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Growth plate disorders causing familiar short stature


Authors: L. Plachý;  D. Zemková;  Š. Průhová;  J. Lebl
Authors‘ workplace: Pediatrická klinika 2. lékařské fakulty Univerzity Karlovy a Fakultní nemocnice Motol, Praha
Published in: Čes-slov Pediat 2018; 73 (2): 110-117.
Category: Review

Věnováno významnému životnímu jubileu prof. MUDr. Lidky Lisé, DrSc.

Overview

Familial short stature (FSS) is characterised by body height lower than -2 SD if compared with mean height for age, sex and background population, that occurs in two or more subsequent generations. Although the cause for FSS remains not clarified in many individual cases, it may result from autosomal dominantly inherited growth plate disorders. The spectrum of clinical features of growth plate disorders ranges from very mildly expressed forms with proportional short stature up to potentially lethal severe skeletal dysplasia with limb deformities.

Growth plate disorders include subgroups according to underlying mechanisms at molecular level – impaired paracrine signalisation, defects of cartilaginous extracellular matrix, or defective fundamental intracellular functions. FGFR3 or NPR2 gene mutations lead to impaired paracrine signalisation. The defects of cartilaginous extracellular matrix include mutations in genes ACAN, FNB1 or in genes encoding individual types collagen (e.g. COL2A1). Heterozygous mutations of SHOX gene cause 2-15 % of idiopathic short stature.

Clarification of specific diagnosis allows a more precise estimation of final body height, for targeted follow-up with regard to potential complications, for appropriate management and relevant genetic counselling. Team collaboration of paediatric endocrinologist, anthropologist, radiologist and genetician is helpful for both diagnosis and management of affected children.

Key words:
familial short stature, growth plate, bone dysplasia, SHOX, ACAN, FGFR3, NPR2, collagenopathys


Sources

1. Lebl J, Al Taji E, Koloušková S, a spol. Dětská endokrinologie a diabetologie. Praha: Galén, 2016: 96–103.

2. Pedicelli S, Peschiaroli E, Violi E, Cianfarani S. Controversies in the definition and treatment of idiopathic short stature (ISS). J Clin Res Pediatr Endocrinol 2009; 1: 105–15.

3. Dauber A, Rosenfeld RG, Hirschhorn JN. Genetic evaluation of short stature. J Clin Endocrinol Metab 2014; 99: 3080–3092.

4. Eggermann T, Binder G, Brioude F, et al. CDKN1C mutations: Two sides of the same coin. Trends Mol Med 2014; 20: 614–622.

5. Baron J, Sävendahl L, De Luca F, et al. Short and tall stature: A new paradigm emerges. Nat Rev Endocrinol 2015; 11: 736–746.

6. Bonafe L, Cormier-Daire V, Hall C, et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet Part A 2015; 167: 2869–2892.

7. Krakow D. Skeletal dysplasias. Clin Perinatol 2015; 42: 301–319.

8. Ornitz DM, Legeai-Mallet L. Achondroplasia: Development, pathogenesis, and therapy. Dev Dyn 2017; 246: 291–309.

9. Andrade AC, Jee YH, Nilsson O. New genetic diagnoses of short stature provide insights into local regulation of childhood growth. Horm Res Paediatr 2017; 88: 22–37.

10. Krakow D, Rimoin DL. The skeletal dysplasias. Genet Med 2010; 12: 327–341.

11. Shah BC, Moran ES, Zinn AR, Pappas JG. Effect of growth hormone therapy on severe short stature and skeletal deformities in a patient with combined Turner syndrome and langer mesomelic dysplasia. J Clin Endocrinol Metab 2009; 94: 5028–533.

12. Fallis A. Junqueira’s basic histology. J Chem Inf Model 2013; 53: 1689–1699.

13. Superti-Furga A, Bonafé L, Rimoin DL. Molecular-pathogenetic classification of genetic disorders of the skeleton. Am J Med Genet – Semin Med Genet 2002; 106: 282–293.

14. Marr C, Seasman A, Bishop N. Managing the patient with osteogenesis imperfecta: A multidisciplinary approach. J Multidiscip Healthc 2017; 10: 145–155.

15. Barat-Houari M, Sarrabay G, Gatinois V, et al. Mutation Update for COL2A1 gene variants associated with type II collagenopathies. Hum Mutat 2016; 37: 7–15.

16. Miyamoto Y, Matsuda T, Kitoh H, et al. A recurrent mutation in type II collagen gene causes Legg-Calvé-Perthes disease in a Japanese family. Hum Genet 2007; 121: 625–629.

17. Deng H, Huang X, Yuan L. Molecular genetics of the COL2A1-related disorders. Mutat Res Rev Mutat Res 2016; 768: 1–13.

