Long-term auxological and endocrinological evaluation of patients with 9p trisomy: a focus on the growth hormone-insulin-like growth factor-I axis

BMC Endocrine Disorders

Maurizio de Martino¹  Francesco Chiarelli³  Sabrina Giglio²  Marilena Pantaleo²  Silvia Guarducci²  Salvatore Seminara¹  Elisabetta Lapi²  Stefano Stagi¹ 

[1] Department of Health’s Sciences, Paediatric Endocrinology Unit, University of Florence, Anna Meyer Children’s University Hospital, Florence, Italy;Genetics and Molecular Medicine Unit, Anna Meyer Children’s University Hospital, Florence, Italy;Department of Paediatrics, University of Chieti, Chieti, Italy

关键词: Scoliosis;    Short Stature;    Growth delay;    Pubertal delay;    Growth hormone deficiency;    Growth Hormone;    Trisomy 9p;   

Others  :  1085374
DOI  :  10.1186/1472-6823-14-3

 received in 2013-06-11, accepted in 2013-12-09,  发布年份 2014

【 摘 要 】

Background

Trisomy 9p is an uncommon anomaly characterised by mental retardation, head and facial abnormalities, congenital heart defects, kidney abnormalities, and skeletal malformations. Affected children may also show growth and puberty retardation with delayed bone age. Auxological and endocrinological data are lacking for this syndrome.

Methods

We describe three girls and one boy with 9p trisomy showing substantial growth failure, and we evaluate the main causes of their short stature.

Results

The target height was normal in all families, ranging from 0.1 and -1.2 standard deviation scores (SDS). The patients had a low birth-weight (from -1.2 to -2.4 SDS), birth length (from -1.1 to -3.2 SDS), and head circumference (from -0.5 to -1.6 SDS). All patients presented with substantial growth (height) retardation at the time of 9p trisomy diagnosis (from -3.0 to -3.8 SDS).

The growth hormone stimulation test revealed a classic growth hormone (GH) deficiency (GHD) in patients 1, 3, and 4. In contrast, patient 2 was determined to have a GH neurosecretory dysfunction (GHNSD). The plasma concentrations of IGF-I and IGFBP-3 were low in all patients for their ages and sexes (from -2.0 to -3.4 SDS, and from -1.9 to -2.8 SDS, respectively).

The auxological follow-up showed that those patients who underwent rhGH treatment exhibited a very good response to the GH therapy, whereas patients 3 and 4, whose families chose not to use rhGH treatment, did not experience any significant catch-up growth.

Conclusions

GH deficiency appears to be a possible feature of patients with 9p trisomy syndrome. These patients, particularly those with growth delays, should be evaluated for GH secretion.

