Exp Clin Endocrinol Diabetes 2013; 121(02): 109-114
DOI: 10.1055/s-0032-1333260
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Bone Geometry and Volumetric Bone Density at the Radius in Patients with Isolated SHOX Deficiency

O. Soucek
1   Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic
,
J. Lebl
1   Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic
,
J. Zapletalova
2   Department of Paediatrics, Faculty of Medicine, Palacky University and University Hospital Olomouc, Olomouc, Czech Republic
,
D. Novotna
3   Department of Paediatrics, Faculty of Medicine, Masaryk University and University Hospital Brno, Brno, Czech Republic
,
I. Plasilova
4   Department of Paediatrics, Faculty of Medicine, Charles University in Prague and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
,
S. Kolouskova
1   Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic
,
D. Zemkova
1   Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic
,
M. Rocek
5   Department of Radiology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic
,
Z. Hlavka
6   Department of Probability and Mathematical Statistics, Faculty of ­Mathematics and Physics, Charles University in Prague, Prague, Czech Republic
,
K. Hirschfeldova
7   Institute of Biology and Department of Medical Genetics, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic
,
Z. Sumnik
1   Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 17. April 2012
first decision 17. Dezember 2012

accepted 21. Dezember 2012

Publikationsdatum:
20. Februar 2013 (online)

Abstract

The short stature homeobox-containing gene (SHOX) plays an important role in bone development and growth. We aimed to assess bone geometry and volumetric bone mineral density at the radius in patients with isolated SHOX deficiency and to relate these bone parameters to the severity of disproportion between the upper and the lower body segment. 17 patients with isolated SHOX deficiency (median age 12.3 yrs, range 6.7–37.2, 12 children and 5 adults) were examined by peripheral quantitative CT (pQCT) at the non-dominant forearm. Results were expressed as Z-scores using published reference data. Linear regression analyses were performed to describe associations between pQCT parameters and the severity of disproportion expressed as sitting height to standing subischial leg height ratio. Trabecular volumetric bone mineral density (vBMD) at the distal radius was normal, whereas cortical vBMD was decreased (mean Z-scores 0.34±1.5, n.s., and −2.2±2.2, p<0.001, respectively). Total bone cross-sectional area was enlarged at the diaphysis (2.1±1.2, p<0.001), while cortical bone cross-sectional area was normal (−0.51±1.4, n.s.). Consequently, cortical thickness was decreased (−1.2±1.3, p<0.01). The polar strength-strain index as a surrogate of long bone strength was normal (0.40±1.4, n.s.). We found no associations between pQCT parameters and the severity of disproportion. Conclusions: Patients with isolated SHOX deficiency are characterized by decreased cortical vBMD and cortical thickness and enlarged diaphysis. As similar changes have been described in girls with Turner syndrome, these findings suggest that haploinsufficiency of SHOX could cause characteristic skeletal anomalies at the radius.

