Abstract
OBJECTIVE: To evaluate bone mineral status and metabolism in a cohort of patients with Williams-Beuren syndrome (WBS). PATIENTS: Thirty-one children (15 females, 16 males; mean age 9.6±2.74 years) and 10 young adults (6 females, 4 males; mean age 21.4±5.11 years) with WBS were cross-sectionally evaluated and compared with two age-, sex-, and body-size-matched paediatric (155 subjects, 75 females and 80 males; mean age 9.7±2.93 years) and adult (50 subjects, 30 females and 20 males; mean age 22.3±5.42 years) healthy controls. MEASUREMENTS: We evaluated ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels, and urinary deoxypyridinoline concentrations. We also calculated the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) z-scores. RESULTS: WBS patients showed a significantly reduced AD-SoS z-score (p <0.001) and BTT z-score (p <0.001) compared with the controls. This finding persisted when we divided the sample into paediatric and adult patients. WBS patients also had significantly higher ionised (p <0.001) and total calcium (p <0.001) levels as well as higher PTH levels (p <0.001) compared with the controls. Furthermore, WBS children and adolescents had significantly lower serum osteocalcin levels (p <0.001) and urinary deoxypyridinoline concentrations (p <0.001) than controls. CONCLUSIONS: WBS subjects exhibit a significant reduction in bone mineral status and impaired bone metabolism. These findings point to the need for close monitoring of WBS patients.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Pober BR, 2010 Williams-Beuren syndrome. N Engl J Med 362: 239–245.
Kaplan P, Wang PP, Francke U, 2001 Williams (Williams Beuren) syndrome: a distinct neurobehavioral disorder. J Child Neurol 16: 177–190.
Strømme P, Bjørnstad PG, Ramstad K, 2002 Prevalence estimation of Williams syndrome. J Child Neurol 17: 269–271.
Stagi S, Bindi G, Neri AS, et al, 2005 Thyroid function and morphology in patients affected by Williams syndrome. Clin Endocrinol (Oxf) 63: 456–460.
Stagi S, Lapi E, Cecchi C, et al, 2014 Williams-Beuren syndrome is a genetic disorder associated with impaired glucose tolerance and diabetes in childhood and adolescence: new insights from a longitudinal study. Horm Res Paediatr 82: 38–43.
Kruse K, Pankau R, Gosch A, Wohlfahrt K, 1992 Calcium metabolism in Williams-Beuren syndrome. J Pediatr 121: 902–907.
Jones KL, 1990 Williams syndrome: an historical perspective of its evolution, natural history, and etiology. Am J Med Genet Suppl 6: 89–96.
Cherniske EM, Carpenter TO, Klaiman C, et al, 2004 Multisystem study of 20 older adults with Williams syndrome. Am J Med Genet A 131: 255–264.
Stagi S, Lapi E, D’Avanzo MG, et al, 2014 Coeliac disease and risk for other autoimmune diseases in patients with Williams-Beuren syndrome. BMC Med Genet 15: 61.
Stagi S, Lapi E, Gambineri E, et al, 2010 Bone density and metabolism in subjects with microdeletion of chromosome 22q11 (de122q11). Eur J Endocrinol 163: 329–337.
Stagi S, Pelosi P, Strano M, et al, 2014 Determinants of Vitamin D Levels in Italian Children and Adolescents: A Longitudinal Evaluation of Cholecalciferol Supplementation versus the Improvement of Factors Influencing 25(OH)D Status. Int J Endocrinol 2014: 58303.
Stagi S, Cavalli L, Bertini F, et al, 2014 Vitamin D levels in children, adolescents, and young adults with juvenile-onset systemic lupus erythematosus: a cross-sectional study. Lupus 23: 1059–1065.
Holick MF, 2007 Vitamin D deficiency. N Engl J Med 357: 266–281.
Stagi S, Cavalli L, Signorini C, et al, 2014 Bone mass and quality in patients with juvenile idiopathic arthritis: longitudinal evaluation of bone-mass determinants by using dual-energy x-ray absorptiometry, peripheral quantitative computed tomography, and quantitative ultrasonography. Arthritis Res Ther 16: R83.
Drozdzowska B, Pluskiewicz W, Halaba Z, Misiolek H, Beck B, 2005 Quantitative ultrasound at the hand phalanges in 2850 females aged 7 to 77 yr: a cross-sectional study. J Clin Densitom 8: 216–221.
Pankau R, Partsch CJ, Gosch A, Oppermann HC, Wessel A, 1992 Statural growth in Williams-Beuren syndrome. Eur J Pediatr 151: 751–755.
