GH treatment, BMI and different genotypes in patients with Prader-Willi syndrome and scoliosis: Is there any relationship?

Tiziana Greggi, E. Pipitone, K. Martikos, F. Lolli, F. Vommaro, E. Maredi, M. Di Silvestre, S. Giacomini, L. Sangiorgi

Medical Genetics, Rizzoli Orthopaedic Institute—I.O.R., Bologna, Italy.
Spine Surgery Department, Rizzoli Orthopaedic Institute—I.O.R., Bologna, Italy.

DOI: 10.4236/jbise.2013.611132                

Abstract

The purpose of this study is to try to find a protocol defining a clinical diagnostic procedure for the patients to be admitted to the authors’ Institute to receive treatment for either suspected or confirmed diagnosis of spine deformity in Prader-Willi syndrome (PWS). The aim is to evaluate every subject from the diagnostic point of view, assessing variability of clinical expression and evolution of spinal deformity in the light of the related genetic aspects, thus providing a univocal protocol. The present series only includes patients (18 cases) with PWS, 7 hospitalized for surgical treatment of scoliosis, 11 followed-up at the authors’ institute only for conservative treatment of scoliosis. Both BMI tracks (weight/height²) and BMI Z-score (only for children older than 2 years) were assessed. Moreover, the GH treatment was evaluated for each group of patients as follows: being administered, suspended or no treatment. Finally, the gene was compared with BMI. No relationship was observed either between GH treatment and mean BMI or between genetics and mean BMI. More patients should be seen by the authors to confirm or refute the current findings.