 
  • References

  • 1 Clement-Jones M, Schiller S, Rao E et al. The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Hum Mol Genet 2000; 9: 695-702
  • 2 Munns CJ, Haase HR, Crowther LM et al. Expression of SHOX in human fetal and childhood growth plate. J Clin Endocrinol Metab 2004; 89: 4130-4135
  • 3 Munns CF, Glass IA, LaBrom R et al. Histopathological analysis of Leri-Weill dyschondrosteosis: disordered growth plate. Hand Surg 2001; 6: 13-23
  • 4 Evans MI, Zador IE, Qureshi F et al. Ultrasonographic prenatal diagnosis and fetal pathology of Langer mesomelic dwarfism. Am J Med Genet 1988; 31: 915-920
  • 5 Binder G. Short stature due to SHOX deficiency: genotype, phenotype, and therapy. Horm Res Paediatr 2011; 75: 81-89
  • 6 Binder G, Schwarze CP, Ranke MB. Identification of short stature caused by SHOX defects and therapeutic effect of recombinant human growth hormone. J Clin Endocrinol Metab 2000; 85: 245-249
  • 7 Rappold GA, Fukami M, Niesler B et al. Deletions of the homeobox gene SHOX (short stature homeobox) are an important cause of growth failure in children with short stature. J Clin Endocrinol Metab 2002; 87: 1402-1406
  • 8 Huber C, Rosilio M, Munnich A et al. High incidence of SHOX anomalies in individuals with short stature. J Med Genet 2006; 43: 735-739
  • 9 Hirschfeldova K, Solc R, Baxova A et al. SHOX gene defects and selected dysmorphic signs in patients of idiopathic short stature and Leri-Weill dyschondrosteosis. Gene 2012; 491: 123-127
  • 10 Binder G, Renz A, Martinez A et al. SHOX haploinsufficiency and Leri-Weill dyschondrosteosis: prevalence and growth failure in relation to mutation, sex, and degree of wrist deformity. J Clin Endocrinol Metab 2004; 89: 4403-4408
  • 11 Flanagan SF, Munns CF, Hayes M et al. Prevalence of mutations in the short stature homeobox containing gene (SHOX) in Madelung deformity of childhood. J Med Genet 2002; 39: 758-763
  • 12 Belin V, Cusin V, Viot G et al. SHOX mutations in dyschondrosteosis (Leri-Weill syndrome). Nat Genet 1998; 19: 67-69
  • 13 Zinn AR, Wei F, Zhang L et al. Complete SHOX deficiency causes Langer mesomelic dysplasia. Am J Med Genet 2002; 110: 158-163
  • 14 Rao E, Weiss B, Fukami M et al. Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet 1997; 16: 54-63
  • 15 Ogata T, Muroya K, Sasaki G et al. SHOX nullizygosity and haploinsufficiency in a Japanese family: implication for the development of Turner skeletal features. J Clin Endocrinol Metab 2002; 87: 1390-1394
  • 16 Rappold G, Blum WF, Shavrikova EP et al. Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency. J Med Genet 2007; 44: 306-313
  • 17 Langer Jr LO. Dyschondrosteosis, a Hereditable Bone Dysplasia with Characteristic Roentgenographic Features. Am J Roentgenol Radium Ther Nucl Med 1965; 95: 178-188
  • 18 Sabherwal N, Bangs F, Roth R et al. Long-range conserved non-coding SHOX sequences regulate expression in developing chicken limb and are associated with short stature phenotypes in human patients. Hum Mol Genet 2007; 16: 210-222
  • 19 Tan YM, Loke KY. Isolated haploinsufficiency of exon 1 of the SHOX gene in a patient with idiopathic short stature. J Clin Pathol 2006; 59: 773-774
  • 20 Prader A, Largo RH, Molinari L et al. Physical growth of Swiss children from birth to 20 years of age. First Zurich longitudinal study of growth and development. Helv Paediatr Acta Suppl 1989; 52: 1-125
  • 21 Kobzova J, Vignerova J, Blaha P et al. The 6th nationwide anthropological survey of children and adolescents in the Czech Republic in 2001. Cent Eur J Public Health 2004; 12: 126-130
  • 22 Neu CM, Rauch F, Manz F et al. Modeling of cross-sectional bone size, mass and geometry at the proximal radius: a study of normal bone development using peripheral quantitative computed tomography. Osteoporos Int 2001; 12: 538-547
  • 23 Rauch F, Schoenau E. Peripheral quantitative computed tomography of the distal radius in young subjects – new reference data and interpretation of results. J Musculoskelet Neuronal Interact 2005; 5: 119-126
  • 24 Rauch F, Schoenau E. Peripheral quantitative computed tomography of the proximal radius in young subjects – new reference data and interpretation of results. J Musculoskelet Neuronal Interact 2008; 8: 217-226
  • 25 Cole TJ. The LMS method for constructing normalized growth standards. Eur J Clin Nutr 1990; 44: 45-60
  • 26 Gordon CM, Bachrach LK, Carpenter TO et al. Dual energy X-ray absorptiometry interpretation and reporting in children and adolescents: the 2007 ISCD Pediatric Official Positions. J Clin Densitom 2008; 11: 43-58
  • 27 R Development Core Team . R: A Language and Environment for Statistical Computing. 2011. Vienna, Austria: R Foundation for Statistical Computing;
  • 28 Soucek O, Lebl J, Snajderova M et al. Bone geometry and volumetric bone mineral density in girls with Turner syndrome of different pubertal stages. Clin Endocrinol (Oxf) 2011; 74: 445-452
  • 29 Binkley TL, Specker BL. pQCT measurement of bone parameters in young children: validation of technique. J Clin Densitom 2000; 3: 9-14
  • 30 Ari M, Bakalov VK, Hill S et al. The effects of growth hormone treatment on bone mineral density and body composition in girls with turner syndrome. J Clin Endocrinol Metab 2006; 91: 4302-4305
  • 31 Gravholt CH, Vestergaard P, Hermann AP et al. Increased fracture rates in Turner’s syndrome: a nationwide questionnaire survey. Clin Endocrinol (Oxf) 2003; 59: 89-96
  • 32 Hanton L, Axelrod L, Bakalov V et al. The importance of estrogen replacement in young women with Turner syndrome. J Womens Health (Larchmt) 2003; 12: 971-977
  • 33 Zinn AR, Roeltgen D, Stefanatos G et al. A Turner syndrome neurocognitive phenotype maps to Xp22.3. Behav Brain Funct 2007; 3: 24