Pankau R, Partsch CJ, Neblung A, et al, 1994 Natural history of body mass index in Williams-Beuren syndrome. Am J Med Genet 52: 51–54.
Partsch CJ, Dreyer G, Gosch A, et al, 1999 Longitudinal evaluation of growth, puberty, and bone maturation in children with Williams syndrome. J Pediatr 134: 82–89.
Cacciari E, Milani S, Balsamo A, et al, 2006 Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest 29: 581–593.
Stagi S, Galli L, Cecchi C, et al, 2010 Final height in patients perinatally infected with the human immunodeficiency virus. Horm Res Paediatr 74: 165–1071.
Tanner JM, Whitehouse RH, 1976 Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 51: 170–179.
Stagi S, Cavalli L, Iurato C, et al, 2013 Bone health in children and adolescents: the available imaging techniques. Clin Cases Miner Bone Metab 10: 166–171.
Krieg MA, Barkmann R, Gonnelli S, et al, 2008 Quantitative ultrasound in the management of osteoporosis: the 2007 ISCD Official Positions. J Clin Densitom 11: 163–187.
Chin KY, Ima-Nirwana S, 2013 Calcaneal quantitative ultrasound as a determinant of bone health status: what properties of bone does it reflect? Int J Med Sci 10: 1778–1783.
Hocking DR, McGinley JL, Moss SA, et al, 2010 Effects of external and internal cues on gait function in Williams syndrome. J Neurol Sci 291: 57–63.
Nordstrøm M, Hansen BH, Paus B, Kolset SO, 2013 Accelerometer-determined physical activity and walking capacity in persons with Down syndrome, Williams syndrome and Prader-Willi syndrome. Res Dev Disabil 34: 4395–4403.
Nordstrøm M, Paus B, Andersen LF, Kolset SO, 2015 Dietary aspects related to health and obesity in Williams syndrome, Down syndrome, and Prader-Willi syndrome. Food Nutr Res 59: 25487.
Culler FL, Jones KL, Deftos LJ, 1985 Imparied calcitonin secretion in patients with Williams syndrome. J Pediatr 107: 720–723.
Mathias RS, 2000 Rickets in an infant with Williams syndrome. Pediatr Nephrol 14: 489–492.
Sangun O, Dundar BN, Erdogan E, 2011 Severe hypercalcemia associated with Williams syndrome successfully treated with Pamidronate infusion therapy. J Pediatr Endocrinol Metab 24: 69–70.
Knudtzon J, Aksnes L, Akslen LA, Aarskog D, 1987 Elevated 1,25-dihydroxyvitamin D and normocalcaemia in presumed familial Williams syndrome. Clin Genet 32: 369–374.
Pronicka E, Rowihska E, Kulczycka H, et al, 1997 Persistent hypercalciuria and elevated 25-hydroxyvitamin D3 in children with infantile hypercalcaemia. Pediatr Nephrol 11: 2–6.
Lameris AL, Geesing CL, Hoenderop JG, Schreuder MF, 2014 Importance of dietary calcium and vitamin D in the treatment of hypercalcaemia in Williams-Beuren syndrome. J Pediatr Endocrinol Metab 27: 757–761.
Kruse K, Pankau R, Gosch A, Wohlfahrt K, 1992 Calcium metabolism in Williams-Beuren syndrome. J Pediatr 121: 902–907.
Barnett C, Krebs JE, 2011 WSTF does it all: a multifunctional protein in transcription, repair, and replication. Biochem Cell Biol 89: 12–23.
Kitagawa H, Fujiki R, Yoshimura K, Oya H, Kato S, 2011 Williams syndrome is an epigenome-regulator disease. Endocr J 58: 77–85.
Letavernier E, Rodenas A, Guerrot D, Haymann JP, 2012 Williams-Beuren syndrome hypercalcemia: is TRPC3 a novel mediator in calcium homeostasis? Pediatrics 129: e1626–e1630.
Caraveo G, van Rossum DB, Patterson RL, Snyder SH, Desiderio S, 2006 Action of TFII-I outside the nucleus as an inhibitor of agonist-induced calcium entry. Science 314: 122–125.
Lazebnik MB, Tussie-Luna MI, Hinds PW, Roy AL, 2009 Williams-Beuren syndrome-associated transcription factor TFII-I regulates osteogenic marker genes. J Biol Chem 284: 36234–36239.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Stagi, S., Manoni, C., Scalini, P. et al. Bone mineral status and metabolism in patients with Williams-Beuren syndrome. Hormones 15, 404–412 (2016). https://doi.org/10.14310/horm.2002.1683
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.14310/horm.2002.1683