18. Briggs MD, Wright MJ, Mortier GR. Multiple epiphyseal dysplasia, autosomal dominant. GeneReviews®, 1993.

19. Briggs MD, Wright MJ. Pseudoachondroplasia. GeneReviews®, 2004.

20. Acke FR, Malfait F, Vanakker OM, et al. Novel pathogenic COL11A1/COL11A2 variants in Stickler syndrome detected by targeted NGS and exome sequencing. Mol Genet Metab 2014; 113: 230–235.

21. Gkourogianni A, Andrew M, Tyzinski L, et al. Clinical characterization of patients with autosomal dominant short stature due to aggrecan mutations. J Clin Endocrinol Metab 2017; 102: 460–469.

22. van der Steen M, Pfundt R, Maas SJWH, et al. ACAN gene mutations in short children born SGA and response to growth hormone treatment. J Clin Endocrinol Metab 2016; 102: 1458–1467.

23. Gibson BG, Briggs MD. The aggrecanopathies; An evolving phenotypic spectrum of human genetic skeletal diseases. Orphanet J Rare Dis 2016; 11: 86.

24. Sakai LY, Keene DR, Renard M, De Backer J. FBN1: The disease-causing gene for Marfan syndrome and other genetic disorders. Gene 2016; 592: 279–291.

25. Goff C Le, Mahaut C, Wang LW, et al. Mutations in the TGFβ binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias. Am J Hum Genet 2011; 89: 7–14.

26. Hasegawa K, Numakura C, Tanaka H, et al. Three cases of Japanese acromicric/geleophysic dysplasia with FBN1 mutations: a comparison of clinical and radiological features. J Pediatr Endocrinol Metab 2017; 30 (1): 117–121.

27. Wang J, Zhou J, Cheng CM, et al. Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth. J Endocrinol 2004; 180:247–255.

28. Stagi S, Azzali A, La Spina L, et al. Growth hormone axis in skeletal dysplasias. In: Restricted Growth – Clinical, Genetic and Molecular Aspects. InTech 2016 Oct 12. http://www.intechopen.com/books/restricted-growth-clinical-genetic-and-molecular-aspects/growth-hormone-axis-in-skeletal-dysplasias.

29. Li J, Dong S. The signaling pathways involved in chondrocyte differentiation and hypertrophic differentiation. Stem Cells International 2016; 2016: 2470351.

30. Deng C, Wynshaw-Boris A, Zhou F, et al. Fibroblast growth factor receptor 3 is a negative regulator of bone growth. Cell 1996; 84: 911–921.

31. Massart F, Miccoli M, Baggiani A, Bertelloni S. Height outcome of short children with hypochondroplasia after recombinant human growth hormone treatment: a meta-analysis. Pharmacogenomics 2015; 16: 1965–1973.

32. Miccoli M, Bertelloni S, Massart F. Height outcome of recombinant human growth hormone treatment in achondroplasia children: A meta-analysis. Horm Res Paediatr 2016; 86: 27–34.

33. Vasques GA, Arnhold IJP, Jorge AAL. Role of the natriuretic peptide system in normal growth and growth disorders. Horm Res Paediatr 2014; 82: 222–229.

34. Vasques GA, Hisado-Oliva A, Funari MFA, et al. Long-term response to growth hormone therapy in a patient with short stature caused by a novel heterozygous mutation in NPR2. J Pediatr Endocrinol Metab 2017; 30: 111–116.

35. Choi WB, Seo SH, Yoo WH, et al. A Leri-Weill dyschondrosteosis patient confirmed by mutation analysis of SHOX gene. Ann Pediatr Endocrinol Metab 2015; 20:162–165.

36. Binder G. Short stature due to SHOX deficiency: Genotype, phenotype, and therapy. Horm Res Paediatr 2011; 75: 81–89.

37. von Bohlen AE, Böhm J, Pop R, et al. A mutation creating an upstream initiation codon in the SOX9 5’ UTR causes acampomelic campomelic dysplasia. Mol Genet Genomic Med 2017; 5: 261–268.

38. Machol K, Mendoza-Londono R, Lee B. Cleidocranial dysplasia spectrum disorder. GeneReviews®. Seattle (WA): University of Washington, 1993-2018. 2006 Jan 3 [updated 2017 Nov 16].

39. Kayemba-Kay’s S, Tripon C, Heron A, Hindmarsh P. Pseudohypoparathyroidism type IA subclinical hypothyroidism and rapid weight gain weight as early clinical signs. A clinical study of 10 cases. J Clin Res Pediatr Endocrinol 2016; 8: 432–438.

40. Cho SY, Jin D-K. Guidelines for genetic skeletal dysplasias for pediatricians. Ann Pediatr Endocrinol Metab 2015; 20: 187.

Labels
Neonatology Paediatrics General practitioner for children and adolescents
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