Keywords

Scoliosis; Prader-Willi; GH; BMI

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Grugni, G., Crinò, A., Bertocco, P. and Marzullo, P. (2009) Body fat excess and stimulate growth hormone levels in adult patients with Prader-Willi syndrome. American Journal of Medical Genetics, 149A, 726-731.
[2]	Orphanet (2010). Prevalence of rare diseases: Bibliographic data.
[3]	Feigerlová, E., Diene, G., Conte-Auriol, F., Molinas, C., Gennero, I., Salles, J.P., Arnaud, C. and Tauber, M. (2008) Hyperghrelinemia precedes obesity in Prader-Willi syndrome. The Journal of Clinical Endocrinology & Metabolism, 93, 2800-2805.
[4]	Horsthemke, B. and Wagstaff, J. (2008) Mechanisms of imprinting of the Prader-Willi/Angelman region. American Journal of Medical Genetics, 146A, 2041-2052. http://dx.doi.org/10.1002/ajmg.a.32364
[5]	Ledbetter, D.H., Riccardi, V.M., Airhart, S.D., Strobel, R.J., Keenan, B.S. and Crawford, J.D. (1981) Deletions of chromosome 15 as a cause of the Prader-Willi syndrome. The New England Journal of Medicine, 304, 325-329. http://dx.doi.org/10.1056/NEJM198102053040604
[6]	Nicholls, R.D., Knoll, J.H., Butler, M.G., Karam, S. and Lalande, M. (1989) Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome. Nature, 342, 281-285. http://dx.doi.org/10.1038/342281a0
[7]	Buiting, K., Saitoh, S., Gross, S., Dittrich, B., Schwartz, S., Nicholls, R.D., et al. (1995) Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15. Nature Genetics, 9, 395-400. http://dx.doi.org/10.1038/ng0495-395
[8]	Sinnema, M., van Roozendaal, K.E., Maaskant, M.A., Smeets, H.J., Engelen, J.J., Jonker-Houben, N., et al. (2010) Different distribution of the genetic subtypes of the Prader-Willi syndrome in the elderly. European Journal of Human Genetics, 18, 993-998. http://dx.doi.org/10.1038/ejhg.2010.67
[9]	Whittington, J.E., Butler, J.V. and Holland, A.J. (2007) Changing rates of genetic subtypes of Prader-Willi syndrome in the UK. European Journal of Human Genetics, 15, 127-130. http://dx.doi.org/10.1038/sj.ejhg.5201716
[10]	Grugni, G., Crino, A., Bosio, L., Corrias, A., Cuttini, M., De Toni, T., et al. (2008) The Italian National Survey for Prader-Willi syndrome: An epidemiologic study. American Journal of Medical Genetics, 146, 861-872. http://dx.doi.org/10.1002/ajmg.a.32133
[11]	Holm, V.A., Cassidy, S.B., Butler, M.G., Hanchett, J.M., Greenswag, L.R., Whitman, B.Y., et al. (1993) PraderWilli syndrome: Consensus diagnostic criteria. Pediatrics, 91, 398-402.
[12]	Gunay-Aygun, M., Schwartz, S., Heeger, S., O’Riordan, M.A. and Cassidy, S.B. (2001) The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria. Pediatrics, 108, E92. http://dx.doi.org/10.1542/peds.108.5.e92
[13]	Goldstone, A.P., Holland, A.J., Hauffa, B.P., Hokken-Koelega, A.C. and Tauber, M. (2008) Recommendations for the diagnosis and management of Prader-Willi syndrome. The Journal of Clinical Endocrinology & Metabolism, 93, 4183-4197. http://dx.doi.org/10.1210/jc.2008-0649
[14]	Fillion, M., Deal, C. and Van Vliet, G. (2009) Retrospective study of the potential benefits and adverse events during growth hormone treatment in children with Prader-Willi syndrome. Journal of Pediatrics, 154, 230-233.
[15]	Lin, H.Y., Lin, S.P., Tsai, L.P., Chao, M.C., Chen, M.R., Chuang, C.K., Huang, C.Y., Tsai, F.J., Chou, I.C., Chiu, P.C., Huang, C.H., Yen, J.L., Lin, J.L. and Kuo, P.L. (2008) Effects of growth hormone treatment on height, weight, and obesity in Taiwanese patients with Prader-Willi syndrome. Journal of the Chinese Medical Association, 71, 305-309.
[16]	de Lind van Wijngaarden, R.F., de Klerk, L.W., Festen, D.A. and Hokken-Koelega, A.C. (2008) Scoliosis in Prader-Willi syndrome: Prevalence, effects of age, gender, body mass index, lean body mass and genotype. Archives of Disease in Childhood, 93, 1012-1016. http://dx.doi.org/10.1136/adc.2007.123836
[17]	Nakamura, Y., Nagai, T., Iida, T., Ozeki, S. and Nohara, Y. (2009) Epidemiological aspects of scoliosis in a cohort of Japanese patients with Prader-Willi syndrome. Spine Journal, 9, 809-816. http://dx.doi.org/10.1016/j.spinee.2009.06.017
[18]	Sinnema, M., Maaskant, M.A., van Schrojenstein Lantman-de Valk, H.M., Caroline, V.N.I., Drent, M.L., Curfs, L.M., et al. (2011) Physical health problems in adults with Prader-Willi syndrome. American Journal of Medical Genetics, 155, 2112-2124. http://dx.doi.org/10.1002/ajmg.a.34171
[19]	Butler, M.G., Haber, L., Mernaugh, R., Carlson, M.G., Price, R. and Feurer, I.D. (2001) Decreased bone mineral density in Prader-Willi syndrome: Comparison with obese subjects. American Journal of Medical Genetics, 103, 216-222. http://dx.doi.org/10.1002/ajmg.1556