【 授权许可】

   
2014 Stagi et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Temtamy SA, Kamel AK, Ismail S, Helmy NA, Aglan MS, El Gammal M, El Ruby M, Mohamed AM: Phenotypic and cytogenetic spectrum of 9p trisomy. Genet Couns 2007, 18:29-48.
• [2]Rethoré MO, Larget-Piet L, Abonyi D, Boeswillwald M, Berger R, Carpentier S, Cruveiller J, Dutrillau B, Lafourcade J, Penneau M, Lejeune J: Sur quatre cas de trisomie pour le bras court du chromosome 9: individualisation d’une nouvelle entite morbide. Ann Genet 1970, 13:217-232.
• [3]Huret JL, Leonard C, Forestier B, Rethore MO, Lejeune J: Eleven new cases of del(9p) and features from 80 cases. J Med Genet 1988, 25:741-749.
• [4]Seghezzi L, Maraschio P, Bozzola M, Maserati E, Tupler R, Marchi A, Tiepolo L: Ring chromosome 9 with a 9p22.3-p24.3 duplication. Eur J Pediatr 1999, 158:791-793.
• [5]Schinzel A: Catalogue of unbalanced chromosome aberrations in man. 2nd edition. New York: W de Gruyter Berlin; 2001.
• [6]Morrissette JJ, Laufer-Cahana A, Medne L, Russell KL, Venditti CP, Kline R, Zackai EH, Spinner NB: Patient with trisomy 9p and a hypoplastic left heart with a tricentric chromosome 9. Am J Med Genet 2003, 123A:279-284.
• [7]Nakagawa M, Kato H, Aotani H, Kondo M: Ebstein’s anomaly associated with trisomy 9p. Clin Genet 1999, 55:383-385.
• [8]Federico A, Tomasetti P, Zollino M, Diomedi M, Dotti MT, De Stefano N, Gualdi GF, Neri G, Gigli GL: Association of trisomy 9p and band heterotopia. Neurology 1999, 53:430-432.
• [9]Stern JM: The epilepsy of trisomy 9p. Neurology 1996, 47:821-824.
• [10]Schinzel A: Trisomy 9p, a chromosome aberration with distinct radiologic findings. Radiology 1979, 130:125-133.
• [11]Wilson GN, Raj A, Baker D: The phenotypic and cytogenetic spectrum of partial trisomy 9. Am J Med Genet 1985, 20:277-282.
• [12]Haddad BR, Lin AE, Wyandt H, Milunsky A: Molecular cytogenetic characterisation of the first familial case of partial 9p duplication (p22p24). J Med Genet 1996, 33:1045-1047.
• [13]Fujita H, Shimazaki M, Takeuchi T, Hayakawa Y, Oura T: 47,+(9q-) in unrelated three children with plasma growth hormone deficiency. Hum Genet 1976, 31:271-282.
• [14]Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, et al.: Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest 2006, 29:581-593.
• [15]Stagi S, Galli L, Cecchi C, Chiappini E, Losi S, Gattinara CG, Gabiano C, Tovo PA, Bernardi S, Chiarelli F, de Martino M: Final height in patients perinatally infected with the human immunodeficiency virus. Horm Res Paediatr 2010, 74:165-171.
• [16]Bercu BB, Shulman D, Root AW, Spiliotis BE: Growth hormone (GH) provocative testing frequently does not reflect endogenous GH secretion. J Clin Endocrinol Metab 1986, 63:709-716.
• [17]Ghizzoni L, Mastorakos G, Vottero A, Ziveri M, Ilias I, Bernasconi S: Spontaneous growth hormone (GH) secretion is not directly affected by ghrelin in either short normal prepubertal children or children with GH neurosecretory dysfunction. J Clin Endocrinol Metab 2004, 89:5488-5495.
• [18]Tanner JM, Whitehouse RH: Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976, 51:170-179.
• [19]Greulich WW, Pyle SI: Radiographic Atlas of Skeletal Development of the Hand and Wrist. Stanford, CA: Stanford University Press; 1959.
• [20]Bayley N, Pinneau SR: Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards. J Pediatr 1952, 40:423-441.
• [21]Hermanussen M, Cole J: The calculation of target height reconsidered. Horm Res 2003, 59:180-183.
• [22]Claussen U, Michel S, Mühlig P, Westermann M, Grummt UW, Kromeyer-Hauschild K, Liehr T: Demystifying chromosome preparation and the implications for the concept of chromosome condensation during mitosis. Cytogenet Genome Res 2002, 98:136-146.
• [23]Shaffer L, Slovak M, Cambell L, ISCN: An International System for Human Cytogenetic Nomenclature. Basel: Karger; 2009.
• [24]Bussani Mastellone C, Giovannucci Uzielli ML, Guarducci S, Nathan G: Four cases of trisomy 9p syndrome with particular chromosome rearrangements. Ann Genet 1991, 34:115-119.
• [25]Pinkel D, Segraves R, Sudar D, Clark S, Poole I, Kowbel D, Collins C, Kuo WL, Chen C, Zhai Y, Dairkee SH, Ljung BM, Gray JW, Albertson DG: High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 1998, 20:207-211.
• [26]Shaffer LG, Bejjani BA: Medical applications of array CGH and the transformation of clinical cytogenetics. Cytogenet Genome Res 2006, 115:303-309.
• [27]Hacihanefioğlu S, Güven GS, Deviren A, Silahtaroğlu AN, Yosunvkaya Fenerci E, Ozkiliç A, Yüksel A: Trisomy 9p syndrome in two brothers: with new clinical findings and review of the literature. Genet Couns 2002, 13:41-48.
• [28]Gustavson KH, Wahlström J: Trisomy 9p syndrome and XYY syndrome in siblings. Clin Genet 1977, 11:67-72.
• [29]Mehta A, Hindmarsh PC, Mehta H, Turton JP, Russell-Eggitt I, Taylor D, Chong WK, Dattani MT: Congenital hypopituitarism: clinical, molecular and neuroradiological correlates. Clin Endocrinol (Oxf) 2009, 71:376-382.
• [30]Haeusler G, Frisch H, Guchev Z, Hadziselimovic F, Neuhold A, Vormittag W: Hypoplasia of the corpus callosum and growth hormone deficiency in the XXXXY syndrome. Am J Med Genet 1992, 44:230-232.
• [31]Cameron FJ, Khadilkar VV, Stanhope R: Pituitary dysfunction, morbidity and mortality with congenital midline malformation of the cerebrum. Eur J Pediatr 1999, 158:97-102.
• [32]Rappaport R, Czernichow P: Disorders of growth and prolactin secretion. In Pediatric Endocrinology. Physiology, Pathophysiology, and Clinical Aspects. Edited by Bertrand J, Rappaport R, Sizonenko PC. Baltimore: Williams & Wilkins; 1993:220.
• [33]Wang ED, Drummond DS, Dormans JP, Moshang T, Davidson RS, Gruccio D: Scoliosis in patients treated with growth hormone. J Pediatr Orthop 1997, 17:708-711.
• [34]Vidil A, Journeau P, Soulie A, Padovani JP, Pouliquen JC: Evolution of scoliosis in six children treated with growth hormone. J Pediatr Orthop B 2001, 10:197-200.
• [35]Clayton PE, Cowell CT: Safety issues in children and adolescents during growth hormone therapy–a review. Growth Horm IGF Res 2000, 10:306-317.