A. 2008;146A(2):212–8. https://doi.org/10.1002/ajmg.a.32085.

    Article  CAS  PubMed  Google Scholar 

  48. Adachi M. Case of a Japanese female presenting severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) syndrome with a K650M mutation in the fibroblast growth factor receptor 3 gene. No To Hattatsu. 2008;40(6):478–82 Japanese.

    PubMed  Google Scholar 

  49. Kitoh H, Brodie SG, Kupke KG, Lachman RS, Wilcox WR. Lys650Met substitution in the tyrosine kinase domain of the fibroblast growth factor receptor gene causes thanatophoric dysplasia type I. Mutations in brief no. 199. Online. Hum Mutat. 1998;12(5):362–3.

    CAS  PubMed  Google Scholar 

  50. •• Tachibana K, Suwa S, Nishiyama S, Matsuda I. A study on the height of children with achondroplasia based on a national wide survey [in Japanese]. Shounikashinryo (Journal of Pediatrics). 1997;60:1363–9. This study is a Japan nationwide survey describing the characteristics of growth in achondroplasia.

    Google Scholar 

  51. •• Dai WQ, Gu XF, Yu YG. Exploring the clinical genetic characteristics and height for age growth curve of 210 patients with achondroplasia in China. Zhonghua Er Ke Za Zhi. 2020;58(6):461–7. https://doi.org/10.3760/cma.j.cn112140-20200217-00096. This report collects growth information in achondroplasia and adds growth charts for the Chinese achondroplasia population.

    Article  CAS  PubMed  Google Scholar 

  52. Bellus GA, Spector EB, Speiser PW, Weaver CA, Garber AT, Bryke CR, et al. Distinct missense mutations of the FGFR3 Lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype. Am J Hum Genet. 2000;67(6):1411–21. https://doi.org/10.1086/316892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mortier G, Nuytinck L, Craen M, Renard JP, Leroy JG, de Paepe A. Clinical and radiographic features of a family with hypochondroplasia owing to a novel Asn540Ser mutation in the fibroblast growth factor receptor 3 gene. J Med Genet. 2000;37(3):220–4. https://doi.org/10.1136/jmg.37.3.220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Winterpacht A, Hilbert K, Stelzer C, Schweikardt T, Decker H, Segerer H, et al. A novel mutation in FGFR-3 disrupts a putative N-glycosylation site and results in hypochondroplasia. Physiol Genomics. 2000;2(1):9–12. https://doi.org/10.1152/physiolgenomics.2000.2.1.9.

    Article  CAS  PubMed  Google Scholar 

  55. Heuertz S, Le Merrer M, Zabel B, Wright M, Legeai-Mallet L, Cormier-Daire V, et al. Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia. Eur J Hum Genet. 2006;14(12):1240–7. https://doi.org/10.1038/sj.ejhg.5201700.

    Article  CAS  PubMed  Google Scholar 

  56. Castro-Feijóo L, Loidi L, Vidal A, Parajes S, Rosón E, Álvarez A, et al. Hypochondroplasia and acanthosis nigricans: a new syndrome due to the p.Lys650Thr mutation in the fibroblast growth factor receptor 3 gene? Eur J Endocrinol. 2008;159(3):243–9. https://doi.org/10.1530/EJE-08-0393.

    Article  CAS  PubMed  Google Scholar 

  57. Blomberg M, Jeppesen E, Skovby F, Benfeldt E. FGFR3 mutations and the skin: report of a patient with a FGFR3 gene mutation, acanthosis nigricans, hypochondroplasia and hyperinsulinemia and review of the literature. Dermatology. 2010;220(4):297–305. https://doi.org/10.1159/000297575.

    Article  CAS  PubMed  Google Scholar 

  58. Chen CP, Su YN, Lin TH, Chang TY, Su JW, Wang W. Detection of a de novo Y278C mutation in FGFR3 in a pregnancy with severe fetal hypochondroplasia: prenatal diagnosis and literature review. Taiwan J Obstet Gynecol. 2013;52(4):580–5. https://doi.org/10.1016/j.tjog.2013.10.023.

    Article  CAS  PubMed  Google Scholar 

  59. Wang H, Sun Y, Wu W, Wei X, Lan Z, Xie J. A novel missense mutation of FGFR3 in a Chinese female and her fetus with hypochondroplasia by next-generation sequencing. Clin Chim Acta. 2013;423:62–5. https://doi.org/10.1016/j.cca.2013.04.015.