[20]	Kroonen, L.T., Herman, M., Pizzutillo, P.D. and Macewen, G.D. (2006) Prader-Willi Syndrome: Clinical concerns for the orthopaedic surgeon. Journal of Pediatric Orthopaedics, 26, 673-679. http://dx.doi.org/10.1097/01.bpo.0000226282.01202.4f
[21]	Festen, D.A., de Lind van Wijngaarden, R., van Eekelen, M., Otten, B.J., Wit, J.M., Duivenvoorden, H.J. and Hokken-Koelega, A.C. (2008) Randomized controlled GH trial: Effects on anthropometry, body composition and body proportions in a large group of children with Prader-Willi syndrome. Clinical Endocrinology, 69, 443-451.
[22]	Crinò, A., Di Giorgio, G., Schiaffini, R., Fierabracci, A., Spera, S., Maggioni, A. and Gattinara, G.C. (2008) Central precocious puberty and growth hormone deficiency in a boy with Prader-Willi syndrome. European Journal of Pediatrics, 167, 1455-1458.
[23]	Galassetti, P., Saetrum Opgaard, O., Cassidy, S.B. and Pontello, A. (2007) Nutrient intake and body composition variables in Prader-Willi syndrome—Effect of growth hormone supplementation and genetic subtype. Journal of Pediatric Endocrinology and Metabolism, 20, 491-500.
[24]	Costeff, H., Holm, V.A., Ruvalcaba, R. and Shaver, J. (1990) Growth hormone secretion in Prader-Willi syndrome. Acta paediatrica Scandinavica, 79, 1059-1062. http://dx.doi.org/10.1111/j.1651-2227.1990.tb11383.x
[25]	Myers, S.E., Whitman, B.Y., Carrel, A.L., Moerchen, V., Bekx, M.T. and Allen, D.B. (2007) Two years of growth hormone therapy in young children with Prader-Willi syndrome: Physical and neurodevelopmental benefits. American Journal of Medical Genetics, 143, 443-448. http://dx.doi.org/10.1002/ajmg.a.31468
[26]	Tauber, M. and Cutfield, W. (2007) KIGS highlights: Growth hormone treatment in Prader-Willi Syndrome. Hormone Research, 68, 48-50.
[27]	Caixàs, A., Giménez-Palop, O., Broch, M., Vilardell, C., Megía, A., Simón, I.,Giménez-Pérez, G., Mauricio, D., Vendrell, J., Richart, C. and González-Clemente, J.M. (2008) Adult subjects with Prader-Willi syndrome show more low-grade systemic inflammation than matched obese subjects. Journal of Endocrinological Investigation, 31, 169-175.
[28]	Frankenfield et al. (2001) Limits of body mass index to detect obesity and predict body composition. Nutrition, 17, 26-30. http://dx.doi.org/10.1016/S0899-9007(00)00471-8
[29]	Deurenberg-Yap et al. (2000) The paradox of low body mass index and high body fat percentage among Chinese, Malays, and Indians in Singapore. International Journal of Obesity and Related Metabolic Disorders, 24, 1011-1017. http://dx.doi.org/10.1038/sj.ijo.0801353
[30]	Berkey, C.S. and Colditz, G.A. (2007) Adiposity in adolescents: Change in actual BMI works better than change in BMI z score for longitudinal studies. Annals of Epidemiology, 17, 44-50.
[31]	Goldstone, A.P., Holland, A.J., Hauffa, B.P., HokkenKoelega, A.C., Tauber, M. and Speakers Contributors at the Second Expert Meeting of the Comprehensive Care of Patients with PWS (2008) Recommendations for the diagnosis and management of Prader-Willi syndrome. The Journal of Clinical Endocrinology & Metabolism, 93, 4183-4197.
[32]	Sode-Carlsen, R., Farholt, S., Rabben, K.F., Bollerslev, J., Schreiner, T., Jurik, A.G., et al. (2010) One year of growth hormone treatment in adults with Prader-Willi syndrome improves body composition: Results from a randomized, placebo-controlled study. The Journal of Clinical Endocrinology & Metabolism, 95, 4943-4950. http://dx.doi.org/10.1210/jc.2010-0907
[33]	Hoybye, C., Hilding, A., Jacobsson, H. and Thoren, M. (2003) Growth hormone treatment improves body composition in adults with Prader-Willi syndrome. Clinical Endocrinology, 58, 653-661. http://dx.doi.org/10.1046/j.1365-2265.2003.01769.x
[34]	Bertella, L., Mori, I., Grugni, G., Pignatti, R., Ceriani, F., Molinari, E., et al. (2007) Quality of life and psychological well-being in GH-treated, adult PWS patients: A longitudinal study. Journal of Intellectual Disability Research, 51, 302-311. http://dx.doi.org/10.1111/j.1365-2788.2006.00878.x
[35]	Mogul, H.R., Lee, P.D., Whitman, B.Y., Zipf, W.B., Frey, M., Myers, S., et al. (2008) Growth hormone treatment of adults with Prader-Willi syndrome and growth hormone deficiency improves lean body mass, fractional body fat, and serum triiodothyronine without glucose impairment: results from the United States multicenter trial. The Journal of Clinical Endocrinology & Metabolism, 93, 1238-1245. http://dx.doi.org/10.1210/jc.2007-2212