    Article  CAS  PubMed  Google Scholar 

  60. Nagahara K, Harada Y, Futami T, Takagi M, Nishimura G, Hasegawa Y. A Japanese familial case of hypochondroplasia with a novel mutation in FGFR3. Clin Pediatr Endocrinol. 2016;25(3):103–6. https://doi.org/10.1297/cpe.25.103.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Hirai H, Hamada J, Hasegawa K, Ishii E. Acanthosis nigricans in a Japanese boy with hypochondroplasia due to a K650T mutation in FGFR3. Clin Pediatr Endocrinol. 2017;26(4):223–8. https://doi.org/10.1297/cpe.26.223.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Chen J, Yang J, Zhao S, Ying H, Li G, Xu C. Identification of a novel mutation in the FGFR3 gene in a Chinese family with Hypochondroplasia. Gene. 2018;641:355–60. https://doi.org/10.1016/j.gene.2017.10.062.

    Article  CAS  PubMed  Google Scholar 

  63. •• Yao G, Wang G, Wang D, Su G. Identification of a novel mutation of FGFR3 gene in a large Chinese pedigree with hypochondroplasia by next-generation sequencing. Medicine. 2019;98(4):e14157. https://doi.org/10.1097/MD.0000000000014157. This report describes a large Chinese pedigree with hypochondroplasia due to a novel mutation, adding more data about genetic and clinical variability in this condition.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ramos Mejía R, Aza-Carmona M, del Pino M, Heath KE, Fano V, Obregon MG. Clinical and radiologic evaluation of an individual with hypochondroplasia and a novel FGFR3 mutation. J Pediatr Genet. 2020;09(01):048–52. https://doi.org/10.1055/s-0039-1695056.

    Article  Google Scholar 

  65. De Rosa MLG, Fano V, Araoz HV, Chertkoff L, Obregon MG. Homozygous N540K hypochondroplasia-first report: radiological and clinical features. Am J Med Genet. 2014;164(7):1784–8. https://doi.org/10.1002/ajmg.a.36504.

    Article  CAS  Google Scholar 

  66. Hoover-Fong JE, Schulze KJ, McGready J, Barnes H, Scott CI. Age-appropriate body mass index in children with achondroplasia: interpretation in relation to indexes of height. Am J Clin Nutr. 2008;88(2):364–71. https://doi.org/10.1093/ajcn/88.2.364.

    Article  CAS  PubMed  Google Scholar 

  67. Ismail S, Thomas MM, Hosny LA, Ashaat EA, Ashaat NA, Moushira EZ. Growth charts for Egyptian children with achondroplasia. J Clin Diagn Res. 2019;13(5):GC01–5. https://doi.org/10.7860/JCDR/2019/39555.12837.

    Article  Google Scholar 

  68. Appan S, Laurent S, Chapman M, Hindmarsh PC, Brook CGD. Growth and growth hormone therapy in hypochondroplasia. Acta Paediatr. 1990;79(8-9):796–803. https://doi.org/10.1111/j.1651-2227.1990.tb11557.x.

    Article  CAS  Google Scholar 

  69. Pinto G, Cormier-Daire V, Le Merrer M, Samara-Boustani D, Baujat G, Fresneau L, et al. Efficacy and safety of growth hormone treatment in children with hypochondroplasia: comparison with an historical cohort. Horm Res Paediatr. 2014;82(6):355–63. https://doi.org/10.1159/000364807.

    Article  CAS  PubMed  Google Scholar 

  70. Matsui Y, Yasui N, Kimura T, Tsumaki N, Kawabata H, Ochi T. Genotype phenotype correlation in achondroplasia and hypochondroplasia. J Bone Joint Surg (Br). 1998;80(6):1052–6. https://doi.org/10.1302/0301-620x.80b6.9277.

    Article  CAS  Google Scholar 

  71. Fofanova OV, Takamura N, Kinoshita E, Meerson EM, Iljina VK, Nechvolodova OL, et al. A missense mutation of C1659 in the fibroblast growth factor receptor 3 gene in Russian patients with hypochondroplasia. Endocr J. 1998;45(6):791–5. https://doi.org/10.1507/endocrj.45.791.

    Article  CAS  PubMed  Google Scholar 

  72. Prinster C, Carrera P, Del Maschio M, Weber G, Maghnie M, Vigone MC, et al. Comparison of clinical-radiological and molecular findings in hypochondroplasia. Am J Med Genet. 1998;75(1):109–12. https://doi.org/10.1002/(sici)1096-8628(19980106)75:1<109::aid-ajmg22>3.0.co;2-p.

    Article  CAS  PubMed  Google Scholar 

  73. Grigelioniené G, Eklöf O, Laurencikas E, Ollars B, Hertel NT, Dumanski JP, et al. Asn540Lys mutation in fibroblast growth factor receptor 3 and phenotype in hypochondroplasia. Acta Paediatr. 2000;89(9):1072–6. https://doi.org/10.1080/713794579.

    Article  PubMed  Google Scholar 

  74. Shin YL, Choi JH, Kim GH, Yoo HW. Comparison of clinical, radiological and molecular findings in Korean infants and children with achondroplasia and hypochondroplasia. J Pediatr Endocrinol Metab. 2005;18(10):999–1005. https://doi.org/10.1515/jpem.2005.18.10.999.

    Article  CAS  PubMed  Google Scholar 

  75. Korkmaz HA, Hazan F, Dizdarer C, Tükün A. Hypochondroplasia in a child with 1620C>G (Asn540Lys) mutation in FGFR3. J Clin Res Pediatr Endocrinol. 2012;4(4):220–2. https://doi.org/10.4274/jcrpe.787.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Rousseau F, Bonaventure J, Legeai-Mallet L, Schmidt H, Weissenbach J, Maroteaux P, et al. Clinical and genetic heterogeneity of hypochondroplasia. J Med Genet. 1996;33(9):749–52. https://doi.org/10.1136/jmg.33.9.749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Grigelioniené G, Hagenäs L, Eklöf O, Neumeyer L, Haereid PE, Anvret M. A novel missense mutation Ile538Val in the fibroblast growth factor receptor 3 in hypochondroplasia. Mutations in brief no. 122. Online. Hum Mutat. 1998;11(4):333. https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<333::AID-HUMU18>3.0.CO;2-G.

    Article  PubMed  Google Scholar 

  78. Deutz-Terlouw PP, Losekoot M, Aalfs CM, Hennekam RC, Bakker E. Asn540Thr substitution in the fibroblast growth factor receptor 3 tyrosine kinase domain causing hypochondroplasia. Hum Mutat. 1998;11(S1):S62–5. https://doi.org/10.1002/humu.1380110122.

    Article  Google Scholar 

  79. Thauvin-Robinet C, Faivre L, Lewin P, De Monléon J, François C, Huet F, et al. Hypochondroplasia and stature within normal limits: another family with an Asn540Ser mutation in the fibroblast growth factor receptor 3 gene. Am J Med Genet. 2003;119A(1):81–4. https://doi.org/10.1002/ajmg.a.10238.

    Article  PubMed  Google Scholar 

  80. Leroy JG, Nuytinck L, Lambert J, Naeyaert J, Mortier GR. Acanthosis nigricans in a child with mild osteochondrodysplasia and K650Q mutation in the FGFR3 gene. Am J Med Genet. 2007;143A(24):3144–9. https://doi.org/10.1002/ajmg.a.31966.

    Article  PubMed  Google Scholar 

  81. Berk DR, Del Carmen Boente M, Montanari D, Toloza MG, Primc NB, Prado MI, et al. Acanthosis nigricans and hypochondroplasia in a child with a K650Q mutation in FGFR3. Pediatr Dermatol. 2010;27(6):664–6. https://doi.org/10.1111/j.1525-1470.2010.01331.x.

    Article  PubMed  Google Scholar 

  82. Cossiez Cacard M, Coulombe J, Bernard P, Kaci N, Bressieux J, Souchon P, et al. Familial hypochondroplasia and acanthosis nigricans withFGFR3K650T mutation. J Eur Acad Dermatol Venereol. 2016;30(5):897–8. https://doi.org/10.1111/jdv.13061.

    Article  CAS  PubMed  Google Scholar 

  83. Muguet Guenot L, Aubert H, Isidor B, Toutain A, Mazereeuw-Hautier J, Collet C, et al. Acanthosis nigricans, hypochondroplasia, and FGFR 3 mutations: findings with five new patients, and a review of the literature. Pediatr Dermatol. 2019;36(2):242–6. https://doi.org/10.1111/pde.13748.

    Article  PubMed  Google Scholar 

  84. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, et al. CDC growth charts: United States. Adv Data. 2000;314:1–27.

  85. Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, et al. CDC growth charts for the United States: methods and development. Vital Health Stat. 2002;11(246):1–190.

  86. Ramaswami U, Rumsby G, Hindmarsh PC, Brook CG. Genotype and phenotype in hypochondroplasia. J Pediatr. 1998;133(1):99–102. https://doi.org/10.1016/s0022-3476(98)70186-6.

    Article  CAS  PubMed  Google Scholar 

  87. Maroteaux P, Falzon P. Hypochondroplasia. Review of 80 cases. Arch Fr Pediatr. 1988;45(2):105–9.

    CAS  PubMed  Google Scholar 

  88. Lejarraga H, del Pino M, Fano V, Caino S, Cole TJ. Growth references for weight and height for Argentinian girls and boys from birth to maturity: incorporation of data from the World Health Organisation from birth to 2 years and calculation of new percentiles and LMS values. Arch Argent Pediatr. 2009;107(2):126–33. Spanish. https://doi.org/10.1590/S0325-00752009000200006.

    Article  PubMed  Google Scholar 

  89. •• del Pino M, Fano V. Height correlations between parents and offspring in achondroplasia population. Am J Med Genet A. 2013;161A(2):396–8. https://doi.org/10.1002/ajmg.a.35721. Findings from this study suggest that there is a positive correlation between parent and child height. This parent-child correlation changes during lifetime, being more noticeable from 3 years of age to adulthood.

    Article  PubMed  Google Scholar 

  90. Murdoch JL, Walker BA, Hall JG, Abbey H, Smith KK, McKusick VA. Achondroplasia--a genetic and statistical survey. Ann Hum Genet. 1970;33(3):227–44. https://doi.org/10.1111/j.1469-1809.1970.tb01648.x.

    Article  CAS  PubMed  Google Scholar 

  91. Nehme AM, Riseborough EJ, Tredwell SJ. Skeletal growth and development of the achondroplastic dwarf. Clin Orthop Relat Res. 1976;116:8–23.

    Google Scholar 

  92. Merker A, Neumeyer L, Hertel NT, Grigelioniene G, Mohnike K, Hagenäs L. Development of body proportions in achondroplasia: sitting height, leg length, arm span, and foot length. Am J Med Genet A. 2018;176(9):1819–29. https://doi.org/10.1002/ajmg.a.40356.

    Article  PubMed  Google Scholar 

  93. Dangour AD, Schilg S, Hulse JA, Cole TJ. Sitting height and subischial leg length centile curves for boys and girls from Southeast England. Ann Hum Biol. 2002;29(3):290–305. https://doi.org/10.1080/03014460110085331.

    Article  CAS  PubMed  Google Scholar 

  94. Wynne-Davies R, Walsh WK, Gormley J. Achondroplasia and hypochondroplasia. Clinical variation and spinal stenosis. J Bone Joint Surg (Br). 1981;63B(4):508–15.

    Article  CAS  Google Scholar 

  95. Saunders CL, Lejarraga H, del Pino M. Assessment of head size adjusted for height: an anthropometric tool for clinical use based on Argentinian data. Ann Hum Biol. 2006;33(4):415–23. https://doi.org/10.1080/03014460600742062.

    Article  PubMed  Google Scholar 

  96. Sawai H, Oka K, Ushioda M, Nishimura G, Omori T, Numabe H, et al. National survey of prevalence and prognosis of thanatophoric dysplasia in Japan. Pediatr Int. 2019;61(8):748–53. https://doi.org/10.1111/ped.13927.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Growth and Development, Hospital Garrahan, Combate de los Pozos 1881, 1245, Buenos Aires, Argentina

    R Ramos Mejia, M del Pino & V Fano

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Ramos Mejia, R., del Pino, M. & Fano, V. Growth Topics in FGFR3-Related Skeletal Dysplasias. Curr Treat Options Peds 7, 82–98 (2021). https://doi.org/10.1007/s40746-021-00222